|Year : 2017 | Volume
| Issue : 1 | Page : 195-200
Effect of preoperative pregabalin versus gabapentin on postoperative pain control after laparoscopic gastric bypass surgery
Khalid G Abd El-Maksoud1, Mokhtar M Younes2, Sherif A Elokda3
1 Department of Anesthesia, ICU and Pain Relief, National Cancer Institute, Cairo University, Cairo, Egypt
2 Lecturer of Anesthesia and Intensive Care, Al-Azher University Hospital, Cairo; Department of Anesthesia, Fakhry Hospital, Al-Khobar, Egypt
3 Department of Anesthesia, ICU and Pain Management, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Khalid G Abd El-Maksoud
Department of Anesthesia, ICU and Pain Relief, National Cancer Institute, Cairo University, Cairo, Egypt; P.O. Box 73371, Al-Khobar 31952
Source of Support: None, Conflict of Interest: None
Background Perioperative gabapentin helps produce a significant opioid-sparing effect and probably also improves postoperative pain scores. Pregabalin is a novel drug with a heightened research interest in the analgesic, sedative, anxiolytic, and opioid-sparing effects, in various pain settings, including postoperative pain. We investigated pregabalin analgesic efficacy in morbid obese patients experiencing acute pain after laparoscopic gastric bypass surgery and compared it with gabapentin and placebo.
Patients and methods A randomized, placebo-controlled study was conducted on 90 morbidly obese patients undergoing laparoscopic gastric bypass surgery. Patients were allocated into one of the three groups; the pregabalin group in which the patients received 300 mg pregabalin, the gabapentin group in which the patients received 1200 mg gabapentin, or the control group in which the patients received placebo 2 h prior to surgery. Postoperative pain was controlled with intravenous fentanyl via patient controlled analgesia (PCA). Fentanyl consumption over 24 h and pain intensity measured by visual analogue score at rest (static) and during cough (dynamic) at recovery time, 1, 2, 6, 12, and 24 h were recorded. Also sedation status, somnolence, dizziness, headache, nausea, and vomiting were monitored.
Results Postoperative 24 h fentanyl consumption was significantly higher in the control group compared with both pregabalin and gabapentin groups (P<0.001). Pain intensity on visual analogue score (static and dynamic) was significantly higher in the control group compared with both pregabalin and gabapentin groups at time of recovery, 1, 2, 6, 12, and 24 h postoperatively. Numeric sedation score was significantly lower in the control group compared with pregabalin and gabapentin groups at time of recovery, 1, 2, and 6 h postoperatively. No significant differences were found among the three groups as regards somnolence, dizziness, headache, nausea, and vomiting.
Conclusion A single dose of 300 mg pregabalin or 1200 mg gabapentin given 2 h before surgery is better than placebo for postoperative pain control for laparoscopic gastric bypass surgery without significant side effects.
Keywords: gabapentin, multimodal analgesia, postoperative pain, pregabalin
|How to cite this article:|
Abd El-Maksoud KG, Younes MM, Elokda SA. Effect of preoperative pregabalin versus gabapentin on postoperative pain control after laparoscopic gastric bypass surgery. Ain-Shams J Anaesthesiol 2017;10:195-200
|How to cite this URL:|
Abd El-Maksoud KG, Younes MM, Elokda SA. Effect of preoperative pregabalin versus gabapentin on postoperative pain control after laparoscopic gastric bypass surgery. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2019 Apr 20];10:195-200. Available from: http://www.asja.eg.net/text.asp?2017/10/1/195/238457
| Introduction|| |
As there is increasing growth of obesity, surgical procedures have progressed to control weight, and reduce the comorbidities of obesity such as hypertension, diabetes, arthritis, cardiovascular and respiratory diseases, etc. This progress also includes gastric bypass surgery, which nowadays is usually laparoscopic.
The pathophysiology of obesity, the comorbidities, and the high incidence of obstructive sleep apnea among morbidly obese patients make safe analgesic management difficult. In particular, the postoperative pain control after bariatric surgery is a major challenge.
As opioids are known for having ventilatory depressing effects, their use in surgical procedures for morbidly obese patients is controversial. Therefore, alternative analgesics are needed to improve anesthetic management for obese patients . So, nonopioid compounds acting as adjuvants are part of the multimodal analgesic techniques postoperatively, aiming to reduce opioid requirements and enhance analgesia.
In recent years, gabapentin and pregabalin have been introduced as adjuncts in the multimodal management of postoperative analgesia .
Gabapentin, a γ-aminobutyric acid (GABA) analogue, was first developed as an anticonvulsant drug and then its potentials as an analgesic drug for the treatment of neuropathic pain was described in the literature ,. The mechanism of action of gabapentin is binding to the α2-δ subunit of the presynaptic voltage-gated-calcium channels and inhibiting calcium release. Most of the reviews and meta-analyses concur that perioperative gabapentin helps produce a significant opioid-sparing effect, and probably also improves postoperative pain score relative to the control group ,. During the immediate postoperative period, however, its activation of descending inhibitory pathways may be more relevant and might explain its synergistic effect with opioids .
Pregabalin, a structural analogue of GABA and a derivative of gabapentin, is a novel drug with a heightened research interest in the analgesic, sedative, anxiolytic, and opioid-sparing effects, in various pain settings, including postoperative pain .
Pregabalin is similar to gabapentin, but it has a more favorable pharmacokinetic profile, including dose-independent absorption. It is also several times more potent than gabapentin while producing less adverse effects .
In this study, we evaluated the analgesic effects of pregabalin compared with gabapentin in postoperative pain management after laparoscopic gastric bypass surgery. Incidence of side effects of pregabalin and gabapentin including headache, dizziness, somnolence, and other symptoms such as nausea and vomiting were also investigated.
| Patients and methods|| |
This randomized, control study was conducted at the Fakhry Hospital in Al-Khobar, Saudi Arabia from February 2014 to October 2015, after approval by the ethics committee and obtaining informed consent from the patients participating in the study. Patients were randomly allocated using a computer randomization schedule into one of the three groups of 30 patients each: the pregabalin group in which the patients received pregabalin 300 mg, the gabapentin group in which the patients received gabapentin 1200 mg, or the control group in which the patients received placebo single oral dose of 2 h preoperatively. All patients were of American Society of Anesthesiologists status II, morbidly obese with a BMI of more than 35 kg/m2, age more than 19 years scheduled for laparoscopic gastric bypass surgery. Exclusion criteria included: patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 s <50% resulting in inability to perform basic normal activities), uncontrolled hypertension, history of hypersensitivity to pregabalin or gabapentin, history of addiction or chronic use of analgesics. After establishing an intravenous line and monitoring by ECG, noninvasive blood pressure, pulse oximetry, and end-tidal carbon dioxide, induction of anesthesia was done using intravenous fentanyl (1.5 μg/kg) and propofol (2 mg/kg). Endotracheal intubation was facilitated by cisatracurium (0.15 mg/kg). Anesthesia was maintained by 50% nitrous oxide in oxygen, cisatracurium (2 mg/30 min), and sevoflurane which was manipulated up and down gradually to keep the patient hemodynamics at around 25% of the basal level. Paracetamol 1 g and lornoxicam 16 mg via intravenous route were given to all patients after induction of anesthesia. In case of hypertension (diastole ≥100 mmHg) intraoperatively, labetalol was titrated in 5 mg shot incremental doses, while in case of hypotension (systolic <90 mmHg) ephedrine was used in 10 mg shot incremental doses to control blood pressure. At the end of the surgery, neostigmine 2.5 mg was given to patients with atropine 1 mg to facilitate complete reversal of action of cisatracurium. The calculation of fluid therapy was performed using standard methods.
Extubation was done in the operating room and then the patients were transferred to the postanesthesia care unit, where monitors and oxygen mask were applied. In postanesthesia care unit, narcotic analgesia was started in the form of intravenous fentanyl via PCA (Lifecare 4200, PCA/Infuser; Abott, North Chicago, Illinois, USA), with a patient activated dose of 20 µg, lockout interval of 10 min, and with a maximum allowable fentanyl dose of 1 µg/kg/h. Additional fentanyl 15 µg intravenously was administered, if requested by the patient during the lockout period. Total fentanyl consumption was recorded from 0 to 24 h postoperatively. Intravenous paracetamol 1 g was given every 6 h for all patients during hospital stay.
Pain intensity was monitored both at rest (static) and during coughing (dynamic) at time of recovery, 1, 2, 6, 12, and 24 h postoperatively by visual analogue scale (VAS). Before surgery, all patients were instructed in the use of VAS (0 cm: no pain, 10 cm: worst pain imaginable). Sedation status using numeric sedation scores (NSS; 1=completely awake, 2=awake but drowsy, 3=asleep but responsive to verbal commands, 4=asleep but responsive to tactile stimulus, 5=asleep and not responsive to any stimuli) was monitored at the time of recovery, 1, 2, 6, 12, and 24 h postoperatively. Somnolence described as mild (NSS=1–2), moderate (NSS=3), or severe (NSS=4) was monitored once at 8 h postoperatively. Incidence of side effects of pregabalin and gabapentin including headache, dizziness, and other symptoms such as nausea and vomiting were also monitored.
Sample size calculation
In a previous study , the group that received pregabalin had a mean VAS score of 5.1±1.1 at recovery, compared with 6.6±1.5 in the control group. Based on the results of this study, a sample size of 21 cases per group was required to elicit the difference at an α level of 0.05 and a power of the study of 95%. Assuming there would be dropout, the final sample size was set at 90 patients.
Data were analyzed using IBM SPSS advanced statistics version 22 (SPSS Inc., Chicago, Illinois, USA). Numerical data were expressed as mean and SD or median and interquartile range as appropriate. Qualitative data were expressed as frequency and percentage. χ2-Test or Fisher’s exact test was used to examine the relation between qualitative variables. For quantitative data, a comparison between the three groups was done using the analysis of variance test then post-hoc ‘Scheffe test’ was used for pairwise comparison. All tests were two-tailed. A P-value of less than 0.05 was considered significant.
| Results|| |
The study was conducted on 90 patients scheduled for laparoscopic gastric bypass surgery. All groups were similar with respect to age, sex distribution, BMI, and duration of surgery ([Table 1]).
|Table 1 Age, sex, BMI, surgical duration, and fentanyl consumption in pregabalin, gabapentin, and control groups|
Click here to view
Postoperative 24 h fentanyl consumption was significantly higher in the control group compared with both pregabalin and gabapentin groups (P<0.001). No statistically significant difference between pregabalin and gabapentin groups was found ([Table 1]).
Pain intensity on VAS at rest (static) and during cough (dynamic) was significantly higher in the control group compared with both pregabalin and gabapentin groups at time of recovery, 1, 2, 6, 12, and 24 h postoperatively ([Table 2] and [Table 3]), but there was no significant difference between pregabalin and gabapentin groups.
|Table 2 Postoperative visual analogue score of pain at rest (static) in pregabalin, gabapentin, and control groups|
Click here to view
|Table 3 Postoperative visual analogue score of pain during cough (dynamic) in pregabalin, gabapentin, and control groups|
Click here to view
NSS was significantly lower in the control group compared with pregabalin and gabapentin groups at time of recovery, 1, 2, and 6 h postoperatively, but pregabalin and gabapentin groups were similar at time of recovery, 1, 2, 6, 12, and 24 h postoperatively. There was no significant difference between the three studied groups at 12 and 24 h ([Table 4]).
|Table 4 Numerical sedation score in pregabalin, gabapentin, and control groups|
Click here to view
Although the number of patients with somnolence (which was described as mild) and dizziness was lower in the control group, no statistically significant difference was found among the three groups. Incidence of nausea and vomiting was higher in the control group compared with pregabalin and gabapentin groups, but this difference was not statistically significant. It was mild and relieved by a single intravenous dose of ondansetron 4 mg. There was no significant difference among the study groups as regards the incidence of headache ([Table 5]).
|Table 5 Nausea and vomiting, headache, dizziness, somnolence in pregabalin, gabapentin, and control groups|
Click here to view
| Discussion|| |
This study showed that there was a reduction in postoperative fentanyl requirements in the two groups of patients receiving a single oral dose of pregabalin 300 mg or gabapentin 1200 mg 2 h before laparoscopic gastric bypass surgery in morbidly obese patients, compared with patients receiving placebo. Pain scores were also reduced, both at rest and during coughing (static and dynamic) in pregabalin and gabapentin groups compared with the control group at time of recovery, 1, 2, 6, 12, and 24 h postoperatively.
Pregabalin, like gabapentin, is an amino acid derivative of GABA. It has a pharmacological profile similar to gabapentin. Pregabalin has been found to have distinct pharmacokinetic advantages over gabapentin. It has a predictable and linear pharmacokinetic profile .
The optimal dose of the gabapentinoids for postoperative pain management is not clear. Further work is needed to better define the optimal dose for specific surgical procedures. Said-Ahmed , who studied the effects of different doses of gabapentin, reported that increasing the preemptive dose of gabapentin (300–1200 mg), significantly decreased the severity of post-myomectomy pain and total opioid consumption during the first 24 h after surgery. In the current study, the single highest safe dose of pregabalin (300 mg) and gabapentin (1200 mg) was selected, which is the same as that used in many other studies for different surgical procedures .
After single oral administration, pregabalin is rapidly absorbed and has an elimination half-life of about 5.5–6.7 h, while for gabapentin, the elimination half-life is about 4.8–8.7 h . It takes 4–12 h after surgery to get the maximal clinical effect of pregabalin/gabapentin. Beyond 24 h, no residual effect of the single dose is expected ,.
Although many trials studied the effects of either pregabalin or gabapentin on postoperative pain control in different surgical procedures, there was one study that compared the effects of both drugs. Anju et al.  compared the effects of preoperative pregabalin 300 mg with gabapentin 900 mg in abdominal hysterectomy. Their study showed that diclofenac consumption was statistically lower in pregabalin, and gabapentin groups versus control group; however, pregabalin and gabapentin groups were comparable. Moreover, the consumption of tramadol was statistically significant among all groups (pregabalin<gabapentin<control). Patients in pregabalin and gabapentin groups had lower pain scores in the initial hour of recovery. However, pain scores were subsequently similar in all groups.
The results of many studies in the literature comparing postoperative pain control effect of preoperative use of either pregabalin or gabapentin versus placebo in different surgical procedures are comparable with the results of our current study.
Mahzad et al.  studied the effect of a single dose of 300 mg of pregabalin preoperatively for morbidly obese patients versus the control group undergoing laparoscopic gastric bypass surgery. They concluded that VAS was significantly lower in the pregapalin group compared with the control group at recovery time, 4, 12, 24 h postoperatively.
Agarwal et al.  studied the effect of preemptive pregabalin 150 mg in laparoscopic cholecystectomy given 1 h preoperatively compared with placebo. They concluded that postoperative pain (static and dynamic) and postoperative patient-controlled fentanyl consumption were reduced in the pregabalin group compared with the placebo group up to 24 h postoperatively. The incidence and severity of sedation were comparable between the two groups, as they used lower doses compared with the current study.
Hegarty and Shorten  studied the effects of pregabalin 300 mg in elective lumbar discectomy given 1 h preoperatively compared with placebo. They concluded that morphine consumption was reduced in the pregabalin group. VAS during movement was not significantly different between groups.
Montazeri et al.  studied the effect of preemptive 300 mg gabapentin or placebo given 2 h before lower extremity orthopedic surgery. They reported that the preemptive use of gabapentin 300 mg orally significantly decreases postoperative pain at time intervals of 2, 4, 12, and 24 h and also analgesic requirements.
Valiollah et al.  studied the effect of preoperative 100 mg of gabapentin for morbidly obese patients undergoing laparoscopic gastric bypass surgery compared with patients receiving placebo. They concluded that this dose was not associated with a reduction in postoperative opioid consumption. However, pain scores at the time of recovery and at the first, second, fourth, and sixth hours were significantly lower in the gabapentin group compared with the placebo group.
Durmus et al.  studied the effects of combining gabapentin 1200 mg and paracetamol, with gabapentin alone and placebo administered 1 h preoperatively in patients undergoing abdominal hysterectomy. They noticed that morphine consumption at 24 h was significantly lower in the two groups receiving gabapentin. VAS scores at movement and at rest were decreased with gabapentin and even more with a combination of gabapentin and paracetamol.
Al-Mujadi et al.  gave gabapentin 1200 mg or placebo 2 h prior to elective thyroidectomy. They concluded that preoperative gabapentin decreased VAS scores postoperatively in the first 24 h and morphine consumption in patients following thyroid surgery.
Lee et al.  studied the efficacy of using gabapentin (600 mg) 1 h preoperatively for thyroid surgery. They showed that the gabapentin group had a lower incidence of postoperative sore throat and a significantly lower VAS scores at 6 and 24 h at rest postoperatively compared with the placebo group. However, there was no significant difference regarding the incidence of postoperative sore throat or VAS score during swallowing.
Yu et al.  performed a systematic review and meta-analysis to determine the effect of gabapentin in the management of postoperative pain after spinal surgery. They showed that oral gabapentin was efficacious in the management of postoperative pain during the first day after surgery, and therefore is efficacious in reducing postoperative pain and narcotic requirements after lumbar spinal surgery.
Ajori et al.  investigated the preemptive use of gabapentin 600 mg before abdominal hysterectomy. This study showed that the gabapentin group had significantly lower VAS scores at every time interval up to 24 h and lower meperidine consumption compared with the placebo group.
In the current study, the sedation levels in the first 6 h in the pregabalin and gabapentin groups were significantly higher than those in the control group. While in the 12th and 24th hours, no difference was observed among the three groups. Sedation with pregabalin and gabapentin use has also been reported in previous studies ,. This is because pregabalin and gabapentin have sedative effects. As after 5–8 h (half-life) after single oral dose administration, plasma concentration of both the drugs will be decreased by about 50% . So with time as the blood level of both drugs declines, the sedative effect becomes much less.
Incidence of somnolence, headache, dizziness, nausea, and vomiting was similar in all groups in the current study. Several studies have been done on preoperative pregabalin or gabapentin versus placebo, which had similar results as compared with our study as regards these symptoms ,,.
| Conclusion|| |
Postoperative analgesia was better with either 300 mg pregabalin or 1200 mg gabapentin than with placebo during the first 24 h after laparoscopic gastric bypass surgery without significant side effects. Preemptive use of pregabalin or gabapentin is effective in the treatment of postoperative pain.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J et al.
Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg 2008; 106:1741–1748.
Mario D, Skerdilajd F, Antonello G, Ludovica C, Roberta C, Alessandro F. Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences. Curr Drug Targets 2009; 10:716–733.
Zapp JJ. Postpoliomyelitis pain treated with gabapentin. Am Fam Physician 1996; 53:2442–2445.
Rosner H, Rubin L, Kestenbaum A. Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain 1996; 12:56–58.
Hartrick C, van Hove I, Stegmann J, Oh C, Upmalis D. Efficacy and tolerability of tapentadol immediate release and oxycodone HCl immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: a 10-day, phase III, randomized, double-blind, active- and placebo-controlled study. Clin Ther 2009; 31:260–271.
Tiippana E, Hamunen K, Kontinen V, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? a systematic review of efficacy and safety. Anesth Analg 2007; 104:1545–1556.
Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis. Reg Anesth Pain Med 2006; 31:237–247.
Bellioti TR, Capiris T, Ekhato IV, Kinsora JJ, Field MJ, Heffner TG et al.
Structure-activity relationships of pregabalin and analogues that target the α2
-δ protein. J Med Chem 2005; 48:2294–2307.
Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004; 45(Suppl 6):13–18.
Mahzad A, Farnad I, Seyyed H, Alireza P, Seyedeh FN, Saeid S. Effect of oral pregabalin premedication on post-operative pain in laparoscopic gastric bypass surgery. Anesth Pain Med 2012; 2:12–16.
Frampton JE, Foster RH. Pregabalin in the treatment of postherpetic neuralgia. Drugs 2005; 65:111–118.
Said-Ahmed HAEF. Dose ranging study of gabapentin for postoperative pain after myomectomy. Acta Anaesth Italica 2007; 58:23–34.
Jokela R, Ahonen J, Tallgren M, Haanpää M, Korttila K. A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy. Pain 2008; 1-2:106–112.
Ghafari MH, Akrami M, Nouraishahi B, Sadegh A. Preoperative gabapentin or clonidine decreases post-operative pain after abdominal hysterectomy. Res J Biol Sci 2009; 4:458–463.
Anju G, Sarla H, Dinesh S, Raman W. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth 2011; 5:252–257.
Agarwal A, Gautam S, Gupta D, Agarwal S, Singh PK, Singh U. Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy. Br J Anaesth 2008; 101:700–704.
Hegarty DA, Shorten GD. A randomised, placebo-controlled trial of the effects of preoperative pregabalin on pain intensity and opioid consumption following lumbar discectomy. Korean J Pain 2011; 24:22–30.
Montazeri K, Kashefi P, Honarmand A. Pre-emptive gabapentin significantly reduces postoperative pain and morphine demand following lower extremity orthopaedic surgery. Singapore Med J 2007; 48:748–751.
Valiollah H, Abdolreza P, Nasim N, Shahla C, Azadeh S, Ali S. The effect of gabapentin on reducing pain after laparoscopic gastric bypass surgery in patients with morbid obesity: a randomized clinical trial. Anesth Pain Med 2015; 5:e22372.
Durmus M, Kadir But A, Saricicek V, Ilksen Toprak H, Ozcan Ersoy M. The post-operative analgesic effects of a combination of gabapentin and paracetamol in patients undergoing abdominal hysterectomy: a randomized clinical trial. Acta Anaesthesiol Scand 2007; 51:299–304.
Al-Mujadi H, A-Refai AR, Katzarov MG, Dehrab NA, Batra YK, Al-Qattan AR. Pre-emptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery. Can J Anaesth 2006; 53:268–273.
Lee JH, Lee HK, Chun NH, So Y, Lim CY. The prophylactic effects of gabapentin on postoperative sore throat after thyroid surgery. Korean J Anesthesiol 2013; 64:138–142.
Yu L, Ran B, Li M, Shi Z. Gabapentin and pregabalin in the management of postoperative pain after lumbar spinal surgery: a systematic review and meta-analysis. Spine 2013; 38:1947–1952.
Ajori L, Nazari L, Mazloomfard MM, Amiri Z. Effects of gabapentin on postoperative pain, nausea and vomiting after abdominal hysterectomy: a double blind randomized clinical trial. Arch Gynecol Obstet 2012; 285:677–682.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]