Effect of Pregabalin on Perioperative Headache in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized Double-Blind, Placebo-Controlled Trial

Abstract

Background Patients with acute aneurysmal subarachnoid hemorrhage (aSAH) experience excruciating headache that is difficult to manage in resource-constrained settings. Pregabalin’s (β-isobutyl-GABA) analgesic, antiepileptic, and antiemetic properties make it an attractive adjuvant in pain management for these patients. Methods We conducted a double-blind, placebo-controlled, randomized clinical trial on 40 aSAH patients undergoing aneurysmal clipping to assess the effect of perioperative pregabalin in decreasing perioperative headache, anesthetic, and opioid requirement. Patients received either pregabalin (75 mg) or placebo twice daily soon after admission till 24-hour postoperative, in addition to paracetamol 650 mg thrice daily. Headache assessed using a visual analog scale (VAS) at five time points was compared using a mixed effects regression model. Results Pain assessed by VAS declined significantly more from the baseline in pregabalin recipients compared with placebo at preinduction (–3.6 vs.–1.8; p = 0.004), 12-hour (4.3 vs. 2.8; p = 0.014), and 24-hour postsurgery (4.7 vs. 2.9; p = 0.007), but not at the 6-hour postoperation (4.9 vs. 3.8; p = 0.065). Pregabalin recipients required a lower minimum alveolar concentration of sevoflurane to maintain a prespecified bispectral index of 40 and 60 (0.8 vs. 0.9; p = 0.014) and required fewer rescue analgesic doses in the 24 hours following surgery (1.8 vs. 3.3; p = 0.005). The intraoperative fentanyl requirement was not significantly different between the groups (10 μg/kg vs. 11.4 μg/kg; p = 0.065). There was no significant difference in the sedation scores. Conclusions Pregabalin 75 mg administered twice daily, during the perioperative period, was an effective adjunct in the management of the severe headache experienced by patients with aSAH and decreased the opioid and anesthetic requirement without significantly increasing sedation.

The effect of step-wised protocol on critical care management of severe aneurysmal subarachnoid hemorrhage

“…SaSAH is a common clinical disease in neurosurgery, which clinically manifested as sudden and excruciating headache (Lionel et al, 2019). In recent years, with the development of microsurgical operative techniques and endovascular embolization techniques, it has greatly improved the prognosis of patients.…”

Safety, Tolerability, and Efficacy of Pain Reduction by Gabapentin for Acute Headache and Meningismus After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study

“…There were no significant differences between the groups when comparing AEs. Blood urea nitrogen ranged between 3 and 24 mg/dL (normal, [7][8][9][10][11][12][13][14][15][16][17][18][19][20] and CrCl ranged between 0.3 and 1.5 mg/dL (normal, 0.6-1.0). We did not observe unexplained worsening of liver or kidney function.…”

“…High doses of opioids can also induce delirium, which may prolong intensive care unit (ICU) length of stay ( 10 , 12 ). This has encouraged the investigation of other analgesic drugs for the management of severe headache experienced by aSAH patients in order to reduce opioid usage ( 13 ).…”

Evaluating common medications utilized in aneurysmal subarachnoid hemorrhage and association with delayed cerebral ischemia

“…DCI has been associated with younger age and high score on the modi ed Fisher scale, however clear risk factors for DCI remain sparse [3,4]. Although promising medical and interventional therapies are undergoing trials to prevent DCI [3], few studies have evaluated associations between DCI and commonly used analgesic and anti-seizure medication dosages already utilized in the management of many SAH patients [6][7][8][9][10][11][12].…”