Care of the Acutely Unstable Patient

Respiratory System

Following assessment of the pattern of breathing and auscultation of the lungs, chest radiography should be performed soon after the trauma patient arrives in the emergency department and in patients with hypoxemia. Many patients with brain injuries are hypoxemic regardless of the mechanism of injury, and an increased degree of pulmonary shunting is associated with a worsened neurologic outcome. Hypoxemia may be due to airway obstruction, hypoventilation, atelectasis, aspiration, and associated lung injuries in trauma patients such as pneumothorax, or pulmonary contusion. On rare occasions, neurogenic pulmonary edema may occur, often in the more devastating injuries. Neurogenic pulmonary edema has been reported after a variety of central nervous system insults, including subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), TBI, spinal cord trauma, acute hydrocephalus, colloid cyst of the third ventricle, seizures, and hypothalamic lesions. An acute rise in ICP often, but not always, accompanies the development of pulmonary edema. Increases in ICP may elicit only the sympathetic activation and cardiopulmonary responses that are essential for the development of edema. The mechanism of neurogenic pulmonary edema is not completely understood. Marked sympathetic activation at the time of the injury may damage the pulmonary capillary endothelium by both hydrostatic and increased permeability mechanisms. Increased pulmonary shunting may also be observed in patients with head trauma in the absence of distinct pulmonary edema or pathologic condition. The increased alveolar-arterial oxygen tension gradient in these patients may be related to airway closure caused by a decreased functional residual capacity in a comatose patient or by neurogenic alterations in ventilation–perfusion matching.

Cardiovascular System

Severe brain injury activates the autonomic nervous system and causes a hyperdynamic cardiovascular response consisting of hypertension, tachycardia, increased cardiac output, and electrocardiogram changes that may mimic myocardial ischemia.

A Cushing response, in which bradycardia accompanies the hypertension, may occur. This response is thought to occur because marked intracranial hypertension causes medullary ischemia as a result of decreased cerebral perfusion pressure (CPP) and brainstem distortion, resulting in activation of medullary sympathetic and vagal centers. Although bradycardia accompanies the hypertension in a classic Cushing response, the presence of a relative tachycardia in a patient with a “blown” pupil may indicate that the patient is hypovolemic. If the patient has outright hypotension, other sources of blood loss (eg, pelvic, thoracic, abdominal) should be sought. An isolated, mild-to-moderate TBI is not generally associated with hypotension because the blood loss from the head wound is usually insufficient to cause hypotension in adults.

Acute brain injury may lead to development of a Takotsubo stress cardiomyopathy (stunned myocardium) characterized by an acute transient ST-elevation left ventricle dysfunction, not related to coronary artery disease, and may be easily confused with an acute myocardial infarction. Transthoracic echocardiography (TTE) should be urgently performed to differentiate from coronary artery disease as it demonstrates classical left ventricular dysfunction with akynesis of apex (ballooning) and hypokynesis of other left ventricle segments. Although the pathophysiology of the phenomenon is not exactly clear, it is believed that dramatic catecholamine release with stress, pain or intracranial bleeding lead to so-called “catecholamine cardiac toxicity,” and, possibly, transient coronary spasm, leading subsequently to global, but transient, heart dysfunction. Most frequently (in about 90% of cases) Takotsubo cardiomyopathy is observed in middle-aged female patients with SAH. On occasion, it can also develop in a variety of CNS injuries such as TBI, ICH, ischemic stroke, and epilepsy. Awake patients may present with classic chest pain and shortness of breath, cardiac enzyme elevation, and ST-segment elevations and negative T waves in anterolateral wall on the EKG. Takotsubo cardiomyopathy can be complicated by profound hypotension, arrhythmias including torsade de pointes, heart failure and ventricular rupture and should be treated symptomatically. Usually, an acute cardiomyopathy resolves within a few weeks, echocardiogram normalizes in 6 weeks and ECG in 10 weeks.

Musculoskeletal System

Lateral cervical spine (C-spine) radiography should be performed immediately because approximately 10% of patients with head injuries have associated cervical spine injuries. The lateral cervical spine film picks up approximately 80% of cervical spine fractures and can display lethal injuries such as atlanto-occipital separation. The remainder of the spine series that is required to “clear the neck” (confirm absence of vertebral injuries) should be performed later, after complete evaluation of the head injury. Many patients with head trauma also have long-bone or pelvic fractures that may cause significant blood loss or fat emboli.

Gastrointestinal System

Every patient with a neurosurgical emergency should be assumed to have a full stomach and to be at risk for aspiration. Patients with acute head trauma may also have intra-abdominal injuries. Delayed gastric emptying may persist for several weeks after severe head injury. Significant blood alcohol levels have been found in more than 50% of head-injured patients.

Coagulation

Patients with head trauma may also have disseminated intravascular coagulation, possibly caused by release of brain thromboplastin into the systemic circulation. Outcome is poorer in patients in whom the condition develops. An increase in fibrin split products may identify patients with head injury who are at high risk for adult respiratory distress syndrome. Coagulation factor levels should be checked in the emergency department, and aggressive replacement of platelets and clotting factors may be required. Use of recombinant factor VII has been advocated in patients with polytrauma that includes TBI ^, and with spontaneous intracranial hemorrhages. However, data are inconsistent regarding mortality benefit, reduction in transfusion requirements, and associated complications from the use of this agent. Given the serious risk of thromboembolic events, recombinant factor VII cannot be recommended as prophylactic therapy in patients without acute bleeding. Prothrombin complex concentrate (PCC), consisting of factors II, VII, IX, and X, and proteins C and S, is a newer agent that has demonstrated superiority to FFP in the rapid reversal of warfarin-associated coagulopathy. ^, Its use has been expanded beyond warfarin reversal and has been shown to be effective in treating both acquired and induced coagulopathy in patients with TBI. Additionally, PCC offers significant cost savings over recombinant factor VII ^, and should be considered as a viable alternative for the treatment of coagulopathy in the setting of TBI.

According to the recently issued by ASA/AHA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage (ICH), patients with severe anticoagulation factor deficiency or thrombocytopenia should receive appropriate replacements of factors or platelets. An effect on outcome of platelet transfusion in patients receiving anti-platelet medications, particularly dual antiplatelet medications combining aspirin with P ₂ Y ₁₂ -ADP inhibitors (clopidogrel, prasugrel, ticagrelor), is not clear and considered a Class IIB recommendation. In cases of oral anticoagulant-associated intracranial hemorrhage, normalization of coagulation by reversing anticoagulant should be performed as soon as possible. In patients receiving warfarin, intravenous vitamin K (5–10 mg) should be given along with FFP (20 mL/kg) or PCC (20–40 IU/kg) to normalize prothrombin time. Administration of PCC (either 3 or 4 factors) may be advantageous in patients in whom fluid overload should be avoided (eg, patients with heart failure) as about 1 liter of FFP is required to normalize coagulation (10–15 mL/kg of FFP raises level of factors by 10–20%). Patients receiving direct thrombin inhibitor dabigatran or factor Xa inhibitors (rivaroxaban and apixaban) may be treated similarly to patients on warfarin with FFP or PCC as there are no reversal agents available. An antibody fragment idarucizumab has been recently advocated for the effective reversal of dabigatran; its safety in neurosurgical patients, however, needs to be proven.

Electrolyte Imbalance

The patient may demonstrate hypokalemia and hyperglycemia in response to stress and trauma. β-Adrenergic receptor stimulation from epinephrine (adrenaline) causes a decrease in serum potassium by driving potassium into the cells. Similarly, when pH is elevated, as is common in the brain-injured patient in whom hyperventilation is used to reduce ICP, potassium is driven into cells as hydrogen ions are released. Decreases in serum potassium values associated with acute hyperventilation and stress do not need to be treated, because total body potassium is unchanged. However, diuretic-induced renal losses of potassium do require replacement to avoid complications of acute intracellular potassium depletion, including potentiation of neuromuscular blockade and cardiac dysrhythmias. Often, in the acutely brain-injured patient, the cause of hypokalemia is multifactorial. Initiation of treatment depends on the predominant clinical circumstances.

Diabetes insipidus may occur in the patient with basilar skull fracture or severe head injury involving the hypothalamus or posterior pituitary. Antidiuretic hormone (ADH) is synthesized in the hypothalamus and secreted by the posterior pituitary. ADH enhances the permeability of free H ₂ O in the distal convoluted tubule and collecting duct of the kidney. Patients with diabetes insipidus can lose large volumes (25 L/day) of dilute urine, resulting in marked increases in serum sodium and osmolality.

Diabetes insipidus should be considered in the differential diagnosis of polyuria in any patient with head trauma or pituitary and hypothalamic lesions. The differential diagnosis of intraoperative polyuria includes excessive fluid administration, osmotic agents (eg, hyperglycemia with serum glucose level greater than 180 mg/dL, mannitol), diuretics, paradoxic diuresis in patients with brain tumor, and nephrogenic and central diabetes insipidus. Diabetes insipidus is diagnosed intraoperatively by the ruling out of iatrogenic causes and hyperglycemia, and through a demonstration of marked increases in serum sodium and osmolality with low urine osmolality.

Treatment of diabetes insipidus involves adequate fluid replacement with half-normal (0.45%) saline and administration of ADH. Five percent dextrose in water may alternatively be used; however, caution should be applied to avoid hyperglycemia. Aqueous vasopressin may be given subcutaneously or intramuscularly (5 to 10 U) every 6 hours or as a slow intravenous infusion (up to 0.01 U/kg/h) for rapid control of intraoperative or postoperative diabetes insipidus. Larger doses may cause hypertension. For less frequent dosage, desmopressin (DDAVP) 1 to 4 μg intravenously or subcutaneously every 12 hours may be administered. Desmopressin may be given more frequently if the diabetes insipidus is not controlled. This agent has less vasopressor activity than aqueous vasopressin and is preferable to vasopressin in patients with coronary artery disease and hypertension.

Hyponatremia may also occur in the acutely brain-injured patient. Hyponatremia may be associated with diminished (eg, diuretic usage, adrenal insufficiency, salt-losing nephritis), expanded (eg, congestive heart failure, renal failure), or normal (eg, hypothyroidism, syndrome of inappropriate ADH secretion) extracellular fluid volumes. Rapid reduction of the serum sodium value to less than 125 to 130 mEq/L may cause changes in mental status and seizures. The first step in diagnosis is to establish the category to which the patient belongs. Although many clinicians are quick to suggest syndrome of inappropriate ADH secretion in patients with brain injury, this diagnosis should be made only after exclusion of other possible causes. In neurosurgical patients, hyponatremia is most commonly associated with intravascular volume depletion caused by diuretic administration or a loss of sodium via the kidney. After SAH, patients may have a primary natriuresis (“cerebral salt wasting”), which, unlike syndrome of inappropriate ADH secretion, is associated with a decreased intravascular volume. Aggressive fluid therapy is required in patients with SAH to maintain a normal intravascular volume.

Blood toxicology screen is indicated in patients with impaired neurological status as alcohol, cocaine and other sympathomimetic drugs are associated with both TBI and spontaneous ICH. Pregnancy test should be performed in women of childbearing age.

Airway

Patients with a GCS score of 8 or less or uncooperative patients who require sedation for neuroimaging require intubation, because patients with suspected head injury should not be sedated without an endotracheal tube in place and control of ventilation ensured. Trauma patients should be assumed to have a cervical spine injury until proven otherwise. Nasal intubation should be avoided in patients with suspected basilar skull fractures and sinus injuries.

The patient’s airway and hemodynamic status should be quickly assessed before a plan for endotracheal intubation is chosen ( Fig. 10.4 ). Rapid sequence induction with cricoid pressure is a standard technique for establishing a definitive airway in the neurologically compromised patient. Comatose patients may not require sedation or paralysis for direct laryngoscopy and endotracheal intubation. In trauma patients, in-line stabilization of the neck should be utilized. Newer airway equipment, such as optical and video laryngoscopes (eg, AirTraq, GlideScope®, McGrath®) and stylets (Shikani Seeing Stylet), may be utilized to improve visualization of the glottic opening. However, fiberoptic laryngoscopy is still considered the “gold standard” for management of the difficult airway, especially if concomitant cervical spine injury is suspected. In some cases, a cricothyroidotomy may be required.

If the airway appears normal, a muscle relaxant should be given to facilitate glottic exposure and reduce coughing. The prevention of the cough by the prior administration of a muscle relaxant appears to be most important in preventing significant increases in ICP with endotracheal intubation. Nondepolarizing neuromuscular blockers have been shown to prevent increases in ICP during tracheal stimulation. Additionally, White and colleagues found that succinylcholine, but not thiopental, fentanyl, or lidocaine, prevented marked rises in ICP with endotracheal suctioning in comatose head-injured patients, because of the greater reduction in coughing after administration of succinylcholine. However, barbiturates and lidocaine were effective in attenuating the increase in ICP due to tracheal stimulation in patients who also received a muscle relaxant. ^, These drugs and narcotics may also be necessary to prevent increases in mean arterial pressure and ICP with endotracheal intubation.

One should assess the patient’s hemodynamic status to choose an anesthesia induction agent that reduces the increase in ICP that accompanies endotracheal intubation. The primary goal is to maintain adequate cerebral perfusion pressure (CPP) by ensuring hemodynamic stability while reducing ICP. Severe hypotension from the inappropriate administration of a large dose of propofol in a hypovolemic patient may be worse for the patient than the transient rise in ICP that accompanies endotracheal intubation. If the patient is hypertensive or hemodynamically stable, a rapid-sequence induction with head and neck stabilization, defasciculation, cricoid pressure, and administration of propofol, lidocaine, and succinylcholine can be used. To avoid hypoxemia and excessive increases in PaCO ₂ , the patient may be manually hyperventilated while cricoid pressure is maintained before intubation. If the patient is hypertensive, administration of narcotics (such as fentanyl), antihypertensive agents, or both may be necessary to prevent severe hypertension and increases in ICP with endotracheal intubation, but extreme caution is required to prevent untoward reductions in CPP in this setting. Esmolol and labetalol have less potential to raise ICP than sodium nitroprusside, which is a marked cerebrovasodilator. Calcium channel blockers nicardipine and clivedipine are potent and safe antihypertensive medications which are widely used, particularly in patients with ICH. ^, If the patient is somewhat hypovolemic (as is common in the patient with multiple injuries), etomidate (0.2–0.4 mg/kg) may be used as an alternative to propofol because it is effective in reducing cerebral blood flow (CBF) and ICP.

There is a renewed interest in ketamine as an induction agent in patients with brain injury. A recent randomized controlled trial proved safety of ketamine (2 mg/kg) while providing similar intubating conditions compared to etomidate in 655 patients with brain injury requiring emergency intubation. If hypertension and tachycardia are of concern, another option would be a mixture of ketamine 0.75 mg/kg and propofol, which provides more stable hemodynamics compared to induction with propofol only. Ketamine (1 mg/kg) was shown to decrease intracranial pressure in adults during anesthesia and recently in ICU children with increased ICP (ketamine 1–1.5 mg/kg).

Although succinylcholine may transiently increase ICP because of greater CO ₂ production or cerebral stimulation from the fasciculations, succinylcholine is the muscle relaxant of choice in emergent endotracheal intubation because of its fast onset of action, short duration, and excellent intubating conditions, unless it is contraindicated. Whether pretreatment with a “defasciculating” dose of nondepolarizing muscle relaxant is effective preventing succinylcholine-induced increase in ICP is not clear. The benefits of rapid intubation and hyperventilation, if required, outweigh the disadvantages of brisk ICP increase during intubation in the acutely injured patient. Succinylcholine can potentially cause hyperkalemia. Rocuronium (0.6–1.2 mg/kg) should be chosen in this circumstance, assuming that the airway is not difficult.

Goals in the Acute Care of the Brain-Injured Patient

The principal aim in the acute medical management of the brain-injured patient is to prevent secondary neurologic injury. Over the last 30 years, an understanding of the pathophysiology and goals of an early treatment of the potential causes of secondary neurologic injury led to a significant decrease in mortality of patients with severe TBI, from 50% to 25–30%.

Secondary brain injury is an important determinant of outcome from severe TBI. Factors contributing to the development of secondary neurologic injury include hypoxia, hypercapnia, hypotension, intracranial hypertension, and transtentorial or cerebellar herniation. Durations of systemic hypotension with systolic blood pressure (SBP) 90 mmHg or lower, hypoxia with arterial O ₂ saturation (SaO ₂ ) 90% or lower, and pyrexia with core temperature 38° C or higher have been found to be strongly associated with mortality after TBI. Many of these factors are potentially treatable. Both CPP greater than 90 mmHg and higher GCS scores correlated with better neurologic outcome, whereas CPP lower than 50 mmHg is independently associated with poor outcome after TBI. Box 10.4 summarizes the aims in the acute care of patients with TBI injuries.

High-dose steroids do not reduce ICP in TBI and do not affect outcome from severe head injury. They are therefore not recommended for the treatment of acute TBI. Steroids may be useful in reducing edema in the rare patient who presents with impending brain herniation from a brain tumor. In such a patient, clinical improvement occurs within hours of the initiation of steroid therapy.

Prevention of Hypoxemia

Prompt and aggressive treatment of hypoxemia in TBI patients is imperative because hypoxemia is associated with the development of secondary brain injury, worsening neurologic outcome, and increasing mortality, especially when associated with systemic hypotension. According to a study of 717 cases in the Traumatic Coma Data Bank, hypoxemia was identified in 22.4% patients with severe TBI and was associated with increases in morbidity and mortality.

Every patient with brain injury should be assessed according to general “ABC” principles of trauma management (airway, breathing, circulation), which is initiated with provision of an adequate airway and breathing/ventilation. Every brain-injured patient should receive supplemental oxygen regardless of initial GCS score. Oxygenation should be monitored whenever possible with pulse oximeter or by measurement of arterial blood gas levels. The minimum goal of oxygenation in patients with brain injury should be to maintain SaO ₂ at 90% or higher or PaO ₂ at 60 mmHg or higher. Patients with severe brain injury should be intubated and ventilated with 100% oxygen until adequate oxygenation is verified.

The possibility has been raised that positive end-expiratory pressure (PEEP) may increase ICP in the brain-injured patient because it may increase cerebral venous volume by reducing cerebral venous outflow. However, 10 cm H ₂ O PEEP improves oxygenation and usually results in clinically inconsequential increases in ICP in patients with severe head trauma. PEEP may affect ICP less in patients with the stiffest lungs, who are presumably the ones who need PEEP the most.

Maintenance of Hemodynamic Stability

Hypotension

When systemic hypotension is defined as SBP less than 90 mmHg, even a single recorded prehospital episode has been shown to correlate with higher morbidity and mortality in patients with TBI. While patients are in the intensive care unit, the duration of hypotension (SBP < 90 mmHg) strongly correlates with worsening of neurologic outcome as assessed by the GCS and with an increase in mortality. Blood pressure should be monitored and SBP should be kept higher than 90 mmHg.

The most common hemodynamic problem in the patient with head trauma and multiple injuries is hypovolemia caused by blood loss, profound diuresis from mannitol, and inappropriate attempts to restrict fluid intake. Because the damaged brain tolerates hypotension poorly, intravenous fluids should be administered in sufficient quantities to rapidly restore intravascular volume and CBF. Intraoperative blood loss may be severe in vascular injuries and skull fractures. Massive volume replacement may be required intraoperatively if a dural sinus is injured. In addition, blood loss may be difficult to quantify because it spills on the drapes and on the floor. Patients with large intracranial hemorrhages, with normal blood pressures in the lower range (SBP 100–120 mmHg), or with relative tachycardia (heartbeat > 100 beats/min), should be considered to be hypovolemic unless proven otherwise. The hypovolemia may manifest as severe hypotension when the brain is decompressed. With the acute reduction of ICP, sympathetic tone and systemic vascular resistance are diminished, unmasking profound intravascular volume depletion. Vasopressors may be helpful in restoring blood pressure while fluid is being given to restore intravascular volume. However, overzealous fluid administration that elevates cerebral venous pressure may exacerbate brain edema.

The presence of hypovolemia is best assessed from clinical signs such as hypotension, tachycardia, an inability to tolerate anesthetic agents, and SBP variations with positive-pressure ventilation. A drop in SBP greater than 10 mmHg with positive-pressure ventilation is a sensitive indicator of a 10% reduction in blood volume ( Fig. 10.5 ). This decrease in SBP is a significantly better indicator than the central venous pressure.

The variation in SBP correlates well with the degree of hemorrhage in dogs and humans. However, placement of a central venous line may be helpful in the acute setting, especially to prevent overhydration, and should ultimately be performed to help guide fluid replacement. Timely evacuation of the brain mass must be accomplished first, with placement of central line later, after surgery has begun and the patient has been stabilized.