Civetta, Taylor, & Kirby's: Critical Care, 4th Edition

Section VI - Shock States

Chapter 59 - Neurogenic Shock

 

Susanne Muehlschlegel

David M. Greer

Neurologically injured patients, regardless of the nature of the injury, frequently experience hypotension and shock. Neurogenic shock refers to a neurologically mediated form of circulatory system failure that can occur with acute brain, spinal cord, or even peripheral nerve injuries. In this chapter, we will explain the epidemiology, pathophysiology, clinical presentation, and management strategies for this special form of shock.

Contrary to common belief, neurogenic shock is not a single entity due to one single pathologic mechanism. The term is sometimes used in nonneuroscience intensive care units to explain hypotension occurring in any brain-injured patient, but neurogenic shock should be considered only after systemic causes of shock have been carefully ruled out. Just like other critically ill patients, neurologically ill patients are prone to developing systemic conditions, such as dehydration, congestive heart failure, acute blood loss, sepsis, pericardial tamponade, or massive pulmonary embolism.

Subtypes of Neurogenic Shock

Once other systemic reasons for shock have been ruled out, neurogenic shock should be considered. Three mechanisms can lead to neurogenic shock (Fig. 59.1):

· Vasodilatory (distributive) shock from autonomic disturbance with interruption of sympathetic pathways, with associated parasympathetic excitation, which causes profound vasodilatation and bradycardia, as seen in spinal cord injury or diseases of the peripheral nervous system (Guillain-Barré syndrome)

· Cardiogenic shock, as frequently seen in subarachnoid hemorrhage (SAH) with stunned myocardium after a catecholamine surge or ischemic stroke, especially those involving the right insula

· Hypopituitarism/adrenal insufficiency.

Although some subtypes of neurogenic shock occur more frequently with certain disease entities—for example, cardiogenic neurogenic shock after SAH, vasodilatory neurogenic shock with spinal cord injury—significant overlap exists between different disease entities (intracerebral hemorrhage [ICH], SAH, traumatic brain injury [TBI], ischemic stroke), and one cannot establish a firm rule by which neurogenic shock occurs. Interestingly, only some patients with neurologic injuries experience true neurogenic shock, and it remains difficult to predict in whom this will be seen.

Incidence of Neurogenic Shock

Due to the small number of prospective epidemiologic studies, it is difficult to establish the natural incidence of neurogenic shock. In a retrospective review of cervical spinal cord injuries, Bilello et al. (1) reported a 31% incidence of neurogenic shock with hypotension and bradycardia after high cervical spinal cord injury (C1–C5) and 24% after low cervical spinal cord injury (C6–C7).

Cardiogenic neurogenic shock has been studied foremost in SAH and ischemic stroke. Banki et al. (2) prospectively studied the incidence of left ventricular (LV) dysfunction with transthoracic echocardiography (TTE) in the first 7-day period after SAH in 173 patients. Thirteen percent had a normal ejection fraction (EF) but had regional wall motion abnormalities that did not correlate with coronary artery territories, and 15% had an LVEF of less than 50%. Others report a 9% incidence of LV wall motion abnormalities, resulting in hypotension requiring vasopressor therapy, as well as pulmonary edema in most (80%) of these patients (3). The spectrum of injury can range from mild to severe systolic dysfunction—the latter defined as an EF less than 30%. Polick et al. (4) observed LV abnormalities on TTE in 4 of 13 patients (31%) studied within 48 hours of SAH. Resolution of these neurologically mediated wall motion abnormalities is usually seen (2,3,5).

The third subtype of neurogenic shock, adrenal insufficiency, has been studied primarily in traumatic brain injury. In the largest study to date, adrenal insufficiency occurred in about 50% of patients and led to hypotension in 26% (6). Although it has been documented in other cases of acute brain injury, the exact incidence and relationship to outcome is not clear (7).

Pathophysiology of Neurogenic Shock

Vasodilatory Neurogenic Shock

This variation of neurogenic shock is commonly seen with spinal cord injuries and Guillain-Barré syndrome (acute demyelinating peripheral neuropathy) but also with traumatic brain injuries, large hemispheric ischemic strokes, and intracerebral hemorrhages. The hallmark of vasodilatory neurogenic shock is the combination of bradycardia with fluctuating blood pressures and heart rate variability due to interruption of sympathetic output and excitation of parasympathetic fibers.

The sympathetic fibers originate in the hypothalamus, giving rise to neurons projecting to autonomic centers in the brainstem—the periaqueductal gray matter in the midbrain, the parabrachial regions in the pons, and the intermediate reticular formation located in the ventrolateral medulla. From here, neurons project to nuclei in the spinal cord. The sympathetic preganglionic neurons originate in the intermediolateral cell column within the spinal cord gray matter between T1 and L2 and are therefore called the thoracolumbar branches. From here, they exit the spinal cord and project to 22 pairs of paravertebral sympathetic trunk ganglia next to the vertebral column. The main ganglia within the sympathetic trunk are the cervical and stellate ganglia. The adrenal medulla receives preganglionic fibers and thus is equivalent to a sympathetic ganglion. Blood pressure control depends on tonic activation of the sympathetic preganglionic neurons by descending input from the supraspinal structures (8).

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Figure 59.1. Neurogenic shock consists of three pathomechanisms. CNS, central nervous system; CO, cardiac output; CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; SAH, subarachnoid hemorrhage; TBI, traumatic brain injury.

The parasympathetic nervous system consists of cranial and sacral aspects. The cranial subdivision originates from the parasympathetic brainstem nuclei of cranial nerves III, VII, IX, X, and XI. The cranial parasympathetic neurons travel along the cranial nerves until they synapse in the parasympathetic ganglia in close proximity to the target organ. The sacral subdivision originates in the sacral spinal cord (S2–S4), forming the lateral intermediate gray zone where preganglionic neurons travel with the pelvic nerves to the inferior hypogastric plexus and synapse on parasympathetic ganglia within the target organs.

Following a spinal cord injury, the sympathetic pathways are interrupted with dissociation of the sympathetic supply from higher control below the level of transection (9,10). Parasympathetic fibers are usually spared. This results in autonomic hyperreflexia with associated hypertension or hypotension with bradycardia, all observed in human studies as well as in animal models (10,11,12,13). Loss of supraspinal control of the sympathetic nervous system leads to unopposed vagal tone with relaxation of vascular smooth muscles below the level of the cord injury, resulting in decreased venous return, decreased cardiac output, hypotension, loss of diurnal fluctuations of blood pressure, reflex bradycardia, and peripheral adrenoreceptor hyperresponsiveness (14). The latter accounts for the excessive vasopressor response repeatedly seen in this clinical scenario. The acute phase, also known as spinal shock, more frequently consists of periods of hypotension. After the acute phase, starting about 2 months after the injury, autonomic dysreflexia occurs in patients with lesions above T5 (15). This state is characterized by sympathetically mediated vasoconstriction in muscular, skin, renal, and presumably gastrointestinal vascular beds, induced by afferent peripheral stimulation below the level of the lesion. For example, stimuli such as urinary catheterization, dressing changes, or surgical stimulation can lead to severe blood pressure spikes out of proportion to the stimulus. In Guillain-Barré syndrome, the autonomic dysregulation is likely caused by acute demyelination not only of sensory and motor fibers, but also of autonomic fibers.

Injury to the brain can also lead to vasodilatory neurogenic shock. Certain cerebral structures, such as the insular cortex, amygdala, lateral hypothalamus, and medulla, have great influence on the autonomic nervous system. Cortical asymmetry is present and is reflected in a higher incidence of tachycardia, ventricular arrhythmias, and hypertension with lesions of the right insula—resulting in loss of parasympathetic input and thus sympathetic predominance—and a higher incidence of bradycardia and hypotension with injuries to the left insula—resulting in a loss of sympathetic input and subsequent parasympathetic predominance (16,17,18) (Fig. 59.2).

Cardiogenic Neurogenic Shock

This form of neurogenic shock is primarily encountered in SAH and TBI but is also seen in ischemic stroke and intracerebral hemorrhage. Cardiac dysfunction is a well-known complication of ischemic and hemorrhagic stroke, first described over 50 years ago (19). It is most often recognized on the electrocardiogram (ECG) as arrhythmias, QRS, ST-segment, and T-wave abnormalities (20,21). Studies of SAH and cardiac injury have shown that the severity of SAH is an independent predictor of cardiac injury, supporting the hypothesis that cardiac neurogenic shock is a neurally mediated process (22). Based on the similarities observed between pheochromocytoma crisis and SAH, the cardiovascular changes have been linked to a catecholamine surge.

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Figure 59.2. Example of a right ischemic stroke resulting in ventricular arrhythmias and cardiogenic shock. A 61-year-old man presents with sudden onset of left hemiparesis affecting his face and arm, left-sided neglect, and a left hemianopia. He presented outside of any acute treatment window and did not undergo thrombolysis. He was admitted to the neurointensive care unit (NICU) for close monitoring of his cardiac and respiratory function. The noncontrast head CT shows a right middle cerebral artery stroke and incidental hemorrhagic conversion. Electrocardiogram on admission showed diffuse T-wave inversion in all leads. Telemetry monitoring revealed frequent premature ventricular complexes and intermittent nonsustained ventricular tachycardia of 4 to 8 beats for the first 72 hours after stroke onset. His systolic blood pressure on admission was elevated at 190 mm Hg but then dropped to 85 mm Hg several hours after admission to the NICU, requiring vasopressor support for 2 days. Troponin T levels were elevated in the emergency room and peaked at 12 hours after stroke onset. Echocardiogram showed global hypokinesis and no regional wall motion abnormalities. No other causes for shock were found, so that the stroke involving the right insula was the most likely cause. The shock slowly resolved over 72 hours, and vasopressor infusion was weaned off successfully. A repeat echocardiogram 2 weeks later showed resolution of the abnormalities.

This hypothesis has been confirmed by many studies. Patients with SAH can have a threefold increase in norepinephrine levels that are sustained for 10 days or longer after SAH but that normalize after the acute phase of injury (23). In an animal model, an increase in plasma catecholamines after experimental SAH causes specific lesions on electron microscopy within 4 hours of SAH (24). Selective myocardial cell necrosis, also known as contraction band necrosis, is the hallmark of catecholamine exposure (25,26,27). The same lesions can be found in patients with pheochromocytoma (28) and SAH (29), underlining the pathologic mechanism of cardiac injury in SAH or other neurologic injuries (Fig. 59.3). The cardiac dysfunction is not related to coronary atherosclerosis, as normal coronary arteries have been documented in these patients studied at autopsy or by coronary angiography (5,29,30,31). In fact, it appears that pre-existing heart disease, such as hypertensive heart disease, might even be protective of this form of neurogenic shock (32). In a case series of 54 consecutive SAH deaths, 42 had myocardial lesions consisting of foci of necrotic muscle fibers, hemorrhages, and inflammatory cells, none of which were found in the control group. Patients with a wider range of heart rate and blood pressure fluctuations were more likely to have myocardial lesions. Pre-existing hypertensive heart disease led to significantly fewer myocardial lesions, possibly reflecting a decreased sensitivity of these patients to the catecholamine surge (32).

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Figure 59.3. Contraction band necrosis. Histologic examination of the myocardium, showing contraction band necrosis, see arrow. (Courtesy of Dr. James R. Stone, M.D., Ph.D., Department of Pathology, Massachusetts General Hospital, Boston, MA.)

Pathologic studies link the central catecholamine release to the posterior hypothalamus. Postmortem studies have found microscopic hypothalamic lesions consisting of small hemorrhages and infarctions in those patients with typical myocardial lesions as noted above (29,32,33,34). However, it appears that raised intracranial pressure (ICP) is not responsible for these hypothalamic changes, as the control group with elevated ICP did not have any hypothalamic injury (32).

Overall, by the described pathomechanism, the catecholamine surge results in direct myocardial injury resulting in decreased inotropy, and in addition an increase in cardiac preload due to venous constriction and increased cardiac afterload by peripheral arterial constriction. As a consequence, stroke volume diminishes, which cannot be compensated for by reflex tachycardia, thus resulting in decreased cardiac output and shock. This transient LV dysfunction with loss of myocardial compliance (stunning of the myocardium) is reflected by a characteristic shape of the cardiac silhouette on a ventriculogram and on chest radiograph, which has given this disease entity its other name, Takotsubo cardiomyopathy, derived from the Japanese word for the Japanese octopus fishing pot, tako-tsubo (35,36,37) (Fig. 59.4).

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Figure 59.4. Takotsubo cardiomyopathy. A: Japanese octopus fishing pot. B: CT brain of a 47-year-old woman with subarachnoid hemorrhage (SAH). C: Chest x-ray view of the same patient with typical cardiac silhouette of Takotsubo cardiomyopathy. An echocardiogram revealed an ejection fraction of 29 degrees with apical ballooning, global hypokinesis, and sparing of the apex. The chest radiograph and echocardiogram became normal within 1 week after her SAH.

Pulmonary edema with concomitant hypoxia is frequently encountered in this context and may result from cardiac congestion but can occur independently from the cardiac dysfunction as its own entity: neurogenic pulmonary edema. Massive increases in pulmonary capillary pressures lead to pulmonary edema and hypoxia, which in turn decreases the uptake of oxygen in a high demand state, contributing to hemodynamic instability. The Vietnam war era head injury series (38) reported the rapid onset of acute pulmonary edema after severe head injury. In addition, experimental models as well as multiple human case reports of TBI and SAH have shown massive sympathetic discharges as the primary cause of neurogenic pulmonary edema (39,40,41). Figure 59.5 summarizes the pathophysiology of cardiogenic neurogenic shock.

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Figure 59.5. Summary of the pathophysiology of the cardiogenic type of neurogenic shock. ICH, intracerebral hemorrhage; LVEF, left ventricular ejection fraction; SAH, subarachnoid hemorrhage; TBI, traumatic brain injury.

Overall, cardiac neurogenic shock, with or without neurogenic pulmonary edema, is usually transient, with resolution within several days to 2 weeks (2,3,4). Prevention of secondary brain injury from hypoxia and decreased cerebral perfusion pressures should be the focus of care in the management of this neurally mediated complication.

Neuroendocrine Neurogenic Shock

Insufficiency of the hypothalamic-pituitary-adrenal axis has been recognized as an important cause for shock. Inappropriately reduced release of cortisol in stress situations can lead to decreased systemic vascular resistance, reduced cardiac contractility, hypovolemic shock, or hyperdynamic shock that can mimic septic shock. Secondary adrenal insufficiency due to injury to the hypothalamic-hypopituitary feedback loop can cause neuroendocrine neurogenic shock. Acute brain injury, particularly TBI and SAH, can commonly lead to injury of the hypothalamus, pituitary gland, or the connecting structures (42). Cohan et al. (6) revealed that adrenal insufficiency after traumatic brain injury occurred in about half of all patients and led to a significantly higher rate of hypotension in these patients. Most cases of adrenal insufficiency developed within 4 days of injury. Importantly, the authors defined adrenal insufficiency using a low random serum cortisol value and highlight the fact that an increase in the cortisol level after a stimulation test does not rule out the presence of adrenal insufficiency. This issue is particularly relevant in TBI patients, in whom the hypothalamus and the pituitary gland are the likely affected organs, and the adrenal glands might well be expected to mount an appropriate response when stimulated. When recognized, primary and secondary adrenal insufficiency can easily be treated.

In septic shock, a low-dose vasopressin infusion has been shown to successfully restore blood pressure in hypotension refractory to standard catecholamine therapy (43,44). Recent studies in SAH have shown that endogenous vasopressin serum levels are elevated during the first 2 days after SAH but decrease to subnormal levels after 4 days (45,46,47). Arginine vasopressin supplementation in SAH at low dose (0.01–0.04 units/min) has been studied in only one single retrospective study (48). The role of vasopressin in the setting of neurogenic shock remains to be studied in a prospective manner, but the changes in endogenous vasopressin levels might indicate neuroendocrine changes in neurogenic shock and potential new treatment options in SAH.

Clinical Manifestations

Figure 59.6 illustrates the clinical manifestations and symptoms seen in neurogenic shock. Acutely, vasodilatory neurogenic shock presents with a “warm and dry” hemodynamic profile. The patient is hypotensive and frequently bradycardic; however, the peripheral vessels are dilated, leading to warm limbs and a normal capillary refill time. Central venous pressure (CVP) is normal or low, and systemic venous resistance (SVR) is always low. Stroke volume and cardiac output are low due to the unopposed vagal tone. When a spinal cord injury is present, a difference in smooth muscle and vasculature tone can be observed between the body parts above and below the level of the injury. For example, in an injury at thoracic level 7 (T7), normal upper limb perfusion might be observed, while vasodilatation below T7 leads to warm and dry lower extremities. Orthostatic hypotension without reflex tachycardia on changing from a supine to an upright position—by standing or with reverse Trendelenburg position—is common. When treating this form of neurogenic shock with a vasopressor infusion (such as phenylephrine or other pressors), extreme caution should be applied, as vasopressor hypersensitivity can lead to severe rebound hypertension, which can be difficult to control.

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Figure 59.6. Clinical manifestations of the different types of neurogenic shock. CO, carbon monoxide; CVP, central venous pressure; EDVI, end-diastolic volume index; PCWP, pulmonary capillary wedge pressure; SV, stroke volume; SVR, systemic vascular resistance.

Cardiogenic neurogenic shock manifests as hypotension and tachycardia, with bradycardia seen rarely. Peripheral vessels are often vasoconstricted, leading to a high SVR and cold and wet skin. Vascular filling, as measured by CVP, pulmonary capillary wedge pressure (PCWP), and end-diastolic volume index (EDVI), is normal or high, with low stroke volumes and cardiac output due to global myocardial dysfunction. Leaking of cardiac enzymes—troponin, creatine kinase (CK), CK-MB—may be seen, but frequently the peak levels are not as high as one would find in myocardial infarction. It is difficult to establish a cutoff value that differentiates stunned myocardium from myocardial infarction with atherosclerotic coronary artery disease. A retrospective study in SAH measuring troponin-I levels has reported an appropriate cutoff value to be 2.8 ng/mL (49), whereas CK-MB did not help differentiate between the two kinds of myocardial injury. Higher levels of troponin should raise the suspicion of true myocardial infarction, and ECG and echocardiography correlation is important.

Neuroendocrine neurogenic shock presents with hypotension that does not respond well to vasopressor infusion. Hemodynamic signs of this category of neurogenic shock are low CVP, SVR, stroke volume, and cardiac output. Low baseline cortisol levels are the hallmark. A cosyntropin stimulation test frequently leads to an appropriate increase in the cortisol level, which does not rule out the presence of neuroendocrine neurogenic shock, as the adrenal gland is usually not the primarily affected organ (6). For this reason, we do not find any clinical utility in this test when neuroendocrine neurogenic shock is suspected. Resolution of the hypotension with the use of hydrocortisone clinically confirms the presence of this shock form.

Diagnostic Considerations

In any case of hypotension and shock in the neurointensive care unit, systemic causes for shock must be ruled out first. Especially in the paralyzed patient (for example, one with a high spinal cord injury), recognition of other life-threatening injuries can be quite difficult. Signs of hypovolemic shock may be absent, even in a patient with profound internal bleeding, because of the absence of sympathetic tone below the level of injury. The usual pallor from vasoconstriction and reflex tachycardia might also be absent. The patient may even be bradycardic while continuing to bleed. For the same reason, signs of peritoneal irritation may be absent in patients with abdominal injuries. The reported incidence of pulmonary embolism (PE) varies tremendously in the neurocritical care patient population—ranging from 0.5% to 20% in ischemic stroke (50,51), to 1% in intracranial hemorrhage (52), to 8.4% in brain tumors (53)—and there are only limited data during the acute phase of subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury (51). Interestingly, according to the study by Skaf et al. (50) using the National Hospital Discharge Survey, the incidence of PE did not change in patients with ischemic and hemorrhagic stroke between 1979 and 2003. However, the death rate from PE in the subgroup with ischemic stroke decreased, likely due to an increased use of antithrombotic prophylaxis over the last 20 years (54). Additionally, over the last two decades, the methods of PE detection have improved immensely—for example, pulmonary CT-angiogram versus nucleotide scan—and autopsy studies report additional asymptomatic cases. In our opinion, the true incidence of PE is underestimated. Pulmonary embolism should always be considered in cases of refractory shock. If profound hypotension is present, or hypotension becomes progressive, reasons other than neurogenic shock should be suspected and thoroughly ruled out.

Every patient should undergo serial ECGs, serial cardiac enzyme measurements, and a chest radiograph. As previously mentioned, pulmonary edema and neurocardiogenic injury may occur together or separately, making chest x-ray films important diagnostic tools. In particular, one should look for pulmonary vascular congestion and evaluate the size and shape of the cardiac silhouette. Hemodynamic monitoring with continuous blood pressure and central venous pressure (CVP) monitoring with an arterial line and central venous line (CVL) should be undertaken. Blood pressure measurements should be done continuously with an arterial line. Arteriosclerosis of the upper extremities is common and should be kept in mind either when there is a large discrepancy between right- and left-sided pressures or when the clinical appearance of the patient does not match the readings from the arterial line. Central venous access is key for determining CVP and for the administration of fluids and medications, especially vasopressors. The site of the placement of the central venous line (CVL) may play an important role in the management of shock in a neurologically injured patient. Subclavian vein catheters are the preferred site in patients with elevated intracranial pressure (ICP), as there is a theoretical risk of venous stasis within the internal jugular vein with venous congestion and higher risk for venous sinus thrombosis, which could result in increased ICP (55). In addition, trauma patients frequently have cervical spine injuries and require cervical collars, making the internal jugular vein accessible only with difficulty.

In patients with cardiogenic neurogenic shock, more extensive hemodynamic monitoring may be necessary with either noninvasive cardiac monitoring devices or a pulmonary artery catheter (PAC). Echocardiography is very important to understanding the etiology of shock. In most cases, a transthoracic echocardiogram is sufficient. The typical echocardiographic appearance is that of apical ballooning, which results from global hypokinesis sparing the apex (56). This part of the heart is devoid of sympathetic nerve terminals, supporting the hypothesis that cardiac injury in SAH is neurally mediated by a sympathetic storm. Segmental wall motion abnormalities not conforming to distinct coronary artery territories is another characteristic echocardiographic finding. However, myocardial infarction from ischemic coronary disease is frequently seen in brain-injured patients, just as in any critically ill patient, and should always be ruled out first as a cause of shock. In the setting of fever and shock, blood cultures must be obtained and the patient appropriately covered with antibiotics until the cultures yield results. However, older and immunosuppressed patients may not mount an appropriate febrile response, and thus sepsis should still be considered in these patients even when they are afebrile, especially in the setting of a rising white blood cell (WBC) count. Cerebral spinal fluid cultures are very important in the neurointensive care unit, with antibiotic coverage of potential central nervous system CNS infections, especially in patients after head trauma with skull fracture or sinus disease, after instrumentation of the head or spinal canal, or in immunocompromised patients. Placement of intracranial pressure measurement devices do not contribute to the diagnostic workup of shock, but they are important tools in the management of neurogenic shock, such as when the goal mean arterial pressure (MAP) is being titrated to the cerebral perfusion pressure. Finally, adrenal insufficiency should always be considered. Random serum cortisol levels should be obtained in the early stages of shock, keeping in mind that in some forms of brain injury, low random serum cortisol levels, and thus adrenal insufficiency, may be encountered for several days after injury (6).

Many neurologically injured patients, especially those with spinal cord injuries, receive steroids while in the neurointensive care unit. The doses administered may be high enough to alter the result of a random serum cortisol level, but often the dose is not enough to treat true adrenal insufficiency appropriately. In these cases, one could either empirically treat with higher doses of steroids that also treat adrenal insufficiency—hydrocortisone, with or without fludrocortisone—or, keeping the potential adverse effects of steroids in acute injury in mind, one could withhold the administration of steroids for 12 hours, then obtain a random cortisol level and resume steroid treatment right after the blood draw. However, hypotension is frequently severe enough that immediate treatment is warranted, and withholding steroids often is not an option. Dexamethasone, which is frequently used in the neurointensive care unit, is the steroid that interferes the least with the cortisol assay after a corticotropin stimulation test and therefore allows for such a test. In cases of high suspicion, a random cortisol level is often preferred because of its simplicity. The cortisol level should be drawn immediately before the steroid dose. However, given the lack of mineralocorticoid activity of dexamethasone, changing to hydrocortisone with or without fludrocortisone is recommended when adrenal insufficiency is suspected.

Management

Two important reasons for early and proactive treatment of patients in neurogenic shock are as follows:

1.   Prevention of secondary brain injury from hypoxia and hypotension

2.   The fact that neurogenic shock, especially cardiogenic and neuroendocrine forms, is easily treatable and transient, with potentially good outcomes despite the moribund appearance of the patient in the acute phase.

Identifying patients at risk has been very difficult, but at least in SAH it appears that poor neurologic grade, age older than 30 years, and ventricular repolarization abnormalities are risk factors for neurogenic shock (57).

Once the diagnosis of neurogenic shock has been established and the pathophysiology (subtype) has been understood, treatment tailored to the specific subtype is initiated. In all cases, euvolemia is of utmost importance and must be achieved before any other treatment can be successful. In general, vasopressor treatment as a continuous infusion is initiated and titrated to a goal MAP and cerebral perfusion pressure (CPP). As an important management tool, an intracranial pressure measurement device is very helpful, allowing the indirect measurement of CPP. We recommend a goal CPP of greater than or equal to 65 mm Hg. The optimal CPP is not known. Data regarding the minimum tolerable CPP comes from TBI patients, in whom the ICP is often elevated. Several studies have suggested an improved outcome when CPP is maintained at greater than 70 mm Hg (58,59). Other studies using physiologic measurements, such as cerebral blood flow and brain tissue PO2 (PbtO2), indicate that adverse changes do not occur unless the CPP is below 50 to 60 mm Hg (60,61).

Vasodilatory neurogenic shock can be difficult to treat. In general, vagal tone predominates; however, in this state, patients frequently have peripheral α-adrenoceptor hyperresponsiveness, limiting the use of norepinephrine, epinephrine, ephedrine, and phenylephrine. In fact, sympathomimetics should be avoided as they can lead to severe blood pressure fluctuations. Since arginine vasopressin (AVP) does not affect α- or β-adrenergic receptors, but acts on V1 receptors, AVP may have an advantage over catecholamines or phenylephrine in this form of neurogenic shock. It has not been studied in neurogenic shock, however, and it remains unclear whether AVP may have adverse effects on neurologically ill patients. This concern is based on animal studies indicating that vasopressin may promote the development of vasospasm in SAH, and indirect experimental studies showing a reduction in brain edema with vasopressin antagonists. No prospective human study has been undertaken to confirm or dismiss this concern, and the only retrospective study on the use of vasopressin in SAH did not show any of these potentially adverse effects (48). In addition to vasopressors, a temporary demand pacemaker and/or atropine may be required in cases of refractory bradycardia and hypotension.

In cardiogenic neurogenic shock, some form of inotropic support may be necessary, either in the form of a dobutamine, milrinone, or norepinephrine infusion. Dopamine is generally avoided because of its proarrhythmic properties. Dobutamine and milrinone also have vasodilatory effects, frequently leading to more hypotension, requiring additional therapy with an α-receptor agonist, such as phenylephrine or norepinephrine. Afterload increases in the former, and tachycardia in the latter, might be limiting factors and need careful monitoring. Cardiac output monitoring may be undertaken with the guidance of a PAC. Beta-blockade is usually not recommended. In neurogenic cardiogenic shock, coronary artery disease is typically not present, and compensatory tachycardia is necessary to maintain cardiac output. Afterload reduction with cautious use of angiotensin-converting enzyme (ACE) inhibitors should be attempted, but further hypotension must be avoided to maintain tenuous cerebral perfusion pressures. Short-acting agents should be used whenever possible. Repeating an echocardiogram several days after the initial one is recommended to monitor the progression/resolution of cardiac dysfunction. The need for an intra-aortic balloon pump to mechanically reduce afterload and improve coronary perfusion pressure may be considered, albeit rarely used.

Once diagnosed, neuroendocrine neurogenic shock from primary, or more often secondary, adrenal insufficiency is treated with steroid replacement therapy. We use the same dosing as in adrenal insufficiency in septic shock: hydrocortisone, 50 mg intravenously every 6 hours. As previously discussed, a cortisol stimulation test is usually not helpful, and empiric treatment after a random cortisol level should be initiated.

Summary

Neurogenic shock is not a single entity, but rather is composed of three subtypes and pathophysiologies: vasodilatory, cardiac, and neuroendocrine. Other causes of hypotension should be ruled out first, prior to making the diagnosis of neurogenic shock. In most cases, neurogenic shock is transient and reversible, making this entity very treatable. Diagnosis and treatment should be tailored to the subtype of neurogenic shock. Maintenance of cerebral perfusion pressures is the key principle of management to prevent secondary brain injury and improve outcome.

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