Clinical anaesthesia
Premedication
Charlotte Steeds
Robert Orme
Abstract
The aims of premedication are anxiolysis, analgesia, anti-emesis and to
reduce perioperative risk to the patient (e.g. with antihypertensives, ant-
acids and antisialogogues). Many factors have contributed to the decline
in premedicant prescription, including changes in anaesthetic agents and
short postoperative stays. As well as considering premedication as part
of the preoperative visit, the anaesthetist should review the patient’s
current medications and decide which drugs should be continued dur-
ing the perioperative period. In general, most drugs are given on the
morning of surgery, but there are important exceptions, some of which
may require discontinuation before hospital admission (e.g. clopidogrel).
Insulin and steroids may need parenteral supplementation. Anxiolytics
are less commonly prescribed than other premedications but are useful
for some cases. Benzodiazepines are the most frequently used ­anxiolytic
agents. Analgesics are sometimes prescribed, especially in the day-
­surgery setting, since paracetamol and non-steroidal anti-inflammatory
drugs reduce perioperative opioid requirements. Caution must be taken
when considering the use of cyclo-oxygenase-2 inhibitors, because of
their association with increased risk of myocardial infarction and stroke.
Topical analgesics are used in children to lessen the pain of cannulation.
Anti-emetics, though commonly given at induction, can be prescribed
as a premedicant. Consideration should also be given to the periopera-
tive use of β-adrenoreceptor antagonists for patients undergoing major
surgery. Antacids (e.g. H2-receptor antagonists and proton-pump inhibi-
tors) should be prescribed for patients at risk from aspiration of gastric
contents. Antisialogogues are rarely needed but may be indicated for
awake fibre-optic intubation.
Keywords analgesia; anti-emesis; anxiolytics; premedication; steroids
Premedication can be defined as the administration of ­medication
before anaesthesia. The practice of premedication has changed
substantially in recent years. The use of strongly sedative
drugs, such as ­morphine and hyoscine, to aid smooth ­induction
Charlotte Steeds, MBBS, FFARCSI, is Specialist Registrar in Anaesthesia at
the Royal United Hospital, Bath. She is currently spending a year in
Chronic Pain Management. She qualified at University College London
and is in training in Anaesthesia in the Bristol region.
Robert Orme, MBChB, FRCA, is Consultant Anaesthetist with an interest
in Intensive Care at Cheltenham General Hospital. He trained in
anaesthesia in Exeter, Dunedin and Oxford. He has developed a
specific interest in echocardiography in the ICU. His current research
interest is in ventilator-associated pneumonia.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 7:11
and reduce ­ salivation has been abandoned with the advent of
modern intravenous and inhalational agents, which have far
fewer side effects and a faster onset. Other factors have also
influenced ­ modern practice and reduced the use of a sedative
­premedication:
• increasing use of day-case surgery
• same-day admissions – patients often do not find a bed until
just before surgery and the preoperative visit is rushed
• changes to the surgical list, making the timing of drug delivery
difficult.
Despite these changes, the main aims of premedication are:
• anxiolysis
• analgesia (systemic and topical)
• anti-emesis
• risk reduction specific to the patient or the type of surgery
(­antihypertensives, antacids, antisialogogues, antibiotic cover).
The decision as to which premedication to prescribe (if any)
is made at the time of the preoperative visit. As well as assess-
ing the patient for any pre-existing conditions, the ­anaesthetist
should also issue clear instructions as to which of the patient’s
current medicines should be given preoperatively. Although
there are exceptions, most drugs should be continued right up to
the time of the operation and restarted immediately ­afterwards.
Drugs for continuation or discontinuation in the
perioperative period
Cardiovascular drugs: antihypertensives, anti-anginal, and anti-
arrhythmic agents are best continued to reduce haemodynamic
instability and the risk of myocardial ischaemia.
The continuation of angiotensin-converting enzyme inhibitors
and angiotensin II receptor antagonists is controversial because
of the risk of profound hypotension under anaesthesia. These
drugs are usually best omitted on the day of surgery.
Diuretics should be omitted if there are concerns about vol-
ume depletion and hypokalaemia or if regional anaesthesia is to
be used when the patient is awake.
Anticoagulants: warfarin should be stopped 5–7 days preop-
eratively, and be converted to heparin, depending on the initial
reason for treatment. Unfractionated heparin infusions should
be stopped 6 hours before surgery, and the activated partial
prothrombin time checked immediately before surgery. Low
­molecular weight heparin should be given at least 12 hours before
surgery. A full clotting screen should be checked preoperatively
when anticoagulants have been used. Aspirin and clopidogrel
may need to be omitted before surgery; however, clopidogrel
should not be stopped if the patient has had a drug-eluting coro-
nary stent inserted within the past year, as there is a risk of stent
occlusion.
Respiratory drugs: bronchodilators should be continued up to
the time of surgery. Inhaled β2-adrenoceptor agonists can be given
immediately before theatre to reduce risk of bronchospasm.
Drugs acting on the central nervous system generally need
to be continued. However, there are some exceptions. ­Tricyclic
a­ntidepressants can have important drug interactions and increase
the risk of arrhythmias and hypotension. They should not be
stopped abruptly. Monoamine oxidase inhibitors (MAOIs) have
393 © 2006 Elsevier Ltd. All rights reserved.
 Clinical anaesthesia

important interactions with pethidine and indirectly acting sym-
pathomimetic drugs (e.g. ephedrine). Irreversible MAOIs should
be stopped 2 weeks preoperatively, and a shorter-acting agent
prescribed. Lithium may potentiate the effect of ­neuromuscular
blocking agents and should be stopped 1–3 days before major
surgery. However, it may be continued for minor surgery, whilst
electrolytes are monitored.
Metabolic and endocrine drugs: patients with diabetes ­mellitus
undergoing moderate or major surgery will require an intra­
venous insulin regimen. For people with type 2 diabetes having
minor surgery, omit oral hypoglycaemic agents on the morning
of surgery, and put the case first on the list.
Steroids: patients on 10 mg prednisolone or more per day within
3 months of surgery will need perioperative supplementation, as
outlined in Table 1 (see Further Reading).
have effect if given too late. The patient may also be left with a
‘hangover’ from the sedative effect of their anxiolytic premedica-
tion, which may delay recovery from anaesthesia. Nevertheless,
anxiolysis and sedation may be required in particular groups
of patients (e.g. children, those with learning difficulties) and
before major surgery (e.g. cardiac surgery) to cover the period
that the patient spends in the anaesthetic room whilst invasive
monitoring is put in place. For major surgery, the sedative ‘hang-
over’ is less of a problem because the patient may be transferred
to intensive care postoperatively.
Benzodiazepines are the most commonly used anxiolytic
agent, and act as agonists at receptors closely linked to the
γ- aminobutyric acid receptor, increasing entry of chloride ions
to hyperpolarize the synaptic membrane. The anxiolytic agents
commonly used are summarized in Table 2. It is important to
ensure that informed consent has been obtained before the
administration of a sedative drug.

Anxiolysis
Anxiety is very common before surgery, and can be unpleasant
for the patient. In many cases patient’s fears can be alleviated at
the preoperative visit. However, some patients request or require
a pharmacological solution to this problem.
Most drugs used for anxiolysis are sedative and can also pro-
voke amnesia. There are usually problems with the timing of
drug administration as the drug may not have sufficient time to
Recommendations for perioperative steroid
supplementation
Type of surgery Dose of steroid cover
Minor Usual dose of corticosteroid on
morning of surgery plus 25 mg
hydrocortisone at induction
Resume normal medication
postoperatively
Moderate Usual dose of corticosteroid on
morning of surgery and 25 mg
hydrocortisone at induction
Then: 25 mg i.v. 8 hourly for
48–72 hours postoperatively;
or 100 mg/24 hours infusion,
stopped at 24–48 hours. Then
resume normal preoperative
dose
Major Usual dose of corticosteroid on
morning of operation plus 25 mg
hydrocortisone at induction
Then: 25 mg i.v. 8 hourly for
48–72 hours postoperatively;
or 100 mg/24 hours infusion,
stopped at 48–72 hours. Then
resume normal preoperative
dose
i.v., intravenously
Table 1
Analgesia
In theory, the use of analgesics before surgery (‘pre-emptive
analgesia’) aims to reduce total analgesic requirements, possibly
sparing the need for opioid administration in recovery. Whether
or not it is clinically effective is controversial. However, the
increase in day surgery has driven the development of multi-
modal analgesia, using a combination of opioids, paracetamol
and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs have received much publicity in recent years. Con-
ventional non-selective NSAIDs inhibit at least two isoforms of
the enzyme cyclo-oxygenase (COX): COX-1 and COX-2. COX-1
is expressed continuously in most tissues, and in the stomach
catalyses production of prostaglandins that protect the ­ gastric
mucosa. COX-2 is less widely expressed, but is readily induced
when tissues are exposed to inflammatory stimuli. As inhibition
of COX-1 is thought to be the main way in which conventional
NSAIDs cause adverse effects, such as gastric irritation, specific
COX-2 inhibitors, known as coxibs, were developed.
However, selective inhibition of COX-2 proved to be more
complex than at first suggested as both isoforms may be impor-
tant in the maintenance of vascular homeostasis and regulation
of platelet function. In September 2004, evidence of an increased
risk of myocardial infarction and stroke in patients who had been
taking rofecoxib for more than 18 months led to its withdrawal
worldwide. In addition, coxibs have a high ‘number needed to
treat’ (about 140 patients) to prevent a single gastrointestinal
bleed (see Further Reading). Based on current evidence, the Com-
mittee on Safety of Medicines advise that coxibs should not be
given to patients with ischaemic heart disease or cerebrovascular
disease. Of the currently available coxibs, only parecoxib has a
licence for postoperative pain. It may be given intravenously at a
dose of 40 mg on induction.
Traditional NSAIDs include diclofenac 50–100 mg given orally
or rectally, and ibuprofen 400 mg given orally. Paracetamol can
be used as a premedication at 1 g in adults orally or rectally. In
children, it is commonly used as a loading dose preoperatively
at 20–30 mg/kg orally or 30-40 mg/kg rectally. Remember, it is
necessary to seek patient and, if appropriate, parental consent to
administer rectal medications under anaesthesia.
Topical anaesthetic creams are commonly prescribed for
­children before cannulation, and are applied under an occlusive

ANAESTHESIA AND INTENSIVE CARE MEDICINE 7:11 394 © 2006 Elsevier Ltd. All rights reserved.
 Clinical anaesthesia

Frequently used anxiolytic agents for premedication

Class Drug Route Dose Preoperative timing Notes

Benzodiazepines Temazepam Oral 10.0–30.0 mg 1 hour Tablet or elixir. Short

duration of action
(90 min)
Midazolam Oral 0.50 mg/kg 1 hour Solutions of 2 or
Intramuscular 2.0–10.0 mg 20–40 min 5 mg/ml available.
Intranasal/sublingual 0.20 mg/kg 20–30 min Bitter taste needs
disguising. Useful in
children
Lorazepam Oral 0.05 mg/kg. 2 hours Can cause marked
Maximum 4.0 mg amnesia
Diazepam Oral 2.0–10.0 mg 2 hours Long half-life. Active
metabolites
Non-benzodiazepines Zopiclone Oral 3.75–7.50 mg 1 hour Hypnotic

Table 2

dressing. EMLA (eutectic mixture of local anaesthetics) contains Antihypertensives

2.5% lidocaine and 2.5% prilocaine, and is applied 60–90 ­minutes
before cannulation. Ametop is a 4% tetracaine gel, works within
30–45 minutes and is effective for 4–6 hours.
Anti-emesis
Postoperative nausea and vomiting is one of the most unpleas-
ant experiences for the patient undergoing anaesthesia.
­Generally, anti-emetic agents are now given intravenously at
induction of anaesthesia and are no longer prescribed as pre-
medication. A combination of agents works more effectively
than ­monotherapy. A brief summary of the anti-emetic drugs is
shown in Table 3.
Many patients who present for surgery are hypertensive, and the
anaesthetist often has to decide whether or not to proceed with
surgery. Currently, it is felt that patients with mild or moder-
ate hypertension and no evidence of coronary artery disease or
end-organ damage may safely undergo surgery without delay.
However, for patients with severe hypertension (systolic pres-
sure ≥ 180 mm Hg and/or diastolic pressure ≥ 110 mm Hg) it is
appropriate to defer surgery if possible, whilst blood pressure is
controlled. Efforts must be made to check that any preoperative
hypertension is not an isolated reading and any recommenda-
tion to postpone elective surgery must be balanced against the
urgency of the planned ­operation.

Drugs available for the prevention of postoperative nausea and vomiting

Class Mode of action Drugs Dose Notes

Antidopaminergic agents Antagonize dopamine Phenothiazines (e.g. 5.0–20.0 mg p.o. or Anti-adrenergic,

Anticholinergic agents
Antihistamines
5-HT3 receptor antagonists
Steroids
receptors in the CTZ.
Extrapyramidal side effects,
especially in children and
young adults
Selective antagonists at
muscarinic receptors
Antagonism at H1-receptors
Act peripherally and
centrally at the CTZ
Mechanism unclear
prochlorperazine) 12.5 mg i.m.
Metoclopramide 10.0 mg p.o., i.m. or i.v.
Hyoscine 0.30–0.60 mg i.m.
Cyclizine 1.0 mg/kg p.o., i.m. or i.v.
Max 50.0 mg
Ondansetron 16.0 mg p.o. 1 hour
preoperatively or 4.0 mg
i.v. at induction
Granisetron 1.0 mg at induction
Dexamethasone 4.0–8.0 mg p.o. or i.v.
anticholinergic and
antihistamine effects
Also used as a prokinetic
Sedating and peripheral
antimuscarinic effects
Peripheral antimuscarinic
effects
Side effects: headache,
constipation, flushing and
altered liver enzymes.
Expensive compared with
other agents

5-HT3, 5-hydroxytryptamine; CTZ, chemoreceptor trigger zone; i.m., intramuscularly; i.v., intravenously; p.o., orally

Table 3

ANAESTHESIA AND INTENSIVE CARE MEDICINE 7:11 395 © 2006 Elsevier Ltd. All rights reserved.
 Clinical anaesthesia
The anaesthetist should also consider the benefits of periop-
erative β-adrenoreceptor blockade in patients undergoing major
surgery who are at risk from perioperative myocardial ischaemia.
Cardiac risk should be assessed to identify which patients should
be treated. Ideally, treatment should be started before hospital
admission.
Antacids
Decreasing gastric residual volume to less than 25 ml and raising
pH to more than 2.5 may reduce the morbidity associated with
pulmonary aspiration of gastric contents. Antacids should be con-
sidered for patients who are particularly at risk, such as those who
are obese, pregnant, those who have diabetes or a hiatus hernia.
In addition, oral administration of clear fluids up to 2 hours before
surgery decreases gastric residual volume and acidity.
Drugs commonly used are:
• ranitidine – an H2-receptor antagonist, 150 mg orally or 50 mg
intravenously 2 hours preoperatively. An additional dose the
night before surgery increases efficacy
• omeprazole – a proton-pump inhibitor, 20–40 mg orally 2 hours
preoperatively or 40 mg by intravenous infusion
• sodium citrate – a non-particulate antacid, 30 ml orally 10 ­minutes
preoperatively is effective for up to 45 minutes
ANAESTHESIA AND INTENSIVE CARE MEDICINE 7:11
• metoclopramide – 10 mg orally or intravenously is used as a
prokinetic agent to reduce gastric volume
Antisialogogues
An antisialogogue (glycopyrrolate 200 μg intramuscularly or
intravenously) may be desirable before ketamine anaesthesia
and awake fibre-optic intubation.
Antibiotics
These agents will be required for patients with certain car-
diac lesions or prosthetic valves undergoing procedures asso-
ciated with bacteraemia. They can be given at induction, or
prescribed on the ward preoperatively. The British National
Formulary (http://www.bnf.org) has guidance for specific
procedures. ◆
Further reading
Taking stock of coxibs. Drug Ther Bull 2005; 43: 1–6.
Howell S J, Sear J W, Foёx P. Hypertension, hypertensive cardiac
disease and cardiac risk. Br J Anaesth 2004; 92: 570–83.
Nicholson G, Burrin J M, Hall G M. Peri-operative steroid
supplementation. Anaesthesia 1998; 53: 1091–1104.
396 © 2006 Elsevier Ltd. All rights reserved.