The International Association for Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage.1,2 Approximately 80% of patients undergoing surgical procedures experience post-operative pain.3 Central sensitisation and hypersensitivity develop after the surgical incision resulting in amplification of post-operative pain. Preventing the establishment of altered central processing by analgesic treatment may result in reduction of post-operative pain and accelerated recovery. A revolution in the management of post-operative pain occurred during the past four decades.4 Although there are many analgesic drugs available for postoperative pain, many patients still find them to be suboptimal for controlling pain.
Laminectomy following lumbar spine herniation is one of the most common surgeries with an incidence of 10 to 40% in neurosurgery. Postoperative pain, in these patients can continue for up to 3 days and 13-43% may become chronic.5 Pain after spine surgery is associated with several complications such as decreased wound healing, increased infections, prolonged hospital stay, readmission after discharge, increase morbidity and costs of hospital which pose a major challenge in post-operative care.6,7 Therefore management of post-surgical pain plays a critical role in quality of the care plan.8,9 Patients who experience intense postoperative pain may suffer from severe nausea and vomiting and are exposed to decreased pulmonary function and the risk of developing thromboembolism due to immobility. Also, cardiac workload, systemic vascular resistance and myocardial oxygen consumption increase due to catecholamine release.10
Opioids were the mainstay for treating moderate to severe post-operative pain, but their use is limited due to adverse effects such as nausea, vomiting, excessive sedation, respiratory depression, pruritis and urinary retention.11 Currently, interest is being rising steadily for the administration of anticonvulsant agents such as gabapentin and pregabalin, as a part of multimodal analgesia technique.
Pregabalin and its predecessor, gabapentin, are analogues of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA). They have anticonvulsant, anti-hyperalgesic and anxiolytic effects, and both bind to the alpha 2-delta (α2-δ) subunit of the presynaptic, voltage-gated calcium channels that are widely distributed throughout the peripheral and central nervous system. The probable mechanism of action of pregabalin/gabapentin is to reduce the release of several excitatory neurotransmitters (e.g. glutamate, substance P, calcitonin, noradrenaline, gene-related peptide) by inhibiting calcium influx via the calcium channels.12,13,14,15
The pharmacological activity of pregabalin is similar to, but not identical with, that of gabapentin.16 Pregabalin is pharmacologically superior to gabapentin due to its higher bioavailability (90% vs. 33%–66%), more rapid absorption (peak plasma level: 1 hour vs. 3–4 hours) and linear increase in plasma concentration when its dose is increased. Lower doses of pregabalin than that of gabapentin (2–4 fold lower doses) have a similar analgesic effect on neuropathic pain, which makes pregabalin more advantageous in terms of lesser side effects.17,18,19,20 Pregabalin has also shown better analgesic efficacy than gabapentin in diabetic peripheral neuropathy and postherpetic neuralgia over a 12-week period.21
In the last decade, gabapentin, and more recently pregabalin, have been used in many prospective randomised trials that evaluated their effectiveness in reducing postoperative pain. In postoperative pain studies, the two drugs have been compared to a placebo in separate designs, but very few studies have compared their analgesic efficacy in post-operative pain, simultaneously in one design in the doses we hypothesised to be effective.
Hence the present study was undertaken to compare the pre-emptive use of gabapentin versus pregabalin for post-operative pain management in lumber laminectomy surgery under general anaesthesia.
The present study highlighted the fact that both gabapentin and pregabalin, can be used for preemptive analgesia, resulting in prolongation of post-operative analgesia and reduced mean VAS scores after general anaesthesia without altering the intra-operative haemodynamics and increasing the incidence of side-effect. Pregabalin 300 mg was found to be a better analgesic than gabapentin 900 mg during post-operative recovery after general anaesthesia in lumbar laminectomy surgery Patients’ demographic characteristics (age, weight, sex, ASA status) were comparable in both groups. The mean duration of surgery (mean± s.d.) of the patients treated with gabapentin was 2.35±0.38 hours. The mean duration of surgery of the patients treated with pregabalin was 2.28±0.15 hours. There was no significant difference in mean duration of surgery of the two groups (P=0.60). Thus the patients of the two groups were matched of their duration of surgery.
Baseline and intra-operative haemodynamic values calculated every 30 minutes after the initiation of surgery( SBP, DBP, MAP and HR) were comparable in both groups.
From the 1st post-operative hour, there was a decrease in mean SBP in group P, which was lower as compared to group G and the difference was statistically significant at 1 hour and 2 hours post surgery. (P<0.01)
There was also a decrease in mean DBP, MAP, HR in group P which was lower as compared to group G and the difference was statistically significant at 1, 2 and 4 hours post surgery.
The SPO2 levels was comparable between the two groups at all intervals observed post-operatively. From analysis of the haemodynamic status it became evident that in group P, the haemodynamic stability was well maintained post-operatively which may be due to better analgesia and anxiolytic effect of pregabalin.
Mean anxiety score of the patients treated with pregabalin was lower than that of the patients treated with gabapentin at 60 minutes after drug administration indicating greater reduction of anxiety by pregabalin but the difference between groups was not statistically significant (P=0.86).
The mean time to first dose of rescue analgesia in the patients treated with gabapentin was lower than that in the pregabalin group (42.06±10.68 minutes vs 29.50±7.20 minutes) and was statistically significant (P<0.0001). The mean number of doses of morphine required in the pregabalin group was significantly lower as compared to the patients receiving gabapentin (2.96±0.80 and 3.80±0.80 respectively; P=<0.0001). The total consumption of morphine in 24 hours was lower in patients treated with Pregabalin than those patients treated with Gabapentin and the difference between the two groups was statistically significant (P<0.01).
From the above analysis it became evident that there was lesser opioid requirement in group P compared to group G which may be due to better pain relief by pregabalin.
Mean VAS of the patients treated with pregabalin was lower than that of the patients treated with gabapentin at the different time intervals indicating better pain relief by pregabalin, though the difference was statistically significant only at 12 hours after surgery (P<0.05). 
 So, the results of this study correlates with our hypothesis that pregabalin has a better analgesic eficacy to gabapentin during lumbar laminectomy surgeries under general anaesthesia.
Mean NSS score of the patients treated with pregabalin was lower than that of the patients treated with gabapentin. The score at 12 hours post surgery was significantly lower (P=0.013) indicating greater sedation with pre-operative pregabalin than gabapentin. At other time intervals difference in the scores between the two groups were not statistically significant (P>0.05).
No significant difference was found in the incidence of side effects in the two groups (P>0.05). |