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.

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 (PbtO2 < 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; Tcore ≥ 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 PbtO2-decrease is directly correlated with the decrease in Tcore (p = 0.002) and higher baseline PbtO2 (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).

Delayed Resolution of Cerebral Edema Is Associated With Poor Outcome After Nontraumatic Subarachnoid Hemorrhage.

Background and Purpose- Global cerebral edema occurs in up to 57% of patients with subarachnoid hemorrhage (SAH) and is associated with prolonged hospital stay and poor outcome. Recently, admission brain edema was successfully graded using a simplified computed tomography-based semiquantitative score (subarachnoid hemorrhage early brain edema score [SEBES]). Longitudinal evaluation of the SEBES grade may discriminate patients with rapid and delayed edema resolution after SAH. Here, we aimed to describe the resolution of brain edema and to study the relationship between this radiographic biomarker and hospital course and outcome after SAH. Methods- For the current observational cohort study, computed tomography scans of 283 consecutive nontraumatic SAH patients admitted to the neurological intensive care unit of a tertiary hospital were graded based on the absence of visible sulci at 2 predefined brain tissue levels in each hemisphere (SEBES ranging from 0 to 4). A score of ≥3 was defined as high-grade SEBES. Multivariable regression models using generalized linear models were used to identify associated factors with delayed edema resolution based on the median time to resolution (SEBES ≤2) in SAH survivors. Results- Patients were 57 years old (interquartile range, 48-68) and presented with a median admission Hunt and Hess grade of 3 (interquartile range, 1-5). High-grade SEBES was common (106/283, 37%) and resolved within a median of 8 days (interquartile range, 4-15) in survivors (N=80). Factors associated with delayed edema resolution were early (<72 hours) hypernatremia (>150 mmol/L; adjusted odds ratio [adjOR], 4.88; 95% CI, 1.68-14.18), leukocytosis (>15 G/L; adjOR, 3.14; 95% CI, 1.24-8.77), hyperchloremia (>121 mmol/L; adjOR, 5.24; 95% CI, 1.64-16.76), and female sex (adjOR, 3.71; 95% CI, 1.01-13.64) after adjusting for admission Hunt and Hess grade and age. Delayed brain edema resolution was an independent predictor of worse functional 3-month outcome (adjOR, 2.52; 95% CI, 1.07-5.92). Conclusions- Our data suggest that repeated quantification of the SEBES can identify SAH patients with delayed edema resolution. Based on its' prognostic value as radiographic biomarker, the SEBES may be integrated in future trials aiming to improve edema resolution after SAH.