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Ismig.irAnesth Pain Med. 2015 February; 5(1): e22372. DOI: 10.5812/aapm.22372 Published online 2015 February 1. The Effect of Gabapentin on Reducing Pain After Laparoscopic Gastric Bypass Surgery in Patients With Morbid Obesity: A Randomized Clinical Trial Valiollah Hassani 1,2; Abdolreza Pazouki 1; Nasim Nikoubakht 1,2,*; Shahla Chaichian 3,4,5; Azadeh Sayarifard 6; Ali Shakib Khankandi 21Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran 2Department of Anesthesiology and Pain Medicine, Rasoul-Akram Medical Center, Iran University of Medical Sciences, Tehran, Iran 3Minimally Invasive Techniques Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran 4Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran 5Pars Advanced Medical Practice Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran 6Center for Academic and Health Policy, Tehran University of Medical Sciences, Tehran, Iran*Corresponding author: Nasim Nikoubakht, Department of Anesthesiology and Pain Medicine, Rasoul-Akram Medical Center, Iran University of Medical Sciences, Tehran, Iran. Tel/ Fax: +98-2166509059, E-mail: [email protected] Received: July 28, 2014; Revised: November 26, 2014; Accepted: December 13, 2014
Background: Pain after laparoscopic gastric bypass surgery (LGBP) is a major problem. Gabapentin is an anticonvulsant drug that can be
effective in postoperative pain control.
Objectives: This study examined the effect of preoperative administration of gabapentin on reducing pain after LGBP in patients with
Patients and Methods: This randomized clinical trial was performed in Hazrat Rasoul Akram Medical Center in Tehran. A total of 60
patients undergoing LGBP were randomly allocated into two groups; one group received 100 mg of oral gabapentin and the other group received placebo. Pain was evaluated at recovery time, and at the first, second, fourth and sixth hour of surgery by visual analog scale. The number and dose of opioid use after surgery and incidence of postoperative complications, such as nausea and vomiting, agitation, and headache, were also recorded.
Results: The mean pain score in the group receiving gabapentin was significantly lower than the placebo group (P < 0.001). Indications
and dose of opioid consumption between the two groups were not statistically significant. Incidence of nausea/vomiting (P = 0.028) as well as agitation (P = 0.037) was significantly lower in the gabapentin group.
Conclusions: Administration of gabapentin before surgery can reduce pain after LGBP. Furthermore, it is not accompanied by significant
short-term adverse effects.
Keywords:Gabapentin; Postoperative Pain; laparoscopic Gastric Bypass Surgery; Morbid Obesity Morbid obesity is a pandemic disease and its preva- faction. Good control of postoperative pain after laparo- lence, accompanied by a rapid increase, is higher in Iran scopic Roux-en-Y gastric bypass surgery is yet a challeng- than developed countries (1-5). Because it is accompa- ing issue and a concern for anesthesiologists (9-11). Local nied by various diseases such as type II diabetes melli- anesthetics, paracetamol, nonsteroidal anti-inflamma- tus, hypertension, cardiovascular diseases, asthma, and tory drugs, and intravenous morphine, patient-con- sleep apnea, it leads to substantial economic and health trolled analgesia pump are used in patients undergoing costs (6). Today, laparoscopic Roux-en-Y gastric bypass laparoscopic surgery for pain control (9). Gabapentin surgery (LGBP) is used for weight loss and reducing is a gamma-aminobutyric acid (GABA) analogue and its the intolerable symptoms of obesity (7, 8). Among nu- mechanism of actions are binding to the alpha-2 delta merous postoperative complications, pain is the main (α2-δ) subunit of the presynaptic voltage gated-calcium adverse event experienced by patients. Good control of channels and inhibiting calcium release. It also has in- postoperative pain in patients is an important factor teraction with N-methyl-D-aspartate (NMDA) receptor for reducing early postoperative complications such as and causes reduction in substance P and glutamate, pulmonary embolism, deep vein thrombosis, ileus, and which has preventive effects on central nervous system respiratory infections, and for decreasing length of stay, excitability by this mechanism (12). Thus, several studies lowering costs, and ultimately increasing patient satis- have been conducted to determine the efficacy of gaba- Copyright 2015, Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM). This is an open-access article distributed under the terms of the Creative Com- mons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
Hassani V et al. pentin in treatment of pain after surgery and assessing diogram, pulse oximetry, and blood pressure measur- the role of gabapentinoids as an analgesic in acute pain ing. Patients were hydrated with infusion of 5 mL/kg of control is in progress (13-15).
0.9% saline. Calculation of blood transfusions and fluid therapy were performed using standard methods. Pain severity was measured by VAS in recovery room, and at Considering the need for postoperative pain control in first, second, fourth, and sixth hour of surgery. If the surgical procedures, which reduces hospital stay as well pain score was > 4, analgesia (IV narcotic opiates) was as complications induced by opioid drugs and anesthe- administered. Number of opioid consumption (anal- sia. The current study investigated the effect of adminis- gesic) and doses were registered. Sedation score was trating 100 mg of gabapentin as premedication in reduc- recorded using Pasero Opioid-induced Sedation Scale ing postoperative pain of patients with morbid obesity (POSS) (16). Incidence of the most common side effects undergoing LGBP surgery.
of gabapentin including headache, agitation, dizziness, blurred vision, and other symptoms such as nausea and 3. Patients and Methods
vomiting were evaluated during the study. Demograph- ic data, pain and medication complications, and other This study was conducted as a double-blind random- information were obtained by a designed data form. ized clinical trial recruiting 18 to 65 year old individuals The collected data were analyzed using SPSS 11.5 (SPSS who underwent LGBP surgery. We estimated the sample Inc, Chicago, Illinois, the United States). Frequency for size for the primary outcome (pain score) based on the qualitative variables and mean and SD for the quanti- results from our pilot study (n = 10), which showed a tative variables were calculated. Kolmogorov–Smirnov mean reduction of 1.3 with standard deviation (SD) of test was used to check the normality of the data distri- 1.5 in pain score, using visual analog scale (VAS). Given bution. Qualitative data analysis was performed using an alpha error of 0.05, power of 90% was estimated, Chi square or Fisher exact test. Quantitative data analy- and sample size was decided at 60. Samples were se- sis was performed using Student's t test or Mann-Whit- lected by convenient sampling method from patients ney U test and Repeated Measures ANOVA. P value < 0.05 with morbid obesity referred to Hazrat Rasul Hospital was considered statistically significant in all statistical during 2012-2013. Informed consent was obtained from analyses. This study conformed to the Helsinki Declara- participants. Inclusion criteria included candidates for tion ethical principles. The study was derived from Dr. the LGBP surgery, age > 18 years, ASA class II or I, morbid N. Nikobakht's postgraduate thesis, supervised by Prof. obesity (body mass index [BMI] ≥ 40 kg/m2). Exclusion V. Hassani, entitled "Assessing the effect of preopera- criteria included one or more of the following: cardio- tional administration of gabapentin on postoperative vascular and respiratory diseases, frequent headaches, pain of patients with morbid obesity, undergoing lapa- dizziness, drug and/or alcohol abuse, use of daily an- roscopic gastric bypass surgery". The study protocol was algesia 48 hours before the surgery, renal failure, and approved by the ethics committee of Iran University of liver dysfunction. Patients were randomly allocated Medical Sciences and recorded in IRCT Center (code, into two groups of gabapentin and placebo, each with sample size of 30 using four-block randomization. Ga- bapentin group received 100 mg of oral gabapentin and placebo group received identical-to-gabapentin placebo 4. Results
capsules one hour before induction of anesthesia. Both We examined 76 patients using the inclusion criteria. patient and the anesthesiologist, who evaluated pain Twelve patients were ineligible for the study because and drug complications, were not aware of the type of of history of coronary artery diseases (n = 4), BMI < 40 the drugs received by each participant. Induction was kg/m2 (n = 2), and refusal to participate (n = 6). A total performed with 2 mg of intravenous (IV) midazolam of 60 patients met the criteria and were randomly allo- hydrochloride, 5 mg/kg of IV thiopental, 0.5 mg/kg of cated to two groups of 30 (Figure 1). Totally, 33 patients IV atracurium besylate, and 3 μg/kg of IV fentanyl. Pa- (55%) were female and 27 (45%) were male. Mean age of tients were intubated and mechanically ventilated. Fen- patients was 34.3 ± 7.6 years (range, 24-60 years). Demo- tanyl (1 µg/kg) was repeated at 30 minute to maintain graphic data of patients as well as the surgery duration general anesthesia. Patients were monitored and kept are given in Table 1. Two groups were homogenous in under maintenance dose of 100 μg/kg per minute of IV demographic data. (Table 1) Sedation scores in the case propofol and atracurium during the surgery. The night and control groups were respectively two and three. before and the morning after the surgery, all patients Mean pain score in recovery and at first, second, fourth, were treated with 150 mg of oral ranitidine and 10 mg and sixth hour of surgery was lower in the gabapentin of oral oxazepam as premedication. In the operating group compared to the placebo group (Figure 2). Mean room, a 10-mg capsule of gabapentin was given to gaba- pain score in recovery (P < 0.001) and at first (P < 0.001), pentin group and placebo capsule to controls. Patients second (P = 0.007), and fourth (P=0.04) hour of surgery underwent standard monitoring including electrocar- was significantly lower in the gabapentin group com- Anesth Pain Med. 2015;5(1):e22372 Hassani V et al. pared to placebo group (Table 2). Mean pain score at in gabapentin group, but the difference was not statisti- sixth hour of surgery was lower in the gabapentin than cally significant (P = 0.08) (Table 3). The number of pa- was in placebo group, but it was not statistically sig- tients with side effects including nausea/vomiting (P = nificant (P = 0.1) (Table 2). The number of patients who 0.028) and agitation (P = 0.037) were significantly lower needed opioid was lower in the gabapentin group than in the group receiving gabapentin than in the control was in controls (P = 0.058) (Table 3); however, no statisti- group. Nonetheless, there was no significant difference cally significant difference was observed among the pa- between two groups regarding the number of patients tients who had received opioids. Opioid dose was lower experiencing headache (P = 0.3).
Assessed for eligibility (n=72) Not meeting inclusion criteria (n=6)Declined to participate (n=6) Other reasons (n=0) Randomised (n=60) A llocated to intervention (n=30) A llocated to intervention (n=30) Received Gabapentin (n=30) Received Placebo (n=30) Did not received Gabapentin (n=0) Did not received Placebo (n=0) Lost to follow-up (n=0) Lost to follow-up (n=0) Discontinued Gapabentin (n=0) Discontinued placebo (n=0) Excluded from analysis (n=0) Excluded from analysis (n=0) Analysis Followup Allocation Enrolment Figure 1. Flow Diagram of Patients in the Trial
Table 1. Demographic and Operative Data of Study Groups a
Placebo (n = 30)
Gabapentin (n = 30)
Surgery Duration, h
a Data are presented as Mean ± SD or No.
b Body mass index.
Anesth Pain Med. 2015;5(1):e22372 Hassani V et al. Figure 2. Comparison of the Mean of Visual Analog Scale in Gabapentin
and Placebo Groups
This study showed that administration of gabapentin before surgery could reduce post-LGBP pain. Gabapen- tin has anticonvulsant, antianxiety, and sedative effects and is used for the management of postoperative pain due to its antihyperalgesic properties (17-19). The present study revealed that the mean of pain score was lower in those receiving gabapentin than in the control group (P < 0.001). These findings were similar to Lee et al. study on thyroid surgery and Ajori et al. study on hysterectomies, which concluded that administration of 600 mg of gab- apentin would reduce pain before surgery (20, 21). Panah Khahi et al. also concluded that administration of 300 mg of gabapentin two hours before the internal fixation of tibia could reduce postoperative pain (22). Moreover, a study by Ture et al. concluded that gabapentin was effec- tive in reducing postoperative pain and might increase sedation and delay the patient's extubation in those un- Time after sugery (hour) dergoing craniotomy (23). In addition, findings from the current study confirmed the results of two meta-analy- Abbreviation: VAS, visual analog scale.
ses by Dauri et al. and Hurley et al. reporting that com- pared to other analgesic drugs, preoperative administra- tion of gabapentin was applicable for postoperative pain Table 2. Mean of Visual Analog Scale Score in Gabapentin and
management with different mechanisms of analgesia Placebo Groups a, b (24, 25). On the other hand, the study by Dierking et al. Mean VAS (range, 0-10)
showed that a total dose of 3000 mg gabapentin before and within 24 hours of surgery had no significant effect Gabapentin
on postoperative pain score, but reduced postoperative morphine consumption after hysterectomy surgery (26). In our study, postoperative opioid consumption was low- Time after surgery
er in the group receiving gabapentin, but this difference Surgery and
was not statistically significant; however, it was expected Assessment, h
that the need for opioids would be reduced with pain reduction. Yet opioid consumption might vary based on differences in the type and severity of postoperative pain and type of surgical procedures. In this study the incidence of nausea/vomiting and agitation was signifi- cantly lower in the case group (receiving gabapentin), a Abbreviation: VAS, visual analog scale.
which could be due to better pain control in gabapentin b Data presented as Mean ± SD.
group. Clivatti et al. investigated 26 randomized clinical trials conducted from 2005 to 2007 to assess the effects of gabapentin administration before and after surgery. Table 3. Opioid Consumption and Frequency of Complications
Some of the above studies showed reduced incidence of in Study Groups a nausea and vomiting after surgery while others showed Study Groups
increased incidence of these complications (27). A study Gabapentin
by Turan et al. showed that patients who received 1200 mg of gabapentin in spinal surgery experienced no ad- Patients Requiring
verse effects (28). Another study concluded that in com- parison with the placebo group, the incidence of nausea Dose of Consumed
and vomiting in patients who had received gabapentin Opioid, mg
before elective hysterectomy was not significant (29). Dauri et al. showed that gabapentin had no preventive effect on postoperative nausea and vomiting (25). Sin- gle-dose administration of 100-mg gabapentin before surgery can reduce pain without significant short-term a Data presented as Mean ± SD or No. (%).
adverse effects after LGBP surgery.
Anesth Pain Med. 2015;5(1):e22372 Hassani V et al. 15. Imani F, Hasani V, Bazargani B, Entezari SR, Mirdehghan MH. Evaluation of oral gabapentin premedication on postoperative The authors wish to acknowledge the contribution of pain after thoracotomy. Razi J Med Sci. 2009;16(62):73–9.
all participating team members who helped us in this 16. Pasero C. Assessment of sedation during opioid administration for pain management. J Perianesth Nurs. 2009;24(3):186–90.
17. Chang CY, Challa CK, Shah J, Eloy JD. Gabapentin in acute postop- erative pain management. Biomed Res Int. 2014;2014:631756.
18. Kavoussi R. Pregabalin: From molecule to medicine. Eur Neuro- psychopharmacol. 2006;16 Suppl 2:S128–33.
The study was supported Iran University of Medical Sci- 19. Shneker BF, McAuley JW. Pregabalin: a new neuromodula- ences, by the grant number 92-01-140-21647.
tor with broad therapeutic indications. Ann Pharmacother. 20. Lee JH, Lee HK, Chun NH, So Y, Lim CY. The prophylactic effects of gabapentin on postoperative sore throat after thyroid surgery. 1. Formiguera X, Canton A. Obesity: epidemiology and clinical as- Korean J Anesthesiol. 2013;64(2):138–42.
pects. Best Pract Res Clin Gastroenterol. 2004;18(6):1125–46.
21. Ajori L, Nazari L, Mazloomfard MM, Amiri Z. Effects of gabapen- 2. Gooren L. Obesity: new aspects. J Mens Health. 2008;5(3):249–56.
tin on postoperative pain, nausea and vomiting after abdominal 3. Kelishadi R, Alikhani S, Delavari A, Alaedini F, Safaie A, Hojatza- hysterectomy: a double blind randomized clinical trial. Arch Gy- deh E. Obesity and associated lifestyle behaviours in Iran: find- ings from the First National Non-communicable Disease Risk 22. Panah Khahi M, Yaghooti AA, Marashi SH, Nadjafi A. Effect of Factor Surveillance Survey. Public Health Nutr. 2008;11(3):246–51.
pre-emptive gabapentin on postoperative pain following lower 4. Esteghamati A, Khalilzadeh O, Mohammad K, Meysamie A, Rashi- extremity orthopaedic surgery under spinal anaesthesia. Singa- di A, Kamgar M, et al. Secular trends of obesity in Iran between pore Med J. 2011;52(12):879–82.
1999 and 2007: National Surveys of Risk Factors of Non-commu- 23. Ture H, Sayin M, Karlikaya G, Bingol CA, Aykac B, Ture U. The anal- nicable Diseases. Metab Syndr Relat Disord. 2010;8(3):209–13.
gesic effect of gabapentin as a prophylactic anticonvulsant drug 5. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the devel- on postcraniotomy pain: a prospective randomized study. Anesth oping world--a growing challenge. N Engl J Med. 2007;356(3):213–5.
6. Mello MM, Studdert DM, Brennan TA. Obesity--the new frontier of 24. Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The public health law. N Engl J Med. 2006;354(24):2601–10.
analgesic effects of perioperative gabapentin on postoperative 7. DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med. pain: a meta-analysis. Reg Anesth Pain Med. 2006;31(3):237–47.
25. Dauri M, Faria S, Gatti A, Celidonio L, Carpenedo R, Sabato AF. 8. Balsiger BM, Poggio JL, Mai J, Kelly KA, Sarr MG. Ten and more Gabapentin and pregabalin for the acute post-operative pain years after vertical banded gastroplasty as primary operation for management. A systematic-narrative review of the recent clini- morbid obesity. J Gastrointest Surg. 2000;4(6):598–605.
cal evidences. Curr Drug Targets. 2009;10(8):716–33.
9. Kilgore TR, Tichansky DS, Madan AK. In patient pain manage- 26. Dierking G, Duedahl TH, Rasmussen ML, Fomsgaard JS, Moiniche ment after laparoscopic gastric bypass. Bariatr Surg Pract Patient S, Romsing J, et al. Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterec- 10. Barth MM, Jenson CE. Postoperative nursing care of gastric by- tomy: a randomized, double-blind trial. Acta Anaesthesiol Scand. pass patients. Am J Crit Care. 2006;15(4):378–87.
11. Schauer PR, Schirmer BD, Brethauer SA. Minimally Invasive Bariat- 27. Clivatti J, Sakata RK, Issy AM. Review of the use of gabapen- ric Surgery.New York: Springer; 2007.
tin in the control of postoperative pain. Rev Bras Anestesiol. 12. Rahimzadeh P. Gabapentinoids in Pain Setting. J Pain Relief. 2013;2.
13. Mathiesen O, Moiniche S, Dahl JB. Gabapentin and postoperative 28. Turan A, Karamanlioglu B, Memis D, Hamamcioglu MK, Tuke- pain: a qualitative and quantitative systematic review, with fo- nmez B, Pamukcu Z, et al. Analgesic effects of gabapentin after cus on procedure. BMC Anesthesiol. 2007;7:6.
spinal surgery. Anesthesiology. 2004;100(4):935–8.
14. Alimian M, Imani F, Hassani V, Rahimzadeh P, Sharifian M, Safari 29. Sen H, Sizlan A, Yanarates O, Emirkadi H, Ozkan S, Dagli G, et al. S. Effects of single-dose pregabalin on postoperative pain in dac- A comparison of gabapentin and ketamine in acute and chronic ryocystorhinostomy surgery. Anesth Pain Med. 2012;2(2):72–6.
pain after hysterectomy. Anesth Analg. 2009;109(5):1645–50.
Anesth Pain Med. 2015;5(1):e22372
Clinical MCQs Assessment – Sample Questions The fol owing 20 clinical MCQs are representative of the style and format of MCQs that candidates wil receive as part of the AACP Stage 2 Clinical MCQ Assessment. The answers and explanatory notes are provided at the end of this document. SQ1. Which ONE of the following patients has the HIGHEST calculated creatinine clearance?