ANZCA Acute Pain Scientific Evidence Update Dec 2007

Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine
ACUTE PAIN MANAGEMENT: SCIENTIFIC EVIDENCE

2ND EDITION
UPDATES
Last update:
DECEMBER 2007
Acute Pain Management: Scientific Evidence 2nd edition (APS:SE 2e) was published in July 2005 and is due for revision in 2010. However, as the field of acute pain medicine is a rapidly changing one, members of the ANZCA/FPM working party responsible for the development of APS:SE 2e decided to periodically update certain topics when new evidence became available. For the purposes of this update, publications rated as Level I evidence (levels of evidence are rated according to the NHMRC designation, as in APS:SE 2e) published since January 2005 were reviewed. Information from a very small number of other publications (evidence level ratings less than Level I) has been included where the working party thought it to be of major importance. This update should be read in conjunction with APS:SE 2e. In some instances the information is new, but any conclusions made in APS:SE 2e remain unchanged. In others, the new information has led to an updated/ changed key message. The content of this update is arranged under headings that correspond with the relevant sections in APS:SE 2e. The contents list of APS:SE 2e is summarised below and sections where information has been updated are marked with as asterisk*: the page numbers listed refer to this update document. Also reproduced is the summary of key messages from APS:SE 2e; those messages that have been updated/ changed are highlighted. Please note that: a. These updates have not been subjected to the Australian National Health and Medical Research Council (NHMRC) processes for guideline development and have not been submitted to the NHMRC for approval. b. As with APS:SE 2e, these updates are intended to be a general guide based on the best evidence available at the time and are subject to the clinicians judgement and the patients preference in each individual case.
Members of the Working Party responsible for the Updates to APS:SE 2e: Dr Pam Macintyre (Chair) Professor Stephan Schug Assoc. Professor David Scott Dr Eric Visser Dr Suellen Walker
Australian and New Zealand College of Anaesthetists 2007
Updates for Acute Pain Management: Scientific Evidence
December 2007
CONTENTS
UPDATED SUMMARY OF KEY MESSAGES ........................................................................................4 1. PHYSIOLOGY AND PSYCHOLOGY OF ACUTE PAIN 1.1 1.2 1.3 1.4* 1.5 2. Applied physiology of pain Psychological aspects of acute pain Progression of acute to chronic pain Pre-emptive and preventive analgesia................................................................ 22 Adverse physiological and psychological effects of pain
ASSESSMENT AND MEASUREMENT OF ACUTE PAIN AND ITS TREATMENT 2.1 2.2 2.3 Assessment Measurement Outcome measures in acute pain management
3.
PROVISION OF SAFE AND EFFECTIVE ACUTE PAIN MANAGEMENT 3.1* 3.2 Education ................................................................................................................... 23 Organisational requirements
4.
SYSTEMICALLY ADMINISTERED ANALGESIC DRUGS 4.1* 4.2* 4.3* Opioids ........................................................................................................................ 24 Paracetamol, NSAIDs and COX-2 selective inhibitors ........................................ 24 Adjuvant drugs .......................................................................................................... 27
5.
REGIONALLY AND LOCALLY ADMINISTERED ANALGESIC DRUGS 5.1* 5.2* 5.3* 5.4* Local Anaesthetics ................................................................................................... 31 Opioids ........................................................................................................................ 31 Adjuvant drugs .......................................................................................................... 32 Anti-inflammatory Drugs .......................................................................................... 33
6.
ROUTES OF SYSTEMIC DRUG ADMINISTRATION 6.1* 6.2 6.3 6.4 6.5* 6.6 Oral route.................................................................................................................... 34 Intravenous route Intramuscular and subcutaneous routes Rectal route Transdermal route ..................................................................................................... 34 Transmucosal routes
7.
TECHNIQUES OF DRUG ADMINISTRATION 7.1* 7.2* 7.3 7.4* 7.5* Patient-controlled analgesia .................................................................................. 35 Epidural Analgesia .................................................................................................... 36 Intrathecal analgesia Regional analgesia and concurrent anticoagulant medications................... 38 Other regional and local analgesic techniques ................................................. 38
8.
NON-PHARMACOLOGICAL TECHNIQUES 8.1* 8.2 8.3 8.4* Psychological interventions..................................................................................... 41 Transcutaneous electrical nerve stimulation Acupuncture Physical therapies ..................................................................................................... 41
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9.
SPECIFIC CLINICAL SITUATIONS 9.1 9.2* 9.3 9.4 9.5 9.6* 9.7* 9.8 9.9* Postoperative pain Acute spinal cord injury ........................................................................................... 42 Acute burns injury pain Acute back pain Acute musculoskeletal pain Acute medical pain ................................................................................................. 42 Acute cancer pain ................................................................................................... 45 Acute pain management in intensive care Acute pain management in emergency departments .................................... 45
10. SPECIFIC PATIENT GROUPS 10.1* The paediatric patient ............................................................................................. 47 10.2* The pregnant patient ............................................................................................... 50 10.3* The elderly patient .................................................................................................... 52 10.4 10.5 10.6 10.7 10.8 Aboriginal and Torres Strait Islander peoples Other ethnic groups and non-English speaking patients The patient with obstructive sleep apnoea The patient with concurrent hepatic or renal disease The opioid-tolerant patient
10.9* The patient with a substance abuse disorder...................................................... 52 REFERENCES ................................................................................................. 53
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UPDATED SUMMARY OF KEY MESSAGES

The key messages below are reproduced from APM:SE 2e. Those that have updated, changed or confirmed are shaded; the original key message remains above (greyed and struck out) so that comparisons can be made.
1. Physiology and psychology of acute pain

Psychological aspects of acute pain 1. Preoperative anxiety, catastrophising, neuroticism and depression are associated with higher postoperative pain intensity (Level IV). 2. Preoperative anxiety and depression are associated with an increased number of patientcontrolled analgesia (PCA) demands and dissatisfaction with PCA (Level IV). ; Pain is an individual, multifactorial experience influenced by culture, previous pain events, beliefs, mood and ability to cope. Progression of acute to chronic pain 1. Some specific early analgesic interventions reduce the incidence of chronic pain after surgery (Level II). 2. Chronic postsurgical pain is common and may lead to significant disability (Level IV). 3. Risk factors that predispose to the development of chronic postsurgical pain include the severity of pre and postoperative pain, intraoperative nerve injury and psychological vulnerability (Level IV). 4. Many patients suffering chronic pain relate the onset to an acute incident (Level IV). Pre-emptive and preventive analgesia 1. The timing of a single analgesic intervention (preincisional versus postincisional), defined as pre-emptive analgesia, does not have a clinically significant effect on postoperative pain relief (Level I). 1. The timing of a single analgesic intervention (preincisional versus postincisional), defined as pre-emptive analgesia, has a significant effect on postoperative pain relief with epidural analgesia and may have a significant effect with local anaesthetic wound infiltration and NSAIDs (Level I). 2. There is evidence that some analgesic interventions have an effect on postoperative pain and/or analgesic consumption that exceeds the expected duration of action of the drug, defined as preventive analgesia (Level I). 3. NMDA (n-methyl-D-aspartate) receptor antagonist drugs in particular may show preventive analgesic effects (Level I).
2. Assessment and measurement of acute pain and its treatment

Measurement 1. Regular assessment of pain leads to improved acute pain management (Level III-3). 2. There is good correlation between the visual analogue and numerical rating scales (Level IV). ; Self-reporting of pain should be used whenever appropriate as pain is by definition a subjective experience. ; The pain measurement tool chosen should be appropriate to the individual patient; developmental, cognitive, emotional and cultural factors should be considered. ; Scoring should incorporate different components of pain. In the postoperative patient this should include static (rest) and dynamic (eg pain on sitting, coughing) pain. ; Uncontrolled or unexpected pain requires a reassessment of the diagnosis and consideration of alternative causes for the pain (eg new surgical/ medical diagnosis, neuropathic pain). Outcome measures in acute pain management ; Multiple outcome measures are required to adequately capture the complexity of the pain experience and how it may be modified by pain management interventions.
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3. Provision of safe and effective acute pain management

1. Preoperative education improves patient or carer knowledge of pain and encourages a more positive attitude towards pain relief (Level II). 2. Implementation of an acute pain service may improve pain relief and reduce the incidence of side effects (Level III-3). 3. Staff education and the use of guidelines improve pain assessment, pain relief and prescribing practices (Level III-3). 4. Even simple techniques of pain relief can be more effective if attention is given to education, documentation, patient assessment and provision of appropriate guidelines and policies (Level III-3). ; Successful management of acute pain requires close liaison with all personnel involved in the care of the patient. ; More effective acute pain management will result from appropriate education and organisational structures for the delivery of pain relief rather than the analgesic techniques themselves.
4. Systemically administered analgesic drugs

Opioids 1. Dextropropoxyphene has low analgesic efficacy (Level I [Cochrane Review]). 2. Tramadol is an effective treatment in neuropathic pain (Level I [Cochrane Review]). 3 Droperidol, dexamethasone and ondansetron are equally effective in prophylaxis of postoperative nausea and vomiting (Level I).
4. Naloxone, naltrexone, nalbuphine and droperidol are effective treatments for opioid-induced pruritus (Level I). 5. In the management of acute pain, one opioid is not superior over others but some opioids are better in some patients (Level II). 6. The incidence of clinically meaningful adverse effects of opioids is dose-related (Level II). 7. Tramadol has a lower risk of respiratory depression and impairs gastrointestinal motor function less than other opioids at equianalgesic doses (Level II). 8. Pethidine is not superior to morphine in treatment of pain of renal or biliary colic (Level II). 9. Supplemental oxygen in the postoperative period improves oxygen saturation and reduces tachycardia and myocardial ischaemia (Level II). 10. In adults, patient age rather than weight is a better predictor of opioid requirements, although there is a large interpatient variation (Level IV). 11. Impaired renal function and the oral route of administration result in higher levels of the morphine metabolites M3G and M6G (Level IV). ; Assessment of sedation level is a more reliable way of detecting early opioid-induced respiratory depression than a decreased respiratory rate. 12. Assessment of sedation level is a more reliable way of detecting early opioid-induced respiratory depression than a decreased respiratory rate. Level III-3 ; The use of pethidine should be discouraged in favour of other opioids. Paracetamol, non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors 1. Paracetamol is an effective analgesic for acute pain (Level I [Cochrane Review]). 1. Paracetamol is an effective analgesic for acute pain; the incidence of adverse effects comparable to placebo (Level I [Cochrane Review]). 2. NSAIDs and COX-2 inhibitors are effective analgesics of similar efficacy for acute pain (Level I [Cochrane Review]). 3. NSAIDs given in addition to paracetamol improve analgesia (Level I). 4. With careful patient selection and monitoring, the incidence of NSAID-induced perioperative renal impairment is low (Level I [Cochrane Review]). 5. Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy (Level I). 5. Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy, except in paediatric patients. (Level I [Cochrane Review]).
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6. COX-2 inhibitors and NSAIDs have similar adverse effects on renal function (Level I). 7. COX-2 selective inhibitors do not appear to produce bronchospasm in individuals known to have aspirin-exacerbated respiratory disease (Level I). 8. Paracetamol, NSAIDs and COX-2 inhibitors are valuable components of multimodal analgesia (Level II). 9. COX-2 inhibitors do not impair platelet function (Level II). 9. COX-2 inhibitors do not impair platelet function; this leads to reduced perioperative blood loss in comparison with NSAIDs (Level II). 10. Short-term use of COX-2 inhibitors results in gastric ulceration rates similar to placebo (Level II). 11. Use of parecoxib followed by valdecoxib after coronary artery bypass surgery increases the incidence of cardiovascular events (Level II). ; Adverse effects of NSAIDs are significant and may limit their use. ; The risk of adverse renal effects of NSAIDs and COX-2 inhibitors is increased in the presence of factors such as pre-existing renal impairment, hypovolaemia, hypotension, use of other nephrotoxic agents and ACE inhibitors. ; Serious cardiovascular complications have been reported with the use of COX-2 inhibitors in some settings and the use of these agents is currently being assessed; no recommendation about their use can be made until further evidence is available. 12. NSAIDs given in addition to PCA opioids reduce opioid consumption and the incidence of nausea, vomiting and sedation (Level I). 13. Perioperative NSAIDs increase the risk of severe bleeding compared with placebo (Level I). 14. Preoperative COX-2 inhibitors reduce postoperative pain and opioid consumption and increase patient satisfaction (Level I). 15. Parecoxib and/or valdecoxib compared with placebo does not increase the risk of cardiovascular adverse events after non-cardiac surgery (Level I). 16 COX-2 inhibitors and NSAIDs are associated with similar rates of adverse cardiovascular effects, in particular myocardial infarction; naproxen may be associated with a lower risk than other NSAIDs (Level I). 17. Short-term use of COX-2 inhibitors does not affect bone healing in spinal fusion (Level II). Adjuvant drugs Nitrous oxide 1. Nitrous oxide is an effective analgesic during labour (Level I). 2. Nitrous oxide is an effective analgesic agent in a variety of other acute pain situations (Level II). ; Neuropathy and bone marrow suppression are rare but potentially serious complications of nitrous oxide use, particularly in at-risk patients. ; The information about the complications of nitrous oxide comes from case reports only. There are no controlled studies that evaluate the safety of repeated intermittent exposure to nitrous oxide in humans and no data to guide the appropriate maximum duration or number of times a patient can safely be exposed to nitrous oxide. The suggestions for use of nitrous oxide are extrapolations only from the information above. Consideration should be given to duration of exposure and supplementation with vitamin B12, methionine, and folic or folinic acid. ; If nitrous oxide is used with other sedative or analgesic agents, appropriate clinical monitoring should be used. N-methyl-D-aspartate receptor (NMDA) antagonists 1. Ketamine has an opioid-sparing effect in postoperative pain although there is no concurrent reduction in opioid-related side effects (Level I). 1. Analgesic doses of ketamine have a postoperative opioid-sparing effect; used in conjunction with PCA morphine, the incidence of postoperative nausea and vomiting is reduced. (Level I [Cochrane Review]). 2. NMDA receptor antagonist drugs may show preventive analgesic effects (Level I). 3. Ketamine improves analgesia in patients with severe pain that is poorly responsive to opioids (Level II).
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4. Ketamine may reduce opioid requirements in opioid-tolerant patients (Level IV). ; Ketamine may be a useful adjunct in conditions of allodynia, hyperalgesia and opioid tolerance. 5. There is no convincing evidence that magnesium reduces postoperative pain intensity or analgesic consumption (Level I). Antidepressant drugs 1. Tricyclic antidepressants are effective in the treatment of chronic neuropathic pain states, chronic headaches and chronic back pain (Level I). 2. In neuropathic pain, tricyclic antidepressants are more effective than selective serotonergic re-uptake inhibitors (Level I). 2. In neuropathic pain, tricyclic antidepressants are as effective as venlafaxine and more effective than selective serotonergic re-uptake inhibitors (Level I [Cochrane Review]). 3. Antidepressants reduce the incidence of chronic neuropathic pain after acute zoster and breast surgery (Level II). ; Based on the experience in chronic neuropathic pain states, it would seem reasonable to use tricyclic antidepressants in the management of acute neuropathic pain. ; To minimise adverse effects, particularly in elderly people, it is advisable to initiate treatment with low doses. Anticonvulsant drugs 1. Anticonvulsants are effective in the treatment of chronic neuropathic pain states (Level I). 1. The anticonvulsants gabapentin, pregabalin and carbamazepine are effective in the treatment of chronic neuropathic pain states; lamotrigine may not be effective (Level I [Cochrane Review]). 2. Perioperative gabapentin reduces postoperative pain and opioid requirements (Level I). 2. Perioperative gabapentinoids (gabapentin/ pregabalin) reduce postoperative pain, opioid requirements, and the incidence of opioid-related adverse effects, but increases the risk of sedation (Level I). ; Based on the experience in chronic neuropathic pain states, it would seem reasonable to use anticonvulsants in the management of acute neuropathic pain. Membrane stabilisers 1. Membrane stabilisers are effective in the treatment of chronic neuropathic pain states, particularly after peripheral nerve trauma (Level I). 2. Perioperative intravenous lignocaine (lidocaine) reduces pain on movement and morphine requirements following major abdominal surgery (Level II). ; Based on the experience in chronic neuropathic pain states, it would seem reasonable to use membrane stabilisers in the management of acute neuropathic pain. ; Lignocaine (lidocaine) (intravenous or subcutaneous) may be a useful agent to treat acute neuropathic pain. Alpha-2 agonists 1. The use of systemic alpha-2-agonists consistently improves perioperative opioid analgesia, but frequency and severity of side effects may limit their clinical usefulness (Level II). Calcitonin 1. Calcitonin is effective in the treatment of acute pain after osteoporosis-related vertebral fractures (Level I). 1. Calcitonin reduces pain and improves mobilisation after osteoporosis-related vertebral fractures (Level I). Cannabinoids 1. Current evidence does not support the use of cannabinoids in acute pain management (Level I). 1. Current evidence does not support the use of cannabinoids in acute pain management but these drugs appear to be mildly effective when used in the treatment of chronic neuropathic pain, including multiple sclerosis-related pain (Level I).
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5. Regionally and locally administered analgesic drugs

Local anaesthetics 1. Continuous perineural infusions of lignocaine (lidocaine) result in less effective analgesia and more motor block than long-acting local anaesthetic agents (Level II). 2. There are no consistent differences between ropivacaine, levobupivacaine and bupivacaine when given in low doses for regional analgesia in terms of quality of analgesia or motor blockade (Level II). 3. Cardiovascular and central nervous system effects of the stereospecific isomers ropivacaine and levobupivacaine are less severe than those resulting from racemic bupivacaine (Level II). 4. Lipid emulsion may be effective in resuscitation of circulatory collapse due to local anaesthetic toxicity, however uncertainties relating to dosage, efficacy and side-effects still remain and therefore it is appropriate to administer lipid emulsion only after advanced cardiac life support has failed(Level IV). ; Case reports following accidental overdose with ropivacaine and bupivacaine suggest that resuscitation is likely to be more successful with ropivacaine. Opioids 1. Intrathecal morphine produces better postoperative analgesia than intrathecal fentanyl after caesarean section (Level I). 2. The combination of an opioid with an epidural local anaesthetic improves analgesic efficacy and reduces the dose requirements of both drugs (Level I). 3. Morphine injected as a single dose into the intra-articular space produces analgesia that lasts up to 24 hours (Level I). 3. Morphine injected into the intra-articular space following knee arthroscopy does not improve analgesia compared with placebo when administered after surgery (Level I). 4. Evidence for a clinically relevant peripheral opioid effect at non-articular sites, including perineural, is inconclusive (Level I). 5. Epidural pethidine produces better pain relief and less sedation than IV pethidine after caesarean section (Level II).
6. Extended release epidural morphine demonstrates analgesic effects for up to 48h in hip arthroplasty and caesarean section patients, however central depressant effects, including respiratory depression, may also be prolonged (Level II). ; No neurotoxicity has been shown at normal clinical intrathecal doses of morphine, fentanyl and sufentanil. ; Neuraxial administration of bolus doses of hydrophilic opioids carries an increased risk of delayed sedation and respiratory depression compared with lipophilic opioids. Adjuvant drugs 1. Evidence that the addition of clonidine to an epidural or intrathecal opioid is more effective than clonidine or the opioid alone is weak and inconsistent (Level I). 2. Epidural ketamine (without preservative) added to opioid-based epidural analgesia regimens improves pain relief without reducing side effects (Level I). 3. Epidural neostigmine combined with an opioid reduces the dose of epidural opioid that is required for analgesia (Level I). 4. Intrathecal neostigmine prolongs the analgesic effect of intrathecal morphine and bupivacaine but increases the incidence of nausea and vomiting unless given in low doses (Level I). 4. Intrathecal neostigmine improves analgesia but increases the incidence of significant side effects (Level I). 5. Epidural and intrathecal clonidine prolong the effects of local anaesthetics (Level II). 6. Epidural adrenaline (epinephrine) in combination with a local anaesthetic improves the quality of postoperative thoracic epidural analgesia (Level II). 7. Clonidine prolongs duration of analgesia and anaesthesia when added to intermediateacting local anaesthetics for axillary and peribulbar blocks (Level I). ; There is conflicting evidence of analgesic efficacy for the addition of clonidine to brachial plexus blocks.
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6. Routes used for systemic drug administration in management of acute pain

1. NSAIDs (including COX-2 selective inhibitors) given parenterally or rectally are not more effective and do not result in fewer side effects than the same drug given orally (Level I [Cochrane Review]). 2. Intermittent subcutaneous morphine injections are as effective as intramuscular injections and have better patient acceptance (Level II). 3. Continuous intravenous infusion of opioids in the general ward setting are associated with an increased risk of respiratory depression compared with other methods of parenteral opioid administration (Level IV). 4. Transdermal fentanyl should not be used in the management of acute pain because of safety concerns and difficulties in short-term dose adjustments needed for titration (Level IV). ; Other than in the treatment of severe acute pain, and providing there are no contraindications to its use, the oral route is the route of choice for the administration of most analgesic drugs. ; Titration of opioids for severe acute pain is best achieved using intermittent intravenous bolus doses as it allows more rapid titration of effect and avoids the uncertainty of drug absorption by other routes. ; Controlled-release opioid preparations should only be given at set time intervals. ; Immediate-release opioids should be used for breakthrough pain and for titration of controlled-release opioids. ; The use of controlled-release opioid preparations as the sole agents for the early management of acute pain is discouraged because of difficulties in short-term dose adjustments needed for titration.
; Rectal administration of analgesic drugs may be useful when other routes are unavailable but
bioavailability is unpredictable and consent should be obtained.
7. Techniques used for drug administration in the management of acute pain

Patient-controlled analgesia (PCA) 1. Intravenous opioid PCA provides better analgesia than conventional parenteral opioid regimens (Level I). 1. Intravenous opioid PCA provides better analgesia than conventional parenteral opioid regimens (Level I [Cochrane Review]). 2. Patient preference for intravenous PCA is higher when compared with conventional regimens (Level I). 2. Patient preference and satisfaction for intravenous PCA are higher when compared with conventional regimens (Level I). 3. Opioid administration by IV PCA does not lead to lower opioid consumption, reduced hospital stay or a lower incidence of opioid-related adverse effects compared with traditional methods of intermittent parenteral opioid administration (Level I). 3. Opioid administration by IV PCA leads to slightly higher opioid consumption. There is no difference in the incidence of nausea and vomiting compared with conventional regimens but the incidence of pruritus is increased. There is no difference in length of hospital stay (Level I). 4. The addition of ketamine to PCA morphine does not improve analgesia or reduce the incidence of opioid-related side effects (Level I). 5. Patient-controlled epidural analgesia for pain in labour results in the use of lower doses of local anaesthetic, less motor block and fewer anaesthetic interventions compared with continuous epidural infusions (Level I). 6. There is little evidence that one opioid via PCA is superior to another with regards to analgesic or adverse effects in general; on an individual patient basis one opioid may be better tolerated than another (Level II). 7. There is no analgesic benefit in adding naloxone to the PCA morphine solution, however the incidence of nausea and pruritus may be decreased (Level II). 8. The addition of a background infusion to intravenous PCA does not improve pain relief or sleep, or reduce the number of PCA demands (Level II). 9. Subcutaneous PCA opioids can be as effective as intravenous PCA (Level II).
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10. Intranasal PCA opioids can be as effective as intravenous PCA (Level II). 11. Patient-controlled epidural analgesia results in lower cumulative doses of the drugs compared with continuous epidural infusions without any differences in pain relief or side effects (Level II). 11. Patient-controlled epidural analgesia results in less effective pain relief and more pruritus compared with continuous epidural infusions, but the incidence of nausea/ vomiting and motor block is less (Level I). 12. The risk of respiratory depression is increased when a background infusion is used (Level IV). ; Adequate analgesia needs to be obtained prior to commencement of PCA. Initial orders for bolus doses should take into account individual patient factors such as a history of prior opioid use and patient age. Individual PCA prescriptions may need to be adjusted. ; The routine addition of anti-emetics to PCA opioids is not encouraged, as it is of no benefit compared with selective administration. ; PCA infusion systems must incorporate antisyphon valves and in non-dedicated lines, antireflux valves. ; Drug concentrations should be standardised within institutions to reduce the chance of programming errors. Epidural analgesia 1. All techniques of epidural analgesia for all types of surgery provide better postoperative pain relief compared with parenteral opioid administration (Level I [Cochrane Review]). 1. For all types of surgery, epidural analgesia (except epidural analgesia using a hydrophilic opioid only) provides better postoperative pain relief compared with parenteral (including PCA) opioid administration (Level I). 2. Epidural local anaesthetics improve oxygenation and reduce pulmonary infections and other pulmonary complications compared with parenteral opioids (Level I). 3. Thoracic epidural analgesia utilising local anaesthetics improves bowel recovery after abdominal surgery (Level I). 3. Thoracic epidural analgesia improves bowel recovery after abdominal surgery (including colorectal surgery); after open abdominal aortic surgery, the duration of tracheal intubation and mechanical ventilation is reduced as is the incidence of myocardial infarction, acute respiratory failure, gastric complications and renal insufficiency (Level I [Cochrane Review]). 4. Thoracic epidural analgesia extended for more than 24 hours reduces the incidence of postoperative myocardial infarction (Level I). 5. Epidural analgesia is not associated with increased risk of anastomotic leakage after bowel surgery (Level I). 6. Thoracic epidural analgesia reduces incidence of pneumonia and need for ventilation in patients with multiple rib fractures (Level II). 7. The combination of thoracic epidural analgesia with local anaesthetics and nutritional support leads to preservation of total body protein after upper abdominal surgery (Level II). 8. Lumbar epidural analgesia reduces graft occlusion rates after peripheral vascular surgery (Level II). 9. Combinations of low concentrations of local anaesthetics and opioids provide better analgesia than either component alone (Level II). 10. The risk of permanent neurologic damage in association with epidural analgesia is very low; the incidence is higher where there have been delays in diagnosing an epidural haematoma or abscess (Level IV). 11. Immediate decompression (within 8 hours of the onset of neurological signs) increases the likelihood of partial or good neurological recovery (Level IV). 12. Chlorhexidine-impregnated dressings of epidural catheters in comparison to placebo- or povidone-iodine-impregnated dressings reduce the incidence of catheter colonisation (Level I) ; The provision of epidural analgesia by continuous infusion or patient-controlled administration of local anaesthetic-opioid mixtures is safe on general hospital wards, as long as supervised by an anaesthesia-based pain service with 24-hour medical staff cover. and monitored by welltrained nursing staff.
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; MRI investigation may be warranted if patients who have had an epidural catheter inserted develop a fever and infection at the catheter insertion site; urgent investigation is especially indicated if there is a third sign present that could indicate an abscess, such as back pain or neurological change. Intrathecal analgesia 1. Combination of spinal opioids with local anaesthetics reduces dose requirements for either drug alone (Level I). 2. Intrathecal morphine at doses of 100200 microgram offers effective analgesia with a low risk of adverse effects (Level II). ; Clinical experience with morphine, fentanyl and sufentanil has shown no neurotoxicity or behavioural changes at normal clinical intrathecal doses. Regional analgesia and concurrent anticoagulant medications 1. Anticoagulation is the most important risk factor for the development of epidural haematoma after neuraxial blockade (Level IV). ; Consensus statements of experts guide the timing and choice of regional anaesthesia and analgesia in the context of anticoagulation, but do not represent a standard of care and will not substitute the risk/benefit assessment of the individual patient by the individual anaesthetist. Other regional and local analgesic techniques 1. Intra-articular local anaesthetics reduce postoperative pain only minimally (Level I). 2. Intra-articular opioids following knee arthroscopy provide analgesia for up to 24 hours (Level I). 2. Morphine injected into the intra-articular space following knee arthroscopy does not improve analgesia compared with placebo when administered after surgery (Level I). 3. Wound infiltration with long-acting local anaesthetics provides effective analgesia following inguinal hernia repair but not open cholecystectomy or hysterectomy (Level I). 3. Wound infiltration with long-acting local anaesthetics provides effective analgesia following inguinal hernia repair and laparoscopic cholecystectomy, but not open cholecystectomy or abdominal hysterectomy (Level I). 4. Topical EMLA cream (eutectic mixture of lignocaine [lidocaine] and prilocaine) is effective in reducing the pain associated with venous ulcer debridement (Level I [Cochrane Review]). 5. Continuous interscalene analgesia provides better analgesia, reduced opioid-related side effects and improved patient satisfaction compared with IV PCA after open shoulder surgery (Level II). 6. Continuous femoral nerve blockade provides postoperative analgesia and functional recovery superior to IV morphine, with fewer side effects, and comparable to epidural analgesia following total knee joint replacement surgery (Level II). 7. Continuous posterior lumbar plexus analgesia is as effective as continuous femoral analgesia following total knee joint replacement surgery (Level II). 8. Wound infiltration with continuous infusions of local anaesthetics improves analgesia and reduces opioid requirements following a range of non-abdominal surgical procedures (Level II). 8. Continuous local anaesthetic wound infusions lead to reductions in pain scores (at rest and with activity), opioid consumption, postoperative nausea and vomiting, and length of hospital stay; patient satisfaction is higher and there is no difference in the incidence of wound infections. (Level I) 9. Compared with opioid analgesia, continuous peripheral nerve blockade (regardless of catheter location) provides better postoperative analgesia and leads to reductions in opioid use as well as nausea, vomiting, pruritus and sedation (Level I). 10. Compared with thoracic epidural analgesia, continuous thoracic paravertebral analgesia results in comparable analgesia but has a better side effect profile (less urinary retention, hypotension, nausea, and vomiting) than epidural analgesia and leads to a lower incidence of postoperative pulmonary complications (Level I). 11. Intraperitonal local anaesthetic after laparoscopic cholecystectomy improves early postoperative pain relief (Level I).
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8. Non-pharmacological techniques
Psychological interventions 1. Combined sensory-procedural information is effective in reducing pain and distress (Level I). 2. Training in coping methods or behavioural instruction prior to surgery reduces pain, negative affect and analgesic use (Level I). 3. Hypnosis and attentional techniques reduce procedure-related pain (Level II). Transcutaneous electrical nerve stimulation (TENS) 1. Certain stimulation patterns of TENS may be effective in some acute pain settings (Level I). Acupuncture 1. Acupuncture may be effective in some acute pain settings (Level I). Physical therapies A summary of findings relating to manual and massage therapies can be found in Evidencebased Management of Acute Musculoskeletal Pain, published by the Australian Acute Musculoskeletal Pain Guidelines Group (2003) and endorsed by the National Health and Medical Research Council.
9. The management of acute pain in specific clinical situations

Postoperative pain Risks of neuropathic pain 1. Acute neuropathic pain occurs after trauma and surgery (Level IV). ; Diagnosis and subsequent appropriate treatment of acute neuropathic pain might prevent development of chronic pain. Acute postamputation pain syndromes 1. There is little evidence from randomised controlled trials to guide specific treatment of postamputation pain syndromes (Level I) 2. Continuous regional blockade via nerve sheath catheters provides effective postoperative analgesia after amputation, but has no preventive effect on phantom limb pain (Level II). 3. Calcitonin, morphine, ketamine, gabapentin and sensory discrimination training reduce phantom limb pain (Level II). 4. Ketamine and lignocaine (lidocaine) reduce stump pain (Level II). 5. Perioperative epidural analgesia reduces the incidence of severe phantom limb pain (Level III-2). ; Perioperative ketamine may prevent severe phantom limb pain. Day surgery 1. The use of NSAIDs or clonidine as adjuncts to local anaesthetic agents in intravenous regional anaesthesia improves postoperative analgesia (Level I). 2. Infiltration of the wound with local anaesthetic agents provides good and long-lasting analgesia after ambulatory surgery (Level II). 3. Peripheral nerve blocks with long-acting local anaesthetic agents provide long-lasting postoperative analgesia after ambulatory surgery (Level II). 4. Continuous peripheral nerve blocks provide extended analgesia after ambulatory surgery and have been shown to be safe if adequate resources and patient education are provided (Level II). 5. Optimal analgesia is essential for the success of ambulatory surgery (Level IV). Acute spinal cord injury 1. Intravenous opioids, ketamine and lignocaine (lidocaine) decrease acute spinal cord injury pain (Level II). 2. Gabapentin is effective in the treatment of acute spinal cord injury pain (Level II). 3. Gabapentinoids (gabapentin / pregabalin) are effective in the treatment of spinal cord injury pain (Level II). ; Treatment of acute spinal cord pain is largely based on evidence from studies of other
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neuropathic and nociceptive pain syndromes. Acute burns injury pain 1. Opioids, particularly via patient-controlled analgesia, are effective in burns pain, including procedural pain (Level IV). ; Acute pain following burns injury can be nociceptive and/or neuropathic in nature and may be constant (background pain), intermittent or procedure-related. ; Acute pain following burns injury requires aggressive multimodal and multidisciplinary treatment. Acute back pain A summary of findings relating to acute back pain can be found in Evidence-based Management of Acute Musculoskeletal Pain, published by the Australian Acute Musculoskeletal Pain Guidelines Group (2003) and endorsed by the National Health and Medical Research Council. The following are selected key messages from these guidelines. 1. Acute low back pain is non-specific in about 95% of cases and serious causes are rare; common examination and investigation findings also occur in asymptomatic controls and may not be the cause of pain (Level I). 2. Advice to stay active, heat wrap therapy, activity-focused printed and verbal information and behavioural therapy interventions are beneficial in acute low back pain (Level I). 3. Advice to stay active, exercises, multimodal therapy and pulsed electromagnetic therapy are effective in acute neck pain (Level I). 4. Soft collars are not effective for acute neck pain (Level I). 5. Appropriate investigations are indicated in cases of acute low back pain when alerting features (red flags) of serious conditions are present (Level III-2). 6. Psychosocial and occupational factors (yellow flags) appear to be associated with progression from acute to chronic back pain; such factors should be assessed early to facilitate intervention (Level III-2). Acute musculoskeletal pain A summary of findings relating to acute musculoskeletal pain can be found in Evidencebased Management of Acute Musculoskeletal Pain, published by the Australian Acute Musculoskeletal Pain Guidelines Group (2003) and endorsed by the National Health and Medical Research Council. The following are selected key messages from these guidelines. 1. Topical and oral NSAIDs improve acute shoulder pain (Level I). 2. Subacromial corticosteroid injection relieves acute shoulder pain in the early stages (Level I). 3. Exercises improve acute shoulder pain in patients with rotator cuff disease (Level I). 4. Therapeutic ultrasound may improve acute shoulder pain in calcific tendonitis (Level I). 5. Advice to stay active, exercises, injection therapy and foot orthoses are effective in acute patellofemoral pain (Level I). 6. Low-level laser therapy is ineffective in the management of patellofemoral pain (Level I). ; A management plan for acute musculoskeletal pain should comprise the elements of assessment (history and physical examination, but ancillary investigations are not generally indicated), management (information, assurance, advice to resume normal activity, pain management) and review to reassess pain and revise management plan. ; Information should be provided to patients in correct but neutral terms with the avoidance of alarming diagnostic labels to overcome inappropriate expectations, fears or mistaken beliefs. ; Regular paracetamol, then if ineffective, NSAIDs, may be used for acute musculoskeletal pain. ; Oral opioids, preferably short-acting agents at regular intervals, may be necessary to relieve severe acute musculoskeletal pain; ongoing need for such treatment requires reassessment. ; Adjuvant agents such as anticonvulsants, antidepressants and muscle relaxants are not recommended for the routine treatment of acute musculoskeletal pain.
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Acute medical pain Abdominal pain 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I). 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I[Cochrane Review]). 2. NSAIDs are superior to parenteral opioids in the treatment of renal colic (Level I [Cochrane Review]). 2. NSAIDs or opioids provide effective analgesia for renal colic: NSAIDs reduce requirements for rescue analgesia and produce less vomiting compared with opioids, particularly pethidine (Level I [Cochrane Review]). 3. The onset of analgesia is faster when NSAIDs are given IV for the treatment of renal colic (Level I). 4. Antispasmodics and peppermint oil are effective in the treatment of acute pain in irritable bowel syndrome (Level I). 5. NSAIDS and vitamin B1 are effective in the treatment of primary dysmenorrhoea (Level I [Cochrane Review]). 6. There is no difference between pethidine and morphine in the treatment of renal colic (Level II). 7. Parenteral NSAIDs are as effective as parenteral opioids in the treatment of biliary colic (Level II). Acute herpes zoster infection 1. Antiviral agents started within 72 hours of onset of rash accelerate acute pain resolution and may reduce severity and duration of postherpetic neuralgia (Level I). 2. Amitriptyline use in low doses from onset of rash for 90 days reduces incidence of postherpetic neuralgia (Level II). 3. Topical aspirin is an effective analgesic in acute zoster (Level II). ; Provision of early and appropriate analgesia is an important component of the management of acute zoster and may have benefits in reducing postherpetic neuralgia. Cardiac pain 1. Morphine is an effective and appropriate analgesic for acute cardiac pain (Level II). 2. Nitroglycerine is an effective and appropriate agent in the treatment of acute ischaemic chest pain (Level IV). ; The mainstay of analgesia in acute coronary syndrome is the restoration of adequate myocardial oxygenation, including the use of supplemental oxygen, nitroglycerine, beta blockers and strategies to improve coronary vascular perfusion. Acute pain in haematological disorders 1. Hydroxyurea is effective in decreasing the frequency of acute crises, life-threatening complications and transfusion requirements in sickle cell disease (Level I). 2. Intravenous opioid loading optimises analgesia in the early stages of an acute sickle cell crisis. Effective analgesia may be continued with intravenous (including PCA) opioids such as morphine, however pethidine should be avoided (Level II). 3. Methylprednisolone decreases acute pain in sickle cell crises (Level II). 3. Parenteral corticosteroids shorten the period of analgesia requirement and hospital length of stay in a sickle cell crisis (Level I [Cochrane Review]). 4. Oxygen supplementation during a sickle cell crisis does not decrease pain (Level II). Acute headache 1. Triptans are effective in the treatment of severe migraine (Level I). 2. Aspirin-metoclopramide is effective in the treatment of migraine with mild symptoms (Level I). 3. Parenteral metoclopramide is effective in the treatment of acute migraine (Level I). 4. Parenteral prochlorperazine, chlorpromazine and droperidol are effective in the treatment of acute migraine (Level II). 5. Addition of caffeine to aspirin or paracetamol improves analgesia in acute tension type headaches (TTH) (Level I).
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6. The incidence of post dural puncture headache (PDPH) may be reduced by using small gauge needles with a non-cutting edge (Level I). 7. There is no evidence that bed rest is beneficial in the prevention of PDPH (Level I). 8. Ibuprofen and paracetamol are effective in the treatment of mild to moderate migraine (Level II). 9. A stratified care strategy is effective in treating migraine (Level II). 10. Simple analgesics such as aspirin, paracetamol, NSAIDs, either alone or in combination, are effective in the treatment of episodic tension-type headache (Level II). 11. Sumatriptan is effective in the treatment of cluster headache (Level II). 12. Oxygen is effective in the treatment of cluster headache (Level II). 13. Epidural blood patch administration may be effective in the treatment of PDPH (Level IV). 14. Psychological interventions reduce the intensity of headache in children (Level 1). 15. Ibuprofen and sumatriptan are effective for paediatric migraine (Level 1). ; Opioids should be used with extreme caution in the treatment of headaches, pethidine should be avoided. ; Frequent use of analgesics, triptans and ergot derivatives in the treatment of recurrent acute headache may lead to medication overuse headache. Neurological disorders ; Treatment of acute pain associated with neurological disorders is largely based on evidence from trials for the treatment of a variety of chronic neuropathic pain states. Orofacial pain 1. NSAIDs, COX-2 selective inhibitors, paracetamol, opioids and tramadol provide effective analgesia after dental extraction (Level I). 2. NSAIDS and COX-2 selective inhibitors provide better analgesia with less adverse effects than paracetamol, paracetamol/opioid, paracetamol/tramadol, tramadol or weaker opioids after dental extraction (Level I). 3. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]). 3. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]), although this is not supported by recent RCTs (Level II). 4. Aspirin and NSAIDs increase reoperation rates for post-tonsillectomy bleeding (Level I). 4. Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy, except in paediatric patients. (Level I [Cochrane Review]). 5. PCA and continuous opioid infusions are equally effective in the treatment of pain in mucositis, but opioid consumption is less with PCA (Level I [Cochrane Review]). 6. Perioperative dexamethasone administration reduces acute pain, nausea and swelling after third molar extraction (Level II). 7. Topical treatments may provide analgesia in acute oral ulceration (Level II). 7. Topical treatments provide analgesia in acute oral ulceration and mucositis (Level I). 8. Intraoperative dexamethasone administration reduces acute pain and nausea/ vomiting after tonsillectomy (Level I). ; Recurrent or persistent orofacial pain requires biopsychosocial assessment and appropriate multidisciplinary approaches. Neuropathic orofacial pain (atypical odontalgia, phantom pain) may be exacerbated by repeated dental procedures, incorrect drug therapy or psychological factors. Acute pain in patients with HIV infection ; Neuropathic pain is common in patients with HIV/AIDS. ; In the absence of specific evidence, the treatment of pain in patients with HIV/AIDS should be based on similar principles to those for the management of cancer and chronic pain. ; Interaction between anti-retroviral and antibiotic medications and opioids should be considered in this population.
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Acute cancer pain 1. Oral transmucosal fentanyl is effective in treating acute breakthrough pain in cancer patients (Level II). 1. Oral transmucosal fentanyl is effective in treating acute breakthrough pain in cancer patients (Level I). 2. Analgesic medications prescribed for cancer pain should be adjusted to alterations of pain intensity (Level III). 3. Opioid doses for individual patients with cancer pain should be titrated to achieve maximum analgesic benefit with minimal adverse effects (Level III). ; Acute pain in patients with cancer often signals disease progression; sudden severe pain in patients with cancer should be recognised as a medical emergency and immediately assessed and treated. ; Cancer patients receiving controlled-release opioids need access to immediate-release opioids for breakthrough pain; if the response is insufficient after 3060 minutes, administration should be repeated. ; Breakthrough analgesia should be one-sixth of the total regular daily opioid dose in patients with cancer pain (except when methadone is used, because of its long and variable half life). ; If nausea and vomiting accompany acute cancer pain, parenteral opioids are needed. Acute pain management in intensive care 1. Daily interruptions of sedative infusions reduce duration of ventilation and ICU stay without causing adverse psychological outcomes (Level II). 2. Gabapentin and carbamazepine are effective in reducing the pain associated with GuillainBarre syndrome (Level II). 3. Patients should be provided with appropriate sedation and analgesia during potentially painful procedures (Level III). ; Observation of behavioural and physiological responses permits assessment of pain in unconscious patients. Acute pain management in emergency departments 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I). 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I). [Cochrane Review]). 2. In patients with renal colic, NSAIDs provide better pain relief with fewer adverse effects compared with opioids (Level I [Cochrane Review]). 2. NSAIDs or opioids provide effective analgesia for renal colic: NSAIDs reduce requirements for rescue analgesia and produce less vomiting compared with opioids, particularly pethidine (Level I [Cochrane Review]). 3. Pethidine does not provide better pain relief than morphine in the treatment of renal colic (Level II). 4. Parenteral NSAIDs provide pain relief in biliary colic that is comparable to opioids and superior to hyoscine-N-butylbromide (Level II). 5. Triptan and phenothiazines (prochlorperazine, chlorpromazine) are effective in at least 75% of patients presenting to the emergency department with migraine (Level II). 6. Femoral nerve blocks in combination with IV opioids are superior to IV opioids alone in the treatment of pain from a fractured neck of femur (Level II). ; To ensure optimal management of acute pain, emergency departments should adopt systems to ensure adequate assessment of pain, provision of timely and appropriate analgesia, frequent monitoring and reassessment of pain.
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10. The management of acute pain in specific patient groups

The paediatric patient Characteristics of pain in children ; Even the most premature neonate responds to nociceptive stimuli. ; In early development more generalised reflex nociceptive responses occur in response to lower intensity stimuli. ; Due to the increased plasticity of the developing nervous system, pain and injury in early life may have adverse long-term consequences. Paediatric pain assessment ; Pain assessment and measurement are important components of paediatric pain management. ; Pain measurement tools are available for children of all ages. ; Pain measurement tools must be matched to the age and development of the child, be appropriate for the clinical context and be explained and used consistently. Managing procedural pain in children 1. Sucrose reduces the behavioural response to heel stick in neonates (Level I [Cochrane Review]). 2. Topical local anaesthetic application, inhalation of nitrous oxide (50%) or the combination of both provides effective and safe analgesia for minor procedures (Level I). 3. Psychological interventions (cognitive-behavioural techniques, hypnosis) reduce procedurerelated distress (Level II). 3. Distraction, hypnosis, and combined cognitive-behavioural interventions reduce pain and distress associated with needle-related procedures in children and adolescents. (Level I [Cochrane Review]) 4. A combination of pharmacological and psychological interventions reduces pain and distress (Level II). 5. Combinations of hypnotic and analgesic agents are effective for procedures of moderate and major severity (Level II). 6. Breastfeeding or breast milk reduces measures of distress in neonates undergoing a single painful procedure compared to positioning or no intervention. Administration of glucose/sucrose has similar efficacy (Level 1[Cochrane Review]). 7. EMLA is an effective topical anaesthetic for children, but amethocaine is superior for reducing needle insertion pain (Level 1 [Cochrane Review]). ; Inadequate monitoring of the child, lack of adequate resuscitation skills and equipment, and the use of multiple drug combinations (particularly three or more) have been associated with major adverse outcomes. Analgesic agents for use in children 1. Aspirin and NSAIDs increase the risk of reoperation for post-tonsillectomy bleeding (Level I). 1. Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy, except in paediatric patients. (Level I [Cochrane Review]). 2. Paracetamol and NSAIDs are effective for moderately severe pain and decrease opioid requirements after major surgery (Level II). 3. The efficacy of oral codeine in children is variable, particularly in individuals with a reduced ability to generate active metabolites (Level II). 4. Safe dosing of paracetamol requires consideration of the age and body weight of the child, and the duration of therapy. 5. Aspirin should be avoided in children, but serious adverse events after NSAIDs are rare in children over 6 months of age. Evidence for safety of NSAIDs following tonsillectomy is inconclusive. 6. Intraoperative dexamethasone administration reduces acute pain and nausea/ vomiting after tonsillectomy (Level I)
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Opioid infusions and patient-controlled analgesia in children 1. Effective PCA prescription in children incorporates a bolus that is adequate for control of movement-related pain, and may include a low dose background infusion to improve efficacy and sleep (Level II). 2. Intermittent intramuscular injections are distressing for children and are less effective for pain control than intravenous infusions (Level III-1). ; Intravenous opioids can be used safely and effectively in children of all ages. ; Initial doses of opioid should be based on the age and weight of the child and then titrated against the individuals response. Regional analgesia in children 1. Topical local anaesthetic does not adequately control pain associated with circumcision in awake neonates (Level I [Cochrane Review]). 2. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]). 2. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]), although this is not supported by recent RCTs (Level II). 3. Clonidine prolongs analgesia when added to caudal local anaesthetic blocks (Level I) 4. Clonidine improves analgesia when added to epidural local anaesthetic infusions (Level II). 5. Wound infiltration, peripheral nerve blocks, and caudal local anaesthetic provide effective analgesia after day case surgery (Level II). 6. Caudal local anaesthetic and dorsal penile nerve block provide perioperative analgesia for circumcision (Level II). 7. Epidural infusions of local anaesthetic provide similar levels of analgesia as systemic opioids (Level II). 8. Epidural opioids alone are less effective than local anaesthetic or combinations of local anaesthetic and opioid (Level II). ; Caudal local anaesthetic blocks provide effective analgesia for lower abdominal, perineal and lower limb surgery and have a low incidence of serious complications. ; Continuous epidural infusions provide effective postoperative analgesia in children of all ages and are safe if appropriate doses and equipment are used by experienced practitioners, with adequate monitoring and management of complications. Managing acute pain in children with cancer 1. PCA and continuous opioid infusions are equally effective in the treatment of pain in mucositis, but opioid consumption is less with PCA (Level I [Cochrane Review]). 2. PCA morphine and hydromorphone are equally effective for the control of pain associated with oral mucositis (Level II). ; Procedure and treatment related pain are significant problems for children with cancer. The pregnant patient Managing acute pain during pregnancy 1. Use of non-steroidal anti-inflammatory drugs during pregnancy is associated with increased risk of miscarriage (Level III-2). 2. Use of opioids in pregnancy does not cause fetal malformations, but may result in neonatal abstinence syndrome (Level III-2). ; For pain management in pregnancy non-pharmacological treatment options should be considered where possible before analgesic medications are used. ; Use of medications for pain in pregnancy should be guided by published recommendations; ongoing analgesic use requires close liaison between the obstetrician and the medical practitioner managing the pain. ; NSAIDs should be used with caution in the last trimester of pregnancy and should be avoided after the 32nd week. Pain management during delivery 1. Continuous or one-to-one support by a midwife or trained layperson during labour reduces analgesic use, operative delivery and dissatisfaction (Level I).
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2. Epidural and combined spinal-epidural analgesia provide superior pain relief for labour and delivery compared with systemic analgesics (Level I). 2. Epidural and combined spinal-epidural analgesia provide superior pain relief for labour and delivery compared with systemic analgesics (Level I [Cochrane Review]). 3. Combined spinal-epidural in comparison with epidural analgesia reduces time to effective analgesia and improves maternal satisfaction but increases the incidence of pruritus (Level I [Cochrane Review]). 3. Combined spinal-epidural in comparison with epidural analgesia does not offer significant advantages but increases the incidence of urinary retention (Level I [Cochrane Review]). 4. Epidural analgesia does not increase the incidence of caesarean section and long-term backache (Level I). 4. Epidural analgesia does not increase the incidence of caesarean section and long-term backache (Level I [Cochrane Review]). 5. Epidural analgesia is associated with increased duration of labour and may increase rate of instrumental vaginal delivery (Level I). 5. Epidural analgesia is associated with increased duration of labour and increased rate of instrumental vaginal delivery (Level I [Cochrane Review]). 6. There is no significant difference in any outcome between use of bupivacaine and ropivacaine for epidural labour analgesia (Level I). 7. Patient-controlled epidural analgesia without background infusion reduces local anaesthetic use and motor block compared with continuous epidural infusion (Level I). 8. Single-injection intrathecal opioids provide comparable early labour analgesia to epidural local anaesthetics with increased pruritus (Level I). 9. Systemic opioids in labour increase the need for neonatal resuscitation and worsen acid-base status compared with regional analgesia (Level I). 10. Nitrous oxide has some analgesic efficacy and is safe during labour (Level I). 11. Acupuncture reduces analgesic requirements in labour (Level I [Cochrane Review]). 12.Hypnosis used in labour reduces analgesic requirements and use of labour augmentation and increases the incidence of spontaneous vaginal delivery (Level I). 12.Hypnosis used in labour reduces analgesic requirements and use of labour augmentation and increases the incidence of spontaneous vaginal delivery (Level I [Cochrane Review]). 13. TENS does not reduce labour pain (Level I). 14. Systemic opioids are less effective than regional analgesia for pain in labour (Level II). 15. Paracervical block is more effective than intramuscular opioid analgesia but there is insufficient evidence to support its safety (Level II). 16. Lumbosacral intradermal injection of sterile water is painful, but reduces labour pain (Level II). Pain management during lactation ; Prescribing medications during lactation requires consideration of possible transfer into breast milk, uptake by the baby and potential adverse effects for the baby; it should follow available prescribing guidelines. ; Local anaesthetics, paracetamol and several NSAIDs, in particular ibuprofen, are considered to be safe in the lactating patient. ; Morphine, fentanyl and oxycodone are also considered safe in the lactating patient and should be preferred over pethidine. Pain in the puerperium 1. Routine episiotomy does not reduce perineal pain (Level I). 2. Paracetamol and NSAIDs are effective in treating perineal pain after childbirth (Level I). 3. The use of codeine for perineal pain after childbirth leads to more side effects than the use of NSAIDs (Level II). 4. Paracetamol and NSAIDs are equally, but only modestly effective in treating uterine pain (Level II). 5. The application of cooling, in particular with cooling gel pads, and the use of warm baths is effective in treatment of perineal pain after childbirth (Level II). 6. Bromocriptine should be avoided for the treatment of breast pain in puerperium because of the potential for serious adverse effects (Level II).
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7.
Topical local anaesthetic preparations are not effective for perineal pain after childbirth (Level 1[Cochrane Review]}.
; Pain after childbirth requires appropriate treatment as it coincides with new emotional, physical and learning demands and may trigger postnatal depression. ; Management of breast and nipple pain should target the cause. The elderly patient 1. Experimental pain thresholds to a variety of noxious stimuli are increased in elderly people but there is also a reduction in tolerance to pain (Level I). 2. PCA and epidural analgesia are more effective in elderly people than conventional opioid regimens (Level II). 3. Reported frequency and intensity of acute pain in clinical situations may be reduced in the elderly person (Level III-2). 4. Common unidimensional self-report measures of pain can be used in the elderly patient in the acute pain setting; in the clinical setting, the verbal descriptor scale may be more reliable than others (Level III-2). 5. There is an age-related decrease in opioid requirements; significant interpatient variability persists (Level IV). 6. The use of NSAIDs and COX-2 inhibitors in elderly people requires extreme caution; paracetamol is the preferred non-opioid analgesic (Level IV). ; The assessment of pain and evaluation of pain relief therapies in the elderly patient may present problems arising from differences in reporting, cognitive impairment and difficulties in measurement. ; Measures of present pain may be more reliable than past pain, especially in patients with some cognitive impairment. ; The physiological changes associated with ageing are progressive. While the rate of change can vary markedly between individuals, these changes may decrease the dose (maintenance and/or bolus) of drug required for pain relief and may lead to increased accumulation of active metabolites. Aboriginal and Torres Strait Islander peoples 1. The verbal descriptor scale may be a better choice of pain measurement tool than verbal numerical rating scales (Level III-3). 2. Medical comorbidities such as renal impairment are more common in Aboriginal and Torres Strait Islander peoples and New Zealand Maoris, and may influence the choice of analgesic agent (Level IV). 3. Clinicians should be aware that pain may be under-reported by this group of patients (Level IV). ; Communication may be hindered by social, language and cultural factors. Other ethnic groups and non-English speaking patients 1. Multilingual printed information and pain measurement scales are useful in managing patients from different cultural or ethnic backgrounds (Level IV). 2. With appropriate instruction, PCA may help overcome some of the barriers to postoperative analgesia provision in a multicultural environment (Level IV). ; Ethnic and cultural background can significantly affect the ability to assess and treat acute pain. The patient with obstructive sleep apnoea (OSA) 1. Patients with OSA may be at higher risk of complications after surgery and from opioid analgesia (Level III-3). 2. Continuous positive airway pressure (CPAP) does not increase the risk of anastomotic leak after upper gastrointestinal surgery (Level III-2). ; Management strategies that may increase the efficacy and safety of pain relief in patients with OSA include the provision of appropriate multimodal opioid-sparing analgesia, CPAP, monitoring and supervision (in a high-dependency area if necessary) and supplemental oxygen.
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The patient with concurrent hepatic or renal disease ; Consideration should be given to choice and dose regimen of analgesic agents in patients with hepatic and particularly renal impairment. The opioid-tolerant patient 1. Opioid-tolerant patients report higher pain scores and have a lower incidence of opioidinduced nausea and vomiting (Level III-2). 2. Ketamine may reduce opioid requirements in opioid-tolerant patients (Level IV). ; Usual preadmission opioid regimens should be maintained where possible or appropriate substitutions made. ; Opioid-tolerant patients are at risk of opioid withdrawal if non-opioid analgesic regimens or tramadol alone are used. ; PCA settings may need to include a background infusion to replace the usual opioid dose and a higher bolus dose. ; Neuraxial opioids can be used effectively in opioid-tolerant patients although higher doses may be required and these doses may be inadequate to prevent withdrawal. ; Liaison with all clinicians involved in the treatment of the opioid-tolerant patient is important. Patients with a substance abuse disorder ; Naltrexone should be stopped at least 24 hours prior to elective surgery. ; Patients who have completed naltrexone therapy should be regarded as opioid nave; in the immediate post-treatment phase they may be opioid-sensitive. ; Maintenance methadone regimens should be continued where possible. ; Buprenorphine maintenance may be continued; if buprenorphine is ceased prior to surgery conversion to an alternative opioid is required. ; There is no cross-tolerance between CNS stimulants and opioids.
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UPDATES
This update should be read in conjunction with APS:SE 2e. In some instances the information is new, but any conclusions made in APS:SE 2e remain unchanged. In others, the new information has led to an updated/ changed key message. Where there is information that is additional to a point made in APS:SE 2e, this original point is reproduced in brackets preceding the new information and [faded]; where new information contradicts a previous point, the original point is reproduced preceding the new information but [faded and struck out]. This is so that comparisons can more easily be made. Where key messages have been updated/ changed, the original key message (with its original number) remains above but faded and struck out, so that comparisons can be made. New key messages are numbered from the last key message in the relevant section in APS:SE 2e.
1. 1.4
PHYSIOLOGY AND PSYCHOLOGY OF ACUTE PAIN PRE-EMPTIVE AND PREVENTIVE ANALGESIA
[Clinical studies have failed to confirm a significant effect of timing of analgesia when comparing preincisional (ie pre-emptive) and postincisional interventions (Miniche et al 2002, Level I)] The efficacy of different pre-emptive analgesic interventions (epidural analgesia; local anaesthetic wound infiltration; systemic NMDA antagonists; systemic opioids and systemic NSAIDs) was analysed in relation to different analgesic outcomes (pain intensity scores; supplemental analgesic consumption; time to first analgesic). The effect size was most marked for epidural analgesia (0.38, CI 0.28-0.47) and improvements were found in all outcomes. Preemptive effects of local anaesthetic wound infiltration (0.29, CI 0.17-0.4), and NSAID administration (0.39, CI 0.27-0.48) were also demonstrated by improvements in analgesic consumption and time to first analgesia, but had no effect on pain intensity scores. Reductions in analgesic consumption ranged from 44% to 58%, which the authors regarded as clinically significant, but associated changes in side-effects were not analysed. Results were equivocal for systemic NMDA antagonists (0.09, CI -0.03 to 0.22) and there was no clear evidence for a preemptive effect of opioids (-0.10, CI -0.26 to 0.07) (Ong, CK, Lirk, P, Seymour, RA, et al. 2005 Level I). Pre-emptive thoracic epidural analgesia (local anaesthetic +/- opioid) reduced the severity of acute pain on coughing following thoracotomy in an analysis of 6 RCTs. Acute pain at rest was not statistically different at 24 hours and was only marginally improved at 48 hours. Although acute pain was a predictor of chronic pain at 6 months in 2 studies, there was no statistically significant difference in the incidence of chronic pain in the pre-emptive versus control groups (39.6% vs 48.6%). The presence or absence of pain at 6 months was reported in only 3 trials and the intensity of chronic pain was not evaluated (Bong, CL, Samuel, M, Ng, JM, et al. 2005 Level I). Updated key message 1. The timing of a single analgesic intervention (preincisional versus postincisional), defined as pre-emptive analgesia, does not have a clinically significant effect on postoperative pain relief (Level I). 1. The timing of a single analgesic intervention (preincisional versus postincisional), defined as pre-emptive analgesia, has a significant effect on postoperative pain relief with epidural analgesia and may have a significant effect with local anaesthetic wound infiltration and NSAIDs (Level I).
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3. 3.1
3.1.1
PROVISION OF SAFE AND EFFECTIVE ACUTE PAIN MANAGEMENT EDUCATION

Patients
A systematic review (Johansson, K, Nuutila, L, Virtanen, H, et al. 2005 Level 1) of studies looking at the benefits or otherwise of preoperative education for orthopaedic patients highlighted the difficulties of comparing studies of variable methodological quality. While some individual studies may show benefits of preoperative education, the lack of a consistent pattern with regard to effect was confirmed.
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4. 4.1
4.1.2
SYSTEMICALLY ADMINISTERED ANALGESIC DRUGS OPIOIDS

Specific opioids
Buprenorphine
Please refer to Section 10.9.3. for information on the use of a combination buprenorphine/ naloxone preparation in patients with a substance abuse disorder.
Tramadol
A recent meta-analysis confirmed that tramadol is an effective treatment of neuropathic pain with a NNT of 3.8 (Hollingshead, J, Duhmke, RM and Cornblath, DR 2006 Level I). Confirmed key message 2. Tramadol is an effective treatment in neuropathic pain (Level I [Cochrane Review]).
4.1.3
Adverse effects of opioids
Respiratory depression
Introduction of a numerical pain treatment algorithm in a cancer setting was followed by a review of opioid-related adverse reactions: use of this algorithm, in which opioids were given to patients in order to achieve satisfactory pain scores, resulted in a two-fold increase in the risk of respiratory depression (Vila, H, Jr., Smith, RA, Augustyniak, MJ, et al. 2005 Level III-3). Importantly, the authors noted that respiratory depression was usually not accompanied by a decrease in respiratory rate. Of the 29 patients who developed respiratory depression (either before or after the Introduction of the algorithm), only 3 had a respiratory rates of <12 breaths/min but 27 had a decrease in their level of consciousness (Vila, H, Jr., Smith, RA, Augustyniak, MJ, et al. 2005 Level III-3). As well as confirming that increasing sedation is a more reliable way of detecting opioid-induced respiratory depression, this study highlighted the risk of titrating opioids to achieve a desirable pain score without appropriate patient monitoring.
Nausea and vomiting

A comparison of ECG data in surgical patients was performed before and after the FDA black box warning on droperidol and, despite a reduction in the use of droperidol from 12% to 0% of patients, there was no difference in the incidence of QT prolongation, torsade de pointes, or death within 48 hours of surgery (Nuttall, GA, Eckerman, KM, Jacob, KA, et al. 2007 Level III-3). The authors concluded that for low dose droperidol, the black box warning was excessive and unnecessary. Updated key message ; Assessment of sedation level is a more reliable way of detecting early opioid-induced respiratory depression than a decreased respiratory rate. 12. Assessment of sedation level is a more reliable way of detecting early opioid-induced respiratory depression than a decreased respiratory rate (Level III-3).
4.2
4.2.1
PARACETAMOL, NSAIDS AND COX-2 SELECTIVE INHIBITORS

Paracetamol (acetaminophen)
[Single doses of paracetamol are effective in the treatment of postoperative pain.] Paracetamol shows a dose-dependent effect and 1000 mg is superior to 500 mg (McQuay, HJ and Moore, RA 2007 Level I). Superiority of a dose of 1000 mg over doses below 1000 mg was also confirmed after wisdom tooth extraction; the rate of adverse effects was comparable to placebo (Weil, K,
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Hooper, L, Afzal, Z, et al. 2007 Level I). After oral surgery the NNT of 1000 mg paracetamol is 3 and the NNH 33 (Dodson, T 2007 Level I).
4.2.2
Non-steroidal anti-inflammatory drugs
[Opioid-sparing does not always result in a reduced incidence of adverse opioid-related effects but may have cost advantages compared with using opioid analgesics alone (RCA 1998, Level IV; Philips et al 2002, Level III-2).] Adding NSAIDs to opioids administered via IV PCA reduces opioid consumption by 30-50%, and also the incidence of nausea by 12%, vomiting by 32% and sedation by 29%. The effect on nausea and vomiting is related to the degree of opioid sparing. There was no effect on pruritus, urinary retention and respiratory depression (Marret, E, Kurdi, O, Zufferey, P, et al. 2005 Level I). These beneficial effects were confirmed in another meta-analysis (Elia, N, Lysakowski, C and Tramer, MR 2005 Level I). Similarly, in patients less than 70 years of age undergoing cardiothoracic surgery, the use of NSAIDs reduced pain score and opioid requirements (Bainbridge, D, Cheng, DC, Martin, JE, et al. 2006 Level I).
Adverse effects
Renal An updated meta-analysis confirms that, with careful patient selection and monitoring, the incidence of NSAID-induced perioperative renal impairment is low (Lee, A, Cooper, MG, Craig, JC, et al. 2007 (Level I [Cochrane Review]). Platelet function [NSAID use after tonsillectomy is associated with an increase in reoperation rate (Miniche et al 2003, Level I) and more surgical blood loss (Rusy et al 1995, Level II) compared with paracetamol.] This increased risk of bleeding with NSAIDs after tonsillectomy could not be confirmed in children by a Cochrane review (Cardwell, M, Siviter, G and Smith, A 2005 Level I). However, another meta-analysis looking at the use of NSAIDs after a variety of different operations showed a significant increase in risk of severe bleeding from 0 to 1.7% compared with placebo (NNH 59) (Elia, N, Lysakowski, C and Tramer, MR 2005 Level I). Bone healing [Prostaglandin production has been shown to be important in animal models of bone healing, but there is no good evidence of any clinically significant inhibitory effect of NSAIDs on bone healing (Harder & An 2003; Bandolier 2004).] A retrospective analysis showed that ketorolac may affect the incidence of non-union following spinal surgery in a dose-dependent fashion; short-term use of less than 110 mg/day had no significant adverse effect, while higher doses (120-240 mg/day) resulted in a significant increase in the incidence of non-union. (Reuben, SS, Ablett, D and Kaye, R 2005 Level III-2). Cardiovascular See information below in section relating to COX-2 inhibitors.
4.2.3
Cyclo-oxygenase-2 selective inhibitors (COX-2 inhibitors)
Efficacy
[When given in combination with opioids after surgery, COX 2 inhibitors are opioid-sparing; as with traditional NSAIDs, opioid-sparing results in a reduced (Malan et al 2003, Level II; Gan et al 2004, Level II; Zhao et al 2004, Level II) or comparable (Hubbard et al 2003, Level II; Ng et al 2003; Level II; Reynolds et al 2003, Level II) incidence of adverse opioid-related effects.] Preoperative COX-2 inhibitors reduce postoperative pain and opioid consumption and increase patient satisfaction. (Straube, S, Derry, S, McQuay, HJ, et al. 2005 (Level I)
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Adverse effects
Platelet function COX-2 inhibitors, given after a variety of operations, do not increase the risk of bleeding.Hegi, TR, Bombeli, T, Seifert, B, et al. 2004 [The question has been raised whether COX-2 inhibitors can produce a tendency to thrombosis because they inhibit endothelial prostacyclin production but spare platelet thromboxane synthesis and aggregation. While the pharmacological evidence for a prothrombotic effect of COX-2 inhibitors is plausible, the published data on the clinical risk are conflicting (Clark et al 2004).] See section below. Cardiovascular Information relating to the cardiovascular (CV) risks associated with the use of NSAIDs and COX-2 inhibitors is derived from long-term treatment data and may not reflect the risk of short-term use in the acute setting. The evidence remains contradictory. One recent meta-analysis failed to show any difference in CV risk between celecoxib and placebo or between celecoxib and non-selective NSAIDs (White, WB, West, CR, Borer, JS, et al. 2007 Level I). Another reported that COX 2 inhibitors were associated with a moderate increase in the risk of CV events, as were high dose regimens of ibuprofen and diclofenac, but not high doses of naproxen (Kearney, PM, Baigent, C, Godwin, J, et al. 2006 Level I). A further metaanalysis of observational studies also suggested that celecoxib in commonly used doses may not increase the CV risk but confirmed an increased risk with diclofenac (McGettigan, P and Henry, D 2006 Level III-2). [An increase in the incidence of cerebrovascular and cardiovascular events in patients given parecoxib, then valdecoxib after coronary artery bypass graft surgery has also been reported (Ott et al 2003, Level II; Nussmeier et al 2005, Level II). Therefore, their use is contraindicated after this type of surgery.] However, short-term use of parecoxib and/ or valdecoxib after noncardiac surgery does not increase the risk of CV adverse events (Schug, SA, Camu, F, Joshi, G, et al. 2007 Level I). Bone healing [At present the effect of COX-2 inhibitors on bone healing remains an effect demonstrated under laboratory conditions, but there is no good evidence of any clinically significant inhibitory effect of COX-2 inhibitors on bone healing (Gerstenfeld et al 2003; Harder & An 2003; Bandolier 2004).] An observational study and RCT showed no adverse effect of short-term use of COX-2 inhibitors on bone healing after spinal fusion Reuben, SS, Ablett, D and Kaye, R 2005 Level III-2; Reuben, SS and Ekman, EF 2005 Level II. Updated/ confirmed key messages 1. 4. 5. 5. 9. 9. Paracetamol is an effective analgesic for acute pain; the incidence of adverse effects comparable to placebo (Level I [Cochrane Review]). With careful patient selection and monitoring, the incidence of NSAID-induced perioperative renal impairment is low (Level I [Cochrane Review]). Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy (Level I). Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy, except in paediatric patients. (Level I [Cochrane Review]). COX-2 inhibitors do not impair platelet function (Level II). COX-2 inhibitors do not impair platelet function; this leads to reduced perioperative blood loss in comparison with NSAIDs (Level II).
Additional key messages 12. NSAIDs given in addition to PCA opioids reduce opioid consumption and the incidence of
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nausea, vomiting and sedation (Level I). 13. Perioperative NSAIDs increase the risk of severe bleeding compared with placebo (Level I). 14. Preoperative COX-2 inhibitors reduce postoperative pain and opioid consumption and increase patient satisfaction (Level I). 15. Parecoxib and/or valdecoxib compared with placebo does not increase the risk of cardiovascular adverse events after non-cardiac surgery (Level I). 16 COX-2 inhibitors and NSAIDs are associated with similar rates of adverse cardiovascular effects, in particular myocardial infarction; naproxen may be associated with a lower risk than other NSAIDs (Level I). 17. Short-term use of COX-2 inhibitors does not affect bone healing in spinal fusion (Level II). ; Serious cardiovascular complications have been reported with the use of COX-2 inhibitors in some settings and the use of these agents is currently being assessed; no recommendation about their use can be made until further evidence is available.
4.3
4.3.2
ADJUVANT DRUGS
N-methyl-D-aspartate receptor antagonists
Ketamine
[As an adjuvant to opioids for the treatment of postoperative pain, IV and epidural ketamine have an opioid-sparing effect (Subramaniam et al 2004, Level I). In spite of an opioid-sparing effect, there was no reduction of opioid-related side effects.] Recent meta-analyses have confirmed that ketamine reduces postoperative opioid requirements (Bell, RF, Dahl, JB, Moore, RA, et al. 2006 Level I; Elia, N and Tramer, MR 2005 Level I). While Bell et al (Bell, RF, Dahl, JB, Moore, RA, et al. 2006 Level I) reviewed studies of ketamine given by a variety of routes at a variety of times relative to the surgery, Elia and Tramer Elia, N and Tramer, MR 2005 Level I) concentrated their meta-analysis on the use of ketamine in conjunction with PCA morphine. They concluded that analgesic doses of ketamine reduced PCA morphine requirements and the incidence of postoperative nausea and vomiting, while adverse effects were mild or absent. While a variety of ketamine doses were used in the studies include in this meta-analysis, the authors reported that there appeared to be no increase in opioid-sparing effect above estimated doses of 30 mg ketamine/ 24 hours. Using a more heterogeneous group of studies, Elia et al (Elia, N and Tramer, MR 2005 Level I) did not find that the incidence of postoperative nausea and vomiting was reduced although there was a modest improvement in pain scores and in the time to first request for further analgesia.
Dextromethorphan
A review of the use of perioperative dextromethorphan concluded that while some studies showed a decrease in opioid consumption and opioid-related side effects, any reduction in pain was not clinically significant and that the consistency of the potential opioid-sparing and painreducing effect must be questioned: a meta-analysis was not performed because of the marked differences in methodology and reporting between trials (Duedahl, TH, Romsing, J, Moiniche, S, et al. 2006).
Magnesium
There was no convincing evidence that magnesium reduces postoperative pain intensity or analgesic consumption (Lysakowski, C, Dumont, L, Czarnetzki, C, et al. 2007 Level I). Updated key message 1 Ketamine has an opioid-sparing effect in postoperative pain although there is no concurrent reduction in opioid-related side effects (Level I).
1. Analgesic doses of ketamine have a postoperative opioid-sparing effect; used in conjunction with PCA morphine, the incidence of postoperative nausea and vomiting is reduced. (Level I
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[Cochrane Review]). Additional key message 5. There is no convincing evidence that magnesium reduces postoperative pain intensity or analgesic consumption (Level I).
4.3.3
Antidepressant drugs
[Antidepressants are effective in the treatment of a variety of chronic neuropathic pain states (McQuay et al 1996, Level I; Sindrup & Jensen 1999, Level I; Collins et al 2000, Level I).] An updated Cochrane meta-analysis (Saarto, T and Wiffen, P 2007 Level I) looking at the use of antidepressant drugs in the treatment of neuropathic pain confirmed the effectiveness of tricyclic antidepressants (TCAs). The authors also concluded that venlafaxine appears to be as effective as TCAs and that there is limited evidence of benefit with SSRIs. See revised Table 4.1 below for numbers-needed-to-treat (NNT) and numbers-needed-to-harm (NNH).
REVISED TABLE 4.1 Antidepressants for the treatment of neuropathic pain

Efficacy Overall TCAs Venlafaxine SSRIs Diabetic neuropathy Postherpetic neuralgia HIV-related neuropathies Minor adverse effects Pooled diagnoses Amitriptyline Venlafaxine SSRIs Major adverse effects (withdrawal from study) Pooled diagnoses Amitriptyline Venlafaxine SSRIs
Note:
NNT (95% CI) 3.6 (3.04.5) 3.1 (2.25.1) limited evidence of benefit 1.3 (1.21.5) 2.7 (2.04.1) no evidence of benefit NNH (95% CI) 6.0 (4.210.7) 9.6 (4.213.0) no dichotomous data available NNH (95% CI) 28.0 (17.668.9) 16.2 (8436) not different from placebo
CI = confidence interval; TCA = tricyclic antidepressants; SSRI = selective serotonin re-uptake inhibitors
Source: Adapted from Collins et al (2000), McQuay (2002) and Saarto (2007).
Updated key message 2. In neuropathic pain, tricyclic antidepressants are more effective than selective serotonergic re-uptake inhibitors (Level I). 2. In neuropathic pain, tricyclic antidepressants are as effective as venlafaxine and more effective than selective serotonergic re-uptake inhibitors (Level I [Cochrane Review]).
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4.3.4
Anticonvulsant drugs
Specific anticonvulsant agents used in the treatment of acute pain

Gabapentinoids (gabapentin/ pregabalin) [Perioperative gabapentin leads to substantial reductions in both postoperative analgesic requirements and pain (Dahl et al 2004, Level I)]. A number of recent meta-analyses Peng, PW, Wijeysundera, DN and Li, CC 2007 Level I; Tiippana, EM, Hamunen, K, Kontinen, VK, et al. 2007} Level I; Cepeda, MS, Carr, DB, Lau, J, et al. 2006 Level I; Hurley, RW, Cohen, SP, Williams, KA, et al. 2006 Level I; Ruppen, W, Derry, S, McQuay, HJ, et al. 2006 Level I) have confirmed that perioperative administration of gabapentinoids leads to improved pain relief (at rest and with movement) and a reduction in postoperative opioid consumption compared with placebo, but that the incidence of sedation is increased. Three of these meta-analyses (Peng, PW, Wijeysundera, DN and Li, CC 2007 Level I; Tiippana, EM, Hamunen, K, Kontinen, VK, et al. 2007 Level I; Cepeda, MS, Carr, DB, Lau, J, et al. 2006 Level I) also reported a decrease in vomiting and pruritus; the NNT for nausea was 25 , vomiting 6, and urinary retention 7(Tiippana, EM, Hamunen, K, Kontinen, VK, et al. 2007 Level I). The effect of gabapentin was not dose-dependent in the range of 300-1200 mg utilised in the studies (Tiippana, EM, Hamunen, K, Kontinen, VK, et al. 2007 Level I). Marret et al (Marret, E, Remy, C and Bonnet, F 2007 Level I) looked in particular at the results of studies investigating perioperative administration of gabapentin in patients undergoing abdominal hysterectomy or spinal surgery: pain and postoperative analgesic consumption was reduced in both groups but nausea (not vomiting) was reduced in the hysterectomy group only. The studies included in these meta-analyses used a wide variety of gabapentin dosing regimens and it is therefore not possible to recommend any one particular regimen based on the information currently available. The current data also do not permit any conclusions to be made about treatment duration or the long-term benefits of the use of these compounds.
Specific anticonvulsant agents used in the treatment of chronic neuropathic pain

Carbamazepine [In a systematic review, carbamazepine was found to have an NNT of 2.6 in trigeminal neuralgia and 3.3 in diabetic neuropathy (Backonja 2002, Level I). The NNH was 3.4 for minor adverse effects and 24 for severe adverse effects.] An updated review (Wiffen, PJ, McQuay, HJ and Moore, RA 2005 Level I) of the use of carbamazepine for the treatment of chronic neuropathic pain calculated a NNT of 1.8 (CI 1.42.8) for trigeminal neuralgia; there were insufficient data for an NNT for diabetic neuropathy to be calculated. The NNH for a minor adverse effect compared with a placebo was 3.7 (CI 2.4-7.8); the NNH for a major adverse event was insignificant. Phenytoin A review (Wiffen, P, Collins, S, McQuay, H, et al. 2005) Level I) of the use of phenytoin for the treatment of chronic neuropathic pain calculated a NNT of 2.1 (CI 1.5-3.6) for diabetic neuropathy. The NNH for a minor adverse effect compared with a placebo was 3.2 (CI 2.1-6.3); the NNH for a major adverse event was insignificant. Gabapentin [In the same review the NNTs for gabapentin ranged between 3.2 and 3.8 in the treatment of chronic neuropathic pain states (Backonja 2002, Level I). The NNH for a minor adverse effect compared with a placebo was 2.6 (2.1 to 3.3) (Collins et al 2000, Level I).] An updated review (Wiffen, PJ, McQuay, HJ, Edwards, JE, et al. 2005 Level I) of the use of gabapentin for the treatment of chronic neuropathic pain calculated a NNT of 4.3 (CI 3.5-5.7) overall; NNTs for diabetic neuropathy and postherpetic neuralgia were 2.9 (CI 2.2 to 4.3) and 3.9 (CI 3 to 5.7) respectively. The NNH for a minor adverse effect compared with a placebo was 3.7 (CI 2.4 to 5.4); the NNH for a major adverse event was insignificant. Pregabalin
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In recent meta-analysis, pregabalin was found to have a NNT of 3.24 in diabetic neuropathy (Gutierrez-Alvarez, AM, Beltran-Rodriguez, J and Moreno, CB 2007 Level I). Lamotrigine [The NNT of lamotrigine, based on a limited number of studies in trigeminal neuralgia, is 2.1 (1.3 6.1) (Backonja 2002, Level I).] A recent review of lamotrigine concluded that it is unlikely to be of benefit for the treatment of neuropathic pain (Wiffen, PJ and Rees, J 2007 Level I). Updated key messages 1. Anticonvulsants are effective in the treatment of chronic neuropathic pain states (Level I). 1. The anticonvulsants gabapentin, pregabalin and carbamazepine are effective in the treatment of chronic neuropathic pain states; lamotrigine may not be effective (Level I [Cochrane Review]). 2. Perioperative gabapentin reduces postoperative pain and opioid requirements (Level I). 2. Perioperative gabapentinoids (gabapentin/ pregabalin) reduce postoperative pain, opioid requirements, and the incidence of opioid-related adverse effects, but increases the risk of sedation (Level I).
4.3.5
Membrane stabilisers
Both lignocaine (lidocaine) and mexiletine are more effective than placebo in the treatment of chronic neuropathic pain; there is no difference in efficacy or adverse effects compared with carbamazepine, morphine, amantadine, or morphine (Challapalli, V, Tremont-Lukats, IW, McNicol, ED, et al. 2005 Level I).
4.3.7
Calcitonin
[Calcitonin, given parenterally, intransally or rectally, has been shown to have analgesic efficacy in this setting (Blau & Hoehns 2003, Level I).] Another meta-analysis (Knopp, JA, Diner, BM, Blitz, M, et al. 2005 Level I) confirmed the analgesic efficacy (at rest and with movement) of calcitonin given to treat acute pain resulting from osteoporosis-related vertebral compression fracture; mobilisation was improved and side effects were minor and mainly gastrointestinal. Updated key message 1. Calcitonin is effective in the treatment of acute pain after osteoporosis-related vertebral fractures (Level I). 1. Calcitonin reduces pain and improves mobilisation after osteoporosis-related vertebral fractures (Level I).
4.3.8
Cannabinoids
[Insufficient rigorous scientific evidence was found to support the use of cannabinoids in clinical practice.] Although the number of clinical trials is small, cannabinoids appear to be mildly effective in the treatment of chronic neuropathic and multiple sclerosis-related pain; the most common adverse effect is dizziness (33% of patients) (Iskedjian, M, Bereza, B, Gordon, A, et al. 2007 Level I). Updated key message 1. Current evidence does not support the use of cannabinoids in acute pain management (Level I). 1. Current evidence does not support the use of cannabinoids in acute pain management but these drugs appear to be mildly effective when used in the treatment of chronic neuropathic pain, including multiple sclerosis-related pain (Level I).
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4.3.9
Complementary and alternative medicines
A review of trials looking at the effectiveness of herbal medicines for low back pain (a mix of acute, subacute and chronic pain) found that, not surprisingly, Salix Alba (White Willow Bark) was provides better analgesia than placebo; Harpagophytum Procumbens (Devil's Claw) was also more effective; and there was moderate evidence that Capsicum Frutescens (Cayenne) may be better than placebo (Gagnier, JJ, van Tulder, M, Berman, B, et al. 2006 Level I).
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5. 5.1
5.1.1
REGIONALLY AND LOCALLY ADMINISTERED ANALGESIC DRUGS LOCAL ANAESTHETICS

Short duration local anaesthetics
Lignocaine, compared with bupivacaine, prilocaine and procaine, increases the risk of developing transient neurological symptoms (TNS) pain in the buttocks or lower limbs after full resolution of a subarachnoid block (Zaric, D, Christiansen, C, Pace, NL, et al. 2005 Level I). The relative risk is 7.16 (CI 4.02 - 12.75). This typically resolves spontaneously within 5 days. Myofascial trigger point injection of lignocaine was superior to placebo and dry-needling for chronic neck disorders with a NNT of 3 (mean difference score -1.36, CI -1.93 to -0.80). (Peloso, P, Gross, A, Haines, T, et al. 2007 Level I). Where radicular findings were present, epidural lignocaine reduced neck pain and improved function more than when given by intramuscular route at oneyear follow-up.
5.1.2
Long duration local anaesthetics
Intravenous infusion of lipid emulsion has been advocated for the treatment of circulatory collapse due to bupivacaine toxicity. This is based on animal experimental data (Weinberg, G, Ripper, R, Feinstein, DL, et al. 2003 Weinberg, GL, VadeBoncouer, T, Ramaraju, GA, et al. 1998 and a few case reports of successful resuscitation following bupivacaine (Rosenblatt, MA, Abel, M, Fischer, GW, et al. 2006), ropivacaine (Litz, RJ, Popp, M, Stehr, SN, et al. 2006) and levobupivacaine toxicity (Foxall, G, McCahon, R, Lamb, J, et al. 2007). A recent review of animal and human literature has concluded that uncertainties relating to dosage, efficacy and sideeffects still remain and therefore it is appropriate to administer lipid emulsion only after advanced cardiac life support has commenced (Corman, SL and Skledar, SJ 2007 Level IV).
5.1.3
Topical Local Anaesthetics
When compared with EMLA cream, topical amethocaine provided superior analgesia for superficial procedures in children, especially intravenous cannulation. (Lander, JA, Weltman, BJ and So, SS 2006 Level I) See section 10.1.4 Topical tetracaine, liposome-encapsulated tetracaine, and liposome-encapsulated lidocaine are as effective as EMLA cream for dermal instrumentation analgesia in the emergency department (Eidelman, A, Weiss, JM, Lau, J, et al. 2005 Level I) Additional key message 4. Lipid emulsion may be effective in resuscitation of circulatory collapse due to local anaesthetic toxicity, however uncertainties relating to dosage, efficacy and side-effects still remain and therefore it is appropriate to administer lipid emulsion only after advanced cardiac life support has failed(Level IV).
5.2 OPIOIDS
5.2.1 Neuraxial Opioids
Extended release epidural morphine is morphine bound in a lipofoam matrix to prolong its analgesic effect. A number of small clinical trials have demonstrated clinical efficacy in opioid reduction over 48 h and improved analgesia compared with standard epidural morphine (5 mg) over at least 24 h with doses of 10 mg or more, especially in hip arthroplasty patients (Viscusi, ER, Martin, G, Hartrick, CT, et al. 2005 Level II; Viscusi, ER, Kopacz, D, Hartrick, C, et al. 2006 Level II) and to some extent following caesarean section (Carvalho, B, Riley, E, Cohen, SE, et al. 2005
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Level II; Carvalho, B, Roland, LM, Chu, LF, et al. 2007 Level II). Side effects including sedation and respiratory depression occurred frequently (4% of patients requiring naloxone), especially in elderly patients, and justify careful monitoring and assessment for at least 48 hours. Additional key message 6. Extended release epidural morphine demonstrates analgesic effects for up to 48h in hip arthroplasty and caesarean section patients, however central depressant effects, including respiratory depression, may also be prolonged (Level II).
5.2.2
Peripheral opioids
[In clinical practice, morphine injected as a single dose into the knee intra-articular space produces analgesia which may last up to 24 hours, but evidence for a peripheral rather than a systemic effect is not conclusive (Gupta et al 2001, Level I; Kalso et al 2002, Level I) Confounding variables that hinder analysis included the pre-existing degree of inflammation, type of surgery, the baseline pain severity and the overall relatively weak clinical effect (Gupta et al 2001, Level I)] When published trials were analysed taking these confounding factors into consideration, including the intensity of early post-operative pain, the data did not support an analgesic effect for intra-articular morphine following arthroscopy compared with placebo (Rosseland, LA 2005 Level I). Updated key message 3. Morphine injected as a single dose into the intra-articular space produces analgesia that lasts up to 24 hours (Level I). 3. Morphine injected into the intra-articular space following knee arthroscopy does not improve analgesia compared with placebo when administered after surgery (Level I).
5.3
5.3.1
ADJUVANT DRUGS
Clonidine
Plexus Blocks
[There is evidence of analgesic benefit with the addition of clonidine to local anaesthetics for brachial plexus blocks (Murphy et al 2000, Level I) but many of the studies have methodological limitations. Later reports show both lack of postoperative analgesic benefit from the addition of clonidine to bupivacaine for interscalene (Culebras et al 2001, Level II) and levobupivacaine for axillary brachial plexus block (Duma et al 2005, Level II), and prolongation of analgesia when clonidine is added to ropivacaine for axillary brachial plexus block (El Saied et al 2000, Level II).] Clonidine prolongs duration of analgesia and anaesthesia when added to local anaesthetics for axillary and peribulbar blocks. Side-effects are dose-related and minimal at doses up to 150 micrograms McCartney, CJ, Duggan, E and Apatu, E 2007 Level I). Evidence of benefit is lacking for the use of clonidine as an adjunct to local anaesthetics for continuous catheter techniques.
5.3.3
Other adjuvants
Neostigmine
[The addition of intrathecal neostigmine to local anaesthetic reduces postoperative analgesic requirements (Liu et al 1999, Level II; Walker et al 2002, Level I; Almeida et al 2003, Level II; Yegin et al 2003, Level II) but increases the incidence of nausea and vomiting (Walker et al 2002, Level I; Almeida et al 2003, Level II) unless given in low doses.] Intrathecal neostigmine for perioperative and peripartum analgesia results in a slight improvement in pain scores and reduces need for rescue medication. However, it increases nausea and vomiting (OR 5), bradycardia requiring atropine (OR 2.7) and anxiety, agitation and restlessness (OR 10.3) (Ho, KM, Ismail, H, Lee, KC, et al. 2005 Level I). The authors concluded that the significant side effects outweighed any clinical benefit.
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Updated key message 4. Intrathecal neostigmine prolongs the analgesic effect of intrathecal morphine and bupivacaine but increases the incidence of nausea and vomiting unless given in low doses (Level I). 4. Intrathecal neostigmine improves analgesia but increases the incidence of significant side effects (Level I). Additional key message ; There is conflicting evidence of analgesic efficacy for the addition of clonidine to brachial plexus blocks. 7. Clonidine prolongs duration of analgesia and anaesthesia when added to intermediateacting local anaesthetics for axillary and peribulbar blocks (Level I).
5.3.4
Botulinum Toxin A
Following direct intramuscular injection, botulinum toxin acts to irreversibly bind to the acetylcholine receptor and induce a chemical denervation with resultant muscular paralysis. The extent and duration of paralysis depends on the dose administered. Systemic weakness may follow high cumulative doses. Reinnervation may occur over a period of weeks to months. In treating pain and related muscle spasm in multiple sclerosis, current data on the use of botulinum toxin are conflicting and of low quality Shakespeare, DT, Boggild, M and Young, C 2003). Similarly, the current evidence does not support the use of botulinum toxin injection in trigger points for myofascial pain (Ho, KY and Tan, KH 2007 Level I). In subacute and chronic neck disorders intramuscular Botulinum toxin injections have similar effects to saline in improving pain (pooled mean difference: -0.39, CI -1.25 to 0.47) (Peloso, P, Gross, A, Haines, T, et al. 2007 Level I).
5.4 ANTI-INFLAMMATORY DRUGS

5.4.1 Corticosteroids
Intra-articular corticosteroid injections would be expected to have a direct analgesic effect in inflammatory arthropathies. Subacromial injections of corticosteroids have been shown to be effective in treating rotator cuff tendonitis for up to 9 months, and are superior to oral NSAIDs (NNT 2.5 (CI 1 9)) (Arroll, B and Goodyear-Smith, F 2005 Level I).
5.4.2
Topical NSAIDs
Topical NSAIDs may exert their effects by a direct local action, systemic absorption or a combination of both. When applied to acute sprains and strains, topical NSAIDs were effective for up to one week in reducing acute pain with a pooled relative benefit of 1.6 (95% CI 1.4 - 1.7) when compared with placebo, and a NNT of 3.8 (95% CI 3.4 to 4.4) (Mason, L, Moore, RA, Edwards, JE, et al. 2004 Level I). They were well tolerated. Ketoprofen was found to be the most effective individual agent and indomethacin similar to placebo. Oral NSAIDs had similar efficacy to the topical route. In traumatic corneal abrasions, topical NSAIDs are effective in providing analgesia although causing transient stinging on application Calder, LA, Balasubramanian, S and Fergusson, D 2005 Level I). The overall weighted mean difference was small however, with a reduction in pain by 1.30 points (CI -1.56 to -1.03) on a 10-point pain scale.
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6. 6.1
ROUTES OF SYSTEMIC DRUG ADMINISTRATION ORAL ROUTE
[Indirect comparisons, where the individual drugs have been compared with a placebo, have been used to generate a league table of analgesic efficacy (see Table 6.1). This table is based on randomised, double-blind, single-dose studies in patients with moderate to severe pain and shows the number of patients that need to be given the active drug (number-needed-to-treat or NNT) to achieve at least 50% pain relief in one patient compared with a placebo over a 46 hour treatment period (Moore et al 2003).]
TABLE 6.1 Oxford league table of analgesic efficacy (commonly used analgesic doses)
For the 2007 version of this table go to: http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/lftab.html
6.5
6.5.2
TRANSDERMAL ROUTE
Non-steroidal anti-inflammatory drugs
Topically applied NSAIDs provide effective analgesia after traumatic corneal abrasions (Calder, LA, Balasubramanian, S and Fergusson, D 2005 Level I).
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7. 7.1
7.1.1
TECHNIQUES OF DRUG ADMINISTRATION PATIENT-CONTROLLED ANALGESIA

Efficacy of intravenous PCA
[Intravenous (IV) opioid PCA provides better analgesia than conventional (intramuscular [IM], subcutaneous [SC]) opioid regimens when all pain outcomes (pain intensity, pain relief and requirement for rescue analgesia) are combined. There is also some evidence of a decreased risk of postoperative pulmonary complications but no differences in opioid consumption, duration of hospital stay or opioid-related adverse effects (Walder et al 2001, Level I).] Another meta-analysis (Hudcova, J, McNicol, E, Quah, C, et al. 2006 Level 1) has confirmed that intravenous (IV) opioid PCA provides better pain relief than conventional parenteral analgesia and that there is no difference in length of hospital stay. It also showed that patient satisfaction was higher; that patients using IV PCA used (slightly) higher amounts of opioid; and that while there was no difference in the incidence of nausea and vomiting, patients using IV PCA reported a higher rate of pruritus. Similarly, following cardiac surgery (a much smaller total number of patients), IV PCA resulted in improved pain relief compared with nurse-administered analgesia, and an increase in morphine consumption (Bainbridge, D, Martin, JE and Cheng, DC 2006 Level I). In this patient group, no difference in patient satisfaction, opioid-related adverse effects or length of stay in the intensive care unit or hospital was found. However, the authors note that these outcomes were generally under-reported in the studies included in their analysis.
7.1.5
Epidural PCA
Postoperative patient-controlled epidural analgesia

Comparison with continuous epidural infusions [Patients prescribed patient-controlled epidural analgesia (PCEA) with bupivacaine and fentanyl use lower cumulative doses of the drugs compared with continuous epidural infusions without any differences in pain relief or side effects (Silvasti & Pitkaanen 2001, Level II; Standl et al 2003, Level II).] A recent meta-analysis reported that patients prescribed patient-controlled epidural analgesia (PCEA) had significantly more pain at rest and with movement compared with patients prescribed continuous epidural infusions for postoperative pain relief; they had a lower incidence of nausea and vomiting and motor block but a higher incidence of pruritus (Wu, CL, Cohen, SR, Richman, JM, et al. 2005 Level I). There was no differentiation made between PCEA regimens using bolus doses only or bolus doses plus background infusion. Updated key messages 1. Intravenous opioid PCA provides better analgesia than conventional parenteral opioid regimens (Level I) 1. Intravenous opioid PCA provides better analgesia than conventional parenteral opioid regimens (Level I [Cochrane Review]). 2. Patient preference for intravenous PCA is higher when compared with conventional regimens (Level I). 2. Patient preference and satisfaction for intravenous PCA are higher when compared with conventional regimens (Level I [Cochrane Review]). 3. Opioid administration by IV PCA does not lead to lower opioid consumption, reduced hospital stay or a lower incidence of opioid-related adverse effects compared with traditional methods of intermittent parenteral opioid administration (Level I). 3. Opioid administration by IV PCA leads to slightly higher opioid consumption. There is no
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difference in the incidence of nausea and vomiting compared with conventional regimens but the incidence of pruritus is increased. There is no difference in length of hospital stay (Level I [Cochrane Review]). 11. Patient-controlled epidural analgesia results in lower cumulative doses of the drugs compared with continuous epidural infusions without any differences in pain relief or side effects (Level II). 11. Patient-controlled epidural analgesia results in less effective pain relief and more pruritus compared with continuous epidural infusions, but the incidence of nausea/ vomiting and motor block is less (Level I).
7.2
7.2.1
EPIDURAL ANALGESIA
Efficacy
[Regardless of analgesic agent used, location of catheter, type of surgery and type or time of pain assessment, it provides better pain relief than parenteral opioid administration (Block et al 2003, Level I; Werawatganon & Charuluxanum 2004, Level I).] A recent meta-analysis of PCA versus epidural analgesia concluded that epidural analgesia provides better pain relief at rest and with movement after all types of surgery with the exception of epidural analgesia using only hydrophilic opioids; the epidural group had a lower incidence of nausea/ vomiting and sedation but a higher incidence of pruritus, urinary retention and motor block (Wu, CL, Cohen, SR, Richman, JM, et al. 2005 Level I). Another meta-analysis reviewed studies performed over the last 3 decades, looking at the benefits of epidural analgesia in addition to general anaesthesia (Guay, J 2006 Level I). It included a wide variety of surgical procedures and epidural regimens and reported a reduction in a range of adverse outcomes with epidural analgesia. More focussed meta-analyses looked at pain relief after intra-abdominal surgery also confirmed better pain relief compared with parenteral opioid administration (Marret, E, Remy, C and Bonnet, F 2007 Level I Nishimori, M, Ballantyne, JC and Low, JH 2006 Level I Werawatganon, T and Charuluxanun, S 2005 Level I). After colorectal surgery, duration of postoperative ileus was also reduced, but there was no difference in length of hospital stay; the incidences of pruritus, urinary retention and hypotension were increased (Marret, E, Remy, C and Bonnet, F 2007 Level I). After intra-abdominal surgery (mixed), pruritus was also noted to be more likely after epidural than PCA (Werawatganon, T and Charuluxanun, S 2005 Level I). The majority of trials included in both reviews used thoracic epidural analgesia with a local anaesthetic/ opioid infusion. Epidural analgesia after abdominal aortic surgery improves pain relief in the first three postoperative days compared to systemic opioid administration. It also reduces duration of endotracheal intubation and mechanical ventilation and overall renal, gastric and cardiac complications including myocardial infarction, but not perioperative mortality (Nishimori, M, Ballantyne, JC and Low, JH 2006 Level I). Thoracic epidural anaesthesia for thoracotomy started preoperatively in comparison to postoperatively reduced the severity of acute postoperative, but not the incidence of chronic pain (Bong, CL, Samuel, M, Ng, JM, et al. 2005 Level I).
7.2.5
Adverse effects
Neurological injury
[Permanent neurological damage is the most feared complication of epidural analgesia. Reported incidences in large case series are in the range of 0.0050.05% (Kane 1981, Level IV; Dahlgren & Tornebrandt 1995, Level IV; Aromaa et al 1997, Level IV; Giebler et al 1997, Level IV). A recent retrospective survey from Sweden puts the risk of a severe neurological complication after obstetric epidural analgesia at 1:25,000 and for all other patients at 1:3600; 67% resulted in permanent neurologic deficit (Moen et al 2004, Level IV).] An updated review of the risk of
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neurological injury associated with epidural and other regional anaesthesia and analgesia, differentiated between the risk of permanent (neurological deficit lasting more than 12 months) neurological injury and transient neuropathy. (Brull, R, McCartney, CJ, Chan, VW, et al. 2007 Level IV) This review focussed on adverse neurological sequelae associated with the technique, and did not address the overall risk of epidural haematoma or abscess. [The incidence of transient neuropathy after epidural analgesia in large case series was in the range of 0.0130.023% (Xie & Liu 1991, Level IV; Tanaka et al 1993, Level IV; Auroy et al 1997, Level IV).] In the more recent review, the incidence of transient neuropathy (radiculopathy) after epidural anaesthesia was estimated to be 2.19:10,000. The risk of permanent neurological injury was less and the incidences reported in the studies included in this review ranged from 0 7.6:10,000. The rates of paraplegia and cauda equina syndrome associated with epidural anaesthesia were estimated to be 0.09:10,000 and 0.23:10,000 respectively. (Brull, R, McCartney, CJ, Chan, VW, et al. 2007 Level IV) The worst case estimate for persistent neurological injury after epidural anaesthesia for vascular and cardiothoracic surgery is 1 in 4,600 based on a meta-analysis of cohort studies with an event rate of zero in 14,105 patients; the risk of transient neurological injury was 1 in 1,700. (Ruppen, W, Derry, S, McQuay, HJ, et al. 2006 Level IV)
Epidural haematoma and abscess

[A review including case series involving over 1,335,000 patients with epidural analgesia reported 7 cases of haematoma (0.0005%) (Wulf 1996, Level IV).] [Serious neuraxial infections following epidural anaesthesia have previously been reported as rare. However, prospective studies have found rates in the range of 0.0150.05% (Kindler et al 1996, Level IV; Rygnestad et al 1997, Level IV; Wang et al 1999, Level IV).] A recent meta-analysis of the risks of epidural haematoma and neurological injury associated with epidural anaesthesia/ analgesia in cardiac, vascular and thoracic surgery patients concluded that the maximum risks of epidural haematoma were 1 in 1,700, 1 in 1,700 and 1 in 1,400 respectively (Ruppen, W, Derry, S, McQuay, HJ, et al. 2006 Level I). However, this was a calculated risk only; there were actually no cases of epidural haematoma reported in the studies (14,105 patients) used in this analysis. In another analysis of a case series after cardiac surgery the risk was calculated at 1:12,000 (95% CI of 1:2100 to 1:68,000) and comparable to an obstetric population. It was in the same risk range as receiving a wrong blood product (or the yearly risk of having a fatal traffic accident in a Western country) (Bracco, D and Hemmerling, T 2007 Level IV). Audit data from a single (nonobstetric) tertiary institution showed that 8,210 epidural catheters were inserted over a 16 year period for postoperative pain relief and that two spinal haematomas and six epidural abscesses were diagnosed during this time: only one patient (with an epidural abscess) required surgical decompression and no patient suffered any long-term neurological loss (Cameron, CM, Scott, DA, McDonald, WM, et al. 2007 Level IV). The authors stress the importance of appropriate patient monitoring and early diagnosis using magnetic resonance imaging (MRI). In five of their six patients diagnosed with an epidural abscess, both fever and epidural insertion site infection were present. They therefore suggest that MRI investigation may be warranted if this combination is present: urgent investigation is especially indicated if there is a third sign present that could indicate an abscess, such as back pain or neurological change. If the diagnosis of epidural abscess can be made before the onset of any neurological deficit, conservative treatment (antibiotics only) may be effective (Cameron, CM, Scott, DA, McDonald, WM, et al. 2007). Chlorhexidine-impregnated dressings of epidural catheters in comparison to placebo or povidone-iodineimpregnated dressings reduce the incidence of catheter colonisation (Ho, KM and Litton, E 2006 Level I).
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Updated key messages 1. All techniques of epidural analgesia for all types of surgery provide better postoperative pain relief compared with parenteral opioid administration (Level I [Cochrane Review]). 1. For all types of surgery, epidural analgesia (except epidural analgesia using a hydrophilic opioid only) provides better postoperative pain relief compared with parenteral (including PCA) opioid administration (Level I). 3. Thoracic epidural analgesia utilising local anaesthetics improves bowel recovery after abdominal surgery (Level I). 3. Thoracic epidural analgesia improves bowel recovery after abdominal surgery (including colorectal surgery); after open abdominal aortic surgery, the duration of tracheal intubation and mechanical ventilation is reduced as is the incidence of myocardial infarction, acute respiratory failure, gastric complications and renal insufficiency (Level I [Cochrane Review]). Additional key messages 12. Chlorhexidine-impregnated dressings of epidural catheters in comparison to placebo- or povidone-iodine-impregnated dressings reduce the incidence of catheter colonisation (Level I) ; MRI investigation may be warranted if patients who have had an epidural catheter inserted develop a fever and infection at the catheter insertion site; urgent investigation is especially indicated if there is a third sign present that could indicate an abscess, such as back pain or neurological change.
7.4
7.4.1
REGIONAL ANALGESIA AND CONCURRENT ANTICOAGULANT MEDICATIONS

Neuraxial blockade
Unfractionated IV and SC heparin Thromboprophylaxis with SC heparin is not a contraindication to neuraxial blockade. To identify heparin-induced thrombocytopenia, a platelet count should be done prior to removal of an epidural catheter in patients who have had more than 4 days of heparin therapy. Intraoperative anticoagulation with IV heparin should start no sooner that 1 hour after placement of the epidural or spinal needle. Epidural catheters should be removed 24 hours after the last heparin dose and following an evaluation of the patients coagulation status. A bloody tap may increase the risk, but there are insufficient data to support cancellation of a case. Unfractionated SC heparin Thromboprophylaxis with SC heparin is not a contraindication to neuraxial blockade. To identify heparin-induced thrombocytopenia, a platelet count should be done prior to removal of an epidural catheter in patients who have had more than 4 days of heparin therapy. Epidural catheters should be removed a minimum of 6 hours after the last heparin dose and not less than 2 hours before the next dose. Unfractionated IV heparin Intraoperative anticoagulation with IV heparin should start no sooner that 1 hour after placement of the epidural or spinal needle. Epidural catheters should be removed after normalisation of the patients coagulation status. A bloody tap may increase the risk, but there are insufficient data to support cancellation of a case.
7.5
7.5.1
OTHER REGIONAL AND LOCAL ANALGESIC TECHNIQUES

Continuous peripheral nerve blockade
Compared with opioid analgesia, continuous peripheral nerve blockade (regardless of catheter location) provides better postoperative analgesia and leads to reductions in opioid use as well as reductions in nausea, vomiting, pruritus and sedation (Richman, JM, Liu, SS, Courpas, G, et al.
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2006 Level I).
Thoracic paravertebral blocks

Continuous thoracic paravertebral blockade was confirmed as being as effective as thoracic epidural analgesia for pain relief after thoracotomy, with a better side effect profile (less urinary retention, hypotension and nausea and vomiting) than epidural analgesia and resulting in a lower incidence of postoperative pulmonary complications (Davies, RG, Myles, PS and Graham, JM 2006 Level I).
7.5.2
Intra-articular analgesia
[Intra-articular opioids following knee joint arthroscopy are moderately effective for up to 24 hours if at least 5mg morphine is injected into the joint (Kalso et al 2002, Level I). Intra-articular analgesia with opioids is not effective following total knee joint replacement surgery (Badner1997, Level II; Maurerhan et al 1997; Klassen et al 1999).] A recent meta-analysis shows that intra-articular morphine following arthroscopy does not improve analgesia compared with placebo (Rosseland, LA 2005 Level I).
7.5.3
Wound infiltration including wound catheters
[Wound infiltration with long-acting local anaesthetics has been shown to lengthen the time until first analgesic request in a number of investigations. A systematic review found that this was most effective following surgery for inguinal hernia repair, where up to 7 hours relief was obtained in comparison with saline. Procedures involving deeper or intracavity structures such as hysterectomy or cholecystectomy showed no benefit (Miniche et al 1998, Level I).] A recent meta-analysis reviewed outcomes following postoperative analgesia using continuous local anaesthetic wound infusions (Liu, SS, Richman, JM, Thirlby, RC, et al. 2006 Level I). Analyses were performed for all surgical groups combined and for the four subgroups (cardiothoracic, general, gynaecology-urology and orthopaedics). While there were some minor variations between the subgroups, the results overall (i.e. for all surgical groups combined) showed that this technique led to reductions in pain scores (at rest and with activity), opioid consumption, postoperative nausea and vomiting, and length of hospital stay; patient satisfaction was higher and there was no difference in the incidence of wound infections (Liu, SS, Richman, JM, Thirlby, RC, et al. 2006 Level I). Early postoperative abdominal pain is improved after laparoscopic cholecystectomy by the use of intraperitoneal local anaesthetic; the effect is better when given at the start of the operation compared with instillation at the end of surgery, and no local anaesthetic toxicity was reported (Boddy, AP, Mehta, S and Rhodes, M 2006 Level 1). Another study after laparoscopic cholecystectomy also showed beneficial effects of infiltration of the incision sites with local anaesthetic (Gupta, A 2005 Level 1). Updated key messages 2. Intra-articular opioids following knee arthroscopy provide analgesia for up to 24 hours (Level I). 2. Morphine injected into the intra-articular space following knee arthroscopy does not improve analgesia compared with placebo when administered after surgery (Level I). 3. Wound infiltration with long-acting local anaesthetics provides effective analgesia following inguinal hernia repair but not open cholecystectomy or hysterectomy (Level I). 3. Wound infiltration with long-acting local anaesthetics provides effective analgesia following inguinal hernia repair and laparoscopic cholecystectomy, but not open cholecystectomy or abdominal hysterectomy (Level I). 8. Wound infiltration with continuous infusions of local anaesthetics improves analgesia and reduces opioid requirements following a range of non-abdominal surgical procedures (Level II). 8. Continuous local anaesthetic wound infusions lead to reductions in pain scores (at rest and
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with activity), opioid consumption, postoperative nausea and vomiting, and length of hospital stay; patient satisfaction is higher and there is no difference in the incidence of wound infections. (Level I) Additional key messages 9. Compared with opioid analgesia, continuous peripheral nerve blockade (regardless of catheter location) provides better postoperative analgesia and leads to reductions in opioid use as well as nausea, vomiting, pruritus and sedation (Level I). 10. Compared with thoracic epidural analgesia, continuous thoracic paravertebral analgesia results in comparable analgesia but has a better side effect profile (less urinary retention, hypotension, nausea, and vomiting) than epidural analgesia and leads to a lower incidence of postoperative pulmonary complications (Level I). 11. Intraperitonal local anaesthetic after laparoscopic cholecystectomy improves early postoperative pain relief (Level I).
7.5.5.
Safety
Nerve injury
[In a prospective study, the incidence of neurologic injury following peripheral nerve blocks was 1.9 per 10,000 (Auory et al 1997, Level IV).] An updated review of the risk of neurological injury associated with epidural and other regional anaesthesia and analgesia differentiated between the risk of permanent neurological injury and transient neuropathy (Brull, R, McCartney, CJ, Chan, VW, et al. 2007 Level IV). The incidence of transient neuropathy (radiculopathy) after three common forms of peripheral nerve blockade interscalene brachial plexus block, axillary brachial plexus block and femoral nerve block ) was estimated to be 2.84%, 1.48% and 0.34% respectively. The risk of permanent neurological injury after peripheral neural blockade was much less. In all the studies included in this review, only one case was reported, making it a very rare event (Brull, R, McCartney, CJ, Chan, VW, et al. 2007 Level IV).
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8. 8.1
8.1.2
NON-PHARMACOLOGICAL TECHNIQUES PSYCHOLOGICAL INTERVENTIONS

Relaxation and attentional strategies
Attentional techniques
[Music does not reduce anxiety levels or pain in patients undergoing surgery or invasive procedures (Evans 2002, Level I).] A recent meta-analysis (Cepeda, MS, Carr, DB, Lau, J, et al. 2006 Level I) looked at the effect of music on pain (acute, chronic and cancer), pain relief and analgesic use. After surgery, music may lead to lower pain intensity levels and opioid requirements, but the magnitude of the difference is small and the clinical significance is therefore unclear (Cepeda, MS, Carr, DB, Lau, J, et al. 2006 Level I). A systematic review of nursing preoperative education for adult orthopaedic patients reported results from 11 included studies. Preoperative education increased patients knowledge levels but had little influence on anxiety. In two studies, patient education reduced postoperative analgesic requirements but there was insufficient data for a meta-analysis (Johansson, K, Nuutila, L, Virtanen, H, et al. 2005 Level I).
8.4
8.4.2
PHYSICAL THERAPIES
Heat and cold
Evidence supporting the use of heat or cold therapy for acute pain remains limited. Heat-wrap therapy may provide short term pain relief for acute or subacute low back pain but no conclusions can be drawn about the use of cold therapy (French, SD, Cameron, M, Walker, BF, et al. 2006 Level I).
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9. 9.2
SPECIFIC CLINICAL SITUATIONS ACUTE SPINAL CORD INJURY
Treatment of acute neuropathic pain after spinal cord injury

[Valproate was ineffective in the treatment of spinal cord injury pain (Drewes et al 1994, Level II) whereas gabapentin decreased pain intensity and frequency, and improved quality of life (Levendoglu et al 2004, Level II).] A recent study has also shown that pregabalin is effective for the treatment of neuropathic pain resulting from spinal cord injury (Siddall, PJ, Cousins, MJ, Otte, A, et al. 2006 Level II). Updated key message 2. Gabapentin is effective in the treatment of acute spinal cord injury pain (Level II). 3. Gabapentinoids (gabapentin / pregabalin) are effective in the treatment of spinal cord injury pain (Level II).
9.6
9.6.1
ACUTE MEDICAL PAIN

Abdominal pain
[A common misconception is that analgesia masks the signs and symptoms of abdominal pathology and should be withheld until a diagnosis is established. Pain relief does not interfere with the diagnostic process in acute abdominal pain in adults (McHale & LoVecchio 2001, Level I; Thomas et al 2003, Level II) or in children (Kim et al 2002, Level II).] This has been confirmed by other recent meta-analyses Manterola, C, Astudillo, P, Losada, H, et al. 2007 Level I; Ranji, SR, Goldman, LE, Simel, DL, et al. 2006 Level I).
Renal colic
[NSAIDs are effective analgesics in renal colic (Labrecque et al 1994, Level I), providing superior pain relief, less vomiting and decreased requirements for rescue analgesia compared with parenteral opioids (Holdgate & Pollock 2004, Level I).] NSAIDs or opioids provide effective analgesia for renal colic: NSAIDs reduce requirements for rescue analgesia and produce less vomiting compared with opioids, particularly pethidine. (Holdgate, A and Pollock, T 2005 (Level 1).
Primary dysmenorrhea
[NSAIDS are of benefit in the treatment of dysmenorrhoea (Marjoribanks et al 2003, Level I) including naproxen (NNT= 2.4), ibuprofen (NNT=2.6) and mefenamic acid (NNT=3.0); ibuprofen had the least adverse effects. Aspirin and paracetamol were less effective than NSAIDs (Zhang & Li Wan Po 1998, Level I)]. Nonsteroidal anti-inflammatory drugs also reduce bleeding and pain associated with intrauterine-device use (Grimes, DA, Hubacher, D, Lopez, LM, et al. 2006 Level 1). Updated key messages 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I). 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I)[Cochrane Review]. 2. NSAIDs are superior to parenteral opioids in the treatment of renal colic (Level I [Cochrane Review]). 2. NSAIDs or opioids provide effective analgesia for renal colic: NSAIDs reduce requirements for rescue analgesia and produce less vomiting compared with opioids, particularly pethidine (Level I [Cochrane Review]).
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9.6.3
Acute cardiac pain
In acute coronary syndrome, hyperbaric oxygen therapy reduced time to relief of ischaemic pain (Bennett, M, Jepson, N and Lehm, J 2005 Level I).
9.6.4
Acute pain and haematological disorders
Sickle cell disease

Opioids [Morphine either by IV infusion or oral sustained release preparation was effective in treating acute sickle cell pain (Jacobson et al 1997, Level II).] Oral sustained release morphine is as effective as parenteral morphine for the treatment of acute pain in sickle cell disease (Dunlop, RJ and Bennett, KC 2006 Level 1). Parenteral corticosteroids shorten the period of analgesia requirement and hospital length of stay. (Dunlop, RJ and Bennett, KC 2006 Level 1) Updated key message 3. Methylprednisolone decreases acute pain in sickle cell crises (Level II). 3. Parenteral corticosteroids shorten the period of analgesia requirement and hospital length of stay in a sickle cell crisis (Level I [Cochrane Review]).
9.6.5
Acute headache
Migraine
Simple analgesics [Patients who experience mild migraine-related headache and disability may be effectively treated with simple analgesics] Ibuprofen 200-400mg is more effective than placebo in reducing migraine pain or achieving pain free status within 2 hours, but is no different to placebo for pain outcomes at 24 hours Suthisisang, C, Poolsup, N, Kittikulsuth, W, et al. 2007 Level I). Dipyrone is effective for the treatment of migraine and episodic tension-type headaches (Ramacciotti, AS, Soares, BG and Atallah, AN 2007 Level I).
UPDATED TABLE 9.2

Analgesic regimen Aspirin 600900mg +metoclopramide 10mg Paracetamol 1000mg Ibuprofen 200400mg
*
Simple analgesics for the treatment of migraine

NNT* 3.2 5.2 8.0 Source Oldman et al 2002, Level I Lipton et al 2000b, Level II Suthisisang et al 2007 Level I
Simple analgesics for the treatment of migraine: 2-hour pain response (nil or mild residual headache at 2 hours).
Paediatric migraine Psychological interventions, such as relaxation training, biofeedback and cognitive-behavioural therapy reduce the intensity of headache in children, and treatment success can be maintained for at least 1 year (Trautmann, E, Lackschewitz, H and Kroner-Herwig, B 2006 Level I). Comparative efficacy with pharmacological treatments has not been investigated. In children with acute migraine, current evidence shows benefit for ibuprofen and sumatriptan for relief of headache (NNT 2.4 and 7.4 respectively) and complete pain relief (NNT 4.9 and 6.9 respectively); Paracetamol, zolmitriptan, rizatriptan and dihydroergotamine were not significantly better than placebo, but the number of RCTs in children is small. (Silver, S, Gano, D and
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Gerretsen, P 2007 Level I).
Post dural puncture headache

The odds of developing a post-dural puncture headache are significantly lower for males than for non-pregnant females (Wu, CL, Rowlingson, AJ, Cohen, SR, et al. 2006 Level I). Additional key messages 14. Psychological interventions reduce the intensity of headache in children (Level 1). 15. Ibuprofen and sumatriptan are effective for paediatric migraine (Level 1).
9.6.6
Acute pain associated with neurological disorders
Multiple sclerosis
Although the number of clinical trials is small, cannabinoids appear to be mildly effective when used in the treatment of chronic neuropathic and multiple sclerosis-related pain; the most common adverse effect is dizziness (33% of patients) (Iskedjian, M, Bereza, B, Gordon, A, et al. 2007 (Level I).
9.6.7
Orofacial pain
Paracetamol is a safe and effective drug for the treatment of postoperative pain following dental extraction. (Weil, K, Hooper, L, Afzal, Z, et al. 2007 Level I) After oral surgery the NNT for1000 mg paracetamol is 3 and the NNH 33. (Dodson, T 2007 Level I) A dose of 1000 mg was significantly more effective than lower doses.
Acute pain associated with sinusitis and otitis media

[In children, antibiotics provided only a small improvement (NNT 15) in pain associated with acute otitis media after 2 days of treatment (Glasziou et al 2003, Level I).] In selected children, antibiotics improved pain (NNT 3-4) associated with acute otitis media. (Rovers, MM, Glasziou, P, Appelman, CL, et al. 2006 Level I). Local anaesthetic ear drops result in pain reduction in otitis media; however the overall effectiveness of eardrops in this condition is unclear (Foxlee, R, Johansson, A, Wejfalk, J, et al. 2006 Level I).
Acute post-tonsillectomy pain

[There is no evidence that perioperative local anaesthetic infiltration improves postoperative pain control after tonsillectomy (Hollis et al 1999, Level I).] However, recent RCTs show that injection of local anaesthesic in the tonsillar fossa may improve pain scores, reduce time to first oral intake, and reduce the incidence of referred ear pain following tonsillectomy (Naja, MZ, El-Rajab, M, Kabalan, W, et al. 2005 Level II; Somdas, MA, Senturk, M, Ketenci, I, et al. 2004 Level II. [ aspirin (Krishna et al 2003, Level I) and NSAIDs (number-needed-to-harm [NNH] 2960) increased the risk of reoperation for post-tonsillectomy bleeding (Marret et al 2003, Level I; Miniche et al 2003, Level I) (see also Sections 4.2.2 and 10.1.5).] This increased risk of bleeding with NSAIDs after tonsillectomy could not be confirmed in children by a Cochrane review (Cardwell, M, Siviter, G and Smith, A 2005 Level I). [In children, the administration of IV dexamethasone after tonsillectomy decreased postoperative vomiting and shortened time to starting a soft diet although there were no specific data on pain (Steward et al 2002, Level I).] More recent evidence has shown that dexamethasone produced a significant but moderate reduction in post-tonsillectomy pain on the first postoperative day (Afman, CE, Welge, JA and Steward, DL 2006 Level I). Peri-operative antibiotics do not reduce post-tonsillectomy pain up to day 7 (Dhiwakar, M, Eng, CY, Selvaraj, S, et al. 2006 Level I; Burkart, 2005 #196} Level I; Iyer, S, DeFoor, W, Grocela, J, et al. 2006 Level I).
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Acute pain associated with oral ulceration including acute mucositis

[In treating the pain of cancer-related acute mucositis, there was no significant difference in analgesia between PCA and continuous opioid infusion except that PCA was associated with lower opioid requirements and reduced duration of pain (Worthington et al 2004, Level I).] (Clarkson, JE, Worthington, HV and Eden, OB 2007 Level I) [Lignocaine (lidocaine) solutions, chlorhexidine and sulcrafate were of no more benefit that simple salt and soda water mixtures; allopurinol mouthwash, vitamin E, immunoglobulin and human placental extract may improve outcomes in acute mucositis but the evidence is inconclusive (Worthington et al 2004, Level I).] There is weak evidence that allopurinol mouthwash, granulocyte macrophage-colony stimulating factor (GM-CSF), immunoglobulin or human placental extract improves or eradicates mucositis. Benzydamine HCl, sucralfate, tetrachlorodecaoxide, chlorhexidine, lidocaine solution, diphenhydramine hydrochloride and aluminum hydroxide suspensions were ineffective (Clarkson, JE, Worthington, HV and Eden, OB 2007 Level I). Polymyxin E, tobramycin and amphotericin B (PTA), GM-CSF, oral cooling and amifostine, significantly reduced the incidence and severity of oral mucositis (Stokman, MA, Spijkervet, FK, Boezen, HM, et al. 2006 Level I). Povidone-iodine mouthwash significantly reduced the severity of oral mucositis compared with sterile water, however chlorhexidine was ineffective (Potting, CM, Uitterhoeve, R, Op Reimer, WS, et al. 2006 Level I). Updated key messages 3. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]), 3. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]), although this is not supported by recent RCTs (Level II). 4. Aspirin and NSAIDs increase the risk of reoperation for post-tonsillectomy bleeding (Level I). 4. Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy, except in paediatric patients. (Level I [Cochrane Review]). 7. Topical treatments may provide analgesia in acute oral ulceration (Level II). 7. Topical treatments provide analgesia in acute oral ulceration and mucositis (Level I). Additional key message 8. Intraoperative dexamethasone administration reduces acute pain and nausea/ vomiting after tonsillectomy (Level I).
9.7
ACUTE CANCER PAIN
[In an emergency situation, IV titration with fentanyl (Soares et al 2003, Level II) or use of transmucosal fentanyl (Farrar et al 1998, Level II; Coluzzi et al 2001) has been successful.] Oral transmucosal fentanyl is an effective treatment in the management of breakthrough pain (Zeppetella, G and Ribeiro, MD 2006 Level I). Breakthrough medication doses should be titrated for each patient according to their response to these doses and separate from the background medication (Hagen, NA, Fisher, K, Victorino, C, et al. 2007 Level II). Updated key messages 1. Oral transmucosal fentanyl is effective in treating acute breakthrough pain in cancer patients (Level II). 1. Oral transmucosal fentanyl is effective in treating acute breakthrough pain in cancer patients (Level I).
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9.9
ACUTE PAIN MANAGEMENT IN EMERGENCY DEPARTMENTS
9.9.2 Analgesia in specific conditions Abdominal pain

[Previous dogma suggested that analgesia should be withheld from patients with abdominal pain until a diagnosis is made. However there is good evidence showing that provision of early analgesia does not affect diagnostic accuracy in adults or children (McHale & LoVecchio 2001, Level I; Kim et al 2002, Level II; Thomas & Silen 2003, Level II; Thomas et al 2003, Level II).] This has been confirmed by other meta-analyses (Manterola, C, Astudillo, P, Losada, H, et al. 2007 Level I; Ranji, SR, Goldman, LE, Simel, DL, et al. 2006 Level I).
Renal colic
[NSAIDS produced clinically significant reductions in pain scores, less vomiting and a decreased requirement for rescue analgesia when compared with opioids (Holdgate & Pollock 2004, Level I).] NSAIDs or opioids provide effective analgesia for renal colic: NSAIDs reduce requirements for rescue analgesia and produce less vomiting compared with opioids, particularly pethidine. (Holdgate, A and Pollock, T 2005(Level 1).
Procedural pain
Topical tetracaine, liposome-encapsulated tetracaine, and liposome-encapsulated lignocaine are as effective as EMLA cream for dermal instrumentation analgesia in the emergency department (Eidelman, A, Weiss, JM, Lau, J, et al. 2005 Level I). Ketamine-midazolam is more effective and has fewer adverse events than fentanyl-midazolam or propofol-fentanyl for the reduction of paediatric fractures in the emergency department (Migita, RT, Klein, EJ and Garrison, MM 2006 Level I). Key messages 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I). 1. Provision of analgesia does not interfere with the diagnostic process in acute abdominal pain (Level I). [Cochrane Review]). 2. In patients with renal colic, NSAIDs provide better pain relief with fewer adverse effects compared with opioids (Level I [Cochrane Review]). 2. NSAIDs or opioids provide effective analgesia for renal colic: NSAIDs reduce requirements for rescue analgesia and produce less vomiting compared with opioids, particularly pethidine (Level I [Cochrane Review]).
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10.
SPECIFIC PATIENT GROUPS
10.1 THE PAEDIATRIC PATIENT

10.1.3. Paediatric pain assessment
Two systematic reviews have analysed the psychometric properties of self-report and behavioural tools for acute pain assessment in children (>3 years) and adolescents (Stinson, JN, Kavanagh, T, Yamada, J, et al. 2006 Level I; von Baeyer, CL and Spagrud, LJ 2007 Level I). There is still no single gold standard for pain assessment as requirements vary with the age and developmental stage of the child, the type of pain (eg. procedural vs postoperative), and the context (e.g. clinical utility versus research reliability). However, based on current data the following tools were recommended for pain measurement in children (over 3 years) and adolescents: 1. Observational / behavioural measures (von Baeyer, CL and Spagrud, LJ 2007 Level I). a. acute procedural pain : FLACC and CHEOPS b. postoperative pain : FLACC c. postoperative pain managed by parents at home : Parents Postoperative Pain Measure (PPPM) d. intensive care : COMFORT 2. Self-report is preferred when feasible, and six tools have well-established evidence of reliability and validity (Pieces of Hurt tool; Faces Pain Scale & FPS-R; Oucher; Wong-Baker Faces; VAS). Although chronological age may not always be an accurate indicator of developmental stage the following tools are recommended for different general age ranges: a. 3-4 years : Pieces of Hurt tool b. 4-12 years : Faces Pain Scale-Revised
c. over 8 years : 0-100 visual analogue scale (VAS) 10.1.4 Management of procedural pain Types of procedures
[IV ketamine plus midazolam was more effective than IV fentanyl plus midazolam (Kennedy et al 1998, Level II). ] Ketamine-midazolam is more effective and has fewer adverse events than fentanyl-midazolam or propofol-fentanyl for the reduction of paediatic fractures in the emergency department (Migita, RT, Klein, EJ and Garrison, MM 2006 Level I).
Pharmacological
Topical local anaesthetics In a comparison of EMLA and amethocaine for intravenous cannulation or venepuncture in children aged 3 months to 15 years, amethocaine provided greater reduction in self- and observer-reported pain scores for needle pain, regardless of whether application time was short (30-60 minutes), long (> 60 minutes) or as recommended by the manufacturer. When used specifically for intravenous cannulation, amethocaine was more efficacious, but there was insufficient data to specifically compare efficacy for venepuncture. Amethocaine was more likely to produce erythema, whereas blanching was observed after EMLA, but there was insufficient data to compare the ease or success of insertion (Lander, JA, Weltman, BJ and So, SS 2006 Level I).
Nonpharmacological
Breast feeding or drinking breast milk reduces distress in neonates undergoing painful procedures. The degree of change is similar as seen following administration of sucrose, and is greater than associated with positioning the neonate alone (eg. swaddling) or no intervention. These effects have not been confirmed for multiple procedures, and efficacy has not been compared with
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pharmacological treatments (Shah, PS, Aliwalas, LI and Shah, V 2006 Level I). The efficacy of psychological interventions for needle-related pain (most commonly immunization and injections) in children and adolescents (2-19yrs) has been analysed in a metaanalysis. Distraction, hypnosis, and combined cognitive-behavioural interventions reduced both self-reported and observer reports of pain and distress (Uman, LS, Chambers, CT, McGrath, PJ, et al. 2006 Level I). Updated key messages 3. Psychological interventions (cognitive-behavioural techniques, hypnosis) reduce procedurerelated distress (Level II). 3. Distraction, hypnosis, and combined cognitive-behavioural interventions reduce pain and distress associated with needle-related procedures in children and adolescents. (Level I [Cochrane Review]) Additional key messages 6. Breastfeeding or breast milk reduces measures of distress in neonates undergoing a single painful procedure compared to positioning or no intervention. Administration of glucose/sucrose has similar efficacy (Level 1[Cochrane Review]). 7. EMLA is an effective topical anaesthetic for children, but amethocaine is superior for reducing needle insertion pain (Level 1 [Cochrane Review]).
10.1.5 Analgesic agents Nonsteroidal anti-inflammatory drugs

A combination of individually titrated intraoperative opioids and regularly administered perioperative mild analgesics (NSAID and/or paracetamol) is required for management of tonsillectomy pain (Hamunen, K and Kontinen, V 2005 Level 1). Adverse effects [The risk of post-tonsillectomy haemorrhage with aspirin was significantly higher than in the ibuprofen and diclofenac group (Krishna et al 2003, Level I) and it was concluded that these NSAIDS but not aspirin were safe. Although the rate of postoperative bleeding was not significantly increased (Miniche et al 2003) the risk of reoperation for post-tonsillectomy bleeding (number-needed-to-harm [NNH] 2960) was increased by NSAIDs (Marret et al 2003, Level I; Miniche et al 2003, Level I) and it was concluded that NSAIDs should be used cautiously until further evidence is available (Miniche et al 2003).] This increased risk of bleeding with NSAIDs after tonsillectomy could not be confirmed in children by a Cochrane review (Cardwell, M, Siviter, G and Smith, A 2005 Level I)
Corticosteroids
[The effect of dexamethasone on pain following tonsillectomy could not be assessed from current studies, but a reduction in vomiting and earlier return to diet was confirmed (Steward et al 2003, Level I). Dexamethasone reduces vomiting and results in an earlier return to soft diet following tonsillectomy. (Steward et al 2003, Level I).] A recent analysis of 8 RCTs investigating pain following paediatric tonsillectomy +/adenoidectomy has shown that a single dose of intraoperative dexamethasone reduces pain (by 1 on VAS scale 0-10) on the first postoperative day (Afman, CE, Welge, JA and Steward, DL 2006 Level I). Doses have varied (0.4-1mg/kg; maximum 8-50mg) and further studies are required to determine optimum dosing.
Other pharmacological therapies

Acute otitis media is common in children, but antibiotics may provide only marginal improvements. A recent sub-group analysis reported that antibiotics are most beneficial (i.e. reduce the proportion of children still experiencing pain and/or fever at 3-7 days) in children younger than 2 years with bilateral acute otitis media (NNT 4), and in children with both acute otitis media and otorrhoea (NNT 3) (Rovers, MM, Glasziou, P, Appelman, CL, et al. 2006 Level I).
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Analysis of 4 RCTs investigating topical LA drops for pain associated with acute otitis media, found insufficient evidence to evaluate efficacy or adverse effects (Foxlee, R, Johansson, A, Wejfalk, J, et al. 2006 Level I). In children with acute migraine, current evidence shows benefit for ibuprofen and sumatriptan for relief of headache (NNT 2.4 and 7.4 respectively) and complete pain relief (NNT 4.9 and 6.9 respectively)(Silver, S, Gano, D and Gerretsen, P 2007 Level I). Paracetamol, zolmitriptan, rizatriptan and dihydroergotamine were not significantly better than placebo, but the number of RCTs in children is small. Updated key messages 1. Aspirin and NSAIDs increase the risk of reoperation for post-tonsillectomy bleeding (Level I). 1. Aspirin and some NSAIDs increase the risk of perioperative bleeding after tonsillectomy, except in paediatric patients. (Level I [Cochrane Review]). Additional key message 6. Intraoperative dexamethasone administration reduces acute pain and nausea/ vomiting after tonsillectomy (Level I)
10.1.6 Opioid infusions and PCA Opioid infusions

In ventilated neonates, opioid infusions have been used for analgesia and have been postulated to improve neurological outcome by increasing respiratory and cardiovascular stability. Infants given opioids had reduced PIPP (premature infant pain profile) scores following procedural interventions, but heterogeneity in the included data limit the strength of this finding, and the degree of change may not be clinically significant (1.71 points on scale 0-21). No statistically significant differences in mortality, duration of ventilation, or improvements in short or long-term neurological outcomes have been demonstrated by routine use of opioid infusions in ventilated neonates (Bellu, R, de Waal, KA and Zanini, R 2005 Level I).
10.1.7 Regional analgesia Tonsillectomy

[Although the number of suitably designed studies is limited, local anaesthetic applied to the tonsillar bed does not reduce pain following tonsillectomy (Hollis et al 1999, Level I).] However, recent RCTs show that injection of local anaesthesic in the tonsillar fossa may improve pain scores, reduce time to first oral intake, and reduce the incidence of referred ear pain following tonsillectomy (Naja, MZ, El-Rajab, M, Kabalan, W, et al. 2005 Level II; Somdas, MA, Senturk, M, Ketenci, I, et al. 2004 Level II.
Central neural blockade

Epidural analgesia Complications A recent audit of 10,633 paediatric epidurals performed in the UK and Ireland reported five serious incidents: two epidural abscess, and one each of meningism, severe PDPH requiring autologous blood patch, and a drug volume error resulting in cauda equina syndrome (which was the only case associated with residual symptoms at 12 months). Peripheral or nerve root damage was reported in 6 cases: 3 resolved spontaneously, 2 required chronic pain referral and gabapentin but resolved by 12 months, and one had residual symptoms at 1 year. Compartment syndromes were reported in 4 children, but symptoms were not masked by the epidural infusion.Llewellyn, N and Moriarty, A 2007
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Updated key message 2. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]), although this is not supported by recent RCTs (Level II). 2. Perioperative local anaesthetic infiltration does not improve analgesia after tonsillectomy (Level I [Cochrane Review]), although this is not supported by recent RCTs (Level II).
10.1.8 Acute pain in children with cancer Treatment-related pain

[A systematic review (which included mainly adult studies) found no difference in pain control between PCA and continuous infusion, but reduced hourly opioid requirement and shorter duration of pain with PCA (Worthington et al 2004, Level I)].(Clarkson, JE, Worthington, HV and Eden, OB 2007 Level 1)
10.2 THE PREGNANT PATIENT

10.2.1 Management of acute pain during pregnancy Drugs used in pregnancy
[Drugs that might be prescribed during pregnancy have been categorised according to fetal risk by the Australian Drug Evaluation Committee (ADEC).] An updated list of these drugs is available from the following web site - http://www.tga.gov.au/docs/html/medpreg.htm
10.2.2 Management of pain during delivery Epidural and combined spinal-epidural analgesia in labour pain
[Epidural analgesia is more effective in reducing pain than non-regional methods of analgesia (Howell 1999, Level I; Liu & Sia 2004, Level I).] Epidural analgesia provides better pain relief than non-epidural analgesia (weighted mean difference WMD -2.6; CI -3.82 to -1.38; VAS 0-10) and is associated with an increased risk of instrumental vaginal birth (RR 1.38; CI 1.24-1.53), an increased use of oxytocin (RR 1.18; CI 1.03-1.34), and a longer second stage of labour (WMD 15.6 minutes; CI 7.5-23.6), which did not appear to have an acute adverse affect on the infant, as there was no increase in the incidence of low neonatal 5-minute Apgar Scores (RR 1.18; CI 0.92-1.5) (AnimSomuah, M, Smyth, R and Howell, C 2005 Level I). Epidural analgesia did not increase the rate of caesarean delivery (RR 1.07; CI 0.93-1.23) and was not associated with long-term backache (RR 1.0; CI 0.89-1.12) (Anim-Somuah, M, Smyth, R and Howell, C 2005 Level I). The timing of neuraxial analgesia is based on the degree of cervical dilatation in some centres. In nulliparous women, on-demand administration of neuraxial analgesia from early labour (<4 cm cervical dilation) provided more effective pain relief and did not increase the rate of Caesarean delivery or instrumental vaginal delivery when compared to commencement of epidural analgesia later in labour (Marucci, M, Cinnella, G, Perchiazzi, G, et al. 2007 Level I). By contrast, women receiving early systemic opioid analgesia before late epidural analgesia had a higher incidence of instrumental vaginal delivery. Infants of mothers receiving early neuraxial analgesia had improved neonatal acid-base status, a reduced requirement for naloxone, but no measurable difference in Apgar scores when compared to infants of mothers receiving parenteral opioid analgesia (Marucci, M, Cinnella, G, Perchiazzi, G, et al. 2007 Level I). However, it was also noted that many of the included studies did not score highly for quality, and a lack of blinding may produce bias. [Combined spinal-epidural in comparison with epidural analgesia reduces time to effective analgesia and maternal satisfaction but increases the incidence of pruritus (Hughes et al 2004, Level I).] Combined spinal-epidural analgesia in labour does not offer any significant advantage over epidural analgesia alone, but increases the risk of urinary retention (Simmons, SW, Cyna, AM,
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Dennis, AT, et al. 2007 Level I).
Complementary and other methods of pain relief in labour pain

[Hypnosis increases satisfaction with pain relief and acupuncture decreases the need for analgesics (Smith et al 2003, Level I). Hypnosis used in labour also leads to a decreased requirement for pharmacological analgesia, increased incidence of spontaneous vaginal delivery and decreased use of labour augmentation (Cyna et al 2004, Level I).] Non-pharmacological or complementary therapies may be used during labour. Acupuncture decreased the need for pain relief (RR 0.7; CI 0.49-1.0). Women taught self-hypnosis had reduced pharmacological requirements (RR 0.53; CI 0.36-0.79), a slight decrease in need for epidural analgesia (RR 0.3; CI 1.15-4.71), and increased satisfaction compared with controls. The efficacy of acupressure, aromatherapy, audio analgesia, relaxation or massage has not been established. Few complementary therapies have been carefully studied in well designed trials with clinically relevant outcomes, and sample sizes have been small (Smith, CA, Collins, CT, Cyna, AM, et al. 2006 Level I). Updated key messages 2. Epidural and combined spinal-epidural analgesia provide superior pain relief for labour and delivery compared with systemic analgesics (Level I). 2. Epidural and combined spinal-epidural analgesia provide superior pain relief for labour and delivery compared with systemic analgesics (Level I [Cochrane Review]). 3. Combined spinal-epidural in comparison with epidural analgesia reduces time to effective analgesia and improves maternal satisfaction but increases the incidence of pruritus (Level I [Cochrane Review]). 3. Combined spinal-epidural in comparison with epidural analgesia does not offer significant advantages but increases the incidence of urinary retention (Level I [Cochrane Review]). 4. Epidural analgesia does not increase the incidence of caesarean section and long-term backache (Level I). 4. Epidural analgesia does not increase the incidence of caesarean section and long-term backache (Level I [Cochrane Review]). 5. Epidural analgesia is associated with increased duration of labour and may increase rate of instrumental vaginal delivery (Level I). 5. Epidural analgesia is associated with increased duration of labour and increased rate of instrumental vaginal delivery (Level I [Cochrane Review]). 12.Hypnosis used in labour reduces analgesic requirements and use of labour augmentation and increases the incidence of spontaneous vaginal delivery (Level I). 12.Hypnosis used in labour reduces analgesic requirements and use of labour augmentation and increases the incidence of spontaneous vaginal delivery (Level I [Cochrane Review]).
10.2.4 Pain in the puerperium

Ergot alkaloids during the third stage of labour increase the requirement for analgesia for pain after birth due to persistent uterine contraction (RR 2.53; CI 1.34-4.78), but also decrease mean blood loss and the incidence of postpartum haemorrhage when compared to no uterotonic drugs (Liabsuetrakul, T, Choobun, T, Peeyananjarassri, K, et al. 2007 Level I).
Perineal pain
Nonpharmacological For women without prior vaginal delivery, antenatal perineal massage (from 35 weeks gestation) reduced the incidence of perineal trauma requiring suturing (NNT 14; CI 9-35) and the requirement for episiotomy (NNT 23; CI 13-111). Effects on acute postpartum pain have not been reported, but a reduction in the incidence of pain at 3 months postpartum was reported only in women who had previously given birth vaginally (Beckmann, MM and Garrett, AJ 2006 Level I).
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Pharmacological [The topical application of lignocaine (lidocaine) ointment to the perineum during the second stage of labour reduces immediate perineal pain briefly but it is not an effective treatment of established perineal pain (Minassian et al 2002, Level II).] Five trials measuring pain up to 24 hours following childbirth found no difference in pain relief between topical local anaesthetic (lignocaine, cinchocaine, pramoxine plus hydrocortisone preparations) and placebo. One trial reported a reduction in supplemental analgesic requirements with epifoam (1% hydrocortisone and 1% pramoxine in muco-adhesive base), which was not seen following lignocaine preparations. The use of systemic analgesics was not standardized across studies and may be a confounding factor (Hedayati, H, Parsons, J and Crowther, CA 2005 Level I). Additional key message 7. Topical local anaesthetic preparations are not effective for perineal pain after childbirth (Level 1[Cochrane Review]}.
10.3 THE ELDERLY PATIENT

10.3.3 Assessment of pain Cognitive impairment
A systematic review confirmed that postoperative cognitive dysfunction (POCD) is relatively common after noncardiac surgery and that the elderly patient is particularly at risk (Newman, S, Stygall, J, Hirani, S, et al. 2007 Level 1).
10.9 THE PATIENT WITH A SUBSTANCE ABUSE DISORDER

10.9.3 Drugs used in the treatment of substance abuse disorders Buprenorphine
Buprenorphine is a partial opioid agonist used in the treatment of opioid addiction and is commonly prescribed in doses of 832mg (Roberts, DM and Meyer-Witting, M 2005). It should be noted that a new sublingual formulation of buprenorphine combined with naloxone in a 4:1 ratio (Suboxone) is now available and widely used. This aims to discourage parenteral abuse; there is negligible absorption of naloxone via the SL route (Harris, DS, Mendelson, JE, Lin, ET, et al. 2004).
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Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine

ACUTE PAIN MANAGEMENT: SCIENTIFIC EVIDENCE

Australian and New Zealand College of Anaesthetists 2007

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

10.9* The patient with a substance abuse disorder...................................................... 52 REFERENCES ................................................................................................. 53

Updates for Acute Pain Management: Scientific Evidence

UPDATED SUMMARY OF KEY MESSAGES

1. Physiology and psychology of acute pain

2. Assessment and measurement of acute pain and its treatment

Updates for Acute Pain Management: Scientific Evidence

3. Provision of safe and effective acute pain management

4. Systemically administered analgesic drugs

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

5. Regionally and locally administered analgesic drugs

Updates for Acute Pain Management: Scientific Evidence

6. Routes used for systemic drug administration in management of acute pain

7. Techniques used for drug administration in the management of acute pain

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

9. The management of acute pain in specific clinical situations

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

10. The management of acute pain in specific patient groups

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

PHYSIOLOGY AND PSYCHOLOGY OF ACUTE PAIN PRE-EMPTIVE AND PREVENTIVE ANALGESIA

Updates for Acute Pain Management: Scientific Evidence

PROVISION OF SAFE AND EFFECTIVE ACUTE PAIN MANAGEMENT EDUCATION

Updates for Acute Pain Management: Scientific Evidence

SYSTEMICALLY ADMINISTERED ANALGESIC DRUGS OPIOIDS

Adverse effects of opioids

Nausea and vomiting

PARACETAMOL, NSAIDS AND COX-2 SELECTIVE INHIBITORS

Updates for Acute Pain Management: Scientific Evidence

Non-steroidal anti-inflammatory drugs

Cyclo-oxygenase-2 selective inhibitors (COX-2 inhibitors)

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

REVISED TABLE 4.1 Antidepressants for the treatment of neuropathic pain

Updates for Acute Pain Management: Scientific Evidence

Specific anticonvulsant agents used in the treatment of acute pain

Specific anticonvulsant agents used in the treatment of chronic neuropathic pain

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

Complementary and alternative medicines

Updates for Acute Pain Management: Scientific Evidence

REGIONALLY AND LOCALLY ADMINISTERED ANALGESIC DRUGS LOCAL ANAESTHETICS

Long duration local anaesthetics

Topical Local Anaesthetics

Updates for Acute Pain Management: Scientific Evidence

Updates for Acute Pain Management: Scientific Evidence

5.4 ANTI-INFLAMMATORY DRUGS