Treating Paroxysmal Sympathetic Hyperactivity in Children: The Known Unknowns Free

In 2014, an international consensus group recommended the term “paroxysmal sympathetic hyperactivity” (PSH) for the syndrome experienced by a subset of survivors of acquired brain injury who exhibit signs of increased sympathetic activity. Despite this, “storming,” “dysautonomia,” and at least 29 other synonyms are still commonly heard in the halls of hospital units.¹  As it turns out, standardizing what to call the syndrome was actually the easy part. Carozza et al’s attempt to create a clinical practice guideline for the evaluation and management of PSH in children is a worthwhile goal, but the paucity of evidence to guide therapy cannot be overstated. Case studies and case series represent the large majority of available literature, with virtually no studies in children. This makes any attempt to standardize clinical practice in children with PSH arguably premature and vulnerable to unintended consequences.

Although it is common for patients with PSH to require >1 medication, promulgating a paradigm that manages the syndrome exclusively as a collection of signs and symptoms risks unnecessary polypharmacy. A patient with PSH may experience different clinical manifestations at any given moment. Vital sign instability such as tachycardia and tachypnea may be the sole or dominant features 1 moment, with episodes of apparent pain and dystonia dominating the next.²  Yet, these clinical manifestations have the same physiologic root cause. In the same way that a patient with diabetic ketoacidosis may experience nausea, solely administering an antiemetic to that patient would miss the mark.

Although high-quality evidence to guide pharmacotherapy remains sparse, our understanding of PSH pathophysiology has come into focus in recent years, suggesting a path toward a more holistic and stepwise approach. In their prospective study of patients with PSH, Baguley et al lent further credence to the currently accepted model: Impaired inhibitory mechanisms which fail to modulate afferent stimuli that the body would typically perceive as benign.³  Perhaps it is not coincidence that, in their review of the many medications used to treat PSH, Perkes et al identified a gamma-aminobutyric acid analog, intrathecal baclofen, as possessing the strongest available evidence in terms of study design.⁴  Acknowledging intrathecal baclofen’s invasiveness and cost, they narrowed the contenders further to enteral agents with the relatively best evidence: Gabapentin, β blockers, opioids, benzodiazepines, and centrally-acting α agonists.⁵  Unfortunately, no study to date has been able to elucidate which of these medications work “upstream” to prevent the catecholamine cascade and treat the underlying disease process, or if they are primarily mitigating the impact of the resulting symptoms. Nevertheless, the available literature does provide us some possible clues.

Gabapentin, another gamma-aminobutyric acid analog, has yielded encouraging results in patients refractory to other therapeutics. Baguley hypothesizes that gabapentin’s benefit is not isolated to the treatment of neuropathic pain, but may help to increase spinal inhibitory mechanisms and prevent the syndrome’s abnormal response to afferent stimuli.⁶  This is in contrast to the “targeted pharmacotherapy” algorithm proposed by Carozza et al, which confines the use of gabapentin to an analgesic.⁷  Similarly, β blockers make a compelling case for a role in a more holistic treatment strategy. They have long served as the mainstay of therapy at trauma centers for traumatic brain injury patients experiencing signs of increased sympathetic output, including patients with PSH.⁸  Because of its lipophilic properties and ability to cross the blood–brain barrier, nonselective β blockers such as propranolol are particularly well represented in the adult trauma literature, including multiple prospective studies associated with decreased mortality and decreased length of stay.⁹  Specific benefits have included decreased catecholamine levels and associated improvement in tachycardia, tachypnea, hypertension, hyperthermia, and severe agitation.^10,11  Perhaps most intriguing is evidence pointing to a possible benefit of propranolol in PSH-associated dystonia, not a classic indication and 1 that, again, suggests the same root cause for all of the syndrome’s clinical manifestations.^12,13  Like gabapentin, propranolol is another example where Carozza et al recommend a relatively targeted indication (“vital sign abnormalities”) for a medication that may have a broader role to play in modulating this syndrome.

Although Carozza et al do make brief reference to considering “expert consultation,” this is worth emphasizing. Even a seasoned pediatric hospitalist should strongly consider consultation with a pediatric rehabilitation specialist or complex care provider experienced in the evaluation and management of children with PSH. It is not difficult to imagine that the protracted hospitalizations, numerous provider handoffs, and frequent medication starts and stops experienced by these patients can further complicate assessment of which medication regimen is most effective. These experts can aid in assessment, help identify a stepwise medication titration plan, and advise on exactly when and how medications should be weaned.

The work of leaders in PSH research such as Baguley, Perkes and others would suggest that we not lose sight of the potential for a more holistic and comprehensive treatment paradigm: 1 that prevents or decreases the catecholamine cascade in addition to adjunct therapies that mitigate breakthrough symptoms. In the meantime, we should proceed with caution when seeking to standardize clinical practice. Evidence specific to children with PSH is almost nonexistent, let alone any prospective studies that thoughtfully leverage our growing understanding of the syndrome’s pathophysiology.