Association of Onset-to-Treatment Time With Discharge Destination, Mortality, and Complications Among Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Marie-Jeanne Buscot, Ronil V. Chandra, Julian Maingard, Linda Nichols, Leigh Blizzard, Christine Stirling, Karen Smith, Leon Lai, Hamed Asadi, Jens Froelich, Mathew J. Reeves, Nova Thani, Amanda Thrift, Seana Gall
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Rapid access to specialized care is recommended to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH), but understanding of the optimal onset-to-treatment time for aneurysmal SAH is limited. <h3>Objective</h3> To assess the optimal onset-to-treatment time for aneurysmal SAH that maximized patient outcomes after surgery. <h3>Design, Setting, and Participants</h3> This cohort study assessed 575 retrospectively identified cases of first-ever aneurysmal SAH occurring within the referral networks of 2 major tertiary Australian hospitals from January 1, 2010, to December 31, 2016. Individual factors, prehospital factors, and hospital factors were extracted from the digital medical records of eligible cases. Data analysis was performed from March 1, 2020, to August 31, 2021. <h3>Exposures</h3> Main exposure was onset-to-treatment time (time between symptom onset and aneurysm surgical treatment in hours) derived from medical records. <h3>Main Outcomes and Measures</h3> Clinical characteristics, complications, and discharge destination were extracted from medical records and 12-month survival obtained from data linkage. The associations of onset-to-treatment time (in hours) with (1) discharge destination of survivors (home vs rehabilitation), (2) 12-month survival, and (3) neurologic complications (rebleed, delayed cerebral ischemia, meningitis, seizure, hydrocephalus, and delayed cerebral injury) were investigated using natural cubic splines in multivariable Cox proportional hazards and logistic regression models. <h3>Results</h3> Of the 575 patients with aneurysmal SAH, 482 patients (mean [SD] age, 55.0 [14.5] years; 337 [69.9%] female) who received endovascular coiling or neurosurgical clipping were studied. A nonlinear association of treatment delay was found with the odds of being discharged home vs rehabilitation (effective<i>df</i> = 3.83 in the generalized additive model, χ<sup>2</sup>test<i>P</i> = .002 for the 4-<i>df</i>cubic spline), with a similar nonlinear association remaining significant after adjustment for sex, treatment modality, severity, Charlson Comorbidity Index, history of hypertension, and hospital transfer (likelihood ratio test:<i>df</i> = 3, deviance = 9.57, χ<sup>2</sup>test<i>P</i> = .02). Both unadjusted and adjusted cox regression models showed a nonlinear association between time to treatment and 12-month mortality with the lowest hazard of death with receipt of treatment at 12.5 hours after symptom onset, although the nonlinear term became nonsignificant upon adjustment. The odds of being discharged home were higher with treatment before 20 hours after onset, with the probability of being discharged home compared with rehabilitation or other hospital increased by approximately 10% when treatment was received within the first 12.5 hours after symptom onset and increased by an additional 5% from 12.5 to 20 hours. Time to treatment was not associated with any complications. <h3>Conclusions and Relevance</h3> This cohort study found evidence that more favorable outcomes (discharge home and survival at 12 months) were achieved when surgical treatment occurred at approximately 12.5 hours. These findings provide more clarity around optimal timelines of treatment with people with aneurysmal SAH; however, additional studies are needed to confirm the findings.