Paroxysmal Sympathetic Hyperactivity after TBI

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Introduction   

We will begin the course by breaking down what paroxysmal sympathetic hyperactivity means. This will help as we venture through the activation of the sympathetic nervous system to understand why paroxysmal sympathetic hyperactivity is termed paroxysmal sympathetic hyperactivity. The medical definition of paroxysmal is a sudden episode of a relatively brief attack of symptoms that recur (1). Sympathetic refers to the sympathetic nervous features activated during an episode of PSH. These features are discussed in the sections on the neuroanatomy and neurophysiology of the autonomic nervous system and identifying PSH.  Hyperactivity is a state of abnormal or extreme activity. So, for PSH, there are relatively brief but recurrent episodes in which the sympathetic nervous system is in a state of extreme activity. 

Over the past ten to fifteen years, more efforts have been made to standardize terminology, clinical strategies and pathways, and scoring systems to identify earlier and manage PSH more effectively. The urgency and importance of early identification and appropriate management of PSH cannot be overstated. This course is designed to equip us with the knowledge of pathophysiologic theories for PSH, the use of the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM) scale, empiric treatment recommendations, and the identification of gaps in your unit’s practice that can lead to more solid research recommendations for PSH.  

Definitions  

• Agonist: molecules that bind to and functionally activates a target (2) 
• Antagonist: molecules that bind to a target, preventing other molecules from binding (2) 

Case Study  

The client is a 17-year-old with a severe TBI with suspected diffuse axonal injury (DAI) from multiple impacts during the football season, requiring management in an intensive care unit (ICU) and then step-down ICU while waiting for transfer to an acute rehabilitation unit. The client is mechanically ventilated through a surgically placed tracheostomy. Enteral feedings, water flushes, and medications are received through a gastrostomy tube (g-tube). The client voids spontaneously into a diaper but requires a bowel regimen consisting of stool softeners daily and a suppository every other day to manage constipation.  

The client’s baseline vital sign ranges are as follows: HR 60s to 80s beat per minute (BPM), blood pressure 100s/60s, respiratory rate 16 breaths per minute, pulse-ox 97-99% on 21% FiO2. Continuous pulse-oximetry is applied to the client, and BPs are measured every four hours or as needed.  

Let’s first discuss what occurs during a TBI to provide a relationship between TBI, DAI, and PSH.  

Traumatic Brain Injury 

TBI is an injury sustained to the brain by an external mechanical force (e.g., falls, motor vehicle accidents, sports injuries, and non-accidental trauma). TBI is classified as either closed or penetrating. Penetrating means a violation of the skull and dura mater. The dura mater is the tough outer layer, one of the three layers forming the meninges. It covers and protects the brain and spinal cord (3). Closed head injuries are more common than penetrating. The types of closed head injuries include concussion, contusion, diffuse axonal injury (DAI), and intracranial hematoma (4).  

Primary brain injury is direct damage to the brain parenchyma caused by the force of impact (contact) or acceleration-deceleration. When an individual sustains a TBI, there is a significant risk of compromised cerebral blood flow due to cerebral swelling, more specifically, cytotoxic (cellular) cerebral edema. The mechanical force sustained by the brain affects glial, neuronal, and endothelial cells. The mechanical force is the primary injury. Glial cells are non-neuronal cells but are considered the “glue” that binds the neural network together by supporting and protecting neurons and maintaining homeostasis (5). Neurons are the building blocks of the brain, responsible for receiving, processing, and transmitting electrical signals through the entire nervous system (6). The endothelial cells in the brain form the blood-brain barrier and play an essential role in protecting the brain from toxins (7).  

Damage to these cells impairs homeostasis within the central nervous system (CNS), resulting in secondary brain damage (i.e., cerebral edema). Sodium, a cation, enters brain cells freely without a mechanism to clear them. The body attempts to maintain neutrality within the cells by sending anions, which bring along water into the intracellular compartment, resulting in intracellular edema. (4,8). The swelling within the brain’s cells increases intracranial pressure, which decreases cerebral blood flow, depriving the brain of the oxygen it requires to function (4).  

The client in our case study was suspected to have DAI. The most common mechanism for DAI is an accelerating and decelerating motion causing shearing forces to the brain’s white matter tracts (9,10). The white matter in the brain is a network of nerve fibers that exchanges information and communication between the various areas of gray matter (11). The most common etiology for DAI is high-speed motor vehicle accidents. However, sports-related concussions play a significant role in varying degrees of diffuse axonal injury (DAI). The incidence of DAI is not known, but it is estimated that approximately ten percent of clients admitted for a TBI will have some degree of DAI (9,10).  

DAI is a clinical diagnosis and is considered when a client who sustained a TBI maintains a GCS of less than 8 for more than six hours. Radiographic imaging can provide evidence of DAI; however, it is not used to make a definitive diagnosis. Computed tomography (CT) of the head can identify evidence of DAI with small hemorrhages to the white matter tracts. Magnetic resonance imaging (MRI) is preferred to detect DAI. Definitive diagnosis is only made in the postmortem pathologic examination of brain tissue (9).  

The severity of a TBI is classified using the Glasgow Coma Scale (GCS). The GCS measures three functions:  

• Eye-opening 
• Verbal response 
• Motor response  

Eye-opening is rated based on four responses:  

• 4 – spontaneous 
• 3 – to voice 
• 2 – to pain 
• 1 – to none 

The verbal response is rated based on five responses:  

• 5 – normal conversation 
• 4 – oriented conversation 
• 3 – words but not coherent 
• 2 – no words, sounds only 
• 1 – none 

Motor responses are graded based on five responses:  

• 6 – normal 
• 5 – localized to pain 
• 4 – withdraws to pain 
• 3 – decorticate posture 
• 2 – decerebrate posture 

The scores classify the TBI as mild, moderate, and severe. A GCS of 13 to 15 is mild, nine to 12 is moderate, and a GCS of eight and below is severe (9).  

The initial treatment of TBI focuses on the ABCs—airway, breathing, and circulation. Intubation is usually required for clients with GCS eight or below to ensure adequate oxygenation and ventilation and because the client is unable to protect their airway. The client with severe TBI will require intubation and mechanical ventilation.  Hypoxemia causes cerebral vasoconstriction, leading to ischemia, so the goal for intubated clients with TBI is normoxia and normocarbia—oxygen saturation> 90%, PaO2 > 60 mmHg, and PaCO2 35 to 45. Cerebral perfusion pressure is carefully monitored to ensure adequate circulation to the brain. Cerebral perfusion pressure is optimized when the mean arterial pressure is higher and the intracranial pressure is lower (4).  

There are many means to maintain a lower intracranial pressure, such as sedation, in clients with severe TBIs. Sedation with medication is of most importance to note for nursing professionals on an acute rehabilitation unit assuming care for a client with severe traumatic brain injury because sedation can mask PSH. Sedation medication is necessary to reduce agitation to maintain a lower intracranial pressure, helping to prevent secondary brain injury (4). The client may have experienced PSH in the intensive care setting; however, it may not have been detected because of the sedative effects of the continuous sedation indicated for the condition. PSH may have also been overlooked and attributed to another cause, such as medication withdrawal. This will be discussed further in the section on identifying PSH.  

Sympathetic Nervous System 

This course provided a basic synopsis of TBI. To understand why the features of PSH occur, we should review the basics of a normally functioning sympathetic nervous system.  The nervous system is composed of the central and peripheral nervous systems. The structures of the central nervous system are the brain, brainstem, and spinal cord. The spinal cord is divided into thirty-one segments: eight cervical (C) segments, twelve thoracic (T) segments, five lumbar, five sacral (S), and one coccygeal (12).  

The peripheral nervous system structures include the cranial nerves, spinal nerves, peripheral nerves, and neuromuscular junctions. It is divided into sensory and motor. The motor division consists of the somatic (voluntary) and autonomic (involuntary) nervous systems. The autonomic nervous system is further divided into the sympathetic (fight or flight) and parasympathetic (rest and digest) systems and works to maintain homeostasis (13). The following paragraphs examine the afferent (to the brain) and efferent (from the brain) transmissions that regulate sympathetic nervous system activity.  

The brain’s cortical, thalamic, and subcortical pathways process and regulate sensory information, including pain and emotionally significant stimuli such as threats and danger (14). These pathways trigger motor responses by activating the peripheral nervous system. The peripheral nervous system has two motor neurons—preganglionic and postganglionic neurons. The preganglionic neurons extend from the brainstem (cranial nerves) and the spinal cord from T1 to L2, also known as the thoracolumbar outflow. The neurons communicate via neurotransmitters through synaptic connections known as neuromuscular junctions (the space between neurons). Neurotransmitters are considered the body’s chemical messengers transmitting “messages” across synapses between neurons (14).  

The preganglionic motor neurons are called cholinergic neurons because they release the neurotransmitter acetylcholine (ACh) to stimulate the postganglionic neurons. The postganglionic neurons are called adrenergic neurons because they release norepinephrine (noradrenaline) to innervate the target tissue (e.g., cardiac, bronchial smooth muscle). The preganglionic neuron can travel to and synapse directly with the adrenal medulla (13,15). The adrenal medulla is the inner part of the adrenal gland, a small organ located on top of each kidney.  

The adrenal medulla is most notable for producing catecholamines. Catecholamines are essential hormones in the fight-or-flight response, including dopamine, norepinephrine, and epinephrine. The catecholamines are released into the blood and travel to all the target tissues of the sympathetic nervous system. Epinephrine and norepinephrine are also referred to as adrenaline and noradrenaline. This systemic release of epinephrine and norepinephrine is what we sometimes refer to as an adrenaline rush. The adrenal medulla releases a very small amount of dopamine; the majority is epinephrine (80%) and then norepinephrine (20%) (15).  

Activating the sympathetic nervous system is a body-wide response to increase movement and strength. This causes increased energy expenditure and inhibits digestion. Eliciting sympathetic nervous system reaction is necessary during exercise and in situations threatening survival; hence, the term “fight or flight.” The overall goal of the sympathetic nervous system is to deliver oxygenated, nutrient-rich blood to the active skeletal muscles. Let’s first take a look at the cardiopulmonary systems. Innervating the cardiac tissue increases heart rate and cardiac muscle contractility, allowing more blood to circulate per minute.  

Circulation is also impacted by widespread vasoconstriction of vascular smooth muscle to redirect blood flow from metabolically inactive organs and tissues (e.g., gastrointestinal system and kidneys) to the working skeletal muscle. Sympathetic stimulation causes bronchodilation, which enables the lungs to move more air in and out, allowing for maximal oxygen intake and carbon dioxide elimination (13,15).  

The sympathetic nervous system activation decreases gastrointestinal motility; however, the brain and body still require energy sources to maintain the fight-or-flight state (13). The liver has an increased rate of glycogenolysis and gluconeogenesis. Glycogenolysis is the breakdown of glycogen into glucose molecules. Gluconeogenesis is the term for forming glucose from noncarbohydrate sources. The body must maintain an adequate supply of glucose because it is the brain’s primary energy source. Adipose tissue is another source of metabolic energy. There is also an increased rate of lipolysis in adipose tissue. Lipolysis is the breakdown of fats and other lipids into fatty acids that supply energy to the muscles for contraction (13,15).  

Urine output is halted during sympathetic activation by relaxing the detrusor muscle and contracting the urethral sphincter. Additionally, sympathetic activation allows for increased sweating to help with thermoregulation and the ciliary muscles to relax, allowing the pupils to dilate for better distance vision (13,15).  

Although the course focuses on the sympathetic nervous system, we will briefly discuss the parasympathetic nervous system. The reason for briefly discussing the parasympathetic nervous system is that the PSH-AM includes the absence of parasympathetic features in its scoring.  

The parasympathetic nervous system is known for its “rest and digest” features. Activation of the parasympathetic nervous system promotes digestion by increasing salivation, promoting peristalsis from the stomach into the small intestine, and releasing bile salts to digest fat. The parasympathetic nervous system contracts the bladder for urination and constricted sphincters in the large to propel solid waste forward for a bowel movement. The parasympathetic nervous system innervates muscarinic receptors in the heart to decrease heart rate and maintain a resting heart rate. The parasympathetic nervous system also acts on another set of muscarinic receptors in the bronchial smooth muscle to cause bronchoconstriction and increased bronchial secretions. The parasympathetic nervous system is also responsible for lacrimation to keep the eyes lubricated and protected (16,17).  

Practice Gaps 

This sympathetic hyperactivity in TBI clients was first described in the 1950s and was erroneously attributed to midbrain epilepsy (14,18). Research synthesizing practice guidelines found that the medical literature refers to PSH by at least 31 separate terms, including diencephalic or autonomic seizures, brainstem attack, autonomic storming, paroxysmal hyperthermic autonomic dysregulation, and dysautonomia (14,18,19). The term PSH was selected in 2007 and was recommended as the standard term in 2010. Finally, in 2014, a clear definition and diagnostic criteria were established after reviewing 349 cases (18).  

Standardizing the nomenclature and criteria has played an essential role in the early detection of PSH. However, there remains little evidence on understanding the pathophysiology and pharmacological treatment of PSH (14,18,20). There are discrepancies and a lack of uniformity in current treatment protocols (18). The evidence for therapeutic options for PSH is based on case reports and small case series, meaning the evidence for therapeutic options for PSH is very limited (19,20). Introducing practice gaps early in the course addresses why, particularly pharmacologic management, reads as a medley of recommendations and not a clearly defined protocol.  

Etiology 

PSH can occur from any brain lesion sustained from trauma (i.e., TBI), infection, hemorrhage, infarction, brain tumor, global anoxia-ischemia, and encephalitis). Regardless of the etiology, the clinical presentation appears to be the same (18). The majority of PSH cases from a review of 349 case reports occurred from TBI at about 80%, then from a hypoxic brain injury 10%, and 5% after a stroke, and the remaining causes included hydrocephalus, tumor, and infection (19).   

Epidemiology 

PSH is reported to affect up to 10% of TBI survivors (20). The main risk factors are severe TBI based on Glasgow coma score, younger age, and tracheostomy use. One study found that clients with DAI and brainstem lesions are at the highest risk (19, 21).  

Pathophysiology  

Several theories attempt to explain the pathophysiology of PSH. However, the pathophysiologic mechanisms are still not fully understood. This section will discuss four current views of the underlying pathology of PSH.  

Disconnection Theory 

The Disconnection Theory describes PSH as a disassociation between the cortical inhibitory and sympathetic control centers. The disconnection of the cortical inhibitory and sympathetic control centers leads to a loss of inhibition of the spinal excitatory circuits and intensifying sympathetic responses to internal and external stimuli. Structural damage from acquired brain injury disrupts autonomic regulatory centers within the central nervous system. Injury to regulatory centers can cause sympathetic hyperactivity, injury to the fibers connecting the hypothalamus to cortical areas, and inhibitory pathways from the forebrain can also result in sympathetic hyperactivity. This means there is unregulated sympathetic activity perpetuating autonomic instability (19). However, this theory is not as widely accepted any longer because it does not explain the paroxysmal feature of PSH or all the clinical manifestations of PSH (18,21) 

Excitatory/Inhibitory Ratio (EIR) 

This theory describes the pathophysiology of PSH as an imbalance between inhibitory and excitatory neurons. Non–injurious stimuli (e.g., positioning) are incorrectly interpreted as noxious stimuli, resulting in increased motor and sympathetic activity (21). The EIR describes PSH as a two-stage process. The first phase is the excitation starting in the descending inhibitory pathways, and the second phase is the recovery of inhibitory factors, leading to the paroxysm’s resolution (18). Damage to the sympathetic regulatory centers in the brain reduces the inhibition of afferent sensory information, amplifying normally non-nociceptive afferent information from the periphery, leading to a hyperactive sympathetic response. The EIR theory is the more widely accepted model for explaining the pathology of PSH (18).  

Neuroendocrine 

The neuroendocrine explanation for PSH centers around the hypothalamic-pituitary-adrenal axis. A TBI can damage this axis either directly or through secondary injury from vascular compromise, edema of the brain or pituitary gland, or inflammation. This damage can result in an uncontrolled release of adrenergic energy, leading to increased circulating catecholamines, which causes sympathetic excitation. Research has found that adrenocorticotropic hormone, epinephrine, norepinephrine, and dopamine serum levels are markedly elevated during a paroxysm (18,21). Specifically, a two to three-fold increase in catecholamines and about a 40% increase in adrenocortical hormone serum levels (18).  

Neutrophil Extracellular Traps (NETs) 

NET release occurs after a TBI when neutrophils infiltrate the paraventricular nucleus. This stimulates a pathway that promotes sympathetic excitation. Additionally, cerebral contusion, swelling, ischemia, and the distribution of excitatory amino acids can worsen PSH development, along with secondary brain damage from inflammatory cytokines, hyperthermia, and hypoxemia (18). 

Case Study Continued 

The client’s pulse-oximeter and ventilator monitor alarm and the nurse assesses the client at the bedside. The client is diaphoretic with decerebrate posturing. The client’s Temp 1010F axillary, HR is 130s, RR is 20s, BPs are 140s/100s, and SPO2 is 93% on 21% FiO2. The client had a large void, and the nurse and unlicensed assistive personnel (UAP) changed the client and repositioned them. However, there is no resolution to the symptoms. The charge nurse and providers are called to the bedside. 

The providers ordered a one-time dose of lorazepam administered enterally via a g-tube. The nurse and UAP changed the bed linens and the client’s gown, repositioned, dimmed the lights, and had a fan circulating on a low setting.  

Identifying PSH 

Vital signs and assessment findings that should prompt you to go, “Hmmm….my client might be experiencing PSH,” are repeated episodes of rapid-onset tachycardia, hypertension, tachypnea, fever, and diaphoresis (18,19,21). Worsened LOC, dilated pupils, diaphoresis, urinary retention, and ileus may also be observed. The client may experience dystonia, spasms, decorticate or decerebrate posturing, bruxism, and opisthotonos (19). Dystonia is a movement disorder where the muscles contract uncontrollably. Dystonia may persist after the resolution of PSH. It is not fully understood if the residual hypertonia is a sequela of PSH or a consequence of damage to supraspinal motor tracts from the initial brain injury (19).  

Clients with decorticate posturing have their elbows flexed with arms brought to the center of their body, hands are held against their chest, legs are extended, and toes are pointed and turned in. In a client with decerebrate posturing, the arms are extended parallel to the body, the wrists are flexed, and the legs are rigid and extended, with the toes pointed and turned in (22).  Bruxism is clenching, grinding, or gnashing of teeth. Opisthotonos is abnormal posture of the back and neck due to spastic contraction of extensory muscles (23). 

The nurse and provider should perform a thorough physical exam to evaluate for other causes of vital sign changes and potential triggers of complications of PSH, including skin breakdown and heterotopic ossification (19). Heterotopic ossification is when bone tissue grows in the soft tissue, usually occurring three to six months after injury. Heterotopic ossification presents with pain, decreased range of motion (ROM), local edema, effusion, erythema, warmth, and tenderness in the affected tissue or joints. A triple-phase bone scan is the most sensitive for identifying heterotopic ossification. Treatment includes passive ROM exercises, medication management, and surgical resection (24).  

While not all features of PSH will be present, several features must co-occur for PSH to be considered. Parasympathetic features are absent. Continuously elevated blood pressure, heart rate, respiratory rate, and temperature are inconsistent with PSH. The clinical features of PSH can occur at any stage following a traumatic brain injury. They usually develop in the acute phase following brain injury, occurring as early as a week after the initial injury (19).  

Often, PSH manifestations are masked by sedation administered during the acute phase of injury. Some clients do not experience PSH until months after the initial injury during rehabilitation or long-term care. The duration of PSH is variable. It may last less than two weeks or persist for several months. The duration of PSH can last for a few minutes to a couple of hours, depending on client differences and clinical management. One prospective cohort study reported that episodes last on average thirty minutes (ranging from 15-50 minutes) and occur on average five times daily (14,18,19,21). 

According to one study, episodes of PSH were associated with an observable triggering event in 72% of individuals 25). The brain erroneously interprets non-injurious stimuli, such as turning, as noxious stimuli. This occurs because the inhibitory pathways for sympathetic activation are disrupted due to brain injury. The misinterpretation of non-injurious stimuli is called allodynia. Allodynia is the production of pain from a stimulus that is not considered painful under normal physiologic circumstances (14). 

PSH is a diagnosis of exclusion, meaning that other diagnoses must be ruled out first before declaring a diagnosis of PSH. Clients with traumatic brain injury have complex clinical courses, so it is essential to ensure that the most appropriate diagnosis is made. The differential diagnosis, which are the possible conditions that could be causing the signs and symptoms of PSH, include seizures, sepsis, systemic inflammatory response syndrome, infection, intracranial hypertension, hydrocephalus, withdrawal syndrome, noxious stimuli (e.g., fractures, heterotopic ossification), and neuroleptic malignant syndrome. Neuroleptic malignant syndrome presents similarly and should be considered with recent antipsychotic administration (19,26).  

A sepsis work-up may be indicated if a client presents with a fever. An EEG may be indicated for persisting dystonic movements to rule out seizures. Laboratory studies and imaging are not diagnostic for PSH. However, they help evaluate other conditions that have a similar presentation to PSH. Complete blood count and cultures (blood, urine, or sputum) can be assessed for infection. A lumbar puncture was used to collect cerebrospinal fluid (CSF) studies to assess for meningitis. A complete metabolic panel can detect electrolyte abnormalities and assess for nutritional deficiencies that occur as a complication of PSF from diaphoresis and increased metabolic state (19,21,26).  

Imaging can help identify diffuse brain damage and injury to the deep brain structures, including periventricular white matter, corpus callosum, diencephalon, and brainstem, associated with PSH; however, imaging is not diagnostic. Chest X-ray can help provide evidence of pneumonia, and chest computed tomography can rule out pulmonary embolism in presentations of respiratory distress. An electroencephalogram might be considered to rule out seizures. The healthcare team decides whether to collect blood and other specimens, perform imaging based on the client’s presentation, and follow an institutionally developed algorithmic pathway for managing PSH (14, 21).  

In 2014, the PSH-AM was developed. It is a consensus on diagnostic criteria developed by an international, multidisciplinary group to determine PSH diagnostic likelihood. The PSH-AM has two sections: the Clinical Feature Scale (CFS) and the Diagnostic Likelihood Tool (DLT). This section assesses the presence of PSH features. The CFS measures the severity of the features. It is intended to monitor clinical trends and aid in management. The CFS scores features of sympathetic activation (e.g., heart rate, temperature, sweating) from zero to three. The CFS is scored and classified as mild one to six, moderate seven to twelve, and severe thirteen or greater. Pediatric clients have greater variability in heart rate and blood pressure, so a pediatric scoring system was developed in a pediatric rehabilitation center that another children’s hospital further modified to delineate better the severity of diaphoresis and posturing (14,27).  

The DLT assigns a point if the following are present: clinical features occur simultaneously, episodes are paroxysmal, sympathetic over-reactivity to ordinarily non-painful stimuli, features persist three or more consecutive days, features persist two or more weeks post brain injury, features persist despite treatment of alternative differential diagnosis, medication administered to decrease sympathetic features, two or more episodes daily, absence of parasympathetic features during episodes, lack of other presumed cause of features, and antecedent brain injury. 

The subtotal for the DLT is calculated. The subtotal for the CFS and DLT is totaled to determine PSH likelihood. A score of less than eight is considered a diagnosis of PSH unlikely, a score of eight to sixteen is considered a diagnosis of PSH possible, and a score of seventeen or greater is considered a diagnosis of PSH probable (21).  

The PSH-AM has provided reliable diagnostic criteria and stratified the severity of PSH. A prospective study in a neurorehabilitation subacute unit and a retrospective study in an intensive care unit found that the PSH-AM was useful in detecting PSH and stratifying its severity in clients with TBI (28,29). A single institutional case series implemented the PSH-AM for 394 survivors of acquired brain injury in the intensive care setting. The case series included all cases of acquired brain injury regardless of severity or presence of altered mental status and included individuals with TBI, stroke, infectious disease, and encephalopathy. The study found that PSH-AM was helpful in early objective diagnosis, stratifying severity of PSH, and serial evaluation of treatment efficacy (30).  

Treatment Goals/Management of PSH 

There are three main clinical strategies for managing PSH: 1) minimize avoidable stimulation, 2) abort paroxysms with medication, and 3) prevent further episodes (18,19). Pharmacologic and non-pharmacologic approaches should be used when mitigating the symptoms of PSH. The pharmacologic management of PSH is divided into abortive and preventive.  

General medication recommendations for symptomatic control of PSH include opioids, nonselective beta-blockers, alpha-2 agonists, bromocriptine, baclofen, gabapentin, and long-acting benzodiazepines (18). Monotherapy is not typically effective in managing PSH. However, the healthcare team should be judicious in selecting the most appropriate medications, monitoring their effectiveness, and tailoring a treatment plan to the individual client. Multimodal pharmacologic therapy is required in most clients with PSH.  

Research has found that administering moderate doses of multiple medication classes creates synergistic effects and avoids toxicity from using high doses of a single medication (19,21,26). Clients with PSH should have scheduled preventive medications ordered and will likely require medications that abort PSH symptoms. It is also essential to consider the route of administration and duration of administration when assessing effectiveness. The client may require pre-treatment with an opioid or benzodiazepine before any unavoidable triggers, such as repositioning, if previously the specific care results in severe episodes of PSH (26).  

Abortive medications for PSH are given to resolve breakthrough episodes. It is recommended that abortive medications be given the fastest route (i.e., intravenous) to stop the episode. The first-line treatment options are morphine and short-acting benzodiazepines (31). Morphine is a potent opioid receptor agonist used to abort PSH episodes. The mechanism of action for opioid receptor agonists is binding with free opiate receptors to block the release of substance P, a pain neurotransmitter. Morphine improves most symptoms of PHS because it addresses pain control from the allodynic response (14,31).  

In addition to morphine’s analgesic effect, its cholinergic effects and histamine release allow morphine to help manage tachycardia and hypertension (31). The dose is 2-8 mg administered intravenously, with an onset of five to 10 minutes lasting three to six hours (20,31). The side effects include respiratory depression, sedation, hypotension, ileus, emesis, histamine release, and concern for developing tolerance (19).  

In addition to morphine, short-acting benzodiazepines are also front-line agents used to abort PSH episodes. Short-acting benzodiazepines include lorazepam, diazepam, and midazolam. Benzodiazepines are GABAA receptor agonists. GABA is an inhibitory neurotransmitter in the CNS (32) and reduces neuronal excitability by stopping nerve transmission. A GABAA agonist binds to the GABA receptors, decreasing neuronal activity. Benzodiazepines are used to manage the following features of PSH: agitation, hypertension, tachycardia, and posturing (31). The onset of action for these three benzodiazepines is one to three minutes when administered IV (33,34). However, there is a concern for possible worsening of neurologic function in a client with a recent TBI. Careful tapering of benzodiazepines is necessary to prevent sudden withdrawal, which can result in seizures and worsening PSH symptoms (31).  

Dantrolene may be considered for abortive use in episodes of PSH where dystonia and posturing persist. However, it is used cautiously because of the risk of hepatotoxicity. Dantrolene does not work centrally as all the other PSH abortive and preventive medications do. Dantrolene works directly on skeletal muscle. It prevents calcium ions from being released from the sarcoplasmic reticulum, causing a decreased force of contraction within the skeletal muscle. The starting dose is 0.5-2 mg/kg/IV every six to twelve hours or 24 mg daily administered enterally. The maximum dose is 10 mg/kg/IV or 400 mg four times per day administered enterally. The side effects of dantrolene are severe hepatoxicity, respiratory depression, and muscle weakness (19). Liver function tests should be closely monitored in clients receiving dantrolene (31).  

In cases of refractory PSH, when symptoms do not abate with first-line medications, then continuous IV medications such as propofol or dexmedetomidine. It is crucial to abort PSH episodes to prevent secondary brain injury from hypertension, hyperthermia, or cardiac damage (31). Clients receiving these drips require transfer to an intensive care unit.  

Propranolol and labetalol are noncardioselective beta-blockers used preventatively for tachycardia, hypertension, and fever in clients with PSH. Labetalol is, more specifically, a selective alpha1-adrenergic receptor antagonist. A noncardioselective beta-blocker is indicated because tachycardia and hypertension resulting from PSH are issues with the nervous system, not the cardiac. The nonselective beta-blockers block epinephrine and norepinephrine in the heart and the rest of the body. Using a cardioselective beta blocker (i.e., metoprolol) is unlikely to have therapeutic benefits.  

Propranolol is also effective for managing diaphoresis in clients experiencing PSH. The starting dose of propranolol is 10 milligrams (mg) three times per day, administered enterally with a max daily dose of 320 mg. The onset of action is one to two hours, with an expected duration of eight to 12 hours when administered enterally (20). The side effects of propranolol are bradycardia, hypotension, and sleep disturbance. It is contraindicated in clients with asthma and heart block. The starting dose of labetalol is 50 mg twice daily, administered enterally. The onset of action when administered enterally is twenty minutes to two hours and is expected to last between eight to twenty-four hours. The side effects of labetalol are hypotension and bradycardia (19,20). 

Clonidine is a central alpha2-adrenergic receptor agonist that can be used as both an abortive and preventive to improve tachycardia, hypertension, and fever (19,31). Clonidine works by binding to alpha-2 adrenergic receptors to prevent catecholamines from binding to prevent excitation of the SNS (31). The starting dose is 0.1-0.3 mg twice daily, administered centrally, with a maximum dose of 2.4 mg/day. When administered enterally, the onset of action for clonidine is thirty to sixty minutes, with an expected duration of eight to twelve hours. The side effects of clonidine include bradycardia, hypotension, and sedation (19,20).  

Bromocriptine is a dopamine D2 receptor agonist. Dopamine receptor agonists mimic endogenous dopamine. It prevents sympathetic excitatory structures from managing centrally-mediated fever, dystonia, and posturing (31,35). Bromocriptine can lower the seizure threshold. Other side effects include confusion, agitation, dyskinesia, nausea and emesis, and orthostatic hypotension (19). The starting doses are 1.25-2.5 mg every 12 hours, administered enterally with a maximum dose of 20-40 mg/day. The onset of action is sixty to ninety minutes, with an expected duration of eight to twelve hours (19,20).  

Baclofen is a GABAB agonist that inhibits spinal cord reflexes and the brain. It is administered preventively to treat spasticity and improve mobility. It accomplishes this by decreasing the frequency and severity of spasms to improve hypertonicity and dystonia. The starting dose is five milligrams every eight hours, administered enterally, with a maximum dose of 80 mg/day. The onset of action when administered orally is two to three hours, with an expected duration of eight to 12 hours (20). The side effects include sedation and muscle weakness. For more severe dystonia and rigidity, intrathecal baclofen or botulinum toxin injection has been found to improve symptoms (19).  

When posturing persists despite using enteral baclofen, intrathecal infusion baclofen (ITB) may be required. Intrathecal baclofen is delivered directly into the spinal canal from a surgically implanted pump. The pump, placed near the abdomen, contains a catheter that delivers the baclofen into the spinal column. Studies have shown immediate improvement in controlling spasms and tone with ITB (31). The risks of ITB include CSF leak, infection, and mechanical problems with the catheter or pump. The side effects you may observe if the pump delivers an incorrect dose of baclofen include drowsiness, nausea, headache, muscle weakness, and lightheadedness. Abrupt cessation of ITB can cause the “loss of drug effect,” which presents as reappearance of baseline spasticity, pruritus, anxiety, and disorientation. Aside from return to baseline spasticity, the “loss of drug effect” would be challenging to identify in individuals with severe TBI.  However, abrupt cessation of ITB can cause a potentially life-threatening withdrawal syndrome, which presents as hyperthermia, severe spasticity, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure, and multisystem organ failure (36).  

Gabapentin is a preventive medication for PSH, treating spasticity and allodynic response. Gabapentin is structurally very similar to GABA, so it is considered a GABA analog. It was initially developed as an anticonvulsant; however, it has proved to be more beneficial in managing neuropathies, spasticity, and tremors (31). Gabapentin’s mechanism of action is very similar to baclofen. Some providers elect to use gabapentin as an alternative to baclofen. However, no clinical trials have compared the efficacy of gabapentin versus baclofen, nor has gabapentin been evaluated for monotherapy to control spasms and rigidity. One case report noted that the addition of gabapentin 300 mg three times daily markedly improved breakthrough autonomic episodes in a client already receiving ITB for dystonia (31). Gabapentin’s starting dose is 100 – 300 mg three times daily, given enterally, with a maximum dose of 3600-4800 mg/day. The onset of action is two to four hours, with an expected duration of six hours when administered enterally. The side effects of gabapentin are sedation and ataxia (19,20).  

PSH is very distressing to witness for both healthcare providers and family members. As a last resort for persisting symptoms, providers have ordered dopamine receptor antagonists, such as chlorpromazine and haloperidol. The use of antipsychotics for PSH is ill-advised. There are reports that the use of dopamine receptor antagonists in clients with PSH has led to worsening cognitive deficits, psychosis, and neuroleptic malignant syndrome (NMS) (19,31).  NMS presents similarly to PSH. The classic clinical presentation for NMS is mental status changes, fever, muscle rigidity, and autonomic instability (31,37). Treatment of NMS is immediately stopping the causative medication and supportive care to prevent complications. Bromocriptine and dantrolene are administered empirically to manage refractory NMS (37).  

Environmental modification and avoiding triggers (21) are the mainstays for preventing PSH episodes. Environmental modifications include controlling room temperature to minimize stimulation. A pilot study performed on a small cohort of clients experiencing PSH found that lower room temperature (P=.02) and blanket use (P=.009) showed a statistically significant association with increased PSH (38). Triggers include bladder distension, constipation, and tracheal suctioning. Keep in mind that clients with TBIs experience allodynia. Most stimuli may be non-noxious in individuals with an appropriately functioning nervous system; however, they can trigger significant distress in a client with PSH.  If the client is not voiding spontaneously or has an indwelling Foley catheter, the healthcare team should consider scheduled bladder scans every six hours with intermittent catheterization as needed (26). The healthcare team should also consider a bowel regimen to help promote regular bowel movements and avoid constipation.  

PSH causes secondary nutritional complications. During an episode of PSH, the resting energy expenditure is three times higher than normal resting energy expenditure (19,39). The secondary nutritional complications include dehydration, electrolyte disturbances, malnutrition, and muscle wasting. Adequate nutrition is essential to prevent severe weight loss, so consultation with a nutritionist is paramount. Profuse diaphoresis can also contribute to dehydration, so replacing the free water deficit ensures adequate hydration (21,26).  

A retrospective cohort study evaluated the medication administration and effectiveness in 407 children and adolescents with an acquired brain injury who had at least one episode of PSH (20). The study reported that acetaminophen was the most frequently administered medication but did not have significant effects compared to the control for reducing symptoms (i.e., hyperthermia). The fever in PSH is not caused by inflammatory sensors in the hypothalamus, so acetaminophen is unlikely to be effective. If there is a concern for secondary brain injury from hyperthermia, physical cooling measures (i.e., cooling blanket) may be indicated (26).  

Aborting and preventing episodes of PSH through pharmacologic measures and minimizing triggers are essential in preventing complications associated with PSH, such as cardiac damage. Sustained and prolonged sympathetic hyperactivity may lead to tachyarrhythmia and stress-induced cardiomyopathy. Other complications include heterotopic ossification pulmonary edema, intracranial hypertension, rhabdomyolysis, and skin breakdown (19). Nursing staff should ensure physical therapy is part of the client’s interdisciplinary team to address and prevent contractures adequately. Repeated episodes of PSH, particularly with tachypnea as a clinical feature, can interfere with the healthcare team’s decisions to wean from the ventilator and hopefully decannulate.  

Treatment for PSH should focus on identifying and addressing precipitating causes, selecting and titrating preventive and abortive pharmacologic treatments, correcting electrolyte imbalance, and minimizing noxious stimulation, including spasticity and dystonia. At this point, the treatment for PSH is empirical, meaning the recommendations are based on observation. The acute phase of treatment will likely require titrating the current medication or switching and adding medicines from a different class. For severe bruxism, a dental consultation should be considered for possible mouthpieces to protect teeth. Clients with TBIs benefit greatly from rehabilitation. Rehabilitation strategies seek to stabilize or optimize function and prepare for interventions as the clinical course progresses. Joint contractures can be prevented with resting splints and a passive range of motion (19).  

Case Study Continued 

The client’s vital signs returned to baseline within 40 minutes after the interventions. The nurse documented the event and reviewed the client’s data. The client had not received their scheduled suppository from the day before or had a bowel movement in three days. The team was notified and recommended that the nurse administer the suppository and order a PRN dose of lorazepam to abort a PSH episode if it recurs. The client receives the suppository and produces a large, firm bowel movement without precipitating further PSH episodes. The client continues to be turned every two hours, and vital signs remain at baseline for the remainder of the shift.  

Nursing Implications 

The bedside nurse is the BEST person to identify the symptom cluster of PSH and which medications help and which do not. Nurses must process significant amounts of information and decisions, especially for pathologies like PSH that are still not fully understood or with clearly defined protocols. Typically, we use terminology like observe, monitor, and assess when discussing nursing roles and responsibilities. However, these terms do not capture nurses’ complex and autonomous work. The term observation is typically a passive process and excludes the critical component of the evaluation of data, which is central to the nursing process. Assessment is collecting AND evaluating data at a solitary point in time. Monitoring captures the evaluation component of nursing work but does not reflect the analytic and decision-making skills (40).  

The term surveillance better captures our work at the bedside. Nurses are the twenty-four-hour professional presence at the bedside. The Nursing Intervention Classification defines nursing surveillance as “the purposeful and ongoing acquisition, interpretation, and synthesis of client data for clinical decision-making (40).” Nurses are essential in caring for and advocating for clients experiencing PSH. Advocating for clients includes communicating specific information regarding PSH episodes to all healthcare team members, including providers, physical and occupational therapists, speech therapists, and nutritionists so that each dimension of the client’s care is appropriately addressed. The bedside nurse should recognize the constellation of symptoms that point to sympathetic hyperactivity. Prompt intervention can reduce complications associated with PSH. The complications of PSH also involve longer hospital stays, higher hospital costs, and less neurologic recovery in acute care (19).  

Nurses can identify triggers and maintain professional, open communication with unlicensed assistive personnel caring for clients at the bedside and can communicate triggers when performing care. Nurses should also discuss with the healthcare team when premedication is necessary for interventions that precipitate PSH.  Nurses should also advocate for a multidisciplinary approach to managing a client’s PSH, including physical therapy to manage dystonia and a nutritionist to ensure adequate caloric and protein intake. The nurse should meticulously follow the client’s baseline vital signs and trends to identify symptoms of PSH early; many of these are identified by vital sign changes.   

Nurses caring for clients with PSH must be meticulous with medication management. The five rights of medication administration are the right client, the right medication, the right route, the right time, and the right dose. Some studies name up to twelve rights to address inadequacies in the original five rights of medication administration, including the right documentation, the right client response, and the right indication (42). The pharmacologic management of PSH is aimed at aborting PSH episodes and preventing PSH episodes. Properly assessing and documenting the client’s response is essential in determining if the medication regimen is most appropriate for the particular client and avoiding polypharmacy.  

When documenting medication effectiveness, the nurse should not only consider the onset of action, but also that medications like baclofen and gabapentin take time to reach a steady state (14). Before administrating abortive medications, the nurse should ensure that the indication (e.g., persisting dystonia or tachycardia) should be included in the order. Studies have found that there is not a uniform response to the medications, including abortive medications, used for managing PSH. Documenting the client’s response to the medication, especially for acute paroxysms, aids in developing a more effective, client-centered medication regimen (14). The nurse should also review the medication list to identify medications that are linked to MNS, such as antipsychotics and metoclopramide (19). It is important to note that preventing medication errors and developing a client-centered medication regimen is the responsibility of the interprofessional team (e.g., providers, pharmacists, and nurses) (41). However, medication management is highlighted in this course because, to reiterate, nurses are present 24/7 at the bedside and are in the best position to communicate the effectiveness of the client’s medication management.  

Nurses also play a central role in collecting and surveilling client’s weights, intake, and output. Closely following this allows the nurse to intervene early for possible PSH triggers, specifically urinary holding and constipation. Diaphoresis with PSH can be profound, so ensuring the client receives adequate hydration is necessary to replete fluid losses. Profound diaphoresis is a risk for electrolyte imbalances, including sodium, chloride, and potassium (42). A metabolic panel measures fluid and electrolyte levels. If there is concern for electrolyte imbalance due to the episodes of PSH, the nurse should suggest a metabolic panel to determine the client’s electrolyte status and replete as necessary.  

Witnessing PSH episodes is very troubling for families; dystonia and posturing with PSH may be misinterpreted as seizure activity. It is essential to explain why PSH occurs, suspected triggers, and preventive and abortive therapies. Explaining that the client is not having a seizure despite the abnormal posturing is also essential. Clients with serious TBIs require ongoing care, and it is important to equip their family members, who may assume the role of caregiver, with concrete information and provide anticipatory guidance. Nurses are crucial in building caregivers’ confidence by providing clear, understandable information. Studies have demonstrated that caregivers who report more confidence in managing their injured or ill family members report less depression, anxiety, and fatigue (43).  

Documentation is commonly seen as the bane of nurses’ work. Admittedly, it is substantial, frequently feels burdensome, and feels like a distraction from client care. Research validates the perceived documentation workload. Nurses in Canada spend approximately 26% of their time documenting, in Great Britain 17%, and in the United States between 25% and 41% (44). Organized, accurate, and timely documentation serves many purposes, including evidence in legal matters, regulation and legislation, reimbursement, and credentialing. It enables the healthcare team to provide high-quality continuity of care.  

More specifically, to our focus on PSH, thorough documentation is essential from a research and performance improvement perspective. Data extracted from documentation provides details of client characteristics and care outcomes used in research. Performance outcomes are measured against predetermined standards using documentation as the primary source. The data extracted from documentation speaks to the quality improvement activities (45). Now, why are two paragraphs of this course dedicated to documentation?  It is to both empathize with the burden of documentation AND emphasize the necessity of documentation in advancing research and performance improvement, especially in pathologies like PSH, where there is still a paucity of data on the most effective approaches to its management.  

And despite the paucity of data for the management of PSH, there are institutions, both adult and pediatric, synthesizing randomized control trials, case-control, and controlled cohort trials, observational studies, case series, and case reports to develop clinical-practice guidelines or algorithmic pathways to provide a streamlined approach to diagnosing and managing PSH that are rooted in evidence-based treatment and aims to use resources efficiently (14,21).  

The institution that developed the algorithmic pathway for managing PSH in TBI specifically looked to minimize missed diagnoses and misdiagnoses. By improving the recognition and diagnosis of PSH, the goal was to avoid excessive medication administration and improve the prognosis for TBI clients. Although the algorithmic pathway has yet to be validated by experimental findings, it raised awareness of PSH and possibly led to the development of standardized guidelines for PSH management. The clinical pathway developed at the pediatric institution acknowledges that the quality of evidence to guide the management of PSH is low. However, the pathway is beneficial because it provides consistent management with the best evidence available (19).  

The development and implementation of clinical pathways have gained more popularity since the 1980s (46, 47). Clinical pathways are tools that guide evidence-based practice within all healthcare settings. The most accurate description of a clinical pathway is a structured multidisciplinary care plan for a specific condition or disease. It is based on evidence and details the actions in a treatment course. Clinical pathways have been found to decrease variation in clinical practice, promote safe, evidence-based care, and reduce complications and treatment errors (46,47). Streamlined clinical practice leads to cost–savings and more efficient use of resources. However, the pathway should continue to evolve as new research and practice guidelines are presented. Both institutions address this as they acknowledge that their frameworks for managing PSH are based on low-quality evidence.  

Conclusion

PSH is complex and challenging to identify, especially in clients with complex clinical cases like those with severe traumatic brain injuries. Nurses are professionals who are continuously at the bedside and are in the best position to acquire and interpret clients’ clinical presentations and responsiveness to treatment. Though there is only a paucity of data regarding PSH management, nursing professionals are in the best position to relay the current treatment regimen efficacy and other clinical concerns regarding their clients with PSH.  

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