Interactions between Gabapentin and Cisatracurium in Experimental Animals and in Patients Undergoing Spinal Surgeries : Pharmacological and Clinical Study

Abstract

Background: gabapentin was originally discovered over 40 years ago by the Japanese, who initially were looking for an antispasmodic or muscle relaxant, but, later it was used as an antiepileptic and multimodal perioperative drug. Objective of this randomized study is to assess the some cardiovascular effects of gabapentin as well as its effect on the neuromuscular blockade induced by Cisatracurium. The interactions between both of them was also done in cats and rats & in patients undergoing elective spinal surgeries. Materials & Methods: The pharmacological study was carried out at the pharmacological lab of Al-Azhar University. The effect of different doses of cisatracurium (0.25 -4 µg/ml) and Gabapentin (6-96 µg/ml) & interactions between gabapentin (24µg/mL) and cisatracurium (0.25-4 µg/mL) were also done to test the effect on the amplitude of contraction of isolated Rat phrenic nerve -diaphragm preparation. Effect of intravenous (IV) injection of cisatracurium (1-16 mg/kg) and Gabapentin (15-240 mg/kg) and interactions between gabapentin (60mg/kg) and cisatracurium (1-16 mg/kg) on mean arterial blood pressure (MAP) and electrocardiogram (ECG) were also studied on anesthetized cats. Each experiment was done on six preparations. The clinical Study was carried out at Al-Zahraa University Hospital on 90 patients (ASA I or II) of both sexes undergoing spinal operations were randomized into three equal groups (30 patients) for each; one hour preoperatively they received oral capsules, group I; gabapentin (1200mg), group II gabapentin (800mg) and group III; placebo capsules. After induction of anesthesia with (IV) fentanyl, thiopental and cisatracurium & tracheal intubation, anesthesia was maintained by isoflurane (0.5-2%), Patients were assessed for heart rate (HR), MAP, neuromuscular blockade. Isoflurane concentration, fentanyl needed and cisatracurium consumption were recorded. Results: Experimentally: In-vitro study: Cisatracurium besylate (0.25-4µg/ml) produced dose-dependent significant reductions on the amplitude of muscle contractions. Gabapentin (6-96µg/ml) produced dose-dependent significant reductions on the amplitude of muscle contractions at 24-96 µg/mL while the first two doses 6-12 µg/mL have no effect. On interactions Gabapentin (24 µg/ml) produced synergistic effect on neuromuscular blocker effect of cisatracurium (0.25-4 µg/mL). In-vivo study cisatracurium, IV, (1-16 mg/kg) produced no effect on both mean arterial blood pressure (MAP) and heart rate (HR) of anesthetized cats. Gabapentin (15- 240 mg/kg) caused dose-dependent significant reductions on the MAP and the HR of the anesthetized cats except the first two doses (15-30 mg/kg). On interactions Gabapentin (60 mg/kg) potantiated the effect of cisatracurium (1-16mg/kg) and caused significant reduction on mean arterial blood pressure and heart rate. Clinically: Gabapentin 1200mg produced highly significant reduction in MAP&HR at pre-induction and immediately after intubation which extended for 120min. It also prolonged the duration of neuromuscular blockade of cisatracurium 0.15 mg/kg for 100min. While Gabapentin 800mg produced significant reduction in MAP &HR at pre-induction, immediately after intubation which extended for 45min. It also prolonged the duration of neuromuscular blockade of cisatracurium 0.15mg/kg up to for70min. Conclusion: Gabapentin has a neuromuscular blocking effect on interactions Gabapentin produced synergeistic effect on the neuromuscular blocker effect of cisatracurium. It also has considerable hypotensive as well as negative chronotropic effect. On interactions, gabapentin potantiated the effect cisatracurium on MAP&HR and caused significant decrease in MAP & HR on experimental animals and on patients undergoing elective spinal surgeries.