Early Markers of Systemic Inflammation are not Related to Pain Burden After Aneurysmal Subarachnoid Hemorrhage: A Multicenter Observational Study

Abstract

Background: Headache is nearly ubiquitous in the immediate aftermath of nontraumatic, aneurysmal pattern subarachnoid hemorrhage (SAH); however, pain experiences vary significantly throughout the intensive care unit (ICU) course across patients and may challenge the establishment of effective analgesic treatment. Acute abortive management often relies on opioids. The pathophysiologic factors driving persistent pain after SAH are likely related to the inflammatory response to blood-brain barrier breakdown and heme degradation. Scarce data on predictors for a course of refractory headache preclude the ability to risk stratify and identify patients who could benefit from targeted, opioid-sparing pain management strategies. We aimed to identify clinical and laboratory predictors of a persistently high pain burden during the ICU course.

Methods: We performed a retrospective, multicenter observational study in patients with SAH. Pain scores were abstracted from the electronic health record. Study participants were divided into quartiles based on the average burden of daily pain, and predictors of pain burden were identified by univariate analysis and ordinal logistic regression. We performed a sensitivity analysis restricted to patients able to verbally report pain scores in the ICU.

Results: Of the 523 patients in the final analysis, the mean age was 55 years, 352 (67%) were female, the median Hunt-Hess score was 3 (interquartile range 2-3), and 465 (89%) had a modified Fisher score of 3 or 4. Older age was associated with lower ICU pain burden (odds ratio 1.01, 95% confidence interval 1.01-1.03). Chronic opioid use (odds ratio 0.59, 95% confidence interval 0.38-0.90) was associated with a higher ICU pain burden. Conversely, blood inflammatory biomarkers were not associated with high ICU pain burden in the univariate or multivariate analysis. The results were similar among the subgroup of patients able to verbally report pain scores throughout admission.

Conclusions: In this multicenter study, young age and chronic opioid use are associated with higher ICU pain burden, whereas inflammatory blood biomarkers lack an association. Further study is required to elucidate the biological pathways and psychosocial determinants of protracted pain after aneurysmal SAH.

Keywords: Biomarkers; Headache; Pain; Subarachnoid hemorrhage.