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ORIGINAL ARTICLE
Year : 2009  |  Volume : 3  |  Issue : 1  |  Page : 25-28

Comparing oral gabapentin versus clonidine as premedication on early postoperative pain, nausea and vomiting following general anesthesia


Department of Anesthesiology, School of Medicine, Medical sciences/University of Tehran, Dr Shariati hospital.

Correspondence Address:
Sussan Soltani Mohammadi
M.D., Department of Anesthesiology, Dr Shariati Hospital

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-354X.51831

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Date of Web Publication18-Jul-2009
 

   Abstract 

Background. Prevention and treatment of postoperative pain and postoperative nausea and vomiting (PONV), continue to be a major challenge in the postoperative care. This study was designed to compare the effects of small dose of oral gabapentin versus clonidine as premedication on early postoperative pain and on PONV in patients undergoing elective abdominal surgery under general anesthesia.
Methods. In a randomized placebo controlled study, 120 ASA I and II patients scheduled for elective abdominal surgery were randomly assigned to receive either 0.2mg oral clonidine (n=40) or 300mg gabapentin (n=40) or placebo (n=40) 1hr before surgery. They were anesthetized using the same technique. Demographic data, post operative visual analogue scale (VAS), PONV and total morphine consumption by PCA pump were recorded in the recovery room and during first 6 hr after surgery.
Results. Two patients in gabapentin compared with 13 patients in clonidine group (p<0.05) and 29 patients in placebo group (p<0.05) had VAS >3 in recovery room. The mean morphine consumptions were 4.75±7.5, 1.95±5.51 and 1.56±1.5mg in placebo, clonidine and gabapentin group with significant differences (P<0.05). These measurements were 18±15.8, 13.1±12.6 and 12.1±12.9 mg respectively during first 6 hr after surgery with significant differences (P<0.05). PONV was not statistically different between the study groups in the recovery room and during first 6 hr after the surgery.
Conclusion. This study showed that oral premedication with 300mg gabapentin reduces postoperative pain and total morphine consumption but not PONV during recovery and in the first 6 hr after abdominal surgery.

Keywords: Gabapentin; Clonidine; pain ; PONV.


How to cite this article:
Mohammadi SS, Seyedi M. Comparing oral gabapentin versus clonidine as premedication on early postoperative pain, nausea and vomiting following general anesthesia. Saudi J Anaesth 2009;3:25-8

How to cite this URL:
Mohammadi SS, Seyedi M. Comparing oral gabapentin versus clonidine as premedication on early postoperative pain, nausea and vomiting following general anesthesia. Saudi J Anaesth [serial online] 2009 [cited 2020 Feb 29];3:25-8. Available from: http://www.saudija.org/text.asp?2009/3/1/25/51831


   Introduction Top


Prevention and treatment of postoperative pain and PONV continue to be a major challenge in postoperative care and plays an important role in the early mobilization and well-being of the surgical patient. Opioid analgesics, with their well known side effects, continue to represent a cornerstone in postoperative pain control, and testing new analgesics as well as combination of analgesics in order to reduce the need for opioids , is a key area in acute pain research. Gabapentin is an anticonvulsant that has anti-nociceptive and anti-hyperalgesic properties. In pain models it has shown anti­hyperalgesic properties, possibly by reducing central sensitization [8].

Following single oral dose of 300 mg gabapentin the mean maximum plasma concentration attained in 2-3 hr. Bio-availability of a single 300 mg oral dose of gabapentin is 60% and decreases with increasing the dose. Elimination of gabapentin is through renal clearance and is about 5-7 hr following a single oral dose of 200 to 400 mg [3]. The a2-agonist clonidine has shown positive effects in reducing sympathetic activity, the incidence of shivering, oxygen consumption and PONV [2],[7]. Recently an open clinical study demonstrated that gabapentin has anti­emetic effect in patients treated with chemotherapeutic agents [4]. In another on 250 patients underwent laparoscopic cholecystectomy, gabapentin as premedication was effective in reducing PONV and post-operative rescue analgesic requirement [6].

Therefore we conducted this study to compare the effects of 300mg oral gabapentin doses with 0.2mg clonidine as premedication; on early postoperative pain, and PONV in patients undergoing elective abdominal (gynecological or general) surgery under general anesthesia.


   Methods Top


The study protocol was approved by the investigational review board of our hospital with written informed consent obtained from all patients. Hundred and twenty ASA physical status I or II patients aged 20 to 60yr scheduled to undergo elective abdominal surgery under general anesthesia were studied. Exclusion criteria included patients with mental impairment, chronic pain, history of cardiovascular, psychiatric disease, use of psychotropic drugs and pregnancy.

The patients were randomly assigned to receive either 0.2mg oral clonidine (C group, n=40), 300mg gabapentin (G group, n=40) or placebo (P group, n=40) 1hr before surgery. Randomization was based on computer generated codes that were concealed until interactions were assigned.

The day before surgery patients were instructed about the Verbal Analog Scale (VAS) in which 0=no pain and 10=worst pain imaginable and how to use the PCA pump for postoperative pain management. Drugs were given by an independent anesthetist in the ward therefore both the anesthesiologist and the patient were blinded to the group assignment. Upon arrival to the operating room, ECG electrodes and non invasive blood pressure monitor were applied and oxygen saturation was monitored by pulse oxymeter.

Patients were anesthetized with the same technique including fentanyl 3µg.kg-¹, thiopentone 5mg.kg-¹ and atracurium 0.5mg.kg-¹ to facilitate tracheal intubation. General anaesthesia was maintained with isoflurane (0.4-1.6%) and 50% nitrous oxide in oxygen. Intra operative analgesia was maintained by fentanyl l µg.kg-¹.h-¹.

Neuromuscular blockade was then reversed with intravenous neostigmine 2.5 mg and atropine 0.5 mg. Demographic data , duration and type of surgery were recorded. PONV, total amount of morphine consumption and VAS scores at rest and on movement (deep breathing and coughing) were also recorded in the recovery room at 1 and 6 hr after the operation by trained nurse staff who was blinded to randomization.

Postoperative PCA orders were written in a standardized fashion and were activated in the recovery room. Patients were treated with morphine sulfate with 2mg i.v. every 10 min up to VAS < 3.0. The patients who were severely sedated were omitted from the opioid titration.

Statistical analysis

A sample size of 40 patients in each group will be sufficient to detect a 30% difference in the incidence of postoperative pain between the study groups assuming power of 85% and a significance level of 5%. Normality of distribution was tested by Kolmogorov Smirnov test. Data were analyzed by SPSS version 11.5(SPSS Inc,Chicago,IL) and were compared by using one way ANOVA and post hoc­Tukey tests, Kruskal wallis and Chi-square. P<0.05 was considered statistically significant.


   Results Top


Demographic data, duration and type of surgery (gynecologic/general) were not statistically different between the study groups [Table 1]. VAS score >3 was considered as sign of postoperative pain management. Two patients in gabapentin compared with 13 patients in clonidine and 29 patients in placebo group had VAS >3 in recovery room. Patients in placebo and clonidine groups experienced more pain than gabapentin group (p<0.05) during first six hr after operation [Table 2]. The mean values of morphine consumption were 4.75±7.5, 1.95±5.51 and 1.56±1.5mg in P, C and G groups respectively. These measurements were 18±15.8, 13.1±12.6 , 12.1±12.9 mg during first 6 hr after operation in the same groups respectively with significant difference between P and both C and G groups (P<0.05) and non-significant difference between G and C groups (P>0.05). No patients received any other oral or IV rescue medication. PONV was not statistically different between the study groups during the first 6 hr after surgery [Figure 1], [Figure 2]. Two patients in gabapentin group had dizziness and headache, and 3 patients in clonidine group had dry mouth preoperatively.


   Discussion Top


This study showed that oral premedication with 300mg gabapentin reduces postoperative pain and total morphine consumption compared with 0.2mg clonidine. PONV was not statistically different between the study groups during recovery and at the first 6 hr after abdominal surgery. The aim of combining different analgesic drugs is to obtain synergistic or additive analgesia, allowing a smaller dose of each drug with an improved safety profile. This can be achieved by combining analgesics withdifferent mechanism of actions. Anti­hyperalgesic drugs such as gabapentin may have a role in postoperative pain, and the combination with other antinociceptive drugs may produce synergistic analgesic effect [9]. Gabapentin enhanced the analgesic effect of morphine in healthy volunteers and the combination produced better analgesia in comparison with morphine alone [1],[9]. In this study we compared the effect of oral gabapentin versus clonidine on acute postoperative pain, total postoperative morphine consumption, and on PONV. We found that both gabapentin and clonidine reduce postoperative pain and total morphine consumption. Our results for gabapentin were similar to results presented in a systemic review about qualitative and quantitative effects of gabapentin on postoperative pain presented by mathiesen et al [5]. Turan et al investigated the efficacy of gabapentin on postoperative pain and tramadol consumption after abdominal hysterectomy in 50 patients who were randomized to receive oral gabapentin. They found that preoperative gabapentin decreased pain scores and postoperative tramadol consumption in patients after abdominal hysterectomy [9]. In our study there was no differences in incidence of PONV between the two study groups during the first 6 hr after surgery. These results were not in accordance with pandy et al study in which 600mg gabapentin as premedication for laparascopic cholecystectomy effectively reduces incidence of PONV. These difference may be due to their different doses of gabapentin used [6]. Gabapentin has been also reported to be effective in the treatment of emesis in patients receiving cytotoxic drugs [4].

In conclusion, this study showed that oral premedication with 300mg gabapentin reduces postoperative pain and total morphine consumption but not PONV during recovery and in the first 6 hr after abdominal surgery. Further studies on larger sample size are required to confirm our results.

Acknowledgment. Authors would like to special thanks to Dr. Fatemeh Esfahani, the consultant of development research center of Dr Shariati Hospital, for statistical review and staff nurses for recording VAS scores and data. This study was supported by a grant from Tehran University of Medical Sciences.

 
   References Top

1.Eckhardt K, Ammon S, Hofman U, et al. Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesth Analg 2000;91:185-91.  Back to cited text no. 1    
2.Ghignone M, Calvillo O, Quintin L. Anesthesia and hypertension:the effect of clonidine on preoperative hemodynamics and isoflurane requirements. Anesthesiol 1987;67:3-10.  Back to cited text no. 2    
3.Goa KL, Sorkin EM. Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993;46:409-27.  Back to cited text no. 3    
4.Guttuso T Jr, Roscoe J, Griggs J. Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Lancet 2003;361:1703-5.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Mathiesen O, Moiniche S,Dahl JB. Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiol 2007, 7: 6.  Back to cited text no. 5    
6.Pandey CK, Priye S, Ambesh SP, Singh S,Singh U, Singh PK.Prophylactic Gabapentin for prevention postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy:A randomized double-blinded placebo­controlled study. J Postgrad Med 2006; 52: 97-101.  Back to cited text no. 6  [PUBMED]  Medknow Journal
7.Quintin L, Viale JP, Annat G, et al. Oxygen uptake after major abdominal surgery: effect of clonidine. Anesthesiol 1991;74:236-41.  Back to cited text no. 7    
8.Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia 2002;57:451-62.  Back to cited text no. 8    
9.Turan A, Karamanlioglu B, Memis D, Usar P, Pamukcu Z, Ture M.The analgesic effects of gabapentin after total abdominal hysterectomy.Anesth Analg 2004;98:1370-3.  Back to cited text no. 9    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]


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[Pubmed] | [DOI]



 

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