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COMPLEX AND CHALLENGING PROBLEMS IN TRAUMA SURGERY

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MANAGEMENT OF COMPLICATED NEUROLOGIC INJURIES


John Peter Gruen, MD, and Martin Weiss, MD

DEFINITION

Any injury to nervous system tissue is complicated if it is associated with injury in another organ system which jeopardizes the neurologic outcome. A simple neurologic injury is one in which neural tissue is damaged in the absence of significant injury to another organ system. Complicated injuries can occur because of injury to tissue surrounding or contiguous with traumatized nervous tissue-most frequently bone or blood vessels. Bone can lacerate or compress neural tissue. Blood irritates neural tissue and, as it accumulates, can be a source of mass effect. Another complicated neurologic injury is one in which an injury to an organ system at a distance from the site of neural injury affects neural tissue. Cardiac arrest (in the setting of primary heart trauma or secondary to hypovolemia) can complicate what would otherwise be a simple concussion, contusion, or extraparenchymal hematoma. Complicated is not descriptive of the neurologic condition of the patient. In many uncomplicated injuries, in which nervous tissue is injured to the exclusion of other injuries, such as in a complete, clean laceration of a peripheral nerve, transection of the spinal cord, or diffuse axonal brain stem injury, the neurologic condition and prognosis of the patient may be far worse than in complicated injuries. Examples of uncomplicated neurologic injuries include (1) clean transection of a superficially located peripheral nerve which damages only axons, myelin sheath, and endoneurium, perineurium, and/or epineurium, while sparing major arteries, veins, and soft tissues; (2) transection by a missile of the

From the Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles, California

SURGICAL CLINICS OF NORTH AMERICA


VOLUME 76 NUMBER 4 * AUGUST 1996

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spinal cord. Actually, these penetrating spinal injuries, even if they spare vascular, bone, and soft tissue, are usually "complicated" by associated dural violation with cerebrospinal fluid (CSF) fistula formation, but these usually resolve spontaneously without significant impact on the clinical picture; and ( 3 ) cerebral concussion. In actuality, trauma significant enough to alter nervous function rarely spares contiguous tissues. Truly "uncomplicated" neurologic injuries are rare. The frequent association between nervous and adjacent tissue injury has been well documented. A recent review noted that one in five patients with facial fracture also has an associated closed head i n j ~ r y . ~ Another review found a large number of temporal bone fractures with CSF leakage and facial nerve paralysis in a group of more than 100 trauma patients with closed head injury.z2Orthopedic and intra-abdominal-thoracic injuries associated with closed head injury have been extensively reviewed elsewhere. Secondary injury to nervous tissue can occur as a result of damage at a distance to microscopic or macroscopic structures. Fat embolization to cerebral vessels is an example of a neurologic complication secondary to a non-nervous injury. Recent reviews have looked at long bone injuries,'' facial fractures: and temporal bone fracturesZZ in the setting of head trauma.
CHARACTERISTIC ASPECTS OF NEUROLOGIC INJURY Physical

Physical injury results from the direct effects of shear, rotation, and traction forces on neural tissue. At the macroscopic level, such injuries appear as contusions or hemorrhage within neural tissue. There may be deformation of the shape of the tissue. At the histologic level, physical forces result in microhemorrhages and disruption of the myelin sheaths surrounding neural elements, in addition to disruption of axonal neuronal processes. The other mechanism of physical injury is secondary through disruption of normal homeostatic mechanisms. Physical injury to certain neural areas, frequently the hypothalamus, can cause changes in homeostatic regulatory systems such as those for osmolality, temperature, and emotional readiness. The syndrome of inappropriate antidiuretic hormone (SIADH) release can result in hyponatremia sufficient to precipitate seizures and to alter mental status.

Vascular Injury

Trauma severe enough to damages accompanying blood with injury to vessels large and Vascular complications can be tissue injury.

cause damage to neural tissue frequently also vessels. Intracranial trauma can be associated small, epidural or intradural, arterial or venous. more life threatening than the primary neural

Autoregulation Loss

Because the oxygen, glucose, and other metabolic demands of the brain are enormous and constant, with total deprivation for just minutes resulting in

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irreversible neural cellular and tissue injury, the vasculature of the brain has developed a system of coordinated arterial smooth muscle contraction with decreased luminal diameter and increased resistance (by Poiseuilles law) to maintain perfusion pressure even in the face of systemic hypotension. The pressure in the cerebral vasculature fluctuates very little compared with the systemic changes that elicit them. Although the mediators are not known, severe head trauma is frequently associated with a loss of vascular autoregulation, with the consequence that the cerebral arterial pressure varies passively in parallel with the systemic blood pressure. Intracranial pressure in turn rises and falls passively as systemic blood pressure (and thereby intravascular blood) rises and falls.

Hyperemia The cerebral vasculature not only autoregulates in response to variations in systemic blood pressure but also responds with regional increases or decreases in flow, depending on local metabolic demands. Not only is autoregulation lost, but there is also a tendency for excessive blood flow globally throughout the brain, resulting in a condition of hyperemia inappropriate to regional metabolism.

Edema Brain edema can be classified by mechanism. Such a classification is misleading because cerebral edema is invariably due to a combination of mechanisms. Vasogenic cerebral edema results from loss of the integrity of the vascular endothelial intracellular tight junctions due to mechanisms not yet fully elucidated but presumed to be related to the release of various endogenous cytokines and vasodilatory and inflammatory substances. The mechanism controlling the release of these substances following head trauma is not fully understood. Cerebral endothelial hemostatic function compromise was found in an in vitro study. Human cerebral vessels lost their normal reactivity when evaluated 1 hour or 24 hours after percussion. Cells that were previously cultured with free radical scavengers retained the ability to block platelet adherence, which nonprotected cells lost shortly after the percussive injury. The authors proposed that free radicals mediate the compromise of hemostatic Loss of integrity of the blood-brain barrier favors movement of osmotically active substances through the now-permeable cerebral vasculature into brain parenchyma. These osmotically active substances carry water with them. Cerebral edema is nothing more than an abnormally high water content in brain parenchyma. Excessive parenchymal water is not necessarily confined to the extracellular compartment. Cells rely on the ubiquitous sodium-potassium ATPase as well as other energy- and oxygen-dependent ionic pumps to maintain physiologic intracellular and extracellular electrical and chemical potentials. At the time of injury, the brain may be transiently deprived of oxygen, frequently as a result of hypotension and hypoxia, which complicate many head injuries. Oxygen deprivation results in energy-dependent ionic pump failure. The presence of excess numbers of large, multiple, negatively charged intracellu-

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lar proteins favors movement of water molecules into the cell. As water enters, cells swell, resulting macroscopically in "cytotoxic" edema. Edema in and of itself is a source neither of neurologic dysfunction nor of irreversible neural tissue damage. It is the associated changes in relative anatomic position of neural structures which threaten the integrity of nervous tissues.
Herniation

Herniation complicates many injuries to the brain. Herniation is movement of tissue from its intended anatomic compartment into a contiguous compartment. Intracranially, herniation is movement of brain tissue from one side, fossa, or cistern into another. Herniations of the brain include those of the mesial temporal lobe (usually including the uncus) over and across the tentorium, between the middle and posterior fossae. As it moves over the tentorium into the posterior fossa, the herniating tissue approaches, contacts, and then compresses the medially situated midbrain and ipsilateral third cranial nerve. Herniation of the cerebellar tonsils through the foramen magnum can compress the central nervous system at the cervicomedullary junction, whereas subfalcine herniation may be associated with compression the pericallosal artery or its branches. Even in the absence of one of the above-mentioned focal herniations, edema can cause mass distortions of cerebral tissue which result in upward movement of this tissue with respect to that of the midbrain, causing distortion and dysfunction of arteries and cranial nerves in the vicinity.
Increased lntracranial Pressure (ICP)

The skull is rigid and cannot expand to accommodate an increase in the volume of any of its contents. The Monro-Kellie hypothesis states that the pressure in the nonexpandable intracranial compartment is the sum of the pressures due to the volumes of (1) brain parenchyma and contiguous soft tissue masses such as clots or tumors, (2) intravascular blood, and (3) CSF. As intracranial pressure rises, so does the resistance to inflow of arterial blood carrying needed oxygen and glucose. At a sufficiently elevated ICP, forward movement of blood is blocked and tissue becomes ischemic. The simple equation of cerebral perfusion pressure and its relation between the difference of the mean arterial pressure minus the intracranial pressure (CPP = MAP - ICP) represents the mathematical expression of this relationship. Intracranial pressure elevation is thus a global mechanical force that can lead to decreased cerebral perfusion, tissue ischemia, hypoxia or anoxia, and ultimately, infarction.
Increased Cerebrospinal Fluid Pressure

Every minute the choroid plexus produces 0.3 mL of CSF. If CSF outflow is blocked as the result of either communicating or noncommunicating pathology, the CSF pressure can rise to the point that it exceeds the pressure of the brain parenchymal fluid. In this case the hydrostatic pressure gradient favors movement of CSF from the ventricles into the brain substance. Radiographically,

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this is seen on CT as low-density brain surrounding the CSF-filled ventricles, so-called transependymal edema.
Ischemia

Ischemia is a state of deprivation of blood flow. Many of the injuries that accompany neurologic trauma result in decreased neural tissue perfusion or even outright ischemia. Neural tissue is exquisitely dependent on substrateoxygen and glucose-for its metabolic machinery. Neurons in the brain die after a few minutes of hypoxia. Trauma to vascular structures supplying neural tissue can result in disruption of the endothelial, muscular medial, and/or adventitial layers of arteries to the brain, spinal cord, and peripheral nerves. Depending on the extent and depth of vessel wall involvement, there can be local thrombus formation leading to obstruction or embolization, dissection of blood between vessel wall layers with luminal compromise or blockage, weakening of the inner layers without dissection but with aneurysm formation, or disruption of all three vessel wall layers with extravasation of blood into the tissue surrounding the vessel-the angiographic "pseud~aneurysm."~ Vasospasm is a common occurrence after subarachnoid hemorrhage, in which blood extravasates into the CSF-filled space through which cerebral blood vessels travel. Some single or combination of chemical factors in blood (hemoglobin has been implicated most often in both in vitro and in vivo models of subarachnoid hemorrhage) irritates the vessels and causes their muscular layers to constrict. If the constriction is sufficient it can lead to luminal compromise to the extent that distal perfusion is diminished even to the point of ischemia. Nervous tissue already compromised by the primary traumatic insult may succumb with the added effect of ischemia. Complicating ischemia is thought to be important in the mechanism of neuronal injury by excitatory amino acids.
TOXIC/METABOLIC CHANGES IN NEUROLOGIC INJURY Oxygen

Oxygen delivery is compromised in states of alkalosis (such as hypovolemia secondary to major hemorrhage or due to hyperventilation) in which the hemoglobin-oxygen dissociation curve is left-shifted. Hypoxia is frequently associated with severe head injury, resulting in airway compromise or depression of normal ventilatory reflexes.
Glucose

Metabolic rates for glucose are depressed following experimental brain injury. Depending on the severity of the head injury, these derangements can last for several days.
Electrolytes

Hydrogen Ion An increase in the concentration of hydrogen ions, measured as a decrease in tissue fluid pH, is detrimental to nervous tissue. Acidosis complicates neuro-

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trauma, usually when decreased tissue perfusion results in a regional shift to anaerobic metabolic pathways with the generation of lactate. Experimental data support the theoretical contraindication to administration of glucose in the hypoxic and ischemic states frequently attendant to head injury.Ih
Sodium/Potassium

Neurologic injuries associated with trauma to the hypothalamus not infrequently result in an (usually transient) excessive release of hypothalamic antidiuretic hormone with consequent "inappropriate" release (SIADH) of this important sodium homeostasis maintenance factor.
Calcium

The normal intracellular to extracellular calcium gradient is approximately 50,000 to 1. Calcium is an important regulator of intracellular metabolism, largely because of the frequency with which it is a cofactor for enzymatic activity. With too little intracellular calcium, enzymatic activity grinds toward a halt; with too much calcium, enzymatic activity becomes too fast, wreaking havoc on the balance between intracellular protein anabolism and catabolism. The normal physiologic intracellular to extracellular ratio of calcium is maintained by the continuous activity of energy-dependent transmembrane calcium exchange pumps. These pumps are powered by breakdown of high-energy phosphate bonds. High-energy bond production occurs only in the presence of oxygen. As noted above, neurologic injuries are frequently complicated by ischemia and tissue oxygen deprivation.
Excitotoxic Amino Acids

Much recent research has been focused on the consequences of excessive release of glutamate to ischemic neurons. Neurotransmitters are the mediators of interneuronal communication. Neurotransmitters are classified as excitatory or inhibitory according to the effect they have on action potential generation on postsynaptic cells. Some of these molecules, such as acetylcholine and epinephrine, occur not only in the brain but throughout the body. Glutamate, an amino acid, is the major excitatory neurotransmitter in the brain. In addition to glutamate itself, several synthetic morphologically similar molecules interact with postsynaptic membrane glutamate receptors. N M D A is the abbreviation for the chemical name of a molecule that binds most strongly with the subclass of glutamate receptors thought to be most closely associated with cellular injury. A molecule can bind the receptor without activating it. The activating molecule is called the agonist; a molecule that occupies the binding site but is ineffective in eliciting a receptor response is called an antagonist. At the time of head trauma some signal (perhaps from the hypothalamus) reaches glutaminergic (glutamine-producing and releasing) neurons and commands them to produce and release more glutamate. Whatever regulatory or feedback signals normally operate to regulate intracellular and extracellular glutamate levels are overwhelmed by the neuropathologic forces that accompany head injury. Excess glutamate is thus released into the synaptic cleft between the presynaptic and postsynaptic neurons. This excess glutamate occupies glutamate

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receptors on the postsynaptic neurons cell membrane. The NMDA receptor is particularly active. This receptor controls the opening and closing of a passive calcium-potassium exchange channel, which maintains the physiologic balance of calcium and potassium between the intracellular and extracellular milieu. Under normal physiologic conditions, a limited number of channels are open at any one time, thereby restricting entry of calcium into the cell. Excess receptor activation opens more of the normally homeostatic channels and allows calcium to pour into the cell along its concentration gradient. The cell senses itself being overwhelmed by the influx of calcium and activates a calcium-hydrogen active exchange pump fueled by breakdown of high-energy ATP terminal phosphate bonds. The overactivated pump working against the lopsided calcium concentration gradient rapidly depletes the supply of ATP. As cellular energy stores are exhausted, more ATP must be produced at precisely the time when oxygen is scarce. Frequently head trauma is associated with at least transient hypoxia, hypotension, or both. These result in inadequate O2 for production of high-energy phosphate bonds. ADP cannot be converted into ATP and accumulates along with its metabolites-inosine, xanthine, and hypoxanthine. Xanthine oxidase is activated by the increase in intracellular hydrogen ions resulting from failure of the energy-dependent calcium-hydrogen ion pump. The activated xanthine oxidase catalyzes the conversion of the accumulating ADP and its metabolites into uric acid and free radicals. Free radicals, molecules containing oxygen with unstable high-energy unpaired electrons such as OH- and 02, interact with the stable lipid molecules of the cell membrane, exchanging electrons that change the electrical properties and configurations of these molecules such that they become activated perpetuators of an electron transfer cascade that results in large numbers of configurationally and functionally altered molecules. Such altered cell membrane phospholipid molecules do not align themselves as well as in their original form and thus allow increased permeability of the membrane. This permeability favors further entry of calcium down its concentration gradient, which fuels the cell injury cycle by calciums activation of several proteolytic enzymes capable of breaking down essential cell cytoplasmic proteins. If the injury is severe enough, compensatory mechanisms are overwhelmed and the cell dies. Injury can be prevented or at least inhibited by blocking any step in the above outline pathway of glutamate-initiated cellular dysfunction and damage.
Apoptosis

Much interest has recently focused on the concept of programmed cell death, or apoptosis. Recent evidence suggests that a sequence of genetically coded cellular events can be set in motion by as yet incompletely understood mechanisms, including head injury, that lead inexorably to the death of the cell.
DIAGNOSTIC AND MONITORING PROCEDURES

Imaging A problem that sometimes arises between trauma surgeons and neurosurgeons relates to the amount of time that has to be diverted from the evaluation

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of neurologic injuries versus other systemic injuries. Neurosurgeons are concerned when attention is diverted away from the possible ongoing neural compromise, whereas trauma surgeons are preoccupied with several unlikely entities that may be difficult to diagnose rapidly with certainty. Delays in necessary intracranial surgery are less often due to completion of a trauma surgical work-up than are delays in necessary abdominal or thoracic surgery due to completing the work-up to clear the brain.28 Trauma surgeons and emergency medicine physicians must frequently make the initial decisions pertaining to imaging evaluation of head-injured patients. They must decide on the basis of limited clinical data who does and does not require a head CT. Masters et allyadeveloped criteria for defining low, medium-, and high-yield patients. A community hospital emergency department (ED) that rarely sees serious head injury reported that these criteria were predictive of actual CT findings between low- and high-yield patients. Development of such criteria will assist emergency medicine and trauma surgeons in determining who needs a CT and who does not.z6 CT scans have become the radiographic standard for the evaluation of acute neurologic system trauma. Skull radiography still has its advocates, but skull films convey little or no information about the intracranial contents. The use of skull radiography in the initial evaluation of even minor head injury is controversial. In an attempt to evaluate its benefits, a retrospective study of 566 cases of minor head injury (Glasgow coma score 13 to 15) concluded that skull radiographs are unnecessary for the decision process in closed minor head injury because management decisions are based primarily on a careful neurologic examination.2" The incidence of radiologically detected injury is high even following apparently minor head injury. In a study of 1448 patients who underwent CT scanning following mild head injury, positive findings were present in 119 (8.2%); however, only l l patients (0.76%) required surgical intervention.2 Because of a significant increase in the use of CT scanning early in the management of trauma patients, one center did a retrospective review of 2047 CT scans in 1609 trauma patients. Thirty-eight percent (n = 770) of scans were positive, but less than 30% contributed to patient management. The authors concluded that strict surgical and radiologic oversight of CT scanning as a tool for the evaluation of trauma is essential.27

Monitoring

Of an annual estimated 60,000 patients with severe head injury alive on transport to ED, 50% have ICP elevation upon or shortly after arrival.23 ICP monitoring is necessary to guide potentially complicated therapies such as diuresis, hyperventilation, and barbiturate coma. Because of the free communication among all intracranial compartments, the pressure is the same in the subdural, parenchymal, subarachnoid, and intraventricular spaces. The goal of ICP management is to prevent herniation and to optimize cerebral perfusion. Even transient episodes of post-traumatic cerebral ischemia due to inadequate cerebral perfusion can quickly nullify all resuscitative efforts. The provision of sufficient cerebral blood flow is complicated by the varying degrees of disruption of pressure autoregulation commonly resulting from head trauma. Nervous tissue recovering from trauma requires a higher perfusion pressure than in the uninjured state. A cerebral perfusion pressure of at least 70

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mm Hg is required for adequate delivery of oxygen and substrate to tenuous neurons. It is essential that systemic blood pressure be maintained during all maneuvers for ICP control. Additionally, increasing evidence indicates that significant variation exists in the pathologic processes causing elevated ICP in individual patients. Therefore, goals such as the desired cerebral perfusion pressure should be considered in a patient-specific fashion and allow a targeted approach to therapy.I5 Although intracranial pressure monitoring has been common clinical practice for more than 40 years, the understanding of intracerebral hypertension, its causes and significance, as well as transient alterations in the ICP monitoring waveform continue to be sources of research interest. Two types of intracranial hypertension have been defined: the first, transient intracranial hypertension, is a sudden, rapid rise in ICP followed by a return to below 25 mm Hg. This type of intracranial pressure elevation is associated with an increase in cerebral blood flow (CBF). In refractory intracranial hypertension, progressive increases in ICP lead to neurologic deterioration and death. Cerebral blood flow is maintained in refractory intracranial hypertension despite increased pressure.h It is important to remember that the physiologically important numbers in terms of neural tissue integrity and survival are the cerebral blood flow and cerebral perfusion pressure. Transcranial Doppler ultrasonography (TCD) is a noninvasive technique for the assessment of CBF. TCD for the monitoring of major head trauma was prospectively evaluated in 10 patients, aged 17 to 37, and was found to correlate well with ICP.' TCD is a potential means for monitoring the hypersneic state that precedes edema formation.2' The incidence of delayed intracranial hematoma is high. Near-infrared spectroscopy is a noninvasive method for early detection of hematoma formation which can then prompt more timely CT and intervention.I2 Hyperventilation is used to induce hypercarbia in head-injured patients with suspected elevated ICP. Arterial pressure of carbon dioxide (arterial Pco2) is followed by serial blood gases. A recent study found that end-tidal C02 measurements did not accurately reflect arterial levels4 Important parameters to monitor during management of head injury include cerebral metabolic rate for oxygen as well as arteriojugular venous oxygen difference. Continuous regional cerebral cortical blood flow can be monitored with thermal diffusion flowmetry. Cerebral blood flow can be measured with the Xe-133 clearance method and is a good predictor of outcome. Cerebral oxygen delivery can be measured and may be a better measure of ishemia than CBF. Other monitoring modalities include electrophysiologic techniques such as electroencephalography, brain stem auditory and visual evoked responses, and somatosensory evoked potentials. However, the data from these studies up to the present have primarily prognostic value and seldom enter into management discussions. The notable exceptions to this are electroencephalography or flow studies confirming the clinical diagnosis of brain death.

TREATMENT

As noted above, for uncomplicated neurologic injuries there is frequently no treatment. The limited regenerative potential of the nervous system, the central in particular, severely limits what can be done to repair uncomplicated

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nervous tissue damage. Most realistic efforts seek to prevent further damage, that is, prevent secondary injury. The results of immediate microscopic reanastomosis of uncomplicated superficial peripheral nerve transections are good. This an exception to the rule that nervous injuries cannot be repaired. Unfortunately, neither this nor autologous interposition grafting work in the central as they do in the peripheral nervous system.

Prehospital Care

A recent review emphasized the importance of prehospital care in optimizing outcome after head i n j ~ r y . ~

Elimination of Reversible Ongoing Injurious Forces

Because of the limited capacity for regeneration and limited plasticity of the nervous system, uncomplicated neurologic injuries, particularly in adults, are functionally fixed and not usually progressive over time unless associated injuries result in decreased perfusion with neural tissue ischemia. Treatment of uncomplicated injuries is directed to ensuring the hygiene of wounds and to facilitating whatever limited regenerative potential is available. In complicated injuries, injury to non-nervous tissue, such as to hemorrhaging muscle, can lead to further injury to neural elements. Treatment in these "complicated" cases is thus directed to the associated injury in an effort to prevent secondary injury to nervous tissue. Trauma surgeons and emergency medicine physicians frequently make preliminary intracranial pressure management decisions before a CT has been done or a neurosurgeon consulted. It behooves the non-neurosurgical trauma practitioner to understand the criteria for placement of intracranial monitors, but the decision to place or not to place one of these devices should rest with the neurosurgeon, who is best prepared to handle the infrequent complication. Adherence to protocols limits formulation of judgments based on clinical experience. Trying to formulate a protocol for placement of intracranial pressure monitoring devices according to local, regional, or national standards is difficult, partially because of the lack of uniformity of practice among centers treating head trauma victims. A recent national telephone survey of 624 trauma centers found that only 28% routinely performed intracranial pressure monitoring and 7% never did. Seventy-two percent used ventriculostomy catheters for measuring ICP, but only 44% of the centers used CSF drainage for ICP control. Hyperventilation and osmotic diuretics were used in 83% of centers to reduce ICP. Barbiturates were used in 33%. Surprising, in light of their abandonment by most neurotraumatologists, was the prevalent use of corticosteroids in more than half of the cases in 64% of trauma centers. In spite of complications of hyperventilation and the trend toward a higher Paco2 target, 29% of the telephone-surveyed centers reported aiming for Pam2 values of less than 25 torr.R Management of "complicated" neurologic injuries is a source of trepidation because few of the therapies instituted for ICP management and cerebral perfusion maintenance are physiologically benign. Some of the therapeutic measures used in routine management of head trauma, such as hyperventilation and diuresis, risk converting relatively "uncomplicated" neurologic injuries into

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complicated multisystem injury. Hyperventilation results in alkalosis, which contributes to hypokalemia. Diuresis can provoke hypotension, hypovolemia, and hypokalemia as well. Emergency airway management for protection and hyperventilation has been the source of innumerable disagreements between neurosurgical and emergency medicine colleagues. Neurosurgeons rely heavily on the results of the neurologic examination and the Glasgow coma score for prognostication as well as management decision making. By and large they are opposed to long-lasting paralytic agents, which make meaningful neurologic assessment impossible. Endotracheal tubes preclude determination of the verbal component of the Glasgow coma score in the range 2 to 5. Trauma surgeons and emergency medicine physicians are rightfully concerned about airway compromise and hemodynamic instability in patients requiring airway manipulation. The latter perspective and recommendation for the use of neuromuscular blocking agents are provided in a recent review of the issue of emergency airway management technique in the severely head-injured patient.zs Many of the drugs that have become mainstays of head trauma management may contribute to adverse neurologic outcome. A recent medical record review of 100 patients with head trauma admitted to a university hospital during 1 year found that 72% received one or a combination of the drugs (neuroleptics and other central dopamine receptor antagonists, benzodiazepines, and the anticonvulsants phenytoin and phenobarbitone) that animal studies suggest are detrimental to neurologic recovery.

Substrate

Particularly the brain, but in fact all neural tissue, is exquisitely dependent on an uninterrupted supply of substrate. Oxygen and glucose are the fuels for sustaining the metabolic machinery of neural tissue.
Supply

An adequate amount of oxygen and glucose is essential. Oxygenation depends on adequate intake through the lungs. In the setting of head and spinal injury, adequate blood oxygen tension should be ensured with supplemental oxygen in both spontaneously and mechanically ventilated patients. Hypoglycemia should be avoided if at all possible.
Delivery

Perfusion of tissues is the physiologic mechanism for delivery of substrate to cells. In discussions of complicated head injury management, it is essential to remember that interventions are directed not primarily toward decreasing intracranial pressure, but rather to increasing cerebral perfusion. Intracranial pressure is important, of course, but only as a variable linked to mean arterial pressure (MAP) as expressed in the equation: CPP = MAP - ICP. Ongoing neural injury is more likely in a patient with an ICP of 5 mm Hg and a mean arterial pressure of 50 than it is in a patient with an ICP of 20 and a mean arterial pressure of 110. Masses can compress and compromise the lumina of cerebral arterial ves-

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sels. Removal of such offending lesions is necessary for the restoration of cerebral perfusion. Vasospasm secondary to subarachnoid hemorrhage can be mitigated by the use of calcium channel blockers such as nimodipine. Clinical studies of calcium channel blockers have demonstrated improved neurologic outcome in subarachnoid hemorrhage patients who received these agents, but angiography showed equal amounts of vasospasm in the patients who did not and did receive calcium channel blockers. Thus, calcium channel blockers improve neurologic outcome from vasospasm following spontaneous subarachnoid hemorrhage but perhaps by mechanisms other than calcium channel blockade.

Management of lntracranial Pressure

The Monro-Kellie hypothesis states that in the rigid, nonexpandable cranium the pressure is determined by the quantities (and thus pressure contributions) of the three principal intracranial components: intravascular blood, CSF, and brain parenchyma (and associated mass lesions such as hematomas and tumors). These three volumes are the only ones that can be changed to increase or decrease ICP.

Head Position

The head should be elevated enough to facilitate venous outflow from the head while at the same time not interfering with forward perfusion into the cranium.

Hyperventilation

Hyperventilation works by alkalinizing the blood and decreasing the arterial partial pressure of C02. The CSF is an ultrafiltrate of the blood such that a decrease in hydrogen ion concentration in the former results in a parallel decrease shortly thereafter in the latter. Cerebral arteries, bathed in spinal fluid as they run over the surface of the brain in the subarachnoid space, constrict in response to decreased hydrogen ion concentration. Recent evidence suggests that mechanical ventilation to decrease arterial Pco2down to 30 mm Hg is as effective in decreasing intracranial pressure as is the more vigorous and potentially more damaging hyperventilation to decrease Pco2down to 25 mm Hg. The response of the arteries to a decreased hydrogen ion concentration is transient, lasting 12 to 16 hours, after which hyperventilation has less and less (until virtually no) effect on the caliber of the vessels. The problem associated with hyperventilation is that it decreases blood flow through the cerebral vasculature at a time when the brain is desperately in need of optimal perfusion. Cerebral contusions are hypersensitive to the vasoconstricting effects of hyperventilation, which should be used judiciously in this setting to avoid iatrogenic compromise of recovery. A recent study of routine paralysis for intracranial pressure management found a higher incidence of complications (primarily pneumonia) without significant difference in the Glasgow outcome scale s ~ o r e . ' ~

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Diuresis

Another means of reducing intracranial pressure according to the MonroKellie hypothesis works by reducing the parenchymal (normally 80%) volume component of the intracranial contents. Diuresis decreases the interstitial fluid component of the parenchymal compartment. Mannitol is an osmotically active but metabolically inactive simple sugar that draws fluid from the interstitial to the intervascular space. Unfortunately, mannitol also diffuses into injured tissue without an effective blood-brain barrier, carrying with it water molecules from the blood into the interstitial space. The large volumes of osmotically active mannitol produce a transient increase in the systemic blood volume which, in the cerebral circulation with impaired autoregulation, causes an increase in cerebral intravascular blood. The loop diuretic furosemide is frequently given to blunt the increase in blood volume due to mannitol.

Shunting CSF

Catheters placed into the ventricles for monitoring ICP can do double duty as a means of draining off CSF.

Brain Extirpation

A retrospective review of the management history of 20 blunt head trauma victims treated by lobectomy to reduce elevated ICP found outcome to be favorable (good or moderately disabled) in 11patients and unfavorable (severely disabled, persistently vegetative, or dead) in 9. Higher initial Glasgow coma scale score, younger age, and pupillary reactivity were positive prognostic indicators of favorable outcome. Neither size nor location of the lesion had prognostic significance.'8

PROTECTI0N

Brain protection involves proactive, anticipatory measures intended to forestall the evolution of secondary neural tissue injury due to the mechanisms discussed above: physical disruption, ischemia, or toxic and metabolic abnormalities. Because of the difficulties inherent in physical manipulation of brain as opposed to other tissues, physical restoration is virtually impossible after an injury that has physically disrupted the tissue. Combined with the burgeoning knowledge of neuromolecular biology and pharmacology, prevention of posttraumatic secondary metabolic cellular injury has become the focus of the most intensive basic science research being done in the area of neurotraumatology. The theoretical basis for all brain protection is to attempt to counter the deleterious effects of ischemia, excitotoxins, free radicals, and other potentially pathogenic metabolites.

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Excitotoxic Amino Acids

As noted above, glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. In response to an ischemic or hypoxic insult, supranormal levels of glutamate are released, causing excessive neuronal stimulation of postsynaptic receptors, increased neuronal membrane permeability, and impaired ion homeostasis. A chain reaction can ensue, resulting in neuronal death. In vivo and in vitro studies have shown that administration of NMDA receptor antagonists decreases neuronal injury due to hypoxia and/or ischemia. The NMDA receptor is thought to be most responsible for the damaging effects on neurons of excessive glutamate. NMDA receptor antagonists are being evaluated in several multicenter studies looking at the efficacy of this compound versus placebo in improving neurologic outcome following severe head injury. The therapeutic window is believed to be within a few hours from the time of injury and depends on the level of blood flow to the injured area. Each hour of ischemia increases the degree of tissue death. Treatment within 6 hours from time of injury is thought to be reasonable in balancing the needs for neuroprotection and the practicalities of hospital admission and drug administration. Because the primary brain insult induced on impact is exacerbated by secondary glutamate-induced injury, neuroprotection is probably required for at least the several days during which neurotoxic concentrations of brain glutamate have been detected. Glutamate release inhibitors may be an alternative to receptor antagonists in the treatment of focal cerebral ischemia and stroke.I6 Recognition of the complex biochemical pathophysiology of neural injury has stimulated interest in pharmacologic interventions to prevent further injury and thereby enhance outcome. In addition to free radical scavengers and glutamate receptor antagonists, drugs currently under, pending, or proposed for investigation as cerebroprotective adjuncts in the management of neurologic trauma include 21-aminosteroids, adrenocorticotropic hormone analogues, and omega conopeptides. These are some of the agents being tried to counteract some of the deleterious biochemical events after head injury. The 21-aminosteroids (so-called lazaroids), extremely potent inhibitors of iron-dependent lipid peroxidation and peroxyl radical formation, have been shown in spinal and head trauma models to reduce neurologic sequelae without many of the undesirable side effects (such as inhibition of wound healing) seen with corticosteroid use in the post-traumatic settingz5 One of these 21aminosteroid drugs, tirilizad, was shown to be effective in preserving neurologic function following nontraumatic subarachnoid hemorrhage, but in a multicenter study of head trauma, control patients who did not receive the drug had outcomes equal to those who did. Omega-conopeptides reduce calcium accumulation and are potential therapeutic adjuncts in the treatment of brain injury.I3 Adrenocorticotropic hormone analogue was recently shown to reduce hypoperfusion, blood-brain barrier leakiness, and increased ICP in animal models.'" Methylprednisolone has become standard in nonpenetrating spinal cord injury. Other protective agents and some that work by as yet unknown mechanisms (gangliosides) are also being evaluated for spinal injury.
SPINAL AND PERIPHERAL NERVE INJURIES

The management principles for brain injury are similar to those for spine and peripheral nerve. The bottom line in treatment of neurologic injury is to ensure or restore delivery of oxygen and substrate to injured tissue.

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ASSOCIATED NON-NEUROLOGIC INJURIES

Treatment of multiply traumatized patients frequently requires a combination of therapies, some of which can work at cross purposes. The trauma surgeon equates blood volume with organ perfusion. To the neurosurgeon, intravascular blood is 10% of the intracranial volume that according to the Monro-Kellie hypothesis is one of only three such volumes that can be reduced for ICP control. Neurosurgical practices such as hyperventilation, diuresis, and even barbiturate coma threaten cerebral substrate delivery by decreasing cerebral perfusion. They are resorted to when there is a threat of increased ICP, which itself threatens cerebral perfusion (CPP= MAP - ICP) and is associated with herniation syndromes. In multiply traumatized patients with complicated neurologic injuries, there is no place for unilateral decision making on the part of either the trauma surgeon or the neurosurgeon. Priorities must be set and agreed upon following mutual consultation. Medications that might not otherwise be harmful can be so in the setting of complicated neurologic injury. A recent report documented severe ketonuria developing in a 12-year-old head-injured patient who received propofol sedation. The ketonuria was thought to have resulted from metabolism of the lipid propofol carrier in the setting of therapeutic glucose restriction (to decrease lactic acid formation in cerebral t i s ~ u e ) . ~
Types of Injuries Vascular Injury Complicating Peripheral Nerve Transection

The mechanisms that result in peripheral nerve transection rarely spare surrounding soft tissue or vascular structures. If the vascular or othopedic surgeon encounters a divided nerve while repairing a vascular injury, it is recommended that he or she attach the nerve endings to fascia during closure to facilitate subsequent identification during exploration for neurolysis, reanastomosis, or nerve grafting. Compartment syndromes result from accumulation of extravasated blood and other fluid within the compartments defined by the fascial septations between the muscles of the extremities. The elasticity of the fascial limiting tissue is low. Pressure within the compartment bounded by the fascia rises in the presence of an expanding mass, just as does the ICP under similar circumstances. Increased compartment pressure adversely affects nerves in two ways: First, the vasa nervorum, the small-caliber blood supply to the nerves, is vulnerable to mechanical compression with resultant distal ischemia. Second, distal portions of the axonal processes depend on axonal transport for delivery of newly synthesized proteins and substrate from the cell body. Sufficient pressure around the axon can block axonal transport, resulting in neuronal injury. Surgical compartment decompression may be necessary to save the compressed nerve.
Intervertebral Disc Herniation with Facet Dislocation

Complicating Spinal Cord Injury


Because of proximity to the surrounding bony canal and intervertebral discs, injury to the spinal cord frequently is associated with bone and possibly disc disruption.

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Instability of the vertebral column occurs following compromise of a sufficient portion of the structures-bone, ligament, and disc-that maintain its integrity. The anterior spinal artery supplies blood to the anterior two thirds of the spinal cord. The artery is ideally placed to be compressed by any structure-disc, bone, or hematoma-extending from anterior back into the canal toward the ventral cord. As is true of many vascular pathophysiologic processes, anterior spinal artery compromise can turn an absent or minimal deficit into a major or complete neurologic deficit suddenly and without warning. This neurologic complication can be prevented by imaging the structures anterior to the spinal cord whenever the mechanism of injury makes pathology there plausible. MRI scanning provides visualization of soft tissue structures such as herniated intervertebra1 discs, which can compress the anterior spinal artery. Whereas an "uncomplicated" spinal injury is frequently complete and irreversible, anterior spinal artery compromise complicating spinal injury can sometimes be reversed in time for eventual neurologic recovery. Localization by examination (knowledge of spinal cord pathways) and lesion definition by appropriate imaging are essential for timely management of anterior spinal artery compromise.
Coagulopathy Complicating Transcerebral Missile Injury

The brain contains tissue thromboplastin activator in concentrations higher than in any other organ or tissue. Penetrating trauma to cerebral tissue characteristically causes the release of massive amounts of this enzyme, which breaks down circulating and coagulating thrombin and prothrombin, thereby undermining an important final common pathway of hemostasis and leading to a systemic coagulopathic state. The indications for operation in gunshot wounds must be clear and compelling. During the operative procedure, attention to hemostasis with administration of coagulation products may be necessary. The coagulopathy may not declare itself until the postoperative period; therefore, patients with penetrating cranial injury require postoperative monitoring for this complication.
SUMMARY

Despite measures based on the Monro-Kellie principles for ICP reduction and optimization of cerebral perfusion pressure, the outcome from complicated neurologic injuries remains unsatisfactory. Many patients are "pulled through' the acute event only to remain minimally functional or vegetative for the remainder of their lives. Pharmacologic interventions to protect the brain against the toxic and metabolic consequences of neurologic injury seem to be the future of neurotrauma.
References
1. Boishardy N, Granry JC, Jacob JP, et al: Value of transcranial Doppler ultrasonography in the management of severe head injuries. Ann Francaises Anesth Reanim 13:172-176, 1994

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2. Borczuk P: Predictors of intracranial injury in patients with mild head trauma. Ann Emerg Med 25:731-736, 1995 3. Canivet JL, Gustad K, Leclercq P, et al: Massive ketonuria during sedation with propofol in a 12 year old girl with severe head trauma. Acta Anaesthesiol Belg 45~19-22, 1994 4. Christensen MA, Bloom J, Sutton KR Comparing arterial and end-tidal carbon dioxide values in hyperventilated neurosurgical patients. Am J Crit Care 4116-121, 1995 5. Conforti PJ, Haug RH, Likavec M: Management of closed head injury in the patient with maxillofacial trauma. J Oral Maxillofac Surg 51:298-303, 1993 6. Contant CF Jr, Robertson CS, Crouch J, et al: Intracranial pressure waveform indices in transient and refractory intracranial hypertension. J Neurosci Meth 57:15-25, 1995 7. Garcia JH: Prehospital management of head injuries: International perspectives. Acta Neurochir (Supp1)5714.5151, 1993 8. Ghajar J, Hariri RJ, Narayan RK, et al: Survey of critical care management of comatose, head-injured patients in the United States. Crit Care Med 23:560-567, 1995 9. Giannotta SL, Gruen JP: Vascular complications of head trauma. In Barrow D (ed): Complications and Sequelae of Head Injury. Park Ridge, IL, American Association of Neurological Surgeons, 1992 10. Goldman H, Morehead M, Murphy S Use of adrenocorticotrophic hormone analog to minimize brain injury. Ann Emerg Med 22:103.51040, 1993 11. Goldstein LB: Prescribing of potentially harmful drugs to patients admitted to hospital after head injury. J Neurol Neurosurg Psychiatry 58:753-755, 1995 12. Gopinath SP, Robertson CS, Conant CF, et al: Early detection of delayed traumatic intracranial hematomas using near-infrared spectroscopy. J Neurosurg 83:43&444, 1995 13. Hovda DA, Fu K, Badie H, et al: Administration of an omega-conopeptide one hour following traumatic brain injury reduces 45 calcium accumulation. Acta Neurochir (S~ppl)60:521-523,1994 14. Hsiang JK, Chesnut RM, Crisp CB, et al: Early, routine paralysis for intracranial pressure control in severe head injury: Is it necessary? [see comments Crit Care Med 22:1471-1476, 19941 Crit Care Med 22:1349-1350, 1994 15. Lang EW, Chesnut RM: Intracranial pressure: Monitoring and management. Neurosurg Clin North Am 5:573-605, 1994 16. Leach MJ, Swan JH, Eisenthal D, et al: BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage. Stroke 241036-1067, 1993 17. Leblanc MH, Huang M, Vig V, et al: Glucose affects the severity of hypoxic-ischemic brain injury in newborn pigs. Stroke 24:1055-1062, 1993 18. Litofsky NS, Chin LS, Tang G, et al: The use of lobectomy in the management of severe closed-head trauma. Neurosurgery 34:62&632; discussion 632-633, 1994 19. Malisano LP, Stevens D, Hunter GA: The management of long bone fractures in the head-injured polytrauma patient. J Orthopaed Trauma 8:l-5, 1994 19a. Masters SJ, McClean PM, Arcarese MS, et al: Skull x-ray examination after head trauma: Recommendations by a multidisciplinary panel and validation study. N Engl J Med 316:84-92, 1987 20. Murshid WR Role of skull radiography in the initial evaluation of minor head injury: A retrospective study. Acta Neurochir 129:ll-14, 1994 21. Muttaqin Z, Uozumi T, Kuwabara S, et al: Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial Doppler monitoring. Acta Neurochir 123:76-81, 1993 22. Nageris B, Hansen MC, Lavelle WG, et al: Temporal bone fractures. Am J Emerg Mevd 13:211-214, 1995 23. Olshaker IS. Whve , DW Tr: Head trauma. Emere Med Clin North Am 11:165-186,1993 24. Orfeo T, Doherty JM, Adey G, et al: Sublethi percussion trauma in vitro causes a persisting derangement in the nonthrombogenic properties of brain endothelial cells. J Trauma 37347-357,1994 25. Paxton TP, Miles RH, Gamelli RL: Differential effects of 21-aminosteroids on wound healing. J Trauma 38:920-923, 1995 26. Richless LK, English K, Heller MB, et al: A prospective evaluation of radiologic
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criteria for head injury patients in a community emergency department. Am J Emerg Med 11:327-330, 1993 27. Rizzo AG, Steinberg SM, Flint LM: Prospective assessment of the value of computed tomography for trauma. J Trauma 38:338-342; discussion 342-343, 1995 28. Walls RM: Rapid-sequence intubation in head trauma. Ann Emerg Med 22:10081013, 1993 29. Wisner DH, Victor NS, Holcroft JW: Priorities in the management of multiple trauma: Intracranial versus intra-abdominal injury. J Trauma 35271-276; discussion 276-278, 1993

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