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Intravenous Acetaminophen and Intravenous

Ketorolac for Management of Pediatric Surgical


Pain: A Literature Review

Kit Baley, CRNA, MSN


Kara Michalov, CRNA, MSN
Mark A. Kossick, CRNA, DNSc
Mason McDowell, CRNA, DNAP

Pediatric surgical patients are a population at risk of intravenous (IV) opioids with nonopioid IV analgesics.
inadequate pain management. The American Society Ketorolac and acetaminophen are the 2 nonopioid IV
of Anesthesiologists’ 2012 Practice Guidelines for analgesics currently available for use in the United
Acute Pain Management in the Perioperative Set- States. This article provides a review of the literature
ting recommend a multimodal approach as the most of IV ketorolac and IV acetaminophen regarding their
effective way to prevent and treat pain in children. A pharmacology, analgesic efficacy, limitations, and
multimodal approach entails the use of 2 or more anal- practical considerations, with a focus on patients 16
gesic medications that act by different mechanisms, years of age and younger.
to maximally target a variety of pain receptors and
reduce the potential for side effects. One method for Keywords: Acetaminophen, anesthesia, ketorolac,
incorporating a multimodal approach is to augment multimodal analgesia, pediatric.

T
he historic undertreatment of pain in the pedi- Administration (FDA) approval in 1989. Overall, it has
atric population is a problem that anesthesia a well-established safety profile, but concerns have been
providers are challenged to eliminate. In the raised regarding the potential to exacerbate hemorrhage.
American Society of Anesthesiologists’ (ASA’s) Acetaminophen (Tylenol) has been a mainstay of pain
2012 Practice Guidelines for Acute Pain Man- management for more than 50 years and is currently the
agement in the Perioperative Setting, pediatric patients are most prescribed analgesic and antipyretic in children.5
identified as a subpopulation at risk of inadequate pain The parenteral formulation achieved FDA approval in
control and requiring additional analgesic consideration.1 2010, but has been safely used in Europe for more than
The Practice Guidelines recommend a proactive approach 20 years in adults and children.6,7
to pain management with analgesic therapy based on age This article will review and compare IV ketorolac and
and weight, and embracing a multimodal approach.1 A IV acetaminophen regarding their pharmacologic pro-
multimodal approach may be characterized by the use files, analgesic potentials alone and in conjunction with
of 2 or more analgesic medications that act by different opioids, their limitations, and considerations such as ease
mechanisms, which can be administered via the same or of administration and cost. It will provide a summary of
different routes. It is believed that a combination of medi- each drugs’ risks and benefits, to promote a more edu-
cations optimizes analgesic efficacy while minimizing cated, individualized provision of multimodal pain man-
adverse effects of any one medication used alone.1 agement in surgical patients 16 years of age and younger.
Intravenous (IV) ketorolac and IV acetaminophen are
2 such nonopioid medications, whose administration Pharmacologic Profiles
combined with other analgesics addresses multimodal • Ketorolac. Ketorolac tromethamine is the only IV
therapy, as well as the ASA’s recommendation to initi- NSAID currently available for use in the United States. It
ate a regimen of nonsteroidal anti-inflammatory drugs is administered as a racemic mixture; the S(−) isomer is
(NSAIDs), cyclooxygenase (COX) 2–selective NSAIDS, responsible for the analgesic effects of the medication.8
or acetaminophen in pediatric surgical patients.1 Ketorolac acts at central and peripheral sites in the body.
Intravenous acetaminophen and IV ketorolac have been It inhibits COX-1 and COX-2, with a slightly increased
used successfully, both alone and in conjunction with affinity for COX-1.9 Both COX-1 and COX-2 are enzymes
opioids, to manage surgical pain in various settings that play a role in the formation of chemical mediators
around the world.2-4 Ketorolac has been widely adminis- in the body. Inhibition of these enzymes by ketorolac
tered in the United States since gaining Food and Drug primarily prevents the production of prostaglandin-2

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(PGE2), a chemical mediator and subclass of prostaglan- rates in pediatric patients aged 2 to 6 months13 and aged 6
din active in many body functions, including nociception, to 18 months12 compared with adults. Results from these
inflammation, smooth muscle contraction and relaxation, studies revealed rapid clearance of the S(−) isomer, with
gastric acid and mucus secretion, renal vasculature con- slower clearance of the R(+) isomer. In patients aged 2 to
striction and dilation, and febrile reactions.9,10 Alterations 6 months, mean clearance of the S(−) isomer was found
to these body functions as a result of changes in PGE2 to be 5 mL/min/kg, compared with 1.04 mL/min/kg for
production are responsible for both the desired and un- the R(+) isomer.13 In patients aged 6 to 18 months, mean
desired effects of ketorolac.9,10 Synthesis of thromboxane, clearance of the S(−) isomer was 4.4 mL/min/kg, whereas
a chemical mediator that promotes platelet aggregation, mean clearance of the R(+) isomer was 1 mL/min/kg.12
is also halted through COX-1 inhibition; this plays a part Based on these findings, regular use of ketorolac, and
in ketorolac’s known tendency to increase bleeding.11 possibly more frequent dosing in infants may be tolerated.
However, this effect on thromboxane, like the effect on However, the authors hesitate to encourage this, as the
PGE2, is limited to the duration of action of the medica- effects of buildup of the R(+) isomer remain unknown.
tion; platelet function should return to normal once the • Acetaminophen. Acetaminophen, also known as
medication has been eliminated from the body.8,11 paracetamol (the names are derived from different ab-
To have central nervous system (CNS) effects, ketoro- breviations of their identical chemical name), has been
lac must cross the blood-brain barrier (BBB). In pediatric used as an analgesic and antipyretic for nearly 100 years.
patients, ketorolac does penetrate the BBB, although in However, its exact mechanism of action is still not en-
small amounts.9 A study comparing cerebral spinal fluid tirely understood.15 Possible areas of activity include
(CSF) and plasma concentrations of ketorolac found that N-methyl-D-aspartate (NMDA) receptor inhibition,15,16
CSF concentrations were less than 0.05% of the plasma serotonergic antagonism,15,16 and, primarily, prostaglan-
concentrations. However, CSF peak concentrations cor- din synthesis inhibition, namely PGE2, both centrally and
related positively with the peak analgesic effect of the peripherally.15,17 Through the inhibition of these various
medication, suggesting that this drug has a substantial chemical mediators, the nociceptive pathway is blocked,
CNS mechanism of action. This study further found that and pain impulses are not transmitted. Acetaminophen
CSF concentrations of ketorolac vary inversely with age, appears to have a higher affinity for COX-2 than COX-1,
height, weight, and body surface area, suggesting that which partly explains its lack of effect on platelets and
younger and smaller patients have increased CNS levels bleeding time, because COX-2 has not been shown to
of ketorolac, and possibly an increased CNS mechanism play a role in the production of thromboxane.15
of action.9 Like ketorolac, acetaminophen must be able to cross
For patients 2 years of age and older, the recom- the BBB to exert CNS effects. One study has shown that
mended dosage of IV ketorolac is 0.5 to 1 mg/kg per acetaminophen readily crosses the BBB in children.17 In
dose, up to the maximum of 30 mg per dose, given every that study, CSF levels of acetaminophen were detectable
4 to 6 hours.6,10 The recommended maximum duration within 5 minutes of IV administration. In approximately
of use in the United States is 5 days.6,10 Several studies 1 hour, measured CSF and plasma concentrations of
have verified the effectiveness of this dosing regimen acetaminophen were similar. This coincides with both
and found few serious adverse effects, even in patients as the onset and peak analgesic effect of IV acetaminophen,
young as 2 months of age.6,10,12,13 Ketorolac has an onset which the manufacturer and other researchers state as
of analgesic action of approximately 15 to 20 minutes, being 5 to 15 minutes and 1 hour, respectively.15-17 This
with a peak effect of 30 to 60 minutes9,10 and a duration study further revealed that, unlike ketorolac, there was
of action between 6 and 8 hours.6,10 The average terminal no correlation between CSF concentrations of acetamin-
half-life of ketorolac in pediatric patients is 6.1 hours. ophen and patient age, height, or weight.
The mean volume of distribution at steady state is 0.26 L/ In the United States, IV acetaminophen is approved
kg, nearly twice that found in adult patients, presumably for use in patients 2 years of age and older. It has both an
because of increased body water and slightly decreased onset and peak effect of 15 minutes or less, and a dura-
protein binding.6,14 tion of analgesic effect between 4 and 6 hours.16 Dosing
Ketorolac is metabolized primarily through hepatic depends on patient weight and age, as well as the intended
conjugation with glucuronic acid to inactive metabolites, frequency of administration. For all patients 2 to12 years
and excreted via the kidneys. The clearance of ketorolac of age, and any patient weighing less than 50 kg, the dose
in pediatric patients is 0.7 mL/kg/min, twice the clear- is 12.5 mg/kg per dose if using an every-4-hour schedule,
ance observed in adult patients.6,14 A study in pediatric or 15 mg/kg per dose if using an every-6-hour schedule.
patients found that 56% of an administered IV dose of The maximum single dose for these patients is 15 mg/kg,
ketorolac was recovered unchanged in urine, suggesting or 750 mg, given either dosing schedule. The maximum
that hepatic damage due to buildup of ketorolac is un- daily (24-hour) dose for these patients is 75 mg/kg, or
likely.14 Two other studies also found increased clearance 3,750 mg. For patients 13 years of age and older and

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weighing 50 kg or greater, 1,000 mg of IV acetaminophen ketorolac and acetaminophen use alone, in combination
should be administered every 6 hours. The maximum with each other, and in combination with opioid anal-
daily (24-hour) dose for these patients is 4,000 mg.16 gesics. These studies were selected from peer-reviewed
Intravenous acetaminophen administration in chil- journals because of their focus on common pediatric
dren less than 2 years of age is considered off-label use surgical procedures and their IV administration of at
in the United States, and suggested dosages must there- least one of the drugs of interest for this literature review
fore be gleaned from the results of studies from other (acetaminophen or ketorolac). The primary dependent
countries. Several such studies have been completed, and variable of all these studies was the analgesic efficacy of
they have largely found that IV acetaminophen is well the administered medications. Additionally, these studies
tolerated in infants and small children, even as young examined the effect of ketorolac and acetaminophen
as 28 weeks’ gestation.18-20 These studies showed that on postoperative complications such as sedation and
clearance rates of the drug increase as age increases, postoperative nausea and vomiting (PONV). Nine of the
from 0.132 L/h/kg at 28 weeks’ gestation, up to 0.21 L/h/ studies focused specifically on pediatric patients ranging
kg at 42 weeks’ gestation.18 This correlates with increas- in age from 6 months to 16 years. One study examined
ing maturity of the hepatic system with increasing age. adult patients ranging in age from 13 to 81 years but was
Mean clearance in the older pediatric patient is 0.27 L/h/ deemed relevant in that strabismus surgery is a common
kg.16 Elimination half-life also decreases with age, from pediatric procedure.
an average of 3.5 hours in the neonate to 1.5 to 2 hours • Ketorolac Clinical Trials. Three studies (see Table)
in the pediatric patient.15 The volume of distribution at examined the efficacy of IV ketorolac at dosages of 0.5
steady state in the pediatric patient remains relatively to 1.0 mg/kg given at various times during the periopera-
constant, with a mean of 70.4 L/70 kg.18 tive period. These studies found no decrease in opioid
Acetaminophen is metabolized via glucuronidation consumption with ketorolac administration compared
and sulfation in the liver.15,16 In neonates and children with tramadol,3 morphine,11 or placebo.12 The use of
up to 10 years of age, studies have shown preferential ketorolac did not appear to result in significant improve-
metabolism via sulfation, possibly indicating a decreased ment in recovery or discharge times.3,11,12 In addition,
risk of hepatotoxicity, because hepatotoxicity is primar- ketorolac administration was associated with a statisti-
ily due to the buildup of metabolites from glucuronida- cally significant increase in bleeding time in pediatric
tion.15,19,20 However, even in the absence of supporting patients undergoing inguinal hernia repair,3 as well as
evidence, concerns about hepatotoxicity in infants con- a clinically significant increase in bleeding episodes in
tinue to exist, possibly related to the 100% bioavailability pediatric patients undergoing tonsillectomy.11
of IV acetaminophen compared with the rectal and oral • Acetaminophen Clinical Trials. Four studies (see
formulations. The authors of several studies suggest that Table) focused on the effect of IV acetaminophen on pain
a reduction in dosage (milligrams per kilogram) may control, opioid consumption, and satisfaction scores. The
be warranted, given the immature functioning of the methods for acetaminophen administration among these
neonatal liver.19,20 In other countries, IV acetaminophen studies differed, but overall, the results suggested that
is often used for neonatal and infant pain management IV acetaminophen is an effective adjunct to opioid an-
at dosages of 7.5 to 10 mg/kg.18-20 Practitioners in the algesics.2,4,21,22 However, IV acetaminophen was shown
United States who choose to use IV acetaminophen off- to be an inadequate replacement for opioids in pediatric
label may want to consider this reduced dosage for pedi- patients undergoing dental restoration,2 ureteroneocys-
atric patients less than 2 years of age. tostomy,4 tonsillectomy,21,22 and adenoidectomy.22 The
• Analgesic Efficacy of Ketorolac and Acetaminophen. research further suggests that acetaminophen in combi-
Pain management, an essential component of the anes- nation with opioids may result in less postoperative seda-
thetic plan, is most commonly achieved via administra- tion,2,21 increased readiness for discharge from the post-
tion of opioids. The nonopioid analgesics ketorolac and anesthesia care unit (PACU),2,21 and favorable parent and
acetaminophen are useful adjuncts that may help to staff satisfaction scores compared with opioids alone.4
improve pain control. In pediatric patients these medi- • Ketorolac versus Acetaminophen Clinical Trials. Two
cations may be beneficial, as there is some evidence to studies (see Table) directly compared the analgesic ef-
suggest that they aid in the reduction of opioid-related fectiveness of acetaminophen and ketorolac. In the first
complications such as sedation.1 Furthermore, the ad- study, of patients undergoing strabismus surgery, the
ministration of opioid and nonopioid analgesics in com- authors reported that IV ketorolac, 60 mg, provided
bination is in keeping with the concept of multimodal adequate pain control without additional analgesics.23
pain management, which has been identified as a highly In contrast, oral acetaminophen did not appear to be
effective means of managing pain in pediatric patients.1 effective as a solo agent.23 After this study’s publication
The Table presents a summary of 10 prospective, in 1994, the FDA revised ketorolac dosing recommenda-
double-blind, randomized control trials that examined tions to 30 mg per dose in adults, based on findings of

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56
Surgical procedure Postop adverse effects
Year of analgesic I: PONV II: Bleeding III:
publication/ comparisons Respiratory Depression IV:
Authors Demographics and dosages Anesthetic management Pulse Oximetry Values Results
2011, El Deeb, • n=80 • Inguinal hernia repair • No premedication • I: no statistically significant • Time to first rescue
El-Morsy3 • Age 2-12 years • Group T: IV tramadol 1 mg/kg • Induction: IV thiopental 4-6 mg/kg difference between groups analgesic shorter in group K
• PS I and II • Group K: IV ketorolac 1 mg/kg IV cisatracurium 0.09 mg/kg • II: intra-op bleeding time (P=.003)
• Exclusion criteria: • Study drug given one time • Maintenance: 2% sevoflurane, significantly longer in group K • Total opioid consumption

AANA Journal
renal dysfunction, after induction 50/50 air/oxygen mixture (P=.04) but still within normal limits higher in Group K (P=.001)

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coagulopathy, family • IV fentanyl 1 μg/kg given intra-op • PACU pain scores higher
history of bleeding if BP or HR increased greater than in group K (P=.003) (FLACC
disorders, required 15% above pre-op values scale)
premedication • No other sedatives or opioids given • No statistically significant
during the operation difference between groups
• NMB reversal at end with IV for sedation scores (4-point

February 2014
neostigmine 50 μg/kg and IV scale), PACU discharge

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atropine 20 μg/kg times, or unplanned hospital
• Deep extubation admissions
• PACU: Rectal acetaminophen and IV
fentanyl rescue analgesics if needed
2011, Uysal • n=64 • Tonsillectomy and • PO midazolam 0.5 mg/kg given 30 • I: no statistically significant • No statistically significant
et al22 • Age 6-16 years adenoidectomy minutes before surgery difference between groups difference between groups for

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• PS I and II • Group A: IV acetaminophen • Induction: IV propofol 2-3 mg/kg, postop pain scores (modified
• Exclusion criteria: 15 mg/kg IV fentanyl 1 μg/kg, IV vecuronium Hannallah Pain Scale) or
active and severe • Group T: IV tramadol 1 mg/ 0.1 mg/kg rescue analgesia requirements
renal, respiratory, kg • Maintenance: 1.5-2.5% sevoflurane, • No statistically significant
hepatic, cardiac, • Study drug given one time 50/50 nitrous oxide/oxygen mixture difference between groups
or neuromuscular after induction • No additional opioids given intra-op for Aldrete scores, sedation
disorders • NMB reversal at end with IV scores (4-point scale), parent
neostigmine 0.04 mg/kg and IV and nurse satisfaction scores
atropine 0.02 mg/kg (4-point scale), or incidence of
• Extubated when respirations emergence agitation (PAED
regular and adequate in rate and scale)
depth
• PACU: IV meperidine, PO
ibuprofen, and PO acetaminophen
rescue analgesics if needed

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2010, Hong • n=63 • Ureteroneocystostomy • No premedication • I: higher incidence in group F • On both POD 1 and 2, total
et al4 • Age 6-24 months • Group FA: IV fentanyl 0.5 • Induction: IV thiopental 5 mg/kg, IV (P=.011) dose of fentanyl received
• PS I and II μg/kg and IV acetaminophen rocuronium 0.6 mg/kg by group FA was half that
• Exclusion criteria: 15 mg/kg • Maintenance: 1-4% end-tidal received by group F
kidney or liver • Group F: IV fentanyl 0.5 sevoflurane, air/oxygen mixture with • Cumulative dose of
dysfunction, required μg/kg inspired oxygen equal to 50% fentanyl over 72 hours was
premedication • Initial dose of study • IV fentanyl 1 μg/kg given to all significantly lower in group FA
medications given at patients after induction but before (P<.05)
peritoneal closure incision • Sedation scores higher in
• Post-op, all patients on group F (P=.019) (modified
PCNA pump with basal Ramsey Sedation Scale)
infusion rate, maximum • No statistically significant
duration of usage 72 hours difference in pain scores
• Group FA: IV fentanyl between groups (Children’s

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0.25 μg/kg/hr and IV Hospital of Eastern Ontario
acetaminophen 1.5 μg/kg/hr Pain Scale)
• Group F: IV fentanyl 0.25 • Parent satisfaction scores
μg/kg/hr higher in group FA (P=.02)
(4-point scale)
2010, Hong • n=55 • Unilateral inguinal hernia • No premedication • I: higher incidence in group C • Lower total consumption
et al4 • Age 1-5 years repair • Induction: inhalation of 8% (P=.016) of fentanyl, fewer patients
• Exclusion • Group KA: IV ketorolac 1 sevoflurane in oxygen, IV atracurium • III: no occurrence in either group received rescue fentanyl in
criteria: kidney or mg/kg and IV acetaminophen 0.5 mg/kg PACU in group KA (P=.001
liver dysfunction, 20 mg/kg • Maintenance: 1-4% sevoflurane, for both)
hemorrhagic • Group C: control, IV saline air/oxygen mixture with inspired • Higher pain scores on arrival
diathesis, asthma, • Study drug given one time oxygen equal to 50% to PACU in group C (P=.041)
history of long- after induction • IV fentanyl 1 μg/kg given to all (Wong-Baker FACES Scale)
term analgesic patients after induction but before • Higher incidence of sedation
use, required incision in PACU in group C (P=.023)
premedication • No other opioids given intra-op (modified Ramsey Sedation

AANA Journal
• Awake extubation Scale)

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• PACU: IV fentanyl rescue analgesic • No statistically significant
if needed difference in time to discharge
between groups
2007, • n=40 • Dental restorations • PO midazolam 0.5 mg/kg given 30 • I: no statistically significant • Lower PACU pain scores in
Alhashemi, • Age 3-16 years • Group A: IV acetaminophen minutes before surgery difference between groups group Me (P=.012) (OPS)
Daghistani2 • PS I and II 15 mg/kg • Induction: sevoflurane inhalation or • III, IV: no occurrence in either group • Increased incidence of

February 2014
• Exclusion criteria: • Group Me: IM meperidine IV propofol 2-3 mg/kg sedation in PACU in group Me

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planned extractions, 1 mg/kg • Maintenance: sevoflurane, oxygen/ (P=.0130) (Ramsey Sedation
developmental delay, • Study drug given one time nitrous oxide mixture Score)
renal insufficiency, after induction • IV fentanyl 1 μg/kg given to all • Group A achieved Aldrete
neurologic patients immediately after induction score of 10 and readiness for
dysfunction • No other intra-op analgesics, local discharge faster than group
anesthetics, or anti-emetics given Me (P=.009)

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• Awake extubation
• PACU: IV morphine rescue
analgesic if needed

57
continues on page 58
continued from page 57

58
Surgical procedure Postop adverse effects
Year of analgesic I: PONV II: Bleeding III:
publication/ comparisons Respiratory Depression IV:
Authors Demographics and dosages Anesthetic management Pulse Oximetry Values Results
2007, Lynn • n= 37 • Craniectomy, other • No details of anesthetic • II, IV: no statistically significant • No statistically significant
et al12 • Age 6-18 months neurosurgery, general, management provided difference among groups difference in morphine
• Patients admitted plastic, urologic, and cardiac • No statistically significant difference consumption between groups
after surgery surgical procedures in BUN, creatinine, AST, ALT, or urine • Authors suggest this was

AANA Journal
• Exclusion criteria: • Group P: IV placebo analysis results among groups possibly due to a reluctance

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< 36 weeks gestation • Group K0.5: IV ketorolac 0.5 to wean medication based
at birth, history of mg/kg on satisfactory pain scores
GI bleed, hepatic or • Group K1: IV ketorolac 1 mg/ (FLACC scale) and lack of
renal impairment, kg adverse effects
coagulopathy in • Study drug given one time
patient or family on POD 1

February 2014
member • All patients placed on

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continuous infusion of IV
morphine at 5-30 μg/kg/hr
2006, • n=80 • Tonsillectomy • PO midazolam 0.5 mg/kg given 30 • I, II, III, IV: no statistically significant • No statistically significant
Alhashemi, • Age 3-16 years • Group A: IV acetaminophen minutes before surgery differences between groups difference in pain scores
Daghistani21 • PS I and II 15 mg/kg • Induction: sevoflurane inhalation or between groups (OPS)
• Exclusion criteria: • Group Me: IM meperidine IV propofol 2-3 mg/kg • Group A had a greater

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developmental 1 mg/kg • Maintenance: sevoflurane, oxygen/ number of patients requiring
delay, neurologic • Study drug given onetime nitrous oxide mixture rescue analgesia in PACU
dysfunction, renal after induction • IV fentanyl 1 μg/kg given to all • Increased incidence of
insufficiency patients immediately after induction sedation in group Me (P=.031)
• No other intra-op analgesics given (Ramsey Sedation Scale)
• PACU: IV morphine rescue • Aldrete score of 10 and
analgesic if needed readiness for discharge
achieved sooner in group A
(P=.005 for both)
• No statistically significant
difference between groups
for PACU RN satisfaction with
analgesia (7-point scale)
1995, Gunter • n= 96 • Tonsillectomy • No premedication • I: lower incidence in group K • No statistically significant
et al11 • Age 1-12 years • Group Mo: IV morphine 0.1 • Induction: halothane inhalation in (P=.006) difference between groups
• Exclusion criteria: mg/kg 66% nitrous oxide/33% oxygen • II: higher incidence in group K for supplemental morphine
significant underlying • Group K: IV ketorolac 1 mg/ • Maintenance: halothane and • Study stopped early due to requirements in PACU
medical conditions, kg nitrous oxide increased incidence of major bleeding • No statistically significant
airway abnormalities, • One-time dose of study • No additional intra-op analgesics and bleeding episodes in first 24 difference between groups in
asthma, bleeding medications given after given hours after surgery time to awakening, recovery,
disorders, family surgery completed and • Deep extubation or discharge
history of bleeding hemostasis achieved • PACU: Rectal acetaminophen • No statistically significant
disorders given to all patients on arrival; IV difference between groups for
morphine rescue analgesic if needed unplanned admissions to the
hospital

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1995, Rusy • n=50 • Tonsillectomy with or • No premedication • II: higher incidence in group K • No significant difference in
et al24 • Age 2-15 years without adenoidectomy • Induction: halothane inhalation in (P=.025) pain scores between groups
• PS I and II • Group K: IV ketorolac 1 mg/kg oxygen/nitrous oxide mixture, IV • 8/25 patients in group K required (OPS)
• Exclusion criteria: • Group A: rectal atracurium 0.5 mg/kg additional measures to achieve • Majority of patients in both
renal dysfunction, acetaminophen 35 mg/kg • Maintenance: 70/30 nitrous oxide/ hemostasis groups required additional
egg allergy, bleeding • Study drug given given oxygen mixture, IV propofol 75-300 • 1/25 patients in group A required analgesia in PACU
disorders, family once various times μg/kg/min additional measures
history of bleeding intraoperatively • No opioids given pre- or intra-op
disorders • NMB reversal at end with IV
neostigmine 0.05 mg/kg and IV
glycopyrrolate 0.01 mg/kg
• Awake extubation
• PACU: IV morphine rescue
analgesic if needed

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1994, Morrison, • n= 60 • Strabismus surgery • General inhalational anesthesia or • I: 2 occurrences each in group A • Lower pain scores in group
Repkaa23 • Age 13-18 years • Group A: PO local periocular anesthesia and group I, no occurrence in group K K compared with group A and
• Exclusion criteria: acetaminophen 650 mg Intra-op sedation and IV analgesia • II: no statistically significant group I (P=.001) (VAS)
history of peptic • Group I: PO ibuprofen 600 “held constant” (p.916) regardless difference among groups • 63% group K required no
ulcer disease, mg of anesthetic type additional pain medication,
platelet disorders, • Group K: IV ketorolac 60 mg • No additional details given 100% group I and 80% group
sensitivity to NSAIDs, administered at the end of regarding induction or maintenance A required additional
>3 previous eye surgery, plus PO placebo • IV droperidol 75 μg/kg analgesics (P= .0001)
surgeries • PO medications given one administered to all patients before • No statistically significant
time in PACU 35-40 minutes surgery for PONV prophylaxis difference in sedation scores
after surgery completed • PACU: PO acetaminophen with among groups (VAS)
and without oxycodone rescue
analgesic if needed
Table. Studies Evaluating the Postoperative Analgesic Efficacy of IV Ketorolac and IV Acetaminophen in Common Pediatric Procedures
Abbreviations: n, number of study participants; PS, physical status; IV, intravenous; BP, blood pressure; HR, heart rate; NMB, neuromuscular blockade; PACU, post anesthesia care unit;
FLACC, face legs activity cry consolability; PO, per os/by mouth; PAED, pediatric anesthesia emergence delirium; PCNA, parent/nurse-controlled analgesia; POD, postoperative day;

AANA Journal
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OPS, objective pain scale; PONV, postoperative nausea and vomiting; NSAIDs, non-steroidal anti-inflammatory drugs; VAS, visual analog scale.
a Study enrolled teenagers and adult subjects

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59
limited analgesic efficacy above 30 mg with an increased Seven studies from the anesthesia, pediatric, and surgi-
risk of side effects.10 cal (specifically ear, nose, and throat) literature link IV
In the second study, rectal acetaminophen was found ketorolac administration with the potential for increased
to be equally effective to IV ketorolac in pediatric patients hemorrhage. All of the studies examined hemorrhage or
undergoing tonsillectomy.24 Neither agent was found to coagulopathy as one of the primary outcome measures.
be sufficient as a solo analgesic, because both groups Of these 7 studies, 2 indicated negligible increased risk
required additional morphine in the PACU. Increased of hemorrhage12,29 and 5 demonstrated some degree of
bleeding occurred in the patients receiving ketorolac. coagulopathy.7,11,24,30,31
• Combined Ketorolac-Acetaminophen Clinical Trials. Several studies highlighted the safety of ketorolac and
One study (see Table) examined the efficacy of a combina- the lack of adverse bleeding effects.12,29 A double-blind,
tion of IV acetaminophen and IV ketorolac on total fen- placebo-controlled study involving 37 patients 6 to 18
tanyl requirements in pediatric patients undergoing ingui- months of age demonstrated no association between ke-
nal hernia repair.25 The authors reported reduced fentanyl torolac administration and bleeding.12 The details of this
consumption, improved satisfaction scores, less vomiting, study can be found in the Table. Similarly, a retrospective
and less sedation in the acetaminophen-ketorolac group review of 310 pediatric patients’ medical records found
vs the saline control group. Also, no adverse effects in the no significant difference in frequency of postoperative
acetaminophen-ketorolac group were reported. hemorrhage between patients receiving a 1-time dose
of IV ketorolac in the normal dose range (ie, 0.5-1 mg/
Limitations kg) compared with patients who did not receive ketoro-
• Ketorolac. The analgesic effect of ketorolac is derived lac (2.3% for ketorolac group vs 3.1% for nonketorolac
from the drug’s ability to inhibit prostaglandin synthesis, group, P = 0.71).29
which is also the primary source of the drug’s limitations. Five studies were identified that suggested an associa-
Like other NSAIDs, ketorolac is responsible for 2 catego- tion between ketorolac and bleeding,7,11,24,30,31 including
ries of side effects, those that are predictable and caused a frequently cited article from 1995, which was one of the
by the inhibition of prostaglandins, and those that are un- first studies to demonstrate the adverse hemostatic effects
predictable and caused for unknown reasons. Numerous of ketorolac in pediatric patients.24 In this study, addition-
studies demonstrate that NSAIDs’ suppression of prosta- al hemostatic measures (eg, packing with phenylephrine)
glandin synthesis can result in gastrointestinal ulcerations were required more frequently in the ketorolac group than
and erosions, nephrotoxicity, and abnormal bleeding.26-28 the acetaminophen group (8 vs 1, P = .012). Furthermore,
However, most of these studies did not focus on pediatric measured blood loss was found to be greater in patients
patients, nor did they test short-term intraoperative use of who received ketorolac than those who did not (3 ± 2
IV ketorolac. mL/kg vs 1 ± 1 mL/kg, P = .025). Although the blood loss
• Side Effects. The most troublesome side effect of ke- in the ketorolac group was deemed clinically significant
torolac is the potential for hemorrhage due to blockade because it required extra time and work for the otolaryn-
of the COX-1 system. A 2001 comprehensive review of gologist to correct (the study labeled the bleeding “nui-
the risks and benefits of NSAID use in children speci- sance bleeding”), there were no effects on hemodynamic
fied that ketorolac has been studied primarily in children compromise or patient morbidity.24 Details of the study
older than 1 year of age undergoing minor surgeries such appear in the Table. Similarly, a randomized, prospec-
as tonsillectomy, strabismus correction, myringotomy, tive, placebo-controlled study of 90 children undergoing
hernia repair, and dental work.26 The studies reviewed elective general, orthopedic, or genitourinary procedures
include IV ketorolac administered preoperatively or found that compared with bleeding times before adminis-
postoperatively as a single dose ranging from 0.5 to 1.5 tration of a single dose of 0.75 mg/kg intramuscular (IM)
mg/kg. Although many studies found no increased risk ketorolac, bleeding times at 180 minutes after study drug
of hemorrhage after ketorolac administration, several administration increased 53 ± 75 seconds (P = .006).30
described a correlation between ketorolac administra- The ketorolac groups’ mean bleeding time was still within
tion and postoperative hemorrhage. The authors of the the normal range and no bleeding problems or adverse
review article recommended that during surgeries with effects occurred during the study. Likewise, a chart review
the potential for substantial blood loss, such as tonsil- of 258 adult and pediatric patients undergoing tonsillecto-
lectomy, ketorolac may be administered, 0.5 to 1.5 mg/ my with or without adenoidectomy reported an increased
kg, postoperatively after hemostasis has been achieved. incidence of postoperative hemorrhage, operationalized as
Only a handful of studies have examined the use of ke- an unquantified amount of bleeding requiring surgical or
torolac in children undergoing orthopedic, genitourinary, medical intervention, in patients treated with periopera-
cardiac, or reconstructive surgeries, but notably there are tive IV ketorolac: 10.1% in the ketorolac group vs 2.2% in
no reports of any increase in bleeding complications in the narcotic analgesia group.31
these more extensive procedures.26 In addition to the 3 studies discussed in the previous

60 AANA Journal „ February 2014 „ Vol. 82, No. 1 www.aana.com/aanajournalonline


paragraph demonstrating an association between ketoro- since 2000 in nearly 80 countries.5 Furthermore, more
lac administration and some degree of coagulopathy, 2 than 440 million units of the medication were distributed
studies were terminated after researchers concluded that in Europe from 2002 through April 2010, representing an
there was an undue risk of excessive bleeding in pediat- estimated 65 million patient exposures.16 Although the
ric patients treated with ketorolac undergoing tonsillec- history of IV acetaminophen use in the United States is
tomy.7,11 The preliminary findings from the first study7 relatively short, there is considerable safety data to draw
showed that intraoperative blood loss was significantly on from European studies and the FDA approval process.
higher in the group that received 1 mg/kg IV ketorolac vs • Side Effects. Premarketing clinical trials conducted by
1.5 mg/kg IM codeine (2.2 ± 1.9 mL/kg vs 1.3 ± 0.8 mL/ the manufacturer of IV acetaminophen included 2 active-
kg, P < .05). Furthermore, 5 of the 35 patients treated controlled and 3 open-label safety and pharmacokinetic
with ketorolac experienced bleeding that led to unsched- studies, which enrolled a total of 355 pediatric subjects.16
uled hospital admissions.7 The second study was termi- The most common adverse reactions (reported in * 5% of
nated after 49 children treated with 1 mg/kg of IV ketoro- patients) found were nausea, vomiting, constipation, pru-
lac experienced more bleeding problems than 47 children ritus, agitation, and atelectasis.16 Other reactions reported
receiving 0.1 mg/kg of IV morphine.11 Specifically, the in at least 1or 2 children included anemia, tachycardia,
ketorolac group experienced more bleeding that required abdominal pain, diarrhea, injection site pain, edema,
intervention (5/49 vs 0/47, P = .03) and more bleeding hypoalbuminemia, hypokalemia, hypomagnesemia, hy-
episodes in the first 24 hours postoperatively (0.22 epi- pophosphatemia, hypervolemia, muscle spasm, headache,
sodes per subject vs 0.04 episodes per subject, P < .05). insomnia, oliguria, pulmonary edema, pleural effusion,
The tolerability profile of ketorolac is similar to that stridor, wheezing, rash, hypotension, or hypertension.
of other NSAIDs. In addition to effects on hematologic However, these reactions could not be directly traced to
function, the most clinically important adverse events IV acetaminophen administration. It was also not stated
include damage to renal function10 and the gastrointes- during what timeframe these reactions occurred. In con-
tinal tract.27 Like other NSAIDs, ketorolac has also been trast to side effects reported in the ketorolac literature,
linked to allergic or hypersensitivity reactions,10 but there were no reports of platelet inhibition or surgical site
with the increased knowledge about appropriate dosing bleeding. Additionally, there were no cases of respiratory
regimens and contraindications to NSAID administra- depression, postoperative ileus, sedation, cognitive im-
tion, side effects are exceedingly rare. The safety profile pairment, upper gastrointestinal bleeding, renal toxicity,
and favorable clinical reputation of ketorolac have been or cardiovascular thrombotic events.16
well established since the mid-1990s.32,33 The incidence Independent reviews of IV acetaminophen have been
of gastrointestinal and renal adverse effects is comparable favorable in their reports of tolerability and minimal
to that of placebo when the recommended dosage guide- side effects. A 2009 review of 8 double-blind, placebo-
lines of IV ketorolac are followed (0.5-1 mg/kg every 4-6 controlled clinical trials stated that in patients less than
hours, with a maximum use of 5 days).32 16 years of age, IV paracetamol has a tolerability profile
• Contraindications. Ketorolac should not be given to pa- similar to in adults or with placebo.15 Adverse reactions
tients with sensitivity reactions (eg, bronchospasm) precip- were rare (> 1/10,000 but < 1/1,000) for effects such as
itated by other NSAIDs or aspirin. Ketorolac should be used malaise, hypotension, and increased levels of hepatic
with caution, and in communication with the surgeon, in transaminases and very rare (< 1/10,000) for reactions
children with renal or hepatic impairment, uncorrected such as thrombocytopenia; appropriate acetaminophen
hypovolemia or hypotension, quantitative or qualitative dosing is not associated with hepatotoxicity.15
platelet dysfunction, ongoing or substantial bleeding, co- Two literature reviews published in 201034 and 20115
agulation disorders, and peptic ulcer disease.27,28 Ketorolac also speak to the overall safety profile of IV acetamino-
has been used successfully with newborns, neurosurgical phen. The first, from 2010, evaluated prospective, ran-
patients, children with asthma, and the critically ill, al- domized, controlled trials of IV acetaminophen vs a com-
though the provider should err on the side of caution when parable nonopioid analgesic or placebo in the Medline
weighing the risks and benefits of ketorolac administration and Cochrane libraries from 2000 to 2010. Sixteen ar-
in these vulnerable populations.28 ticles from 9 countries published between 2005 and 2010
• Acetaminophen. For more than 5 decades, acetamin- met inclusion criteria and included 1,464 patients. In all
ophen has been used in oral and rectal preparations for of the articles reviewed, no increased incidence of adverse
the management of pediatric pain and fever in the United effects was found with IV acetaminophen compared with
States, and has developed a reputation for safety and ef- placebo. Similarly, the second focused literature review
ficacy. The IV preparation of acetaminophen (Ofirmev) from 2011 found that the overall risk of adverse effects
was approved by the FDA in 2010 for use in adults and or hepatotoxicity is extremely rare with therapeutic acet-
children 2 years of age and older. Although relatively new aminophen dosing.5
to the United States, IV acetaminophen has been in use Several studies support that daily maximum dose recom-

www.aana.com/aanajournalonline AANA Journal „ February 2014 „ Vol. 82, No. 1 61


mendations and concerns about hepatotoxicity are largely per manufacturer guidelines.16 Intravenous acetamino-
driven by damage caused by uncontrolled outpatient phen should be administered as a 15-minute infusion,
use.5,19,20 Even in premature neonates receiving infusions of and doses less than the total amount in the vial should
IV acetaminophen for up to 4 days, there is no evidence of be drawn up in a separate syringe to prevent accidental
hepatotoxicity.18,20 There is a suggestion that unconjugated overdose.16 Because acetaminophen does not interfere
hyperbilirubinemia can slow clearance and thus mandate with hemostasis, the IV preparation may be given in the
a dose reduction, although the authors do not specify a preoperative area if it facilitates administration. However,
recommended dose reduction amount.18 Currently, the dosing should be timed to ensure that the analgesic
manufacturers of Ofirmev are pursuing FDA approval in effects are still present during the initial recovery period.
children younger than 2 years old, and the authors of this Rectal acetaminophen, ranging in cost from approxi-
review found no studies that indicate increased incidence of mately $0.44 to $2.55 per suppository depending on
adverse advents in neonates or infants. dosage and manufacturer,35 is much cheaper than the IV
• Contraindications. Intravenous acetaminophen preparation. However, it has less predictable absorption
should not be given to children with sensitivity reactions and serum concentration levels, and it may be inappro-
to acetaminophen in any form. It also should not be given priate for certain types of pediatric patients such as im-
to patients with known hypersensitivity to any of the munocompromised patients or those undergoing bowel
inactive ingredients in the IV formulation, which include surgery, in whom intestinal absorption may be impaired.
mannitol, dibasic sodium phosphate, sodium hydroxide, Difficulties also arise in delivering exact doses with rectal
and hydrochloric acid.16 Parenteral acetaminophen is acetaminophen, because of nonhomogeneous spread of
absolutely contraindicated in patients with severe hepatic the medication throughout the suppository, and manufac-
impairment or severe active liver disease. Caution should turer recommendations that suppositories not be divided.
be exercised when administering acetaminophen to chil- When administering IV acetaminophen, anesthesia
dren with hepatic injury, alcohol consumption, chronic providers should adhere to recommended maximum
malnutrition or long-term fasting, severe hypovolemia, or allowable daily (24-hour) doses for acetaminophen: 75
severe renal impairment. mg/kg, or 3,750 mg for children 2 to 12 years of age
or anyone weighing under 50 kg; 4,000 mg for anyone
Practical Concerns weighing 50 kg or greater and 13 years of age or older.16
• Ketorolac. Hospital acquisition prices for ketorolac vary All forms of acetaminophen that may be given to the
based on manufacturer and size of the unit sold; they range patient, such as oxycodone-acetaminophen (Percocet),
from approximately $1.25 to $5.22 for a single dose 60 Tylenol with codeine, or Tylenol suppositories, must be
mg/2 mL or 30 mg/mL vial.35 Ketorolac does not require considered and included in the daily maximum allow-
refrigeration and can be easily stored in the operating room able dose. Administration of IV acetaminophen should
(OR) wherever anesthesia medications are kept. be documented and reported to the provider or parent
If ketorolac is administered intraoperatively, it should assuming care of the pediatric patient so that subsequent
not be given until after surgical hemostasis is achieved; doses of IV, oral, and/or rectal forms of acetaminophen
several studies demonstrated increased bleeding when ke- can be planned accordingly, and the maximum daily al-
torolac was given before hemostasis was achieved.3,11,24 In lowable dose of acetaminophen is not exceeded.
certain surgical populations with risk of substantial bleed-
ing, such as patients undergoing tonsillectomy,11 as well Summary
as patients with preexisting coagulation disorders, ketoro- Based on the studies reviewed, for pediatric surgical
lac use may be inappropriate. Ketorolac should be used patients 15 years of age and younger, ketorolac was not
cautiously in combination with other NSAIDs such as found to improve discharge times,3,11,25 decrease the inci-
ibuprofen that may be administered to pediatric patients dence of unplanned hospital admissions,11 or consistently
postoperatively; synergism between the medications may cut down on total opioid consumption.3,11,12 Therefore, it
worsen side effects.35 Administration of the drug should does not seem likely that its routine use would be ben-
be communicated to the provider or parent assuming care eficial in reducing overall surgical costs for the patient
of the patient, to correctly deliver subsequent doses of or the hospital. However, ketorolac may not be any less
ketorolac and/or other NSAIDs, watch for adverse effects, effective than morphine in providing analgesia,11 and its
and appropriately plan for other analgesic medications. use may help decrease the incidence of opioid-induced
• Acetaminophen. Acetaminophen injection comes in PONV.11,23 In the appropriate patient population then,
a single-dose vial of 1,000 mg/100 mL; the hospital acqui- ketorolac may still be an attractive option for anesthesia
sition cost is approximately $10.18 per vial.36 Single-dose providers interested in an analgesic with a longer dura-
vials of IV acetaminophen can be easily stored in the OR tion of action and a decreased incidence of PONV than
wherever anesthesia medications are kept. No refrigera- what many opioids offer.
tion is required. Once opened, vials are good for 6 hours For pediatric patients undergoing unilateral hernia

62 AANA Journal „ February 2014 „ Vol. 82, No. 1 www.aana.com/aanajournalonline


repair, ketorolac use in combination with IV acetamino- intravenous ketorolac versus tramadol in pediatric inguinal herniotomy:
a randomized double blind study. Egypt J Anaesth. 2011;27(4):207-211.
phen did appear to decrease opioid requirements in the
4. Hong JY, Kim WO, Koo BN, Cho JS, Suk EH, Kil HK. Fentanyl-spar-
PACU.25 Further investigation with other pediatric surgi- ing effect of acetaminophen as a mixture of fentanyl in intravenous
cal populations is warranted, but the analgesic effective- parent-/nurse-controlled analgesia after pediatric ureteroneocystos-
ness of ketorolac and acetaminophen in combination may tomy. Anesthesiology. 2010;113(3):672-677.
extend to other surgeries as well; certainly the concept is 5. Smith HS. Perioperative intravenous acetaminophen and NSAIDs.
Pain Med. 2011;12(6):961-981.
fitting with the multimodal recommendations of the ASA’s 6. Olkkola KT, Maunuksela EL. The pharmacokinetics of postoperative
2012 Practice Guidelines for Acute Pain Management in the intravenous ketorolac tromethamine in children. Br J Clin Pharmacol.
Perioperative Setting. For adult patients undergoing stra- 1991;31(2):182-184.
bismus surgery, ketorolac was found to decrease opioid 7. Splinter WM, Rhine EJ, Roberts DW, Reid CW, MacNeill HB. Peri-
operative ketorolac increases bleeding after tonsillectomy in children.
consumption in the PACU.23 This study also included pa- Can J Anaesth. 1996;43(6):560-563.
tients as young as 13 years of age (the number of 13-year- 8. Ketorolac substance summary. PubChem Substance Website.
olds was not specified), patients potentially classifiable as National Center for Biotechnology Information, US National Library
pediatric patients; therefore the findings may be extend- of Medicine. http://pubchem.ncbi.nlm.nih.gov/summary/summary.
cgi?sid=46507019. Accessed March 15, 2013.
able to younger patients undergoing similar surgeries. 9. Kumpulainen E, Kokki H, Laisalmi M, et al. How readily does
The studies focusing on acetaminophen suggest that ketorolac penetrate cerebrospinal fluid in children? J Clin Pharmacol.
IV acetaminophen may contribute to shortened PACU 2008;48(4):495-501.
stays,2,21 less sedation in the PACU,2,4,21 decreased opioid 10. Gillis JC, Brogden RN. Ketorolac: a reappraisal of its pharmacody-
namics and pharmacokinetic properties and therapeutic use in pain
consumption,4 and fewer opioid-related adverse effects4 management. Drugs. 1997;53(1):139-188.
requiring treatment and intervention. These findings may 11. Gunter JB, Varughese AN, Harrington JF, et al. Recovery and compli-
justify the high cost of the medication. Improved parent cations after tonsillectomy in children: a comparison of ketorolac and
and nurse pain management satisfaction scores4 may also morphine. Anesth Analg. 1995;81(6):1136-1141.
make IV acetaminophen a desirable choice. However, 12. Lynn AM, Bradford H, Kantor ED, et al. Postoperative ketorolac
tromethamine use in infants aged 6-18 months: the effect on mor-
based on the studies examined, IV acetaminophen is phine usage, safety assessment, and stereo-specific pharmacokinetics.
not an appropriate replacement for opioids, because Anesth Analg. 2007;104(5):1040-1051.
most patients required opioid analgesics in addition to 13. Lynn AM, Bradford H, Kantor ED, et al. Ketorolac tromethamine:
stereo-specific pharmacokinetics and single-dose use in postoperative
acetaminophen.2,21,22 Instead, it should be used as an infants aged 2-6 months. Paediatr Anaesth. 2011;21(3):325-334.
adjunctive medication to provide a multimodal approach 14. Mroszczak EJ, Lee FW, Combs D, et al. Ketorolac tromethamine
to analgesic management. absorption, distribution, metabolism, excretion, and pharmacokinet-
Pediatric surgical patients are a population identified ics in animals and humans. Drug Metab Dispos. 1987;15(5):618-626.
as being at risk of the undertreatment of pain.1 Fear of 15. Duggan ST, Scott LJ. Intravenous paracetamol (acetaminophen).
Drugs. 2009;69(1):101-113.
oversedation and narcotic dependency, and unfamiliar- 16. OFIRMEV (acetaminophen) injection. Product monograph. San
ity in recognizing and treating pain in pediatric patients Diego, CA: Cadence Pharmaceuticals; 2010.
contribute to this problem.1 The ASA’s 2012 Practice 17. Kumpulainen E, Kokki H, Halonen T, Heikkinen M, Savolainen J,
Guidelines for Acute Pain Management in the Perioperative Laisalmi M. Paracetamol (acetaminophen) penetrates readily into
the cerebrospinal fluid of children after intravenous administration.
Setting offers a potential solution of multimodal therapy. Pediatrics. 2007;119(4):766-771.
For anesthesia providers, the simplest method for using a 18. Allegaert K, Anderson BJ, Naulaers G, et al. Intravenous paracetamol
multimodal approach to pediatric pain management is to (propacetamol) pharmacokinetics in term and preterm neonates. Eur
administer nonopioid IV analgesics in combination with J Clin Pharmacol. 2004;60(3):191-197.
19. Allegaert K, Rayyan M, De Rijdt T, Van Beek F, Naulaers G. Hepatic
IV opioids. Two frequently used nonopioid IV analgesics tolerance of repeated intravenous paracetamol administration in neo-
that may be beneficial for pediatric patients are ketorolac nates. Paediatr Anaesth. 2008;18(5):388-392.
and acetaminophen. Ultimately, anesthesia providers 20. Palmer GM, Atkins M, Anderson BJ, et al. I.V. acetaminophen
must individualize care for each patient, taking into con- pharmacokinetics in neonates after multiple doses. Br J Anaesth.
2008;101(4):523-530.
sideration patient characteristics, desired analgesic out-
21. Alhashemi JA, Daghistani MF. Effects of intraoperative i.v. acetamino-
comes, the type of surgery being performed, associated phen vs. i.m. meperidine on post-tonsillectomy pain in children. Br J
risks and complications, and the surgical setting. Anaesth. 2006;96(6):790-795.
22. Uysal HY, Takmaz SA, Yaman F, Baltaci B, Başar H. The efficacy of
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1. Apfelbaum JL, Ashburn MA, Connis RT, et al. Practice guidelines after adenotonsillectomy in children. J Clin Anesth. 2011;23(1):53-57.
for acute pain management in the perioperative setting: an updated 23. Morrison NA, Repka MX. Ketorolac versus acetaminophen or ibu-
report by the American Society of Anesthesiologists Task Force on profen in controlling postoperative pain in patients with strabismus.
Acute Pain Management. Anesthesiology. 2012;116(2):248-273. Ophthalmology. 1994;101(5):915-918.
2. Alhashemi JA, Daghistani MF. Effect of intraoperative intravenous 24. Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation of
acetaminophen vs. intramuscular meperidine on pain and dis- ketorolac tromethamine versus acetaminophen in pediatric tonsillec-
charge time after paediatric dental restoration. Eur J Anaesthesiol. tomy: analgesia and bleeding. Anesth Analg. 1995;80(2)226-229.
2007;24(2):128-133. 25. Hong JY, Won Han JS, Kim WO, Kil HK. Fentanyl sparing effects
3. El Deeb A, El-Morsy GZ. Comparison of preemptive analgesic effect of of combined ketorolac and acetaminophen for outpatient inguinal

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hernia repair in children. J Urol. 2010;183(4):1551-1555. pain. Pain Pract. 2010;11(3):290-296.
26. Litalien C, Jacqz-Aigrain E. Risks and benefits of nonsteroidal anti- 35. Medscape Multispecialty Website. WebMD LLC. http://reference.
inflammatory drugs in children: a comparison with paracetamol. medscape.com. Accessed February 14, 2013.
Paediatr Drugs. 2001;3(11):817-858. 36. Buck ML. Intravenous acetaminophen use in infants and chil-
27. Tobias JD. Weak analgesics and nonsteroidal anti-inflammatory dren. Pediatr Pharmacother. April 2011;17(4). http://www.medicine.
agents in the management of children with acute pain. Pediatr Clin virginia.edu/clinical/departments/pediatrics/education/pharm-news/
North Am. 2000;47(3):527-543. current/201104.pdf. Accessed November 30, 2013.
28. Kokki H. Nonsteroidal anti-inflammatory drugs for postoperative
pain: a focus on children. Paediatr Drugs. 2003;5(2):103-123.
29. Agrawal A, Gerson CR, Seligman I, Dsida RM. Postoperative hemor-
AUTHORS
Kit Baley, CRNA, MSN, was a senior student at Western Carolina Univer-
rhage after tonsillectomy: use of ketorolac tromethamine. Otolaryngol
Head Neck Surg. 1999;120(3):335-339. sity's Graduate Program of Nurse Anesthesia at the time this review article
was written. She is currently employed as a CRNA with AllCare Clinical
30. Bean-Lijewski JD, Hunt RD. Effect of ketorolac on bleeding time and
Associates in Asheville, North Carolina.
postoperative pain in children: a double-blind, placebo-controlled
comparison with merperidine. J Clin Anesth. 1996;8(1):25-30. Kara Michalov, CRNA, MSN, was a senior student at Western Carolina
31. Gallagher JE, Blauth J, Fornadley JA. Perioperative ketorolac trometh- University's Graduate Program of Nurse Anesthesia at the time this review
amine and postoperative hemorrhage in cases of tonsillectomy and article was written. She is currently employed as a CRNA with AllCare
adenoidectomy. Laryngoscope. 1995;105(6):606-609. Clinical Associates in Asheville, North Carolina. Email: kemichalov1@
catamount.wcu.edu.
32. Buck ML. Clinical experience with ketorolac in children. Ann Pharma-
cother. 1994;28(9):1009-1013. Mark A. Kossick, CRNA, DNSc, is professor and coordinator of Gradu-
33. Houck CS, Wilder RT, McDermott JS, Sethna NF, Berde CB. Safety of ate Anesthesia Simulation Education at Western Carolina University’s
intravenous ketorolac therapy in children and cost savings with a unit Graduate Program of Nurse Anesthesia, Asheville, North Carolina.
dosing system. J Paediatr. 1996;129(2):292-296. Mason McDowell, CRNA, DNAP, is the assistant director at Western
34. Macario A, Royal MA. A literature review of randomized clinical trials Carolina University’s Graduate Program of Nurse Anesthesia, Asheville,
of intravenous acetaminophen (paracetamol) for acute postoperative North Carolina.

Call for Photos

T
he AANA needs photos of CRNAs giving anesthesia for use in
periodicals, brochures, Nurse Anesthetists Week materials, on the
website, and for other purposes. Photos can be of any type of procedure
in any type of setting. Please send photos on a CD to Christopher Bettin,
Senior Director, Communications, AANA, 222 S. Prospect Ave., Park Ridge, IL
60068, or by using www.yousendit.com, www.dropbox.com or any similar
web based electronic delivery system.

Photo Tips
1. Photos should be high quality, high-resolution (300 pixels per inch).
Photos taken with cell phones generally are not high-enough quality for
publication.
2. Providers in photos must follow practice guidelines, that is, wear masks,
caps, appropriate eye protection, and remove jewelry.
3. It’s best if you center the key elements of the photo (for easier cropping to
fit space needs).
4. Avoid overly graphic images or procedures.
5. Obtain signed photo releases from all those in the photo.

64 AANA Journal „ February 2014 „ Vol. 82, No. 1 www.aana.com/aanajournalonline


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