|Year : 2008 | Volume
| Issue : 6 | Page : 829
Preemptive Gabapentin vs Pregabalin for Acute Postoperative Pain after Surgery under Spinal Anaesthesia
V Saraswat1, Vishal Arora2
1 Prof. and Head, Dept of Anesthesiology and Critical Care, Command Hospital, (Air Force), Airport Road, Bangalore, India
2 P.G..Student, Dept of Anesthesiology and Critical Care, Command Hospital, (Air Force), Airport Road, Bangalore, India
|Date of Acceptance||16-Aug-2008|
|Date of Web Publication||19-Mar-2010|
Dept of Anesthesiology and Critical Care, Command Hospital (Air Force), Airport Road, Bangalore-560007
Source of Support: None, Conflict of Interest: None
Gabapentin and Pregabalin have been used in treatment of neuropathic pain as well as postoperative pain with good results. However there is paucity of studies in comparison with each other. This study was designed to compare their efficacy with respect to increase in duration of analgesia, reduction in total post- operative requirements of analgesics and study side effects and complications.
Sixty patients of either sex in ASA grade I and II were randomly allocated to one of the two groups of thirty each. Patients in Group G were given single dose of gabapentin 1200mg, whereas in Group P were administered pregabalin 300mg one hour prior to administration of spinal anaesthesia. Pain was assessed by Visual Analogue Scale immediate postoperatively and every two hourly thereafter. Time since spinal anaesthesia to first dose of analgesic (diclofenac) and total dose of analgesic in first 24 hours was recorded.
The total postoperative analgesic time was 8.98h in Group G whereas 14.17h in Group P (HS, P < 0.001). Total dose of analgesics in first 24h was 62.5mg in Group P and 72.5mg in Group G and was not significant (P>.05). Dizziness and somnolence were the only side effects noticed in both groups.
Gabapentin and pregabalin, both have been effective in prolongation of post-spinal analgesia, Pregabalin more than Gabapentin and either can be used as part of multimodal therapy if not as sole analgesic.
Keywords: Pregabalin, Gabapentin, Spinal analgesia, Preemptive analgesia
|How to cite this article:|
Saraswat V, Arora V. Preemptive Gabapentin vs Pregabalin for Acute Postoperative Pain after Surgery under Spinal Anaesthesia. Indian J Anaesth 2008;52:829
|How to cite this URL:|
Saraswat V, Arora V. Preemptive Gabapentin vs Pregabalin for Acute Postoperative Pain after Surgery under Spinal Anaesthesia. Indian J Anaesth [serial online] 2008 [cited 2020 Jan 21];52:829. Available from: http://www.ijaweb.org/text.asp?2008/52/6/829/60696
| Introduction|| |
Prevention and treatment of postoperative pain continues to be a major challenge in postoperative care and plays an important role in the early mobilization and well being of the surgical patient.
Traditionally, the pathophysiology and treatment of postoperative pain and neuropathic pain have been considered as separate and distinct. Opioids, NSAIDs and local anaesthetics were the tools of those dealing with acute pain; anticonvulsants and tricyclic antidepressants were for the chronic pain specialist. However, there is considerable overlap in their pathophysiology. Allodynia and hyperalgesia are cardinal signs and symptoms of neuropathic pain but they are also often present after trauma and surgery. Sensitization of neurons in the dorsal horns, a mechanism in neuropathic pain, has been demonstrated in acute pain models. , The persistence of this mechanism may be responsible for the increasingly recognized problem of chronic pain after surgery. ,
Gabapentin is a structural analogue of gammaamino butyric acid, which was introduced in 1994 as an antiepileptic drug, particularly for partial seizures. Large placebo-controlled, double blind trials confirmed their effectiveness in neuropathic post-herpetic pain. , Despite its name, gabapentin does not bind at the GABA A or GABA B receptor. However, it has a high binding affinity for the α2δ subunit of the presynaptic voltage-gated calcium channels  which inhibits calcium influx and subsequent release of excitatory neurotransmitters in the pain pathways.
There is now considerable interest in the potential use of gabapentin for postoperative pain relief. In a recent review,  seven studies of reasonable quality were identified. Significant reductions in postoperative analgesic requirements 24 h after surgery were found in six studies (abdominal hysterectomy, spinal surgery, vaginal hysterectomy, radical mastectomy and laparoscopic cholecystectomy); ,,,,,, whereas significant effects were found in the other study after two days (mastectomy). 
In a more recent systematic review  with focus on procedure-specific effects of gabapentin in postoperative pain, demonstrated that preoperative gabapentin reduces 24-hour postoperative opioid consumption for patients in abdominal hysterectomy and spinal surgery. Nausea may be reduced in abdominal hysterectomy.
Pregabalin is a structural analogue of gammaamino butyric acid, which shares some characteristics with its predecessor, gabapentin. Its mechanism of action is probably the same as gabapentin but it has a superior pharmacokinetic profile.  Its usefulness has already been established in the treatment of peripheral neuropathic pain. ,, It is claimed to be more effective in preventing neuropathic component of acute nociceptive pain of surgery, to produce more opioid sparing effect and for amelioration of perioperative anxiety. The efficacy of pregabalin for treating symptoms of generalized anxiety disorder has been demonstrated in several clinical trials. ,, There are initial studies showing some evidence that it may have efficacy in acute pain similar to that of gabapentin. ,
The aim of present study was to evaluate postoperative analgesic benefit in patients administered gabapentin or pregabalin as premedication for surgery under spinal anaesthesia and to compare their postoperative efficacy with respect to increase in duration of analgesia, reduction in total post-operative requirements of analgesics and study side effects and complications, if any attributable to these drugs.
| Methods|| |
In a prospective randomized study, sixty patients scheduled for infraumbilical surgeries ranging from 20 - 70 years of age in physical status, ASA grade I and II were selected for the study. Clearance from institutional Ethics committee was obtained. They were randomly allocated to one of the two group of thirty each by allocating the patients alternatively to either group. Patients were subjected to pre-anaesthetic assessment and informed consent was obtained from all the patients.
Patients in Group G (n=30) were given single dose of gabapentin 1200mg, whereas in Group P (n=30) were administered pregabalin 300mg. All doses of pregabalin and gabapentin were given per oral one hour prior to administration of spinal anaesthesia. No other premedication was instituted.
Routine monitoring, in the form of NIBP, pulse oximetry and ECG was instituted on arrival in operation theatre. All patients were preloaded with 10ml.kg -1 lactated Ringers solution before being administered spinal anaesthesia for various surgical procedures. Spinal anaesthesia was instituted with 3 ml of 0.5% bupivacaine (15mg). Fluid administration was continued intraoperatively and hypotension, if any was treated with fluid replacement.
Pain was assessed postoperatively by visual analogue scale immediate postoperatively and every two hourly thereafter, which was explained to the patient during preoperative visit. Blinding was done during follow up in ward. Once patient was shifted to the ward, ward nurse was responsible for charting the pain score by VAS scale. Since pain charting was done separately and anaesthesia chart was not attached with the case sheet, she had no way to find out to which group patient belonged. Any patient with VAS score of more than three were administered diclofenac 1mg.kg -1 intramuscularly. Time since spinal anaesthesia to first dose of analgesic and total dose of analgesic in first 24 hours was recorded.
Any complications like dizziness, somnolence, diplopia, vomiting, confusion, pain, and urinary retention were recorded in first 24 hours post- operative period.
| Statistical analysis|| |
Sample size was decided in consultation with statistician. Thirty was the smallest number in each group, where any results could be statistically significant hence this number was selected. Two sample paired T-Test was used to find out significance between two samples. Data was reported as mean value ±S.D. A P-value of < 0.05 was considered statistically significant. Mann Whitney U test was selected for discrete samples.
| Results|| |
Sixty patients, thirty in each group, were included in the study and analyzed. The groups were comparable with respect to demographic characteristics like age, weight, physical status and duration of surgery [Table 1]. The intraoperative hemodynamic values ie mean blood pressure, heart rate and SpO 2 were similar (P>0.05) in the two groups at all measured intervals (data not reported). The type of surgery conducted in two groups were also similar [Table 2].
The total postoperative analgesic duration (time from spinal analgesia to first dose of analgesic) was 8.98h in Group G whereas 14.17h in Group P, which was highly significant (P < 0.001) [Table 3].
In Group G, two patients did not require any analgesic as compared to four in Group P. A single dose was required in first 24 hours in 26 patients in Group G as compared to 25 patients in Group P and only two patients in Group G and one in Group P required two doses in first 24 hours. Total number of analgesic doses given in first 24h was lower in Group P (mean 0.9 as against 1.0 in Group G) but not statistically significant.
The mean total dose of analgesic in first 24h was 72.5mg in Group G, whereas 62.5mg in Group P. Although total dose of analgesics in first 24h was less in Group P, but it was not statistically significant (P>0.05). Pain scores were similar, as patients were given analgesics immediately on reaching the VAS scale of three.
Dizziness and somnolence were the only side effects noticed in both groups. Six patients in either group experienced somnolence and hence was not significant. Dizziness was experienced in five patients (17%) in Group A as compared to four patients (14%) in Group P, which was again not significant (P<0.05).
One patient in the Group G required bladder catheterization following urinary retention. No other side effects such as nausea, vomiting, ataxia, vertigo, visual disturbances and headache were observed in either group.
| Discussion|| |
Preincisional analgesia has been shown to be more effective in control of postoperative pain by protecting the central nervous system from deleterious effects of noxious stimuli and resulting allodynia, and increased pain. Gabapentin and pregabalin have antiallodynic and antihyperalgesic properties useful for treating neuropathic pain and may also be beneficial in acute postoperative pain. Several studies have reported the usefulness of Gabapentin and pregabalin in perioperative settings resulting in reduced postoperative pain, postoperative analgesic requirement, side effects, prolongation of analgesia, and higher patient satisfaction. ,,,
In a recent review of 22 RCTs, metaregression analysis suggested that the gabapentin-induced reduction in the 24-h opioid consumption was not significantly dependent on the gabapentin dose  . Hence, single highest safe dose of gabapentin(1200 mg) and pregabalin (300 mg) was selected for this study, which is same as used in most of the studies. In animal models gabapentin has been reported to be more effective when given preoperatively, however, Pandey et al  in their study reported that gabapentin (600mg), given preemptively or post incision did not have significant difference in fentanyl consumption between pre- and post-incision groups. However, we still used gabapentin and pregabalin preoperatively as analgesic consumption was lower in preoperative regimen.
Our study shows that, in infraumbilical surgery, in absence of opioid or nonopioid analgesics, gabapentin and pregabalin, when given preoperatively, prolong the analgesic effects of spinal analgesia, which far exceeds the normal duration of spinal analgesia. The analgesic effect is longer lasting following pregabalin as compared to gabapentin (8.98h in Gabapentin group Vs 14.17h in Pregabalin group). The difference in two groups was highly significant.
Although total number of analgesic doses and total dose of analgesic in first 24h were lower in Pregabalin group, the difference was not statistically significant hence, it can reasonably be presumed that dose of perioperative analgesics could be reduced.
Somnolence and dizziness are the two most common side effects associated with gabapentin and pregabalin. The incidence reported in present study is similar to earlier studies.  This is usually not disabling and antianxiety effect has been found to be beneficial in some studies. 
Gabapentin and pregabalin also reduce movement-evoked pain and this can lead to enhanced functional postoperative recovery.  Jesper et al  reported substantial reduction in movement-related pain 2 and 4 h after radical mastectomy after a single dose of 1,200 mg oral gabapentin administered preoperatively but reduction was not significant at rest. This could be explained by prevention or reduction of the development of central neuronal hyperexcitability induced by the surgical procedure as only evoked pain during movement was significantly decreased, in contrast to pain at rest.
The limitation of the current study design is that single dose of gabapentin and pregabalin has been used. The half-life of these drugs is 5-7 hours and conclusions about the optimal dose and duration of the treatment cannot be made. Although pregabalin has been more effective than gabapentin in the present study, further studies are needed to determine the long-term benefits, if any, of perioperative gabapentin and pregabalin comprehensively. The real challenge in the clinical setting is not simply to minimize the dose of analgesic drug, but to minimize long-term complications and occurrence of chronic pain syndromes within weeks or months after surgery. Secondly, control/placebo group has not been added to the study as both drugs have proved to increase post operative analgesia and reduce analgesic requirement in most of the studies.
To conclude, gabapentin and pregabalin, both can be an effective tool in the armamentarium of anaesthesiologist in treatment of perioperative pain. It can be used as part of multimodal therapy if not as sole analgesic.
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[Table 1], [Table 2], [Table 3]