The Efficacy of Preemptive

Analgesia for Postoperative Pain

Control: A Systematic Review of
the Literature
BARBARA PENPRASE, PhD, RN, CNE, ANEF; ELISA BRUNETTO, MSN, CRNA;
EMAN DAHMANI, MSN, CRNA; JOLA JANAQI FORTHOFFER, MSN, BSN, CRNA;
SAMANTHA KAPOOR, MSN, RN, CRNA

ABSTRACT
The purpose of preemptive analgesia is to reduce postoperative pain, contributing to
a more comfortable recovery period and reducing the need for narcotic pain control.
The efficacy of preemptive analgesia remains controversial. This systematic review
of the literature evaluated the efficacy of nonsteroidal anti-inflammatory drugs
(NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, and gabapentin as preemptive oral
analgesics for surgical patients. Included articles were limited to studies of adult
patients that compared the difference in postoperative pain between control and
treatment groups. Of 40 studies reviewed, 14 met the inclusion criteria, including
two on NSAIDs, four on COX-2 inhibitors, and eight on gabapentin. Research was
predominantly conducted outside the United States. Gabapentin and COX-2 in-
hibitors were found to be the most effective preemptive analgesics for postoperative
pain control. As part of a collaborative team, perioperative nurses and certified RN
anesthetists are responsible for ongoing pain assessment and management for pre-
emptive analgesic interventions. AORN J 101 (January 2015) 94-105. Ó AORN, Inc,
2015. http://dx.doi.org/10.1016/j.aorn.2014.01.030

Key words: preemptive analgesia, postoperative pain control, nonsteroidal

anti-inflammatory drugs, NSAIDs, cyclooxygenase-2 inhibitors, COX-2
inhibitors, gabapentin.

R
ecent studies have shown that acute post- on improving postoperative pain control. As focus
operative pain continues to be under- is increasingly directed toward controlling pain and
managed even as surgery and anesthesia reducing narcotic use, preemptive analgesia may
become safer.1 Effective postoperative pain man- become more prevalent. A number of clinical trials
agement increases patient satisfaction, improves have suggested that preemptive analgesia leads to a
patient outcomes, and reduces the cost of care.2 decrease in postoperative pain, less total analgesic
Therefore, there has been an increasing emphasis consumption, and improved patient comfort.3 It is

http://dx.doi.org/10.1016/j.aorn.2014.01.030
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important that perioperative nurses understand the surgerydrather than initiating treatment after a
use of preemptive analgesia so they can evaluate noxious event occurs.5
outcomes of treatment, especially as related to The efficacy of preemptive analgesia remains
postoperative pain control. controversial in the United States because the ma-
According to the International Association for jority of studies have been conducted in other
the Study of Pain, pain is an unpleasant sensation countries and multiple medications and modes of
associated with sensory and emotional experiences delivery have been used; in addition, results from
that can cause potential or actual tissue damage.4 trials in humans have been inconsistent. Preemptive
Acute postoperative pain typically is caused by analgesia has been researched widely in oral sur-
mechanical, chemical, and thermal nociceptive gical procedures, especially in countries other than
stimuli (ie, painful, sometimes detrimental or in- the United States, and is becoming popular in a
jurious, stimuli). Acute nociceptive signals associ- variety of surgical procedures, including laparo-
ated with tissue damage initiate alterations in the scopic cholecystectomy, coronary artery bypass
peripheral and central pain pathways. Primary surgery, thyroidectomy, lumbar discectomy, and
afferent neurons detect noxious stimuli from the joint replacements.8-11 If the research shows that
periphery and through transduction conduct pain preemptive analgesia is used successfully to relieve
signals to the dorsal horn of the central nervous postoperative pain in other countries, it would be
system (CNS). An inflammatory response occurs important for health care practitioners in the United
with tissue damage and leads to the release of States to consider its use.
chemical mediators such as substance P, histamine, Although animal studies have shown positive
bradykinin, and prostaglandin. This leads to pe- benefits from preemptive analgesia, clinical trials in
ripheral sensitization caused by increased conduc- humans remain inconsistent regarding efficacy, as
tion of nociceptive stimuli to the CNS. Central well as medication use.3 This inconsistency may be
sensitization occurs as a result of amplification of caused by many factors, such as a lack of unifor-
nociceptive neurons in the dorsal horn of the CNS.5 mity in defining preemptive analgesia, variation in
In addition, severe acute pain is a risk factor for the methodology used for clinical trials, timing of the
development of chronic pain. prestimulus versus poststimulus dose, and lack of
Preemptive analgesia is an antinociceptive treat- an objective standard for pain measurement.2 Re-
ment applied before tissue injury to prevent pe- searchers are just beginning to study what types of
ripheral and central sensitization.6 By decreasing medications are most beneficial for use; thus, the
sensitization, preemptive analgesia is thought to optimal medication treatment choices have not
decrease the incidence of postoperative hyper- been clearly established by the literature.
algesia and allodynia.3 Decreasing sensitization is Preemptive analgesia began to be used more
thought to reduce the magnitude and duration of frequently at our hospital when new anesthesiolo-
postoperative pain. The concept of preemptive gists joined the staff. This practice resulted in con-
analgesia for postoperative pain control was pio- troversy between anesthesia providers regarding
neered in 1913 by George W. Crile, MD, who whether preemptive analgesia is effective. Thus, we
based his assumptions on clinical observations that conducted a systematic review of the literature,
suggested that analgesic interventions were more focusing specifically on the preemptive analgesia
effective when they were administered before a being used at our clinical site. Clinical trials on
surgical procedure.7 Subsequent experimental evi- preemptive analgesia have evaluated different an-
dence suggested that it may be possible to decrease algesics using a variety of administration routes.
or prevent the neurophysiological and biochemical The majority of clinical studies and reviews for
effects of noxious input to the CNSdsuch as preemptive analgesia focus on an individual

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medication or a combination of medications with between 2003 and 2013. We used a broad free-text
IV, intramuscular, and neuraxial modes of admin- search of full-text articles with the following terms:
istration. Research has indicated minimal efficacy pre-emptive analgesia, postoperative analgesia, and
with preemptive analgesic opioids and N-methyl- preincisional analgesia. The retrieved results were
D-aspartate antagonists.12,13 We examined key then limited to studies involving oral NSAIDs, COX-
research findings regarding the use of oral non- 2 inhibitors, and gabapentin because these were the
steroidal anti-inflammatory drugs (NSAIDs), most widely researched oral medications related to
cyclooxygenase-2 (COX-2) inhibitors, and gaba- preemptive analgesia. We also limited our review to
pentin in preemptive analgesia for postoperative studies involving adult patients. Many of the studies
pain control. Because the bioavailability of these that we retrieved were conducted outside the United
medications can vary, we elected to review studies States, but results for all studies were similar.
in which oral medications that share similar phar- We sought studies of quantitative design that
macokinetic profiles were used. were randomized blinded studies so that biases
Perioperative nurses and certified registered were lessened, increasing the rigor of the research
nurse anesthetists (CRNAs) are part of a collabo- findings. We initially identified 100 articles (Figure 1).
rative team with physicians and anesthesiologists Of these, 60 were not specific to our search criteria.
who are responsible We screened the re-
for patients’ ongoing maining 40 articles, of
pain assessment and Perioperative nurses and certified registered which 14 met inclusion
management. When nurse anesthetists are part of a collaborative criteria for this review.
use of preemptive an- team with physicians and anesthesiologists We excluded 26 studies
algesia is planned, it who are responsible for patients’ ongoing for various reasons:
is vital that CRNAs pain assessment and management. two were not available
initiate preoperative in English, two did not
analgesic orders, pre- explain the type of
operative nurses ensure that preemptive analgesics surgery conducted, one was very similar to another
are administered in a timely manner, and postop- study by the same authors, and the rest used different
erative nurses evaluate the outcomes of preemptive medications (ie, multimodal treatments) in different
analgesia. The purpose of preemptive analgesia is experimental groups preoperatively. We identified
to reduce postoperative pain for surgical patients, six studies that met our research criteria for oral
allowing a more comfortable recovery period and NSAIDs for preemptive analgesia; however, four of
reducing the need for narcotic pain control. The pur- these were excluded because of coadministration of
pose of this systematic review of the literature was oral NSAIDs with local anesthetic. Of the 14 studies
to present current research regarding best practices that were included in the review, two discussed
related to preemptive analgesia. We completed this NSAIDs,14,15 four discussed COX-2 inhibitors,16-19
review to help guide future practices for health care and eight discussed gabapentin8-10,20-24 for pre-
providers at our facility regarding the potential bene- emptive analgesia in surgical patients. A summary
fits and risks of using preemptive analgesia for of the literature included in this systematic review
our patients. is presented in Supplementary Table 1.

METHODS NONSTEROIDAL ANTI-INFLAMMATORY

We conducted electronic literature searches using DRUGS
CINAHLÒ, PubMedÒ, and OVIDÒ databases Nonsteroidal anti-inflammatory drugs are among
with restrictions to papers published in English the most popular medications used to relieve pain,

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Figure 1. Of 100 articles identified in the initial search, 40 articles were screened. Of these, 14 met inclusion
criteria for the systematic review of the literature.

fever, and inflammation. In the United States, more medications inhibit the enzymes called cyclo-
than 70 million NSAID prescriptions are written oxygenases and lead to decreased production
annually, and over-the-counter purchases reach a of prostaglandins. Prostaglandins are primary
consumption of 30 billion doses.25 Nonsteroidal chemicals produced by the body that carry out
anti-inflammatory drugs are of particular interest to a variety of important chemical and biological
the practice of anesthesia because, unlike opioids, body functions. By inhibiting the action of COX-1
they do not cause respiratory depression, nausea, and COX-2 and preventing the production of
sedation, or urinary retention. The significance of prostaglandins, NSAIDs decrease inflammation,
using NSAIDs for preemptive analgesia lies in their vasodilatation, capillary permeability, pain, and
peripheral and central mechanism of action; these fever.26

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The two studies on the use of NSAIDs as pre- decreased the intensity of pain. Outside of oral
emptive analgesia that met criteria for this sys- surgical procedures, we found that NSAIDs were
tematic review were randomized double-blind not used widely for preemptive analgesia. It ap-
clinical studies that assessed postoperative pain pears from the research published on preemptive
control in oral surgery. The medications used for analgesia that more effective oral medications have
the studies were ibuprofen and ketoprofen. Both replaced NSAIDs during the past 10 years.
studies were performed outside the United States.
The effectiveness of ketoprofen as a preemptive CYCLOOXIGENASE-2 INHIBITORS
analgesic was studied in Poland by Kaczmarzyk Activation of COX-2 by surgical trauma produces
et al14 in patients undergoing third molar surgery. hyperalgesia, which increases the sensitivity of pe-
A total of 96 patients were randomly divided into ripheral nociceptors.27 Nonsteroidal anti-inflammatory
three groups: pretreatment, posttreatment, and no drugs inhibit both the COX-1 and COX-2 enzymes,
treatment (ie, placebo). Patients in the pretreatment which, along with the desired effects of providing
group (n ¼ 34) received ketoprofen 60 minutes pain relief and inflammation reduction, may lead to
before surgery and a placebo 60 minutes after the inhibition of normal platelet function and gastro-
surgery, patients in the posttreatment group (n ¼ intestinal toxicity.16 The selectivity of COX-2 in-
30) received a placebo 60 minutes before surgery hibitors causes the lack of gastrointestinal and platelet
and ketoprofen 60 minutes after surgery, and pa- function effects; thus, COX-2 inhibition seems to be
tients in the placebo group (n ¼ 32) received a an excellent choice for postoperative pain manage-
placebo 60 minutes before surgery and 60 minutes ment. The COX-2 inhibitors that are commonly used
after surgery. Researchers found that pre- and for preemptive analgesia include celecoxib, rofecoxib,
postoperative administration of ketoprofen resulted valdecoxib, etoricoxib, and lumiracoxib.28 Research
in delayed pain development compared to placebo; indicates that the use of COX-2 inhibitors for pre-
however, postoperative ketoprofen administration emptive analgesia reduces postoperative pain and
was more effective in providing pain control than decreases the overall use of opioids postoperatively.17
preoperative administration. In this review, we found that clinical studies
The second study, by Jung et al,15 was conducted supported the efficacy of using COX-2 inhibitors
in Korea to determine whether ibuprofen provided as a preemptive analgesic for various surgical
postoperative pain relief when started preopera- procedures, including thoracotomies, arthroscopic
tively. Eighty patients undergoing surgical removal knee surgeries, and laparoscopic cholecystectomies.
of the mandibular third molar were divided into a Of the four research studies we reviewed, one study
pretreatment (n ¼ 25), a posttreatment (n ¼ 26), or was a randomized controlled trial,16 two studies
a no-treatment group (n ¼ 29). The posttreatment were double-blinded randomized controlled tri-
group demonstrated the greatest pain relief com- als,17,18 and one study was a retrospective chart re-
pared with the other two groups. The researchers’ view.19 The surgical procedures were more complex
findings indicated that NSAIDs would not be ben- than oral surgical procedures and thus potentially
eficial for preemptive analgesia. However, they resulted in greater postoperative pain. The different
found that postoperative administration provided surgical procedures were valuable to compare and
significant pain relief. evaluate the efficacy of preemptive analgesia for
Both studies focused on patients undergoing oral postoperative pain. Two studies were conducted in
surgery, so the generalizability of the results to the United States; the others were conducted in
other types of surgery is questionable. The findings Thailand and Turkey.
revealed that NSAIDs when administered post- In a study by Horattas et al18 from the United
operatively provided significant pain relief and States, 116 patients undergoing laparoscopic

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cholecystectomies received 50 mg of rofecoxib or group that was given a preemptive selective COX-2
placebo before surgery. This study showed a sig- inhibitor. Thus, COX-2 inhibitors administered as
nificant decrease in postoperative narcotic use and preemptive analgesia decreased the length of stay
an increase in postoperative activity level in the and overall need for narcotic pain control.
treatment group. The study was limited to laparo- A study by Boonriong et al16 showed mixed
scopic cholecystectomies. However, the three other results for a sample of 102 patients in Thailand
studies involving surgical procedures supported undergoing anterior cruciate ligament reconstruc-
that COX-2 inhibitors significantly decreased pain tion. Patients were divided into three groups; the
levels postoperatively in these patients. first group received 120 mg of etoricoxib before
19
Research by Duellman et al focused on com- surgery (n ¼ 35), the second group received 400
paring the effect of preemptive analgesia with mg of celecoxib before surgery (n ¼ 35), and the
patient-controlled analgesia (PCA). The research third group received placebo (n ¼ 32). Although
was conducted in the United States on patients patients in the etoricoxib group had significantly
undergoing total joint arthroplasties and was lower postoperative pain intensity, patients in the
prompted by the adverse effects caused by post- celecoxib group showed no significant difference
operative PCA ad- compared with pa-
ministration, such as tients in the placebo
nausea, decreased Research indicates that the use of group. These findings
rehabilitation partici- cyclooxygenase-2 inhibitors for preemptive distinguished between
pation, and increased analgesia reduces postoperative pain and de- the effectiveness of
length of stay. The creases the overall use of opioids postoperatively. etoricoxib and cele-
researchers’ focus was coxib; etoricoxib sig-
to identify an alterna- nificantly decreased
tive pain relief modality for patients undergoing postoperative pain whereas no significance was
total joint arthroplasty. Fifty-eight patients received noted postoperatively with celecoxib.
200 mg of celecoxib every 12 hours preoperatively In a double-blind placebo-controlled prospective
while they were in the hospital waiting for surgery; study conducted in Turkey involving 60 patients
postoperatively, patients received another 200 mg undergoing thoracotomy,17 half the patients were
of celecoxib every 12 hours with an oral narcotic given 50 mg of rofecoxib preoperatively and the
(ie, oxycodone) during the rest of the hospital stay. other half received placebo. The researchers found
The postoperative medication regimen began when that patients who received rofecoxib before surgery
the patient asked for pain medication, so the reg- had a significant decrease in opioid requirements
imen varied according to patients’ needs. For compared with patients in the placebo group. Al-
breakthrough pain, patients received IV narcotics though each group had only 30 patients, the results
as needed during the postoperative period. In the were promising regarding the effectiveness of
control group, 69 patients received no preoperative COX-2 inhibitors in decreasing postoperative pain.
celecoxib and were treated postoperatively with an Clearly results showed that regardless of the
IV narcotic via the PCA pump for 48 hours and surgical procedure, COX-2 inhibitors adminis-
with an oral narcotic until discharge. The patients tered preoperatively had positive effects on post-
in the PCA group required significantly more operative pain scores, opioid use, and length of
morphine (average dose, 17.7 vs 7.2 mg), had hospital stay. Additional research using COX-2
a longer average hospital stay (3.7 vs 2.7 days), inhibitors for preemptive analgesia should be
and had a significant decrease in participation in conducted, especially in the United States, for
postoperative rehabilitation compared with the surgical procedures that can result in significant

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postoperative pain, such as abdominal or thoracic although pathological pain is reduced, other protec-
surgeries. tive nociceptive mechanisms remain intact with the
use of gabapentin.10 Research results also have
GABAPENTIN demonstrated that the combination of gabapentin
Historically, the mainstay for postoperative pain with other antinociceptive medications produces a
management has been opioids, although adverse synergistic action.22
effects (eg, nausea, vomiting, pruritus, respiratory Although the exact mechanism of action of
depression) may limit their use. In addition, as gabapentin is not clearly understood, it appears
mentioned, NSAIDs are used commonly as ad- there may be multiple mechanisms. Gabapentin
juncts to reduce pain after minor surgery, but their does not act via opioid mechanisms; rather, it binds
use may be limited in patients with bleeding to alpha-2-delta subunits of voltage-gated calcium
diathesis or renal or gastrointestinal problems,20 channels located presynaptically in the dorsal root
and research does not support the use of NSAIDs ganglia.8 This effect reduces the release from
for preemptive anal- sensory neurons of
14,15
gesia. An alterna- excitatory neurotrans-
tive approach to pain Gabapentin has demonstrated an inhibitory mitters involved in
control, gabapentin is effect on preexisting allodynia and hyperalgesia, pain pathways, in-
a structural analogue but it has shown no effect on pain transmission cluding glutamate,
of gamma aminobu- in normal skin. noradrenaline, and
tyric acid and is an substance P.8,20 Addi-
antiepileptic drug for tional proposed mech-
partial seizures; its role in pain management has anisms of pain reduction from gabapentin include
been limited to neuropathic pain, diabetic neu- an increase in the concentration and rate of syn-
ropathy, postherpetic neuralgia, and reflex thesis of gabapentin in the brain, modulation of
21
sympathetic dystrophy. An increasing number glutamate receptors, inhibition of voltage-activated
of studies have suggested that gabapentin used as sodium channels, and an increase in serotonin
a preemptive analgesic has a beneficial effect on concentrations.8,9 Therefore, it is believed that
both pain scores and postoperative opioid con- preoperative dosing of gabapentin exerts its anal-
8-10,20-24
sumption. There has been limited research gesic effects by preemptively decreasing the spinal
conducted in the United States related to the use cord excitation caused by surgical trauma.23
of gabapentin as a preemptive analgesic, which To determine whether preoperative gabapentin
is surprising because gabapentin has been stud- was effective in reducing postoperative pain and
ied extensively in other countries. whether the research findings demonstrated evi-
In clinical studies, gabapentin has been shown to dence of opioid-sparing effects, we identified 16
reduce hypersensitivity induced by inflammation articles according to our research criteria for
and injury. In addition, gabapentin has demon- gabapentin. We eliminated eight because they
strated an inhibitory effect on preexisting allodynia either compared gabapentin to pregabalin, mela-
and hyperalgesia, as well as the development of tonin, or other oral medications; compared its ef-
secondary allodynia and hyperalgesia resulting from ficacy to regional anesthesia; or tried to find the
central sensitization, but it has shown no effect on effective dose for preemptive analgesia.
10
pain transmission in normal skin. Compared with Eight studies met our criteria for postoperative
results found with remifentanil (ie, a synthetic opi- pain between control and treatment groups when
oid analgesic), these results are of considerable preemptive analgesic measures were initiated. Each
importance to postoperative pain relief because study reviewed a different type of surgery, as well

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KEY TAKEAWAYS FOR CLINICAL PRACTICE

Preemptive Analgesia Can Improve Postoperative Pain Control
Why Did We Do This Research? How Can Clinicians Use These Results?
n Preemptive analgesia is used to decrease postoperative n Clinicians: Clinicians need to be aware that gabapentin
pain worldwide, but is not a fully accepted practice in has become the medication of choice for preemptive
the United States. We performed a literature review analgesia and that research does not support the use of
to investigate whether nonsteroidal anti-inflammatory NSAIDs as a preemptive analgesic for postoperative
drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, pain relief.
and gabapentin are effective for reducing postoperative n Managers: Managers should be aware that the practice
pain. of preemptive analgesia is increasing in the United
States, which will affect preoperative preparation.
n Educators: Educators also should be aware of the in-
What Did We Find? crease in the use of preemptive analgesia in the United
n Based on our findings, preemptive administration of States, especially gabapentin, and that perioperative
gabapentin and COX-2 inhibitors is effective for post- nursing teams need to be educated on the uses and
operative pain control, but using NSAIDs for preemptive adverse effects of this form of treatment for post-
analgesia does not improve postoperative pain control. operative pain control.

Penprase B, Brunetto E, Dahmani E, Forthoffer JJ, Kapoor S. The efficacy of preemptive analgesia for postoperative pain
control: a systematic review of the literature. AORN J. 2015;101(1):94-105. Copyright Ó AORN, Inc, 2015.

as multiple gabapentin dosages and administration 50 to 120, and because all studies had a control
times. The surgeries included in this review were group, treatment groups were uniform.
thyroidectomy, tongue reconstruction with antero- We included two studies9,10 that used a preop-
lateral thigh flap, coronary artery bypass graft, erative dose of 300 mg of gabapentin in our anal-
lower-extremity orthopedic surgery, caesarean de- ysis. In both studies, patients in the treatment group
livery, lumbar discectomy, abdominal surgery, and had significantly lower pain scores at all intervals
minilaparoscopic open cholecystectomy. Of the measured in the first 24 hours after surgery. Although
eight studies we reviewed, seven were randomized the two studies involved different opioids for post-
placebo-controlled trials8-10,21-24 and one was a operative pain control, fentanyl9 and morphine,10
nonrandomized retrospective cohort study.20 patients in both treatment groups required less
In all the studies, patients in the gabapentin medication in the first 24 hours after surgery com-
groups received a single preoperative dose of pared with the control groups.
gabapentin ranging between 300 and 1,200 mg. To In the study conducted by Montazeri et al9 in
facilitate analysis of the researchers’ results, we Iran, the researchers reported the total 24-hour
created three subgroups based on preoperative morphine consumption to be, on average, 15.43 mg
doses: 300 mg, 600 mg, and 1,200 mg. Each study for patients in the gabapentin group versus 17.94
included an analysis of pain intensity using pain mg for patients in the control group who underwent
scores, analgesic consumption, and breakthrough lower-extremity orthopedic surgery. The results
pain control. All the researchers also recorded and also demonstrated a significant difference between
analyzed the occurrence of adverse effects related the two groups in the first time a patient requested
to gabapentin administration in addition to post- morphine administration after surgery (31.57 min-
operative pain scores and opioid consumption. utes in the gabapentin group versus 26.71 minutes
The most commonly reported adverse effects were in the placebo group), but no difference in recovery
nausea, vomiting, sedation, dizziness, respiratory duration. Similarly, a study by Pandey et al10 in
depression, and pruritus. Sample sizes ranged from India showed that total fentanyl consumption in

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the first 24 hours after undergoing lumbar dis- 24-hour period after surgery compared with the
coidectomy surgery was significantly less in the control group.
gabapentin group (233.5 mg) than in the control We included two studies involving a preop-
group (359.6 mg). Groups were small in both erative dose of 1,200 mg of gabapentin in our
studies, with only 28 or 35 participants, but it is review.20,24 One study was performed in Kuwait,24
noteworthy that similar results were identified in and the other, in Hong Kong20; surgeries included
two different locations. patients undergoing either thyroidectomy or tongue
We included four studies using a preoperative construction. Both studies showed that postoperative
8,21-23
dose of 600 mg of gabapentin in our analysis. pain assessment scores were significantly lower
21,22
Two studies were conducted in India, one was inthe gabapentin group compared with the control
23
conducted in Canada, group in the first 24
and one was conducted hours after surgery.
8
in Turkey. All four Advanced practice nurses, certified registered For postoperative anal-
studies concluded nurse anesthetists, anesthesiologists, and gesia, both studies used
that pain scores in surgeons should collaboratively establish morphine; morphine
the treatment groups preoperative protocols and practice guidelines consumption was
were significantly lower for the implementation of preemptive analgesia. significantly lower in
than pain scores for the the gabapentin groups
control groups for the compared with the
first 24 hours after surgery both at rest and with control groups. Although sample sizes were different
movement or coughing. In the study by Srivastava (7224 and 5020 participants), the studies were per-
et al,22 two groups consisted of 60 patients each. formed in different countries, and they involved
The researchers assessed pain scores at 24 hours patients undergoing different surgical procedures,
after surgery and found that pain scores were both studies indicated significant reductions in
significantly lower for the group that received postoperative pain with 1,200 mg of gabapentin
gabapentin. At 48 hours, they found pain levels administered preoperatively.
to be comparable in both the treatment and All the studies using gabapentin were conducted
control groups. outside the United States; therefore, there is a gap
Medications used for postoperative pain control in this research related to the value of using gaba-
8,23 21
in the studies included morphine, diclofenac, pentin for preemptive analgesia in the United
and tramadol.22 Gabapentin was used as the pre- States. However, results of these studies show ev-
emptive analgesia before the surgical procedure. In idence of the efficacy of gabapentin (300 mg, 600 mg,
three of the studies, total medication consumption or 1,200 mg) for preemptive analgesia. Adminis-
for postoperative pain and need for breakthrough tration of preoperative gabapentin was effective
pain control were lower in the gabapentin groups.8,21,22 for controlling acute postoperative pain and is the
8
Menda et al found that total morphine consump- medication of choice currently being used for pre-
tion in the first 24 hours after surgery was 57% emptive analgesia throughout the world.8-10,20-24
lower in the gabapentin group versus the control
group. However, a study by Moore et al23 in Can- DISCUSSION AND IMPLICATIONS
ada showed no difference in postoperative opioid Through this review of the literature, we learned
consumption when gabapentin was administered that how preemptive analgesia is delivered varies
preoperatively. The research findings revealed that across the globe. Based on this review, we consider
patients’ pain was decreased and satisfaction scores preemptive analgesia with oral COX-2 inhibitors
were higher in the gabapentin group in the first and gabapentin to be beneficial; the research

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reviewed supports their administration for select the first 24 to 48 hours to maintain an optimal
surgical procedures to benefit patients. Based on our threshold, close observation for any adverse re-
review of NSAIDs, there appears to be no clinical actions from the medications is necessary, and
benefit for their use as preemptive analgesia. there still may be a need for narcotics for post-
Evidence supports that health care providers operative pain control. The primary role of the
should advocate for the use of preemptive COX-2 postoperative nurse has not changed. Nurses must
inhibitors and gabapentin to reduce postoperative ensure that good postoperative pain control is es-
pain. Advanced practice nurses, CRNAs, anesthe- tablished and maintained based on the assessment
siologists, and surgeons should collaboratively of the patient’s pain.
establish preoperative protocols and practice The preoperative use of gabapentin and COX-2
guidelines for the implementation of preemptive inhibitors was found to be the most effective
analgesia. Specific barriers must be considered method for reducing postoperative pain in diverse
when implementing preemptive analgesia in peri- types of surgeries. Additional studies should be
operative practice. For example, patients may re- conducted to continue evaluating their efficacy in
fuse to take the preemptive analgesic medication as reducing postoperative pain. Future research should
prescribed, and some surgeons and anesthesiolo- focus on the best times to administer the medica-
gists may be concerned about the use of preemptive tion(s), what schedule works the best to maintain
analgesic medication because of potential adverse optimal pain control and long-term pain reduction,
effects. The adverse effects of gabapentin include and cost-effectiveness. In addition, future studies
but are not limited to nausea, vomiting, sedation, should focus attention on the effectiveness of
pruritus, constipation, urinary retention, and dizzi- coadministration of these medications as preemp-
ness.22 Potential prothrombotic effects of COX-2 tive analgesics for specific surgeries.
inhibition and delayed wound healing must be
considered.18 Fortunately, as demonstrated by this SUPPLEMENTARY DATA
review, recent studies have shown favorable re- The supplementary table associated with this article
sults regarding the safe use for both medications. can be found in the online version at http://dx.doi
However, concerns about adverse effects when .org/10.1016/j.aorn.2014.01.030.
administering these medications must be considered
for all patients, along with potential drug-to-drug Editor’s notes: CINAHL, Cumulative Index to
interactions when given with other medications. Nursing and Allied Health Literature, is a registered
Preemptive analgesia is widely used in many trademark of EBSCO Industries, Birmingham, AL.
countries. Of studies conducted in the United PubMed is a registered trademark of the US
States, preemptive analgesia has been used in a National Library of Medicine, Bethesda, MD. Ovid
variety of surgical procedures: oral surgery, lapa- is a registered trademark of CDP Technologies,
roscopic cholecystectomy, and total joint arthro- Inc, New York, NY.
plasty. The results of these studies are similar to
results in other countries. Evidence supports the use References
of COX-2 inhibitors and gabapentin as treatment 1. Peng PW, Wijeysundera DN, Li CC. Use of gabapentin
for perioperative pain controlda meta-analysis. Pain Res
options to reduce postoperative pain and signifi- Manag. 2007;12(2):85-92.
cantly decrease the need for narcotics.29 Perioper- 2. Heck U, Mitchell VD. Preemptive analgesia: physiology
and clinical studies. In: Benzon HT, Raja SN, Malloy RE,
ative nurses need to remain aware of how to care Liu SS, Fishman SM, eds. Essentials of Pain Medicine
for patients who are being treated with preemptive and Regional Anesthesia. 2nd ed. Philadelphia, PA:
Elsevier-Churchill Livingstone; 2005:229-234.
analgesia. For example, nurses need to be aware 3. Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy
that the medications must be given on time for of preemptive analgesia for acute postoperative pain

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management: a meta-analysis. Anesth Analg. 2005; 20. Chiu TW, Leung CC, Lau EY, Burd A. Analgesic effects
100(3):757-773. of preoperative gabapentin after tongue reconstruction
4. International Association for the Study of Pain. IASP with the anterolateral thigh flap. Hong Kong Med J. 2012;
Taxonomy. http://www.iasp-pain.org/Education/Content 18(1):30-34.
.aspx?ItemNumber¼1698. Accessed August 13, 2014. 21. Parikh HG, Dash SK, Upasani CB. Study of the effect of
5. Dahl JB, Møiniche S. Pre-emptive analgesia. Br Med oral gabapentin used as preemptive analgesia to attenuate
Bull. 2004;71:13-27. post-operative pain in patients undergoing abdominal
6. Kelly DJ, Ahmed M, Brull SJ. Preemptive analgesia I: surgery under general anesthesia. Saudi J Anaesth. 2010;
physiological pathways and pharmacological modalities. 4(3):137-141.
Can J Anaesth. 2001;48(10):1000-1010. 22. Srivastava U, Kumar A, Saxena S, Mishra AR, Saraswat N,
7. Crile GW. The kinetic theory of shock and its prevention Mishra S. Effect of preoperative gabapentin on post-
through anoci-association. Lancet. 1913;185:7-16. operative pain and tramadol consumption after minilap
8. Menda F, K€oner O, Sayın M, Ergenoglu M, K€uc‚€ukaksu S, open cholecystectomy: a randomized double-blind, placebo-
Aykac‚ B. Effects of single-dose gabapentin on post- controlled trial. Eur J Anaesthesiol. 2010;27(4):331-335.
operative pain and morphine consumption after cardiac 23. Moore A, Costello J, Wieczorek P, Shah V, Taddio A,
surgery. J Cardiothorac Vasc Anesth. 2010;24(5): Carvalho J. Gabapentin improves postcesarean delivery
808-813. pain management: a randomized, placebo-controlled
9. Montazeri K, Kashefi P, Honarmand A. Pre-emptive trial. Anesth Analg. 2011;112(1):167-173.
gabapentin significantly reduces postoperative pain and 24. Al-Mujadi H, A-Refai AR, Katzarov MG, Dehrab NA,
morphine demand following lower extremity orthopedic Batra YK, Al-Qattan AR. Preemptive gabapentin reduces
surgery. Singapore Med J. 2007;48(8):748-751. postoperative pain and opioid demand following thyroid
10. Pandey CK, Sahay S, Gupta D, et al. Preemptive gaba- surgery. Can J Anaesth. 2006;53(3):268-273.
pentin decreases postoperative pain after lumbar dis- 25. Wiegand TJ, Tarabar A. Nonsteroidal anti-inflammatory
coidectomy. Can J Anaesth. 2004;51(10):986-989. agent toxicity. Medscape. http://emedicine.medscape
11. Sandhu T, Paiboonworachat S, Ko-iam W. Effects of .com/article/816117-overview. Updated March 3, 2014.
preemptive analgesia in laparoscopic cholecystectomy: a Accessed August 13, 2014.
double-blind randomized controlled trial. Surg Endosc. 26. Sundy JS. Nonsteroidal anti-inflammatory drugs. In:
2011;25(1):23-27. Koopman WJ, Moreland LW, eds. Arthritis and Allied
12. Møiniche S, Kehlet H, Dahl BD. A qualitative and Conditions: A Textbook of Rheumatology. 15th ed. Phila-
quantitative systematic review of preemptive analgesia delphia, PA: Lippincott Williams & Wilkins; 2005:680-704.
for postoperative pain relief: the role of timing of anal- 27. Reuben SS, Bhopatkar S, Maciolek H, Joshi W, Sklar J.
gesia. Anesthesiology. 2002;96(3):725-741. The preemptive analgesic effect of rofecoxib after
13. Kissin I. Preemptive analgesia. Anesthesiology. 2000; ambulatory arthroscopic knee surgery. Anesth Analg.
93(4):1138-1143. 2002;94(1):55-59.
14. Kaczmarzyk T, Wichlinski J, Stypulkowska J, Zaleska M, 28. Kaye AD, Baluch A, Kaye AJ, Gebhard R, Lubarsky D.
Woron J. Preemptive effect of ketoprofen on postoperative Pharmacology of cyclooxygenase-2 inhibitors and pre-
pain following third molar surgery. A prospective, ran- emptive analgesia in acute pain management. Curr Opin
domized, double-blinded clinical trial. Int J Oral Max- Anaesthesiol. 2008;21(4):439-445.
illofac Surg. 2010;39(7):647-652. 29. Kodali BS, Oberoi JS. Management of postoperative
15. Jung YS, Kim MK, Um YJ, Park HS, Lee EW, Kang JW. pain. http://www.uptodate.com/contents/management-of
The effects on postoperative oral surgery pain by varying -postoperative-pain. Accessed August 13, 2014.
NSAID administration times: comparison on effect of
preemptive analgesia. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod. 2005;100(5):559-563.
16. Boonriong T, Tangtrakulwanich B, Glabglay P,
Nimmaanrat S. Comparing etoricoxib and celecoxib for Barbara Penprase, PhD, RN, CNE, ANEF, is
preemptive analgesia for acute postoperative pain in pa- a professor at the School of Nursing, Oakland
tients undergoing arthroscopic anterior cruciate ligament
reconstruction: a randomized controlled trial. BMC University, Rochester, MI. Dr Penprase has no
Musculoskelet Disord. 2010;11:246. declared affiliation that could be perceived as
17. Celik JB, Gormus N, Gormus ZI, Okesli S, Solak H.
Preoperative analgesia management with rofecoxib in posing a potential conflict of interest in the
thoracotomy patients. J Cardiothorac Vasc Anesth. 2005; publication of this article.
19(1):67-70.
18. Horattas MC, Evans S, Sloan-Stakleff KD, Lee C, Elisa Brunetto, MSN, CRNA, is a certified
Snoke JW. Does preoperative rofecoxib (Vioxx) decrease
registered nurse anesthetist at Promedica, Toledo,
postoperative pain with laparoscopic cholecystecomy.
Am J Surg. 2004;188(3):271-276. OH. Ms Brunettto has no declared affiliation that
19. Duellman TJ, Gaffigan C, Milbrandt JC, Allan DG. could be perceived as posing a potential conflict
Multi-modal, pre-emptive analgesia decreases the length
of hospital stay following total joint arthroplasty. of interest in the publication of this article.
Orthopedics. 2009;32(3):167.

104 j AORN Journal

EFFICACY OF PREEMPTIVE ANALGESIA www.aornjournal.org

Eman Dahmani, MSN, CRNA, is a certified could be perceived as posing a potential

registered nurse anesthetist at McLaren Medical conflict of interest in the publication of this
Center, Flint, MI. Ms Dahmani has no declared article.
affiliation that could be perceived as posing a Samantha Kapoor, MSN, BSN, RN, CRNA,
potential conflict of interest in the publication of is a certified registered nurse anesthetist at
this article. McLaren Hospital, Flint, MI. Ms Kapoor has no
Jola Janaqi Forthoffer, MSN, BSN, CRNA,
declared affiliation that could be perceived as
is a certified registered nurse anesthetist at
posing a potential conflict of interest in the
St John Hospital Medical Center, Detroit, MI.
publication of this article.
Ms Forthoffer has no declared affiliation that

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January 2015 Vol 101 No 1

SUPPLEMENTARY TABLE 1. Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

NSAIDs Jung et al (2005)1 Korea To determine the Randomized, 80 participants Participants were n Participants in Convenience
best administra- double-blind, undergoing randomly the posttreat- sample
tion time for parallel-group, removal of a divided into 3 ment group
ibuprofen in single-center, mandibular third groups: demonstrated
providing post- active-controlled molar n Pretreatment the greatest
operative pain test design (n ¼ 25): pain relief
relief NSAID admin- n Ibuprofen
istered 1 hr administered
before surgery preoperatively
n Posttreatment was not
(n ¼ 26): beneficial
NSAID admin-
istered 1 hr af-
ter surgery
n No treatment
(n ¼ 29): no
NSAID
administered
NSAIDs Kaczmarzyk et al Poland To determine the Prospective, 96 patients under- Participants were n Preoperative Convenience
(2010)2 effect of pre- randomized, going third randomly and post- sample
emptive anal- double-blind, molar surgery divided into 3 operative
gesia (ie, clinical trial groups: administration
ketoprofen) on n Pretreatment of ketoprofen
postoperative (n ¼ 34): keto- resulted in
pain profen 60 mi- delayed pain
nutes before development
surgery and when com-

PENPRASE ET AL
placebo 60 pared with
minutes after placebo
surgery n Postoperative
n Posttreatment ketoprofen
(n ¼ 30): pla- administration
cebo 60 was more
 EFFICACY OF PREEMPTIVE ANALGESIA
SUPPLEMENTARY TABLE 1. (continued) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

minutes before effective in

surgery and providing pain
ketoprofen 60 control than
minutes after preoperative
surgery administration
n No treatment
(n ¼ 32): pla-
cebo 60 mi-
nutes before
and 60 minutes
after surgery
COX-2 Boonriong et al Thailand To compare anal- Randomized 102 patients un- Patients were n Participants in Convenience
inhibitors (2010)3 gesic efficacy controlled trial dergoing ante- divided into 3 the etoricoxib sample
of a single pre- rior cruciate groups: group had
operative ad- ligament n 120 mg of significantly
ministration of reconstruction etoricoxib lower post-
etoricoxib v cel- before surgery operative pain
ecoxib for post- (n ¼ 35) intensity than
operative pain n 400 mg of cel- the other
ecoxib before groups
surgery (n ¼ 35) n Participants in
n Placebo the celecoxib
(n ¼ 32) group showed
no significant
difference
compared with
the placebo
group
AORN Journal j 105.e2

Celik et al (2005)4

www.aornjournal.org
COX-2 Turkey To determine the Prospective, ran- 60 patients Patients were n Patients who Convenience
inhibitors efficacy of pre- domized, undergoing a divided into received rofe- sample
operative anal- double-blind, thoracotomy 2 groups: coxib before
gesia with placebo- n 50 mg of rofe- surgery had a
rofecoxib for controlled trial coxib before significant
(table continued)
105.e3 j AORN Journal

January 2015 Vol 101 No 1

SUPPLEMENTARY TABLE 1. (continued ) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

postoperative surgery decrease in

pain manage- (n ¼ 30) opioid re-
ment in surgical n Placebo quirements
patients (n ¼ 30) compared with
patients in the
placebo group
COX-2 Duellman et al United States To compare the Retrospective 127 patients who 2 groups of pa- Patients who Convenience
inhibitors (2009)5 effect of multi- chart review underwent total tients were received pre- sample
modal preemp- joint arthroplasty reviewed: emptive anal-
tive analgesia v n Postoperative gesia
patient-controlled patient- n Required
analgesia on controlled significantly
postoperative analgesia less pain
nausea, rehabili- n Preemptive medication
tation participa- analgesia with n Had shorter
tion, and length 200 mg of cel- lengths of hos-
of stay ecoxib and pital stay
postoperative n Had increased
pain control participation in
with oral oxy- postoperative
codone and rehabilitation
celecoxib
COX-2 Horattas et al United States To determine the Prospective, ran- 116 patients Patients were n Patients who
inhibitors (2004)6 effects of pre- domized, undergoing divided into received the
emptive anal- double-blind elective laparo- 2 groups: COX-2 inhibitor
gesia with clinical trial scopic chole- n 50 mg of rofe- exhibited a
rofecoxib on cystectomy coxib before significant
surgery (n ¼ 58)

PENPRASE ET AL
postoperative decrease in
pain n Placebo before postoperative
surgery (n ¼ 58) narcotic use
and an in-
crease in
 EFFICACY OF PREEMPTIVE ANALGESIA
SUPPLEMENTARY TABLE 1. (continued ) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

postoperative
activity level
n Rofecoxib was
effective in
decreasing
postoperative
pain
Gabapentin Al-Mujadi et al Kuwait To determine Prospective, 72 patients Patients were n Pain scores Convenience
(2006)7 whether pre- randomized, undergoing divided into were signifi- sample
emptive gaba- double-blind trial thyroidectomy 2 groups: cantly lower in
pentin reduces n 1,200 mg of patients who
postoperative gabapentin received
pain and opioid before surgery gabapentin
demand after (n ¼ 37) n Postoperative
thyroid surgery n Placebo before opioid con-
surgery (n ¼ 35) sumption was
significantly
lower for pa-
tients who
received
gabapentin
Gabapentin Chiu et al (2012)8 Hong Kong To investigate the Nonrandomized 50 patients under- Patients were Patients who Convenience
effectiveness of open-label trial going tongue divided into received gaba- sample
gabapentin in construction 2 groups: pentin before
reducing post- n 1,200 mg of surgery had
operative pain gabapentin n Significantly
before surgery reduced post-
(n ¼ 25) operative pain
AORN Journal j 105.e4

www.aornjournal.org
n No gabapentin scores
(n ¼ 25) n Significantly
less narcotic
use after
surgery
(table continued)
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January 2015 Vol 101 No 1

SUPPLEMENTARY TABLE 1. (continued ) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

Gabapentin Menda et al Turkey To determine the Randomized, 60 patients under-Patients were Patients who Convenience
(2010)9 effects of single- double blind, going coronary randomly received gaba- sample
dose gabapentin placebo- artery bypass assigned to 1 pentin exhibited
on postoperative controlled trial graft surgery of 2 groups: a significant
pain and mor- n 600 mg of n Decrease in
phine consump- gabapentin pain scores
tion after cardiac before surgery compared with
surgery (n ¼ 30) patients in the
n Placebo before placebo group
surgery (n ¼ 30) n Difference in
postoperative
narcotic use
compared with
patients in the
placebo group
Gabapentin Montazeri et al Iran To determine Randomized 70 patients Patients were n Patients in the Convenience
(2007)10 whether double-blind undergoing randomly gabapentin sample
preemptive study lower-extremity assigned to 1 group had
gabapentin orthopedic of 2 groups: significantly
significantly surgery n 300 mg of less pain
reduced post- gabapentin postoperatively
operative pain before surgery n Patients in the
and morphine (n ¼ 35) gabapentin
demand after n Placebo before group required
lower-extremity surgery (n ¼ 35) significantly
orthopedic less narcotic
surgery pain control af-

PENPRASE ET AL
ter surgery
Gabapentin Moore et al Canada To determine Randomized 46 women under- Patients were n At 24 hr, the Convenience
(2011)11 whether gaba- placebo- going scheduled randomly mean pain sample
pentin reduced controlled trial cesarean assigned to 1 of score was
pain after delivery 2 groups: significantly
 EFFICACY OF PREEMPTIVE ANALGESIA
SUPPLEMENTARY TABLE 1. (continued ) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

cesarean n 600 mg of lower in pa-

delivery gabapentin tients in the
before surgery gabapentin
(n ¼ 21) group
n Placebo before compared with
surgery (n ¼ 25) patients in the
placebo group
n There was no
difference in
opioid con-
sumption
noted between
the 2 groups
Gabapentin Pandey et al India To determine Randomized, blin- 56 patients under- Patients were n Patients who Convenience
(2004)12 whether pre- ded, placebo- going single- randomly received gaba- sample
emptive anal- controlled trial disc lumbar assigned to 1 pentin before
gesia using discoidectomy of 2 groups: surgery had
gabapentin de- n 300 mg of less pain and
creases post- gabapentin 2 used less
operative pain hr before sur- opioids
after lumbar gery (n ¼ 28) postoperatively
discoidectomy n Placebo 2 hr
before surgery
(n ¼ 28).
Gabapentin Parikh et al India To determine the Randomized 60 patients under- Patients were n There was a Convenience
(2010)13 effect of oral double-blind going abdominal randomly significant dif- sample
gabapentin study surgery assigned to 1 ference in pain
used as pre- of 2 groups: scores re-
AORN Journal j 105.e6

www.aornjournal.org
emptive anal- n 600 mg of ported among
gesia to lessen gabapentin patients in the
postoperative before surgery gabapentin
pain in patients (n ¼ 30) group after
undergoing surgery
(table continued)
105.e7 j AORN Journal

January 2015 Vol 101 No 1

SUPPLEMENTARY TABLE 1. (continued ) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

abdominal sur- n Placebo before compared with

gery under gen- surgery (n ¼ 30) patients in the
eral anesthesia placebo group
n Patients in the
gabapentin
group required
significantly
less narcotics
after surgery
compared with
patients in the
placebo group
Gabapentin Srivastava et al India To determine the Randomized, 120 patients un- Patients were n Postoperative Convenience
(2010)14 effect of preop- double-blind, dergoing mini- randomly pain scores sample
erative gaba- placebo- laparoscopic assigned to 1 were signifi-
pentin on controlled trial open of 2 groups: cantly lower in
postoperative cholecystectomy n 600 mg of patients in the
pain and trama- gabapentin gabapentin
dol consump- before surgery group at all
tion after (n ¼ 60) points during
minilaparo- n Placebo before postoperative
scopic open surgery day 1; how-
cholecystectomy (N ¼ 60) ever, at 48 hr,
pain scores
were compa-
rable between
the groups

PENPRASE ET AL
 EFFICACY OF PREEMPTIVE ANALGESIA
SUPPLEMENTARY TABLE 1. (continued ) Summary of Literature Discussing Preemptive Analgesia for Surgical Patients

Topic Author/year Country Purpose Design Sample Measurement Findings Limitations

n Total 24-hr
tramadol con-
sumption was
lower in pa-
tients who
received
gabapentin
compared with
those who
received pla-
cebo, but con-
sumption was
similar on day 2
COX-2 ¼ cyclooxygenase-2; NSAIDs ¼ nonsteroidal anti-inflammatory drugs.
1. Jung YS, Kim MK, Um YJ, Park HS, Lee EW, Kang JW. The effects on postoperative oral surgery pain by varying NSAID administration times: comparison on effect of preemptive analgesia. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2005;100(5):559-563.
2. Kaczmarzyk T, Wichlinski J, Stypulkowska J, Zaleska M, Woron J. Preemptive effect of ketoprofen on postoperative pain following third molar surgery. A prospective, randomized, double-blinded clinical trial. Int J
Oral Maxillofac Surg. 2010;39(7):647-652.
3. Boonriong T, Tangtrakulwanich B, Glabglay P, Nimmaanrat S. Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate
ligament reconstruction: a randomized controlled trial. BMC Musculoskelet Disord. 2010;11:246.
4. Celik JB, Gormus N, Gormus ZI, Okesli S, Solak H. Preoperative analgesia management with rofecoxib in thoracotomy patients. J Cardiothorac Vasc Anesth. 2005;19(1):67-70.
5. Duellman TJ, Gaffigan C, Milbrandt JC, Allan DG. Multi-modal, pre-emptive analgesia decreases the length of hospital stay following total joint arthroplasty. Orthopedics. 2009;32(3):167.
6. Horattas MC, Evans S, Sloan-Stakleff KD, Lee C, Snoke JW. Does preoperative rofecoxib (Vioxx) decrease postoperative pain with laparoscopic cholecystecomy. Am J Surg. 2004;188(3):271-276.
7. Al-Mujadi H, A-Refai AR, Katzarov MG, Dehrab NA, Batra YK, Al-Qattan AR. Preemptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery. Can J Anaesth. 2006;53(3):268-273.
8. Chiu TW, Leung CC, Lau EY, Burd A. Analgesic effects of preoperative gabapentin after tongue reconstruction with the anterolateral thigh flap. Hong Kong Med J. 2012;18(1):30-34.
9. Menda F, Ko €ner O, Sayın M, Ergenog lu M, Ku€çu
€kaksu S, Aykaç B. Effects of single-dose gabapentin on postoperative pain and morphine consumption after cardiac surgery. J Cardiothorac Vasc Anesth.
2010;24(5):808-813.
10. Montazeri K, Kashefi P, Honarmand A. Pre-emptive gabapentin significantly reduces postoperative pain and morphine demand following lower extremity orthopedic surgery. Singapore Med J. 2007;48(8):
748-751.
11. Moore A, Costello J, Wieczorek P, Shah V, Taddio A, Carvalho J. Gabapentin improves postcesarean delivery pain management: a randomized, placebo-controlled trial. Anesth Analg. 2011;112(1):167-173.
12. Pandey CK, Sahay S, Gupta D, et al. Preemptive gabapentin decreases postoperative pain after lumbar discoidectomy. Can J Anaesth. 2004;51(10):986-989.
AORN Journal j 105.e8

13. Parikh HG, Dash SK, Upasani CB. Study of the effect of oral gabapentin used as preemptive analgesia to attenuate post-operative pain in patients undergoing abdominal surgery under general anesthesia. Saudi
J Anaesth. 2010;4(3):137-141.

www.aornjournal.org
14. Srivastava U, Kumar A, Saxena S, Mishra AR, Saraswat N, Mishra S. Effect of preoperative gabapentin on postoperative pain and tramadol consumption after minilap open cholecystectomy: a randomized
double-blind, placebo-controlled trial. Eur J Anaesthesiol. 2010;27(4):331-335.