The Efficacy of NSAIDs, COX-2 Inhibitors and Gabapentin ... · management, would play a significant role in preemptive analgesic interventions. Preoperative nurses can ensure that

The Efficacy of NSAIDs, COX-2 Inhibitors and Gabapentin for Preemptive Analgesia

By

Elisa Brunetto, Eman Dahmani, Jola Janaqi Forthoffer, and Samantha Russo

A literature review

submitted in partial fulfillment of the requirements for the degree of

MASTERS OF SCIENCE IN NURSING

2012

Oakland University

School of Nursing

Rochester, Michigan

APPROVED BY:

__________________________________

Faculty Research Advisor Date

PREEMPTIVE ANALGESIA 2

Abstract

The objective of this literature review was to evaluate the efficacy of oral nonsteroidal

anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors (COX-2) and gabapentin as

preemptive oral analgesics. We conducted an electronic literature search by including the

Cumulative Index to Nursing and Allied Health, MEDLINE, PubMED and OVID databases. For

COX-2 inhibitors and gabapentin, fourteen studies were reviewed with a date range between

2002 and 2012. Due to the lack of current research on NSAIDs, significant studies greater than

10 years old were included for review with ranging dates from 1983 to 2010. All of the reviewed

studies were randomized controlled trials. Our goal was to assess postoperative pain scores and

opioid consumption in patients who had received preemptive oral analgesia with one of the

aforementioned drugs. The reviewed results indicated that postoperative pain scores and opioid

consumption was lower in patients who had received preoperative administration of COX-2

inhibitors and gabapentin. However, postoperative administration of NSAIDs resulted in

significantly greater pain relief when compared with preoperative administration. Based on these

findings we would recommend the use of gabapentin and COX-2 inhibitors as preemptive

analgesics, while NSAIDs administration should be implemented postoperatively.

Keywords: preemptive analgesia, postoperative analgesia, preincisional analgesia,

NSAIDs, cyclooxygenase-2 inhibitors, gabapentin


The Efficacy of NSAIDs, COX-2 Inhibitors, and Gabapentin for Preemptive Analgesia

The concept of preemptive analgesia was pioneered by Crile in 1913, who based his

assumptions on clinical observations that suggested analgesic interventions were more effective

if administered prior to a surgical procedure (Dahl & Moiniche, 2004). Subsequent experimental

evidence suggested that it may be possible to decrease or prevent the neurophysiologic and

biochemical effects of noxious input to the central nervous system (CNS) rather than initiating

treatment after occurrence of these events (Dahl & Moiniche, 2004). Preemptive analgesia is an

antinociceptive treatment applied before tissue injury to prevent peripheral and central

sensitization (Kelly, Ahmad, & Brull, 2001). By decreasing sensitization, preemptive analgesia is

thought to decrease the incidence of postoperative hyperalgesia and allodynia (Ong, Lirk,

Seymour, & Jenkins, 2005). This phenomenon is thought to reduce the magnitude and duration

of postoperative pain by administering an analgesic treatment prior to a noxious stimulus as

compared with post-stimuli analgesic administration.

Acute nociceptive signals associated with tissue damage initiate alterations in the

peripheral and central pain pathways. Primary afferent neurons detect noxious stimuli from the

periphery and through transduction conduct pain signals to the dorsal horn of the CNS. An

inflammatory response occurs with tissue damage leading to the release of chemical mediators

such as substance P, histamine, bradykinin, and prostaglandin. This leads to peripheral

sensitization caused by increased conduction of nociceptive stimuli to the CNS. Central

sensitization occurs as a result of amplification of nociceptive neurons in the dorsal horn of the

CNS (Dahl & Moiniche, 2004).

According to the International Association for the Study of Pain (2011), pain is “an

unpleasant sensory and emotional experience associated with actual or potential tissue damage,


or described in terms of such damage” (p. 1). Acute postoperative pain is typically caused by

mechanical, chemical, and thermal nociceptive stimuli. In addition, severe acute pain is a risk

factor for the development of chronic pain. Effective postoperative pain management increases

patient satisfaction, improves patient outcomes, and reduces cost of care (Heck & Mitchell,

2005). Recent studies have shown that acute postoperative pain continues to be undermanaged

even as surgery and anesthesia have become safer (Peng, Wijeysundera, & Li, 2007). Therefore,

there has been increasing emphasis towards the improvement of secondary outcomes including

postoperative pain control. A number of clinical trials have suggested that preemptive analgesia

leads to a decrease in postoperative pain, less total analgesic consumption, and improved patient

comfort (Ong et al., 2005). This would be clinically beneficial to health care providers that are

involved in the management of acute postoperative pain, if the evidence supports the use of

preemptive analgesia.

Clinical nurses, as part of the collaborative team responsible for pain assessment and

management, would play a significant role in preemptive analgesic interventions. Preoperative

nurses can ensure that preemptive analgesics are administered in a timely manner. Certified

registered nurse anesthetists (CRNA) could initiate preoperative analgesic orders as well as

ensure administration occurs prior to surgical incision. Postoperative care nurses would be

responsible for evaluating the outcomes of preemptive analgesia, and if effective this may

increase nursing staff productivity.

The efficacy of preemptive analgesia is controversial, and the optimal technique has not

been clearly established (Moiniche, Kehlet, & Dahl, 2002). Although animal studies have been

very convincing in showing a positive benefit with preemptive analgesia; human clinical trials

remain inconsistent regarding its efficacy (Ong et al., 2005). This inconsistency may be due to


factors such as a lack of uniformity in defining preemptive analgesia; the variation in

methodology of clinical trials; timing of the pre-stimulus versus the post-stimulus dose; and the

lack of an objective standard for pain measurement (Heck & Mitchell, 2005).

Clinical trials on preemptive analgesia have evaluated different analgesics using a variety

of administration routes. Multiple randomized controlled trials and systematic reviews have

indicated minimal efficacy with preemptive analgesic opioids and N-methyl-D-aspartate

antagonists (Kissin, 2000). A majority of clinical studies and reviews on preemptive analgesia

focus individually or in combination with intravenous, intramuscular, and neuraxial modes of

administration. The literature indicates a potential benefit with preemptive selective and

nonselective NSAIDs, and gabapentin. This literature review will evaluate the efficacy of

preemptive oral NSAIDs, COX-2 inhibitors, and gabapentin. Although the bioavailability of

these drugs varies, we chose to review select oral medications as they share a similar

pharmacokinetic profile.

Electronic literature searches were conducted using the Cumulative Index to Nursing and

Allied Health, MEDLINE, PubMED, and OVID databases with restrictions to publications in

English. A broad free text search was used with the following terms: preemptive analgesia,

postoperative analgesia, and preincisional analgesia. The retrieved results were then limited to

oral NSAIDs, COX-2 inhibitors, and gabapentin. Articles that were included in this literature

review consist of clinical trials limited to adult patients that compared the difference in

postoperative pain scores and opioid consumption between control and treatment groups when

preemptive analgesic measures were initiated.


NSAIDs

NSAIDs are one of the most popular drugs used to relieve pain, fever and inflammation.

In the United States more than 70 million prescriptions of NSAIDs are written annually, while

over the counter purchases reach a consumption of 30 billion doses (Wiegand & Lawrence,

2010). NSAIDs are of particular interest to the practice of anesthesia because unlike opioids,

they do not cause respiratory depression, nausea, sedation and urinary retention.

The concept of using NSAIDs as preemptive analgesics lies in their peripheral and

central mechanism of action. NSAIDs inhibit the enzymes called cyclooxygenases leading to a

decreased production of prostaglandins. Prostaglandins are primary chemicals produced by the

body that carry out a variety of important chemical and biological body functions. Up to date

there are a total of five primary prostanoids and 9 prostaglandin receptors present in the human

body, all of which have specific functions and responses (Sundy, 2005). By inhibiting the action

of cyclooxygenase 1 and 2 (COX-1 & COX-2) and preventing the production of prostaglandins,

NSAIDs decrease inflammation, vasodilatation, capillary permeability, pain and fever (Sundy,

2005). A better understanding of the mechanism of action of NSAIDs sparked interest to

evaluate if NSAIDs could be used for preemptive analgesia and led to several studies and

literature reviews.

Our literature search conducted on NSAIDs recognized only 5 suitable studies based on

the criteria identified. Out of the 5 studies, 4 analyzed the use of NSAIDS as preemptive

analgesic on oral surgeries and one analyzed NSAIDs’ preemptive effectiveness in patients

undergoing a mastectomy. The drugs utilized for the studies were ibuprofen and ketoprofen. Of

the five identified studies only one study supported the use of ibuprofen preoperatively for

postoperative pain relief when compared with the standard therapy. This study was conducted by


Dionne, Campbell, Cooper, Hall and Buckingham (1983) and included 107 dental patients

undergoing removal of impacted third molars. A comparison was conducted between

preoperative administration of ibuprofen, placebo, acetaminophen and acetaminophen plus

codeine and the findings indicated that preoperative ibuprofen administration was superior in

providing postoperative pain relief (Dionne et al, 1983).

In 1997, a study evaluated the effectiveness of ibuprofen-arginine as a preemptive

analgesic to reduce post-mastectomy pain syndrome (Lakdja, Dixmerias, Bussieres, Funrouge, &

Lobera, 1997). The study was a double blinded randomized study utilizing 30 patients who were

divided into two equal groups. The first group received ibuprofen 90 minutes preoperatively, 2

hours postoperatively and every 8 hours afterwards for 32 hours. The second group received

placebo during the same times. It was found that ibuprofen was not effective in decreasing

postoperative pain during the first month, nor the occurrence of post-mastectomy pain syndrome.

The effectiveness of ketoprofen as a preemptive analgesic was studied by Kaczmarzyk,

Wichlinski, Stypulkowska, Zaleska and Woron (2010) in patients undergoing third molar

surgery. A total of 96 patients were included in the study who were then randomly divided into

pretreatment, post-treatment and no treatment groups. Ketoprofen was given 60 minutes

preoperatively to the pretreatment group and 60 minutes postoperatively to the post-treatment

group, while a placebo was administered to the no treatment group. The results concluded that

preoperative and postoperative administration of ketoprofen resulted in delayed pain

development when compared with the placebo group; however, postoperative ketoprofen

administration was more effective in providing pain control than preoperative administration.

In 1992, Vogel, Desjardins and Major compared the preoperative and postoperative

efficacy of ibuprofen administration during periodontal surgery. The design of the study was


randomized, double blinded and included 60 patients. The results concluded that postoperative

administration was superior at providing greater pain relief as well as decreased pain intensity.

Another study also looked at the best administration time for ibuprofen in providing

postoperative pain relief in patient undergoing surgical removal of mandibular third molar.

Eighty patients participated in this randomized, controlled study conducted by Jung et al. (2005).

The participants were divided into pretreatment group, post-treatment group and no treatment

group. The post-treatment group demonstrated the greatest pain relief when compared to the

other two groups.

In consideration of the derived findings from the reviewed studies, the use of NSAIDs

would not be a beneficial method for preemptive analgesia; however, when administered

postoperative NSAIDS provided significant pain relief and decreased intensity. Given that

currently NSAIDs are not generally used as a method for preemptive analgesia no change in

practice is recommended.

Cyclooxygenase-2 Inhibitors

Activation of COX-2 by surgical trauma produces hyperalgesia and increases the

sensitivity of peripheral nociceptors (Reuben, Bhopatkar, Maciolek, Wanda, & Sklar, 2002).

NSAIDs inhibits both the COX-1 and COX-2 enzyme, which along with the desired effects of

providing pain relief and inflammation reduction, may lead to the inhibition of normal platelet

function and gastrointestinal toxicity (Boonriong, Glabglay, Nimmaanrat, & Tangtrakulwanich,

2010). The selectivity of COX-2 inhibitors accounts for the lack of gastrointestinal and platelet

function side effects, thus making it an excellent choice for post operative pain management.

COX-2 inhibitors commonly used include celecoxib, rofexocib, valdecoxib, etoricoxib, and

lumiracoxib (Kaye, Baluch, Kaye, Ralf, & Lubarsky, 2008). Recent research shows that the use


of COX-2 inhibitors as a preemptive analgesic improves post operative pain and decreases the

overall use of opioids following surgery (Celik, Gormus, Gormus, Okesli, & Solak, 2005). In

this review, clinical studies supported the efficacy of using COX-2 inhibitors as a preemptive

analgesic for multiple procedures including thoracotomies, arthroscopic knee surgeries, and

laparoscopic cholecystectomies.

Sandhu, Paiboonworachat, and Ko-iam (2011) research was a double-blinded randomized

controlled trial involving laparoscopic cholecystectomy patients. A sample size of 120 patients

were enrolled with half receiving 120 mg etoricoxib plus diazepam and the other half receiving

placebo plus diazepam prior to surgery. The postoperative VAS scores in the etoricoxib group

were significantly decreased overall with an additional reduction in oral analgesic usage

postoperatively (Sandhu, Paiboonworachat, & Ko-iam, 2011). In a similar study by Horattas,

Evans, Sloan-Stakledd, Lee, and Snoke (2004), 116 patients undergoing laparoscopic

cholecystectomies received 50 mg of rofecoxib or a placebo preoperatively. This study also

found a significant decrease in narcotic usage as well as an increase in activity level

postoperatively (Horattas, Evans, Sloan-Stakleff, Lee, & Snoke, 2004).

While the effects of preemptive COX-2 inhibitors on laparoscopic procedures is evident,

the results for orthopedic procedures are not as convincing. Research conducted by Duellman,

Gaffign, Milbrant, and Allan (2009) involved patients undergoing total joint arthroplasty. The

sample consisted of 69 patients who received a post operative patient controlled analagesia

(PCA) pump and 58 patients who received 200 mg of celecoxib preoperatively and then every 12

hours postoperatively during their hospitalization. The PCA group required significantly more

morphine (17.7 mg vs. 7.2 mg average dose), had a longer length of hospital stay (3.7 vs. 2.73

days on average), as well as a decrease in participation of postoperative rehabilitation (Duellman,


Gaffigan, Milbrandt, & Allan, 2009) when compared to the group who received the PCA and

celecoxib. A study by Boonriong, Tangtrakulwanich, Glabglay, and Nimmaanrat (2010) found

mixed results for patients undergoing an anterior cruciate ligament reconstruction. The sample

of 102 patients were divided into three groups with the first receiving etoricoxib 120 mg

preoperatively, the second receiving 400 mg preoperatively, and the third group receiving a

placebo. While the etoricoxib group had significant less pain intensity postoperatively, the

celecoxib group showed no significant difference from the placebo group (Boonriong,

Tangtrakulwanich, Glabglay, & Nimmaanrat 2010).

The last procedure that studied the efficacy of preemptive COX-2 inhibitors use was for

patients undergoing a thoracotomy. Celik, Gormus, Gormus, Okesli, and Solak (2005)

conducted a double-blind, placebo-controlled, prospective study with 60 patients giving half 50

mg of rofecoxib preoperatively while the other half received a placebo. The researchers found

that patients who received rofexocib preoperatively had a significant decrease in opioid

requirements compared to the placebo group (Celik, Gormus, Gormus, Okesli, & Solak, 2005).

Clearly evidence shows that regardless of the surgical procedure, COX-2 inhibitors given

preoperatively have positive effects on postoperative pain scores, opioid use, and length of

hospital stay.

Gabapentin

Historically, the mainstay for postoperative pain management has been opioid, although

side effects including nausea, vomiting, pruritis and respiratory depression may limit their use.

Additionally, NSAIDs are commonly used as adjuncts to reduce pain postoperatively in minor

surgery, but their use may be limited in patients with bleeding diathesis, renal or gastrointestinal

problems (Chiu, Leung, Lau, & Burd, 2012). Therefore, recent studies have explored alternative


approaches to pain control. Gabapentin, a structural analog of gamma aminobutyric acid, is an

antiepileptic drug for partial seizures whose role in pain management has been limited to

neuropathic pain, diabetic neuropathy, post-herpatic neuralgia, and reflex sympathetic dystrophy

(Parikh, Dash, & Upasani, 2010). Recently, an increasing number of studies have suggested that

gabapentin, when used preemptively, has a beneficial effect on both pain scores and

postoperative opioid consumption (Srivasta et al., 2010).

In clinical studies gabapentin has exhibited a reduction in hypersensitivity induced by

inflammation and injury. In addition, it has demonstrated an inhibitory effect on not only the

development but also on preexisting secondary allodynia and hyperalgesia resulting from central

sensitization, while having no effect on pain transmission in normal skin (Pandey et al., 2004).

These effects, which are comparable to those observed with Remifentanil, are of considerable

importance because though pathological pain is reduced, other protective nociceptive

mechanisms remain intact (Pandey et al., 2004). Additionally, it has been shown that the

combination of gabapentin with other antinociceptive drugs produce a synergistic action

(Srivastava et al., 2010).

While the exact mechanism of action of gabapentin is not clearly understood, it appears

there may be multiple mechanisms. It has been proven that gabapentin does not act via opioid

mechanisms, instead it binds to alpha-2-delta subunits of voltage-gated calcium channels, located

presynaptically in the doral root ganglia (Menda et al., 2010). Subsequently, this reduces the

release of excitatory neurotransmitters involved in pain pathways from sensory neurons

including glutamate, noradrenaline, and substance P (Chiu et al., 2012; Menda et al., 2010).

Additional proposed mechanisms of pain reduction from gabapentin include an increase in the

concentration and rate of synthesis of GABA in the brain, modulation of glutamate receptors,


inhibition of voltage activated sodium channels, and an increase serotonin concentrations

(Menda et al., 2010; (Montazeri, Kashefi, & Honarmand, 2007). Therefore, it is thought that

preoperative dosing of gabapentin exerts its analgesic effects by preemptively decreasing the

spinal cord excitation caused by surgical trauma (Moore et al., 2011).

In order to determine if preoperative gabapentin was effective in reducing postoperative

pain and whether it showed evidence of opioid sparing effects eight recent studies were

evaluated between 2004 and 2012. Each study reviewed a different type of surgery, as well as

multiple gabapentin dosages and timing. The variety of surgeries comprised in this review

include thyroidectomy, tongue reconstruction with anterolateral thigh flap, cardiac, lower

extremity orthopedic, cesearean section, lumbar discectomy, abdominal and minilap open

cholecystectomy. Of the eight studies, seven were randomized, placebo controlled studies (Al-

Mujadi et al., 2006; Menda et al., 2010; Montazeri, Kashefi, & Honarmand, 2007; Moore et al.,

2011; Pandey et al., 2004; Parikh, Dash, & Upasani, 2010; Srivastava et al., 2010), where as one

was considered a non randomized retrospective cohort study (Chiu et al., 2012).

In all eight studies, patients in the gabapentin group received it as a single preoperative

dose ranging between 300 and 1200 mg. To facilitate analysis of the eight studies three

subgroups were created based on dosages: (1) group that received 300 mg preoperatively; (2)

group that received 600 mg preoperatively; and (3) group that received 1200 mg preoperatively.

In each study, pain intensity using VAS scores, analgesic consumption and rescue analgesia

requirement were analyzed. In addition to postoperative pain scores and opioid consumption, all

studies recorded and analyzed the occurrence of side effects possibly related to gabapentin

administration. The most commonly reported adverse effects were nausea, vomiting, sedation,


dizziness, respiratory depression, and pruritis. Due to the nature of the literature review side

effects were not discussed.

Gabapentin 300 mg Preoperatively

Two studies using a dose of 300 mg of Gabapentin preoperatively were included in our

analysis. In both studies patients in the treatment group had significantly lower VAS scores at

all time intervals measured in the first 24 hours. Although the two studies utilized different

opioids for postoperative pain control, Fentanyl (Montazeri, Kashefi, & Honarmand, 2007)

versus Morphine (Pandey et al., 2004), both treatment groups required less drug consumption in

the first 24 hours postoperatively. The study conducted by Montazeri, Kashefi and Honarmand

reported the total 24 hour morphine consumption to be on average 15.43 mg in the gabapentin

group versus 17.94 mg in the control group. The research also showed a significant difference

between the two groups in the first time of patient demand for morphine administration after

surgery (31.57 minutes in gabapentin group versus 26.71 minutes in the placebo group)

(Montazeri, Kashefi, & Honarmand, 2007). Similarly, Pandey et al. (2004) reported in their

study that total Fentanyl consumption after surgery in the first 24 hours on average was

significantly less in the gabapentin group (233.5 mg) versus the control group (359.6 mg).

Furthermore, Montazeri, Kashefi, and Honarmand concluded that there was no difference in

recovery duration between the two groups.


Four studies using a dose of 600 mg of gabapentin preoperatively were included in this

analysis. In all four studies the pain scores in the treatment groups were significantly lower than

the control groups for the first 24 hours postoperatively at both rest and with movement or


coughing (Menda et al., 2010; Moore et al., 2011; Parikh, Dash, & Upasani, 2010; Srivastava et

al., 2010). Srivastava et al. (2010) also assessed pain scores beyond 24 hours up to 48 hours and

showed that pain scores at 48 hours were comparable in both treatment and control groups. For

rescue analgesia two studies used Morphine (Menda et al., 2010; Moore et al., 2011), one used

Diclofenac (Parikh, Dash, & Upasani, 2010) and Tramadol was used in the other (Srivastava et

al., 2010). In three of the studies the total drug consumption for postoperative pain and need for

rescue analgesia was lower in the gabapentin groups (Menda et al., 2010; Parikh, Dash, &

Upasani, 2010; Srivastava et al., 2010). In fact Menda et al. (2010) showed that the total

morphine consumption in the first 24 hours postoperatively was 57% lower in the gabapentin

group versus the control group. The fourth study by Moore et al. (2011) did not show a

difference in postoperative opioid consumption but did find that patient pain and satisfaction

scores to be higher in the gabapentin group at both six and 12 hours (Moore et al., 2011).


Two studies using a dose of 1200 mg of gabapentin preoperatively were included in our

analysis. Both studies showed postoperative pain assessment scores to be lower in the

gabapentin group versus the control group in the first 24 hours (Al-Mujadi et al., 2006; Chiu et

al., 2012). For postoperative analgesia both studies utilized Morphine and indicated that the

consumption of Morphine in the gabapentin groups were both significantly lower when

compared to the control groups (Al-Mujadi et al., 2006; Chiu et al., 2012).

We consider this review to be evidence of the efficacy of preemptive gabapentin for

control of acute postoperative pain. The potential benefit would be better postoperative pain

control in a multitude of surgeries.


Discussion and Implications

In our review of the literature we consider preemptive analgesia beneficial with the

administration of oral COX-2 inhibitors and gabapentin and recommend their administration for

select surgical procedures. However, based on our review of NSAIDs, there appears to be no

clinical benefit to their use as a preemptive analgesic. We suggest that nurses incorporate the use

of preemptive COX-2 inhibitors and gabapentin into their practice. To facilitate this into

practice, nursing administration and clinical nurse educators can establish preoperative protocols

to guide clinical nursing staff on its implementation.

Specific barriers must be considered when facilitating such a change in perioperative

practice. Patient and or surgeon refusal may be of particular concern due to the potential

adverse effects of the of gabapentin or COX-2 inhibitors, although recent studies have shown

favorable safety profiles for both drugs. The side effects of Gabapentin include but are not

limited to nausea, vomiting, sedation, pruritus, constipation, urinary retention, and dizziness

(Srivastava et al., 2010). Additionally, potential prothrombotic effects of COX-2 inhibition and

delayed wound healing must be considered (Cicconetti, Bartoli, Ripari, & Ripari, 2004).

Contraindications to administration of either of these drugs must also be considered for every

patient, as well as the drug to drug interactions that can occur.

Once the practice has been changed, the most reliable way to assess the benefits of the

change is to assess the pain scores of the patients 24 hours postoperatively. Since pain scores are

already assessed in the inpatient setting, this would be an excellent approach to evaluate the

effectiveness of preemptive analgesia without increasing cost. Methods to assess the pain scores

would be dependent on the hospitals chosen policy for pain assessment and most commonly

include a VAS score or a functional pain assessment. To assess the overall efficacy of the


change, a quarterly pain audit of the patients who receive those agents preoperatively should be

completed.

The use of preoperative use of gabapentin and Cox-2 inhibitors has demonstrated to be a

valid method for reduction of postoperative pain in a diverse type of surgeries. Further studies

should be conducted to improve incorporation of these drugs into practice. Future research can

focus on the role of timing administration, long term pain reduction and cost effectiveness. In

addition, future studies can look at the effectiveness of co-administration of these drugs as

preemptive analgesics for specific surgeries


References

Al-Mujadi, H., A-Refai, A.R., Katzarov, M.G., Dehrab, N.A., Batra, Y.K, & Al-Qattan, A.R.

(2006). Preemptive gabapentin reduces postoperative pain and opioid demand following

thyroid surgery. Canadian Journal of Anesthesia, 53(3), 268-273. doi:

10.1007/BF03022214

Boonriong, T., Tangtrakulwanich, B., Glabglay, P., Nimmaanrat, S. (2010). Comparing

etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients

undergoing arthroscopic anterior cruciate ligament reconstruction: A randomized

controlled trial. BMC Musculoskeletal Disorders, 11, 246. doi: 10.1186%2F1471-2474-

11-246

Celik, J. B., Gormus, N., Gormus, Z. I., Okesli, S., & Solak, H. (2005). Preoperative analgesia

management with rofecoxib in thoracotomy patients. Journal of Cardiothoracic and

Vascular Anesthesia, 19(1), 67-70.

Chiu, T. W., Leung, C. C. H., Lau, E. Y., & Burd, A. (2012). Analgesic effects of preoperative

gabapentin after tongue reconstruction with the anterolateral thigh flap. Hong Kong

Medical Journal, 18(1), 30-34.

Dahl, J. B., & Moiniche, S. (2004). Pre-emptive analgesia. British Medical Bulletin, 71, 13-27.

Dionne, A. R., Campbell, A. R., Cooper, A. S., Hall, L. D., & Buckingham, B. (1983).

Suppression of postoperative pain by preoperative administration of ibuprofen in

comparison to placebo, acetaminophen, and acetaminophen plus codeine. Journal of

Clinical pharmacology, 23, 37-43.


Duellman, T. J., Gaffigan, C., Milbrandt, J. C., & Allan, G. (2009). Multi-modal, pre-emptive

analgesia decreases the length of hospital stay following total joint arthroplasty.

Orthopedics, 32(3), 167.

Horattas, M. C., Evans, S., Sloan-Stakleff, K. D., Lee, C., & Snoke, J. P. (2004). Does

preoperative rofecoxib decrease postoperative pain with laparoscopic cholecystectomy?

The American Journal of Surgery, 188, 271-276. doi: 10.1016%2Fj.amjsurg.2004.06.007

Heck, U., & Mitchell, V. D. (2005). Preemptive analgesia: Physiology and clinical studies. In H.

T. Benzon, S. N. Raja, R. E. Mallou, S. S. Lui, & S. M. Fishman (Eds.), Essentials of

pain medicine and regional anesthesia (2nd ed., pp. 229-234). Philadelphia:PA:

Elsevier.

International Association for the Study of Pain. (2011). IASP Taxonomy. Retrieved from

http://www.iasp-pain.org/Content/NavigationMenu/GeneralResourceLinks

/PainDefinitions/default.htm

Jung, Y., Kim, M., Um, Y., Park, H., Lee, E., & Kang, J. (2005). The effects on postoperative

oral surgery pain by varying NSAID administration time: Comparison on effect of

preemptive analgesia. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and

Endodontology, 100(5), 559-563. doi: org/10.1016%2Fj.tripleo.2005.02.065

Kaczmarzyk, T., Wichlinski, J., Stypulkowska, J., Zaleska, M., & Woron, J. (2010). Preemptive

effect of ketoprofen on postoperative pain following third molar surgery: A prospective,

randomized, double-blinded clinical trial. International Journal of Oral Maxillofacial

Surgery, 39, 647-652.


Kaye, A. D., Baluch, A., Kaye, A. J., Ralf, G., & Lubarsky, D. (2008). Pharmacology of

cyclooxygenase-2 inhibitors and preemptive analgesia in acute pain management.

Current Opinion in Anesthesiology, 21, 439-445. doi: 10.1097%2FACO.

0b013e3283007e8d

Kelly, D. J.,Ahmed, M., & Brull, S. J. (2001). Preemptive analgesia I: Physiological pathways

and pharmacological modalities. Canadian Journal of Anesthesia, 48(10), 1000-1010.

Kissin, I. (2000). Preemptive analgesia. Anesthesiology, 93(4), 1138-1143. doi: 10.1097%

2F00000542-200010000-00040

Lakdja, F., Dixmerias, F., Bussieres, D., Fonrouge, J., & Lobera, A. (1997). Preemptive

analgesia on postmastectomy pain syndrome with ibuprofen-arginine. Bulletin du

Cancer, 84(3), 259-263.

Menda, F., Köner, O., Sayın, M., Ergenoğlu, M., Küçükaksu, S., & Aykaç, B. (2010). Effects of

single-dose gabapentin on postoperative pain and morphine consumption after cardiac

surgery. Journal of Cardiothoracic and Vascular Anesthesia, 24(5), 808-813. doi:

10.1053/j.jvca.2009.10.023

Moiniche, S., Kehlet, H., & Dahl, B. D. (2002). A qualitative and quantitative systematic review

of preemptive analgesia for postoperative pain relief: The role of timing of analgesia.

Anesthesiology, (96)3, 725-741.

Montazeri, K., Kashefi, P., & Honarmand, A. (2007). Pre-emptive gabapentin significantly

reduces postoperative pain and morphine demand following lower extremity orthopedic

surgery. Singapore Medical Journal, 48(8), 748-751.

Moore, A., Costello, J., Wieczorek, P., Shah, V., Taddio, A., & Carvalho, J.C.A. (2011).

Gabapentin improves postcesarean delivery pain management: A randomized, placebo


controlled study. Anesthesia & Analgesia, 112(1), 167-173. doi: 10.1213/

ANE.0b013e3181fdf5ee

Ong, C. K. S., Lirk, P., Seymour, R. A., & Jenkins, B. J. (2005). The efficacy of preemptive

analgesia for acute postoperative pain management: A meta-analysis. Anesthesia and

Analgesia, 100, 757-773.

Pandey, C. K., Sahay, S., Gupta, D., Ambesh, S. P., Singh, R.B., Raza, M., Singh, P.B. (2004).

Preemptive gabapentin decreases postoperative pain after lumbar discoidectomy.

Canadian Journal of Anesthesia, 51(10), 986-989. doi: 10.1007/BF03018484

Parikh, H. G., Dash, S. K., & Upasani, C. B. (2010). 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 Journal of Anesthesia, 4(3), 137-141.

doi: 10.4103/1658-354X.71409

Peng, P. W. H., Wijeysundera, D. N., & Li, C. C. F. (2007). Use of gabapentin for perioperative

pain control – A meta-analysis. Pain Research & Management: The Journal of the

Canadian Pain Society, 12(2), 85-92.

Reuben, S. S., Bhopatkar, S., Maciolek, H., Wanda, J., & Sklar, J. (2002). The preemptive

analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Ambulatory

Anesthesia, 94, 55-59.

Sandhu, T., Paiboonworachat, S., & Ko-iam, W. (2011). Effects of preemptive analgesia in

laparoscopic cholecystectomy: A double-blind randomized controlled trial. Surgical

Endoscopy, 25, 23-27. doi: 10.1007%2Fs00464-010-1122-y

Srivastava, U., Kumar, A., Saxena, S., Mishra, A. R., Saraswat, N., & Mishra, S. (2010). Effect

of preoperative gabapentin on postoperative pain and tramadol consumption after minilap


open cholecystectomy: A randomized double-blind, placebo-controlled trial. European

Journal of Anesthesiology, 27(4), 331-335. doi: 10.1097/EJA.0b013e328334de85

Sundy, J. S. (2005). Nonsteroidal anti-inflammatory drugs. In W. J. Koopman, & L. W.

Moreland (Eds.), Arthritis and allied conditions: A textbook of rheumatology (15th ed.)

(pp 680-704). Philadelphia, PA: Lippincott Williams & Wilkins.

Vogel, I. R., Desjardins J. P., & Major, V. K. (1992). Comparison of presurgical and immediate

postsurgical ibuprofen on postoperative periodontal pain. Journal of Periodontology,

63(11), 914-918. doi: 10.1902%2Fjop.1992.63.11.914

Wiegand, T. J., & Lawrence, R. A. (2010). Nonsteroidal anti-inflammatory agent toxicity.

Retrieved from http://emedicine.medscape.com/article/816117-overview

Documents

The Efficacy of NSAIDs, COX-2 Inhibitors and Gabapentin ... · management, would play a significant role in preemptive analgesic interventions. Preoperative nurses can ensure that