Paroxysmal sympathetic hyperactivity (PSH) is a life-threatening condition characterized by hyperadrenergic activity and autonomic dysfunction. Also termed autonomic storms, PSH can occur after a variety of cerebral insults, most commonly traumatic brain injury. Limited pediatric literature is available, especially in patients with brain injury from hypoxia. No consensus exists for the terminology, diagnostic criteria, or treatment algorithm for PSH. Thus, the optimal management, including medication selection and dosing, remains unclear. We present the detailed treatment of a 9-year-old, African American male with hypoxic brain injury after pulseless arrest following status asthmaticus, who subsequently developed PSH. The patient began to experience episodes of tachycardia, hypertension, tachypnea, diaphoresis, rigidity, and dystonic posturing on hospital day 5. After ruling out other potential causes, a diagnosis of PSH was made. Episodes of PSH failed to respond to lorazepam or labetalol but were aborted successfully with morphine. Management of PSH after hypoxic brain injury required medications for acute treatment as well as for prevention of PSH. Morphine was found to be highly effective and safe for aborting the autonomic crises. Other agents more commonly described in the literature did not result in an adequate response and were associated with significant adverse effects. A combination of clonazepam, baclofen, and either propranolol or clonidine aided in reducing the frequency of episodes of PSH. We suggest using morphine for aborting severe episodes of PSH that do not respond to antihypertensive agents or benzodiazepines.

Paroxysmal sympathetic hyperactivity (PSH), a condition characterized by hyperadrenergic activity and autonomic dysfunction, has been reported following acute brain injury and other cerebral insults.1–3 In addition, PSH is described as episodic periods of excessive autonomic activity, manifested by tachycardia, hypertension, tachypnea, fever, diaphoresis, dystonic posturing, and rigidity.3 A variety of neurologic injuries may result in PSH, with most reports found in the traumatic brain injury (TBI) population.2 Limited pediatric literature is available, especially in patients with brain injury from hypoxia. No consensus exists for the terminology, diagnostic criteria, or treatment algorithm for PSH. Consequently, most management strategies are based on evidence from small studies and case reports.1,4–13 Here, we describe the detailed treatment of a 9-year-old male with severe PSH following hypoxic brain injury that was intractable to reported therapies, including α-adrenergic agonists, β-adrenergic blockers, and benzodiazepines. Multiple episodes of autonomic crises were successfully aborted with morphine.

A 9-year-old, 34-kg African American boy experienced a pulseless arrest from status asthmaticus lasting longer than 10 minutes and required intubation. His neurologic examination revealed responsive pupils and a positive gag reflex but no response to voice or noxious stimuli. The patient also had extensor posturing movements with suctioning and neck stimulation. Magnetic resonance imaging revealed findings consistent with hypoxic brain injury.

Fentanyl and midazolam continuous infusions were initiated for analgesia and sedation, but he was weaned and medications were discontinued on hospital days 2 and 3, respectively, to better assess neurologic status. Starting on hospital day 4, the patient had periodic episodes of tachycardia, hypertension, dystonic posturing, fever, muscle rigidity, and dilated pupils. Symptoms were thought to be due to opioid and/or benzodiazepine withdrawal, thus fentanyl and midazolam continuous infusions were restarted on hospital day 5. Because of this clinical deterioration, a computed tomography scan was obtained and revealed severe cerebral edema. Management to reduce intracranial pressure was initiated, including hyperventilation, hypertonic saline, mannitol, and vecuronium. Initially, the autonomic instability was attributed to increased intracranial pressure, but symptoms worsened rather than improved as the cerebral edema resolved. Drug withdrawal was eventually ruled out because symptomatic episodes continued despite reinitiation of fentanyl and midazolam; thus, fentanyl and midazolam were tapered and discontinued on hospital days 10 and 18, respectively. In the first week, the events occurred every 3 to 4 days but increased by day 19 to 4 episodes daily. Cardiac etiologies, seizures, and systemic infection were ruled out as potential causes. At this point, the diagnosis of PSH was given.

Clonidine, 0.1 mg enterally twice daily (6 mcg/kg/day), and lorazepam, 1 mg (0.03 mg/kg/dose) intravenously, were initiated as needed for autonomic episodes, but episodes continued to occur 1 to 4 times daily. Clonidine was titrated up to 0.2 mg 3 times daily (18 mcg/kg/day) but was discontinued on day 24 because of severe bradycardia between episodes. Propranolol, 5 mg enterally every 8 hours (0.4 mg/kg/day), with clonazepam, 0.5 mg enterally every 8 hours (0.04 mg/kg/day), was then initiated. Baclofen, 5 mg enterally twice daily (0.3 mg/kg/day), was added on day 28 to reduce spasticity and aid with autonomic episodes. Doses were titrated as needed to reduce symptoms and minimize toxicity. During this time, both lorazepam and later labetalol were found to be ineffective at aborting acute episodes. The autonomic storms did not abate until morphine, 2.5 mg (0.07 mg/kg/dose) intravenously as needed, was started on hospital day 35. Morphine was extremely effective at aborting episodes of PSH. During the next 2 weeks, only 4 more autonomic episodes occurred, and all were aborted with either intravenous or enteral morphine. The patient was eventually discharged on hospital day 54 to a long-term care facility receiving the following enteral medications: propranolol, 10 mg every morning, 5 mg in the afternoon, and 10 mg at night (0.7 mg/kg/day); baclofen, 20 mg every 8 hours (1.8 mg/kg/day); and clonazepam, 0.5 mg every 8 hours (0.04 mg/kg/day). Morphine, 15 mg (0.4 mg/kg/dose) enterally was given as needed for acute episodes.

This case report was exempt from Institutional Review Board approval at the University of Illinois, Chicago.

The development of PSH after brain injury is grave and leads to increased morbidity and mortality.1,2 Excessive catecholamines lead to the characteristic signs and symptoms of PSH: tachycardia, tachypnea, hypertension, fever, diaphoresis, and dystonic posturing and rigidity.3 The time to onset, duration, and frequency of episodes vary greatly among patients, increasing the difficulty in correctly diagnosing this condition.

Currently, there is no consensus in the diagnostic criteria or treatment approach to PSH.3 Even the actual term used to describe this condition varies widely and includes such terminology as PSH, autonomic storms, sympathetic storms, paroxysmal autonomic instability with dystonia, dysautonomia, central autonomic dysfunction, and others. Literature does support this condition as the result of a cerebral insult, most commonly TBI.2 Other causes include hypoxic injury, brain tumors, hydrocephalus, and stroke. It is not clear whether TBI increases the risk of PSH compared with other brain injuries or whether TBI is simply more common. Although several adult studies have demonstrated a greater incidence of PSH after TBI than after other cerebral insults,14,15 a study by Krach and colleagues1 found the opposite result in pediatric patients, with a higher incidence of PSH after hypoxic brain injury (9 of 31 children; 29%) compared with TBI (20 of 166 children; 12%). Studies have additionally found that outcomes are worse in patients who develop PSH secondary to non-traumatic brain injury than they are in those with TBI.1,15 This is consistent with our case because the patient never recovered from his vegetative state after his hypoxic insult.

The exact mechanism by which PSH occurs is unknown. Historically, it was thought to be epileptogenic in nature.2,16 Further research found that no seizure activity is present on electroencephalogram, and PSH does not respond to anticonvulsant therapy. This is consistent with our patient, who had no seizure activity during his extensive workup. Current theories include conventional disconnection and the excitatory:inhibitory (E:I) ratio model, both of which result in excessive adrenergic activity.16 Conventional disconnection theories, in general, describe some type of structural damage to the brain or brainstem that results in a loss of normal autonomic regulation. The E:I ratio model further suggests an allodynic tendency of PSH, which is characterized by a disproportionately large nociceptive response in the body to what should normally be non-noxious stimuli. Our patient was noted to experience some of his episodes after activities like suctioning, bathing, and repositioning, although there were not always any identifiable precipitating factors.

Once PSH is diagnosed, appropriate treatment options to both abort acute episodes and decrease the frequency and severity of future episodes should be initiated.17,18 Many medications have been reported for treating pediatric PSH with inconsistent success in aborting or preventing episodes (see Table). As would be expected with such a rare condition, limited information is available to guide medication dosing recommendations for pediatric patients. Additionally, it would be difficult to design a study to determine the optimal medication regimen for PSH without addressing the heterogeneity of this patient population and the lack of consensus about its diagnostic criteria.

Table.

Summary of Reports of Pediatric Paroxysmal Sympathetic Hyperactivity (PSH)1 ,4–13 

Summary of Reports of Pediatric Paroxysmal Sympathetic Hyperactivity (PSH)1 4–13
Summary of Reports of Pediatric Paroxysmal Sympathetic Hyperactivity (PSH)1 4–13

In our patient, lorazepam was found to be ineffective in aborting PSH episodes; however, morphine was extremely effective in aborting PSH, and rarely was a second dose needed for an individual episode. We used doses of morphine consistent with those for pain control (0.05–0.1 mg/kg intravenously). Morphine is commonly mentioned as a treatment option for PSH in the adult literature17,19; however, that use is based mainly on anecdotal reports with a wide range of doses and variable results.20–29 Likewise, there is a paucity of evidence within the pediatric literature supporting the use of morphine. Additionally, the adult literature suggests that the efficacy of morphine for PSH is dose-dependent16; however, our patient did not require escalation beyond typical doses for improved efficacy.

We propose that morphine was effective because it combated the allodynic tendency of PSH.16 Both propranolol and clonidine were found to be effective in reducing the frequency and severity of episodes, although both resulted in occasional bradycardia between episodes. Propranolol and clonidine were initiated at doses similar to those used for hypertension. Mechanistically, these agents seem ideal because they both counteract the excessive sympathetic response in PSH by reducing the outflow (clonidine) or response (propranolol) to catecholamines. Baclofen has been used in several other case reports as both an oral and intrathecal agent. Oral baclofen was found to be effective as an adjunctive agent for preventing episodes in our patient and was part of his eventual discharge regimen. Although lorazepam did not abort PSH episodes, clonazepam was helpful in the prevention of autonomic storms. Additional medications not used in our patient but used in other case reports include bromocriptine, chlorpromazine, other benzodiazepines, hydralazine, methadone, intrathecal baclofen, and hyperbaric oxygen therapy.1,4–13 

Prompt recognition and treatment of PSH is necessary because of poor outcomes associated with this condition, especially after hypoxic brain injury. Several treatment regimens were used in our patient, with best efficacy found with morphine for acute episodes. For our patient, morphine was the only effective abortive therapy that did not produce unwanted side effects. We suggest early use of intravenous morphine as a safe and effective medication in patients whose autonomic storms do not respond to, or whose side effects limit the use of, antihypertensive agents or benzodiazepines.

E:I

excitatory:inhibitory

IV

intravenous

PRN

as needed

PSH

paroxysmal sympathetic hyperactivity

TBI

traumatic brain injury

1.
Krach
LE
,
Kriel
RL
,
Morris
WF
,
et al
.
Central autonomic dysfunction following acquired brain injury in children
.
Neurorehabil Neural Repair
.
1997
;
11
(
1
):
41
45
.
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
.
3.
Perkes
IE
,
Menon
DK
,
Nott
MT
,
Baguley
IJ.
Paroxysmal sympathetic hyperactivity after acquired brain injury: a review of diagnostic criteria
.
Brain Injury
.
2011
;
25
(
10
):
925
932
.
4.
Boeve
BF
,
Wijdicks
EFM
,
Benarroch
EE
,
Schmidt
KD.
Paroxysmal sympathetic storms (“diencephalic seizures”) after severe diffuse axonal head injury
.
Mayo Clin Proc
.
1998
;
73
(
2
):
148
152
.
5.
Goh
KYC
,
Conway
EJ
,
DaRosso
RC
,
et al
.
Sympathetic storms in a child with a midbrain glioma: a variant of diencephalic seizures
.
Pediatr Neurol
.
1999
;
21
(
4
):
724
744
.
6.
Russo
RN
,
O'Flaherty
S.
Bromocriptine for the management of autonomic dysfunction after severe traumatic brain injury
.
J Paediatr Child Health
.
2000
;
36
(
3
):
283
285
.
7.
Cuny
E
,
Richer
E
,
Castel
JP.
Dysautonomia syndrome in the acute recovery phase after traumatic brain injury: relief with intrathecal baclofen therapy
.
Brain Injury
.
2001
;
15
(
10
):
917
925
.
8.
Rodríguez
N
,
Febrer
A
,
Meléndez
M.
Autonomic dysfunction in children with traumatic brain injury [in Spanish]
.
Rev Neurol
.
2006
;
43
(
3
):
143
146
.
9.
Mehta
NM
,
Bechard
LJ
,
Leavitt
K
,
Duggan
C.
Severe weight loss and hypermetabolic paroxysmal dysautonomia following hypoxic ischemic brain injury: the role of indirect calorimetry in the intensive care unit
.
J Parenter Enteral Nutr
.
2008
;
32
(
3
):
281
284
.
10.
Woo
HJ
,
Park
SH
,
Hwang
SK.
A unique pattern of intracranial pressure in a patient with traumatic paroxysmal sympathetic storm
.
Pediatric Neurosurg
.
2010
;
46
(
4
):
299
302
.
11.
Singh
DK
,
Singh
N.
Paroxysmal autonomic instability with dystonia in a child: rare manifestation of an interpenduncular tuberculoma
.
Pediatr Neurosurg
.
2011
;
47
(
4
):
275
278
.
12.
Lv
LQ
,
Hou
LJ
,
Yu
MK
,
et al
.
Hyperbaric oxygen therapy in the management of paroxysmal sympathetic hyperactivity after severe traumatic brain injury: a report of 6 cases
.
Arch Phys Med Rehabil
.
2011
;
92
(
9
):
1515
1518
.
13.
Deepika
A
,
Reddy
M
,
Shukla
D.
Paroxysmal sympathetic hyperactivity in a child with Moyamoya disease
.
J Neurosurg Anesthesiol
.
2014
;
26
(
1
):
87
88
.
14.
Rabinstein
AA.
Paroxysmal sympathetic hyperactivity in the neurological intensive care unit
.
Neurol Research
.
2007
;
29
(
7
):
680
682
.
15.
Pignolo
L
,
Rogano
S
,
Quintieri
M
,
et al
.
Decreasing incidence of paroxysmal sympathetic hyperactivity syndrome in the vegetative state
.
J Rehabil Med
.
2012
;
44
(
6
):
502
504
.
16.
Baguley
IJ
,
Heriseanu
RE
,
Cameron
ID
,
et al
.
A critical review of the pathophysiology of dysautonomia following traumatic brain injury
.
Neurocrit Care
.
2008
;
8
(
2
):
293
300
.
17.
Rabinstein
AA
,
Benarroch
EE.
Treatment of paroxysmal sympathetic hyperactivity
.
Curr Treatment Options in Neurol
.
2008
;
10
(
2
):
151
157
.
18.
Baguley
IJ
,
Cameron
ID
,
Green
AM
,
et al
.
Pharmacological management of dysautonomia following traumatic brain injury
.
Brain Injury
.
2004
;
18
(
5
):
409
417
.
19.
Hinson
HE
,
Sheth
KN.
Manifestations of the hyperadrenergic state after acute brain injury
.
Curr Opin Crit Care
.
2012
;
18
(
2
):
139
145
.
20.
Baguley
IJ
,
Heriseanu
RE
,
Gurka
JA
,
et al
.
Gabapentin in the management of dysautonomia following severe traumatic brain injury: a case series
.
J Neurol Neurosurg Psychiatry
.
2007
;
78
(
5
):
539
541
.
21.
Bower
RS
,
Sunnarborg
R
,
Rabinstein
AA
,
Wijdicks
EF.
Paroxysmal sympathetic hyperactivity after traumatic brain injury
.
Neurocrit Care
.
2010
;
13
(
2
):
233
234
.
22.
Bullard
DE.
Diencephalic seizures: responsiveness to bromocriptine and morphine
.
Ann Neurol
.
1987
;
21
(
6
):
609
611
.
23.
Diamond
AL
,
Callison
RC
,
Shokri
J
,
et al
.
Paroxysmal sympathetic storm
.
Neurocrit Care
.
2005
;
2
(
3
):
288
291
.
24.
Goddeau
RP
, Jr
Silverman
SB
,
Sims
JR.
Dexmedetomidine for the treatment of paroxysmal autonomic instability with dystonia
.
Neurocrit Care
.
2007
;
7
(
3
):
217
220
.
25.
Huang
P
,
Lin
W
,
Huang
P
,
Khor
GT.
Susceptibility weighted imaging in a patient with paroxysmal sympathetic storms
.
J Neurol
.
2009
;
256
(
2
):
276
278
.
26.
Ko
S
,
Kim
CK
,
Lee
S
,
et al
.
Morphinesensitive paroxysmal sympathetic storm in pontine intracerebral hemorrhage
.
Neurologist
.
2010
;
16
(
6
):
384
385
.
27.
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
.
28.
Oh
SJ
,
Hong
YK
,
Song
E.
Paroxysmal autonomic dysregulation with fever that was controlled by propranolol in a brain neoplasm patient
.
Korean J Internal Med
.
2007
;
22
(
1
):
51
54
.
29.
Srinivasan
S
,
Lim
CCT
,
Thirugnanam
U.
Paroxysmal autonomic instability with dystonia
.
Clin Auton Res
.
2007
;
17
(
6
):
378
381
.

Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria.