Pharmacological Management of Paroxysmal Sympathetic Hyperactivity: A Scoping Review

Paroxysmal sympathetic hyperactivity (PSH) occurs in ∼10% of patients following acute severe brain injury. While PSH is associated with worse outcomes, there are no clinical practice guidelines to inform treatment. We aimed to systematically review the literature on the pharmacological management of PSH. MEDLINE, Embase, and Cochrane library databases were searched from inception to August 2020. Eligible studies met the following criteria: 1) randomized controlled trials, non-randomized controlled trials (case control or controlled cohort), observational studies, case series, and case reports; 2) study population of adult and pediatric patients; 3) exposure to an acute neurological insult complicated by PSH (or historic synonym); 4) description of pharmacological treatment of PSH. Our search retrieved 2729 citations with 83 articles assessed for inclusion. After full text extraction, 56 manuscripts inclusive of 459 patients met eligibility criteria. We identified 31 case reports, 15 case series (152 patients), seven retrospective case control or cohort studies (212 patients), and three prospective observational studies (52 patients). Traumatic brain injury was the most common precipitating insult (407 patients), followed by hypoxic encephalopathy (72 patients) and intracranial hemorrhage (10 patients). There were 48 drugs from 22 classes prescribed for the management of PSH. The most frequently prescribed agents were benzodiazepines, β-blockers, opioids, α-2 agonists, and baclofen. However, route and dose of drug and subsequent outcome were inconsistently reported, such that no summary was possible. While a wide variety of drugs have been reported to treat PSH, there is a lack of even moderate-quality evidence to inform clinical decision making.