Paroxysmal Sympathetic Hyperactivity

  • Christine Hudoba APRN1
  • Hannah L Kirsch MD2
  • Kasey L Malotte PharmD3
  • Neha M Kramer MD1

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Background: Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of provoked episodes of motor posturing and surges of sympathetic tone that occur in up to one third of patients with severe acute brain injuries (1). Traumatic brain injury (79.4%) is the most common cause followed by hypoxia (9.7%), and stroke (5.4%) (2). In children, PSH can be a recognized complication of an underlying degenerative neurologic condition. More than 30 prior terms have been used for PSH, including sympathetic or autonomic storm, autonomic dysfunction, dysautonomia, and diencephalic seizure (1,3,4). It can be highly distressing for patients to experience and for caregivers to witness, negatively impacting quality of life, prognosis, and serious illness decision-making. It is key that clinicians who commonly care for seriously neurologically injured patients be able to identify and manage this often-under-recognized condition.

Pathophysiology:  Brain injuries associated with PSH are typically diffuse or multifocal (4). PSH likely results from the loss of inhibitory modulation of sympathetic centers, and an imbalance between excitation and inhibition from acute injury (4,5). Younger patients are more susceptible (6). Incidence ranges from 5 to 30 percent of brain-injured patients, dependent on the severity and etiology of the injury.

Clinical features:  PSH is a clinical diagnosis in which there is no alternate etiology among relevant differential diagnoses (1). Two or more features should be observed during a PSH episode: tachycardia (almost uniformly present), tachypnea, hypertension (HTN), hyperthermia, sweating, hypertonicity, mydriasis, piloerection, and dystonic posturing (1). Triggers may or may not be identifiable. PSH is usually diagnosed in an ICU after a decrease in or liberalization from sedation (mean time to diagnosis of 8.3 days). However, it can emerge weeks after a brain injury, at which point the patient may have returned home, been transferred to subacute rehabilitation, or transitioned to hospice care. Use of the Clinical Features Scale and Diagnosis Likelihood Tool can aid in distinguishing PSH from mimics such as sepsis, pulmonary embolism, tonic seizures, elevated intracranial pressure, and alcohol withdrawal (1). PSH manifests in sudden episodes lasting up to 30 minutes if untreated. Alternative diagnoses should be considered if symptoms do not resolve between episodes. 

Prognostic features:  Although specific prognostic data is not available, PSH has been shown to be an independent risk factor for worse neurologic outcomes, longer hospital lengths of stay, higher disability scores, and greater mortality (4,5). This is likely because PSH episodes are associated with an increase in metabolic demand, which can lead to dehydration, musculoskeletal complications, neurologic deterioration, weight loss, and metabolic derangements (4,7). Thus, timely diagnosis and appropriate intervention may improve a patient’s survival outcomes (5,7).

PSH triggers:  Patients with brain injuries can have variable levels of consciousness and abilities to communicate, thus, clinicians must be attentive to potential triggers for PSH episodes which include (3,8).

  • Patient-intrinsic triggers: coughing, respiratory distress, pain (e.g., headache, musculoskeletal from spasticity or immobility, post-surgical, abdominal cramping), nausea, constipation, urinary retention.
  • External triggers:  transfers, transportation, repositioning, bathing, toileting, blood draws, catheter insertion, suctioning, sounds (alarms, voices), lights, changes in room temperature, use of blankets.

Educating staff and caregivers: Witnessing PSH episodes can be distressing. Attempts should be made to minimize alarms that are activated during episodes of PSH (e.g., abnormal vital signs), to approach patients calmly, and to utilize verbal cues when transporting patients. Open acknowledgment, reassurance, and education can also decrease caregiver distress (3). 

Pharmacologic management is nearly always needed to complement non-pharmacologic management (4,5,8). The goal should be symptomatic relief with the lowest effective medication dose since overtreatment risks interfering with recovery, vital signs, and/or meaningful interactions. There is no universally established approach; most recommendations are based on expert opinion (4, 9-13). A customized, multimodal approach is often required that includes preventive, abortive, and anticipatory medications given in advance of nursing care and other known triggers (4,9-13). Usually, PSH pharmacotherapy is initiated by the primary inpatient team (e.g., ICU clinicians, neurology). Physical medicine and rehabilitation (PMR) clinicians may be available as a consultative resource. However, generalist clinicians as well as hospice and palliative care specialists may have to assume medication management.  Initial dosing examples below are based on adults without other comorbidities. Clinical decision-making and safety should always be considered prior to medication agent and dose selection.

  • Gamma aminobutyric acid type A (GABAA) receptor agonists: Propofol is a parenteral infusion, usually limited to ICU settings. For patients with critical illness whose sedation is an acceptable side effect, it is a first-line abortive (10 mcg bolus) and preventative agent (5 mcg/kg/min) for tachycardia, HTN, tachypnea, diaphoresis, fever, and posturing. Benzodiazepines are second-line abortive agents for the same symptoms (e.g., midazolam 2-4 mg IV bolus).
  • Opioids:  first-line abortive agents for tachycardia, HTN, tachypnea, diaphoresis, fever, posturing (e.g., morphine 5-15 mg PO or opioid equianalgesic equivalent)
  • Alpha-2-delta ligands (e.g., gabapentin 100mg, pregabalin 25mg PO TID): limited to oral dosing, they are first line preventative agents for tachycardia, HTN, tachypnea, diaphoresis, and fever. 
  • Gamma aminobutyric acid type B (GABAB) receptor agonist (e.g., baclofen 5-10 mg PO TID): administered as a scheduled oral agent or as an intrathecal infusion (under the supervision of a PMR clinician or other specialist) as a first line preventative agent for posturing.
  • Alpha-2 agonists (e.g., clonidine 0.1 mg PO TID/transdermal, dexmedetomidine 0.3 mcg/kg): second-line abortive agents for tachycardia and HTN.
  • Beta-blockers (e.g., propranolol 40 mg PO 2-3x/d): second-line preventative agents for tachycardia, HTN, diaphoresis, and posturing.
  • Peripheral acting skeletal muscle relaxant (e.g., dantrolene 25 mg PO 1-3 times/day): third-line preventative agents for posturing.
  • Dopamine type 2 (D2) receptor agonist (e.g., bromocriptine 1.25mg PO daily): although they are associated with modest improvements as a preventative agent for most PSH symptoms, they are a third-line agent due to known side effects such as confusion, dyskinesia, and seizures.


(1) Baguley IJ, Perkes IE, Fernandez-Ortega JF, et al. Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria. J Neurotrauma. 2014;31(17):1515-1520. doi:10.1089/neu.2013.3301

(2) Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68(2):126-135. doi:10.1002/ana.22066

(3) Levy ER, McVeigh U, Ramsay AM. Paroxysmal sympathetic hyperactivity (sympathetic storm) in a patient with permanent vegetative state. J Palliat Med. 2011;14(12):1355-1357. doi:10.1089/jpm.2010.0444

(4) Scott RA, Rabinstein AA. Paroxysmal Sympathetic Hyperactivity. Semin Neurol. 2020;40(5):485-491. doi:10.1055/s-0040-1713845

(5) Meyfroidt G, Baguley IJ, Menon DK. Paroxysmal sympathetic hyperactivity: the storm after acute brain injury [published correction appears in Lancet Neurol. 2018 Mar;17 (3):203]. Lancet Neurol. 2017;16(9):721-729. doi:10.1016/S1474-4422(17)30259-4

(6) Rabinstein AA. Autonomic Hyperactivity. Continuum. 2020;26:138-53

(7) Hughes JD, Rabinstein AA. Early diagnosis of paroxysmal sympathetic hyperactivity in the ICU. Neurocrit Care. 2014;20(3):454-459. doi:10.1007/s12028-013-9877-3

(8) Mathew MJ, Deepika A, Shukla D, Devi BI, Ramesh VJ. Paroxysmal sympathetic hyperactivity in severe traumatic brain injury. Acta Neurochir (Wien). 2016;158(11):2047-2052. doi:10.1007/s00701-016-2934-x

(9) Thomas A, Greenwald BD. Paroxysmal Sympathetic Hyperactivity and Clinical Considerations for Patients With Acquired Brain Injuries: A Narrative Review. Am J Phys Med Rehabil. 2019;98(1):65-72. doi:10.1097/PHM.0000000000000990

(10) Samuel S, Allison TA, Lee K, Choi HA. Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity After Brain Injury. J Neurosci Nurs. 2016;48(2):82-89. doi:10.1097/JNN.0000000000000207

(11) Cid E, Mella F, Lucchini L, Caracmo M, Monasterio J. Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man. Biopharm Drug Dispos. 1986;7(6):559-66

(12) Rabinstein AA, Benarroch EE. Treatment of Paroxysmal Sympathetic Hyperactivity. Curr Treat Options Neurol. 2008;10:151-7

(13) Zheng RZ, Lei ZQ, Yang RZ, Huang GH, Zhang GM. Identification and Management of Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury. Front Neurol. 2020;11;81. doi:10.3389/fneur.2020.00081

Author Affiliations: 1Rush University, Chicago, IL; 2Stanford University School of Medicine, Palo Alto, CA; 3Cedars-Sinai Medical Center, Los Angeles, CA

Conflicts of Interests: None to report

Version History:  first electronically published in February 2023; originally edited by Sean Marks MD