An Observational Study on the Use of Intravenous Non-Opioid Analgesics and Antipyretics in Poor-Grade Subarachnoid Hemorrhage: Effects on Hemodynamics and Systemic and Brain Temperature

Abstract

Intravenous nonsteroidal anti-inflammatory drugs and nonopioid analgesics are used to achieve normothermia or relieve pain in patients with aneurysmal subarachnoid hemorrhage (aSAH). We investigated the effects of paracetamol (1 g), diclofenac (75 mg) and metamizole (1 g) on systemic and cerebral hemodynamics and temperature during febrile and nonfebrile episodes after aSAH. Prospectively collected data from 77 consecutive poor-grade aSAH patients with invasive neuromonitoring were included. The burden and occurrence of hypotension (mean arterial pressure <70 mmHg), brain tissue hypoxia (P_btO₂ < 20 mmHg), high intracranial pressure (>22 mmHg), low cerebral perfusion pressure (CPP <70 mmHg), and cerebral autoregulation pressure (pressure reactivity index [PRx]) during baseline (1 hour before) and 6 hours after medication were analyzed in febrile (core temperature; T_core ≥ 38.3°C) and nonfebrile episodes. Nine hundred eighty-nine infusions (278 paracetamol, 542 diclofenac, and 169 metamizole) were administered resulting in significant reduction of core and brain temperature during febrile (49%) and nonfebrile (51%) episodes (p < 0.001). In febrile cases, temperature decreased for >1 hour below 37.5°C in 36% of interventions and ≤37°C in 11%. Hemodynamic side effects with hypotension and low CPP occurred in both febrile and nonfebrile episodes (p < 0.001) prompting increased vasopressor support in 31% of cases, even more pronounced during the vasospasm period (4-12 days postictus) (OR 5.4, 95% CI 1.8-16). The magnitude of P_btO₂-decrease is directly correlated with the decrease in T_core (p = 0.002) and higher baseline P_btO₂ (p < 0.001). PRx decreased in febrile and nonfebrile episodes (p < 0.001), indicating improvement of cerebrovascular autoregulation. Antipyretics were insufficient to achieve sustained normothermia in poor-grade aSAH patients. Hemodynamic side effects were common even when given as analgesic drugs. Further studies are needed to weigh hemodynamic side effects to benefits (inter alia improved cerebral autoregulation).

Keywords: antipyretics; subarachnoid hemorrhage.