NEUROTRAUMA/COLLECTIVE REVIEW head injury trauma, brain

The Management of Cerebral Perfusion Pressure

and Intracranial Pressure After Severe Head Injury

From the Department of Neurological Surgery, W'ayne .State University, Detroit, Michigan.

Received for publication August 3, 1992. Accepted for publication October 14, 1992.

Presented at the Neurotrauma: Concepts, Current Practice & Emerging Therapies symposium in Detrok, Michigan, June 1992.

Richard D Fessler, MD Fernando G Diaz, MD, PhD

Neurosurgical intervention attempts to minimize secondary central nervous system injury after severe head injury through the evacuation of mass lesions with subsequent manipulation of cerebral perfusion pressure and intracranial pressure. The normal brain couples blood flow to metabolic demand through autoregulation of the cerebral vasculature. After severe head trauma and its attendant increase in intracranial pressure, marked alterations in cerebral blood flow and perfusion may occur. Currently, intervention is based on maintenance of coro- nary perfusion pressure and aggressive management of intracra- nial pressure. Both may be impacted by manipulation of ventila- tion, systemic blood pressure and volume status, administration of Osmotic diuretics, and head elevation. Such therapy in the patient with severe head injury attempts to maintain coronary perfusion pressure and adequate oxygen delivery in a damaged central nervous system with altered hemodynamics and raised intracranial pressure.

[Fessler RD, Diaz FG: The management of cerebral perfusion pressure and intracranial pressure after severe head injury. Ann Emerg Med June 1993;22:998-1003.]

INTRODUCTION The prognosis after severe head injury is determined largely at the time of injury. Severe head injury as defined by entry criteria into the Traumatic Coma Data Bank is a postresuscitation Glasgow Coma Scale (GCS) score of 8 or less. 1 Clinically, this corresponds to inability to open the eyes spontaneously, follow commands, or engage in comprehensible speech. ~,2 Statistically significant predic- tors of survival include GCS at presentation, age, type of injury, pupillary response, presence of multiple trauma, presence of brain stem injury, and duration of coma. 3-9 Increasing age and presence of mass lesions are indepen- dent predictors of mortality. ~o Shedden et al reported 48% mortality in patients with mass lesions versus 14% mor- tality in patients with diffuse injury so Regarding long- term outcome, initial GCS, presence of brain stem injury,

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coma duration, and cerebral perfusion have been correlated with cognitive recovery6, 7

Raised intracranial pressure (more than 20 to 25 mm Hg) is associated with mortality in 69% to 95% of patients. 1143 As expected, raised intracranial pressure refractory to treatment is associated with the highest mortality 11,,3 In patients with severe head injury and intracranial pressure of more than 20 mm Hg that was reducible with treatment, Alberico et al noted a good outcome in 27% of patients. 11 The aim of neurosurgica] intervention in the head-injured patient is to manipulate the physiologic parameters that will minimize secondary injury related to ischemia and raised intracranial pressure.

CEREBRAL BLOOD FLOW IN THE NORMAL BRAIN

Normal cerebral blood flow varies with brain region but is approximately 50 to 65 mLllO0 g/min. 14 Cerebral blood flow is regulated locally by several factors, including blood pressure, Paco2, and Pao 2. For example, for every 1-mm Hg decrease in Paco 2 between 20 and 60 mm Hg, cerebral blood vessel diameter decreases 2% to 3%. 15 This corresponds to a change in cerebral blood flow of approximately 1.1 mL/min/100 g per mm Hg Paco~.*6 Although the actual cerebral vascular response is a non- linear function of Paco2, cerebral blood flow within the range of 20 to 60 mm Hg Paco 2 approximates a linear function.*6 Cerebral blood flow doubles as Pao 2 declines from 50 to 30 mm Hg. 15 Numerous other elements, including adenosine, .6 neuropeptides, ions, and neuro- genic mechanisms, may play a role in local control of cerebral blood flow, especially during ischemia.*r,*s

Cerebral blood flow also is a function of the cerebral perfusion pressure and the cerebral vascular resistance. Cerebral perfusion pressure, defined as the difference between systemic mean arterial pressure and the intra- cranial pressure, is the pressure gradient across the brain that drives cerebral blood flow. ,9 Because intracranial pressure is higher than the systemic mean venous pres- sure, intracranial pressure is the limiting factor for blood flow out of the brain and is used in defining cerebral perfusion pressure. Cerebral vascular resistance is propor- tional to the fourth power of the vessel radius; therefore, even small changes in vessel caliber translate into signifi- cant alterations in cerebral blood flow. 15 In the basal state, there is a dynamic interplay of vasoconstriction and vasodilatation is by the cerebral vascular bed that allows coupling of cerebral blood flow to metabolic needs over a wide range of cerebral perfusion pressures. This auto- regulation generally is lost if coronary perfusion pressure falls to less than 50 mm Hg. .9

CEREBRAL BLOOD FLOW AFTER HEAD INJURY

Recent clinical research suggests that in some patients, severe central nervous system injury maybe complicated by a marked decline in cerebral blood flow (less than 20 mL/100 g/min) with resultant ischemia and loss of autoregulation. 1<2o In studies of cerebral blood flow performed within six to 12 hours of injury, Bouma et al noted decreased cerebral blood flow in several patients. 1,~ Yoshino et al performed dynamic computed tomography scanning on 42 patients with severe head injury to evalu- ate cerebral hemodynamics and found that 68% of the fatally injured patients (17 of 25) were severely ischemic with diffuse cerebral edema. 2o Nonfatal injuries were associated more often with a hyperemic state. 2o These results are in agreement with earlier studies that noted a marked decrease in cerebral blood flow in patients with fatal injuries, a* In addition, patients surviving the acute injury often exhibit loss of autoregulation within the first three days after injuw.4 Although cerebral blood flow does not correlate with outcome in relation to all head injuries, it appears to be a significant factor in patients with severe injury and low flow. 22

Ischemia and increased intracranial pressure result in vasodilation 0 f the cerebral vascular bed. 14,19,23 Vasodila- tion augments increases in intracranial pressure by increasing cerebral blood volume. ,9 In patients with severe head injury, the coronary perfusion pressure range that supports intact autoregulation actually shifts upward, resulting in impaired autoregulation at levels of coronary perfusion pressure that previously were adequate. 19 Patients surviving the acute phase after head injury may exhibit varying degrees of autoregulatory impairment with cerebral blood flow that is low, normal, or hyperemic. 14,22,24

As many as 40% of patients with severe head injury develop cerebral vasospasm, which occurs as early as 48 hours after injury and reaches its nadir within five to seven days. 25 Cerebral vasospasm may be diagnosed using transcranial Doppler. Vasospasm may be a cause of delayed ischemia in some patients. Clinical trials in which nimodipine is administered after severe head injury have failed to show a statistical benefit. 26

CEREBRAL BLOOD FLOW IN THE PRESENCE OF MASS LESIONS

Intracranial mass lesions are tolerated better in the presence of adequate cerebral perfusion pressure, Experimentally, as systolic arterial blood pressure increases, larger lesions are tolerated for longer periods. 27 Weinstein and Langfitt noted vasodilation in response to an epidural mass of

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increasing diameter followed by vasoconstriction with decreasing mass size. 28 Blood pressure was not manipu- lated, suggesting that as coronary perfusion pressure decreases secondary to increasing intracranial pressure, the cerebral vasculature attempts to compensate by decreasing cerebral vascular resistance through vasodila- tion in an attempt to maintain cerebral blood flow. Schrader et al placed epidural balloon catheters in the epidural space of dogs and cats. An 87% increase in volume tolerance was noted when mean arterial pressure was increased from 60 to 190 mm Hg. 27 Rosner and Coley compared patients with severe head injury (GCS of 7 or less) and coronary perfusion pressure of more than 70 mm Hg with patients with coronary perfusion pressure of less than 70 mm Hg. 29 Their data showed that patients with higher coronary perihsion pressure exhibited lower intracranial pressure (26 + 3 versus 34 + 4 mm Hg), higher systolic arterial blood pressure (107 + 4 versus 83 + 5 mm Hg), and higher central venous pressure (7 ± 1.4 versus 5 i 1.7 mm Hg) when compared to patients with low cerebral perfusion pressure. 29 After mannitol infusion, patients in the low coronary perfusion pressure group showed a 60% decline in intracranial pressure, a 50°/0 to 60% increase in cerebral perfusion pressure, and an average increase in systolic arterial blood pressure of 10 mm Hg. 29 Rosner and colleagues hypothesized that the hemodynamic effects associated with the initial man- nitol bolus result in beneficial autoregulatory responses by the cerebral vasculature that improve oxygen delivery, remove vasoactive metabolites, and decrease cerebral blood velocity through vasoconstriction. ~9,29 Experimentally and clinically, adequate systolic arterial blood pressure, cerebral perfusion pressure, and volume status correlate with better tolerance of increased intra- cranial pressure.

MANAGING CEREBRAL BLOOD FLOW iN THE HEAD-INJURED PATIENT

The initial management of the head-injured patient with increased intracranial pressure typically includes intuba- tion, hyperventilation, and infusion with the osmotic diuretic mannitol. These interventions all impact cerebral blood flow.

The effects of mannitol are myriad. The initial effect is hemodynamic. When given as a bolus, mannitol augments intravascular volume, resulting in a transient increase in blood volume and systolic arterial blood pressure, which improves cerebral perfusion pressure. 19,29 In the presence of borderline or intact autoregulation, this rise in coronary

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perfusion pressure will cause reflex cerebral vasoconstric- tion. 29 This results in a net decrease in cerebral blood velocity with an immediate decline in intracranial pres- sure. When autoregulation is intact, mannitol will decrease intracranial pressure by as much as 27% and improve coronary perfusion pressure without affecting cerebral blood flow. 29-31 In patients with impaired auto- regulation, mannitol infusion decreases intracranial pres- sure approximately 5%, but cerebral blood flow increases by as much as 17%.3o, 31 Vasoconstriction appears to enhance the dehydrating effects of mannitol in patients with autoregulatory responses, whereas altered autoregu- lation allows increased cerebral blood flow with mannitol boluses and appears to attenuate the osmotic effects. 31 The osmotic effects of mannitol typically occur ten to 20 minutes after administration, which is in contrast to the hemodynamic effects that manifest almost immediately. 29 Mannitol also improves flow at the level of the microcircu- lation.3< 32 The hemodilution secondary to mannitol administration decreases blood viscosity, which improves flow (flow is inversely proportional to viscosity) and decreases red blood cell aggregation at the capillary level. Enhanced flow and oxygen delivery lead to clearance of vasoactive metabolites such as adenosine and CO2.3I

After administration, mannitol may result in a transient hypotensive response and decline in peripheral vascular resistance. This response is due to dilatation of skeletal muscle vascular beds. The degree of hypotension has been shown to be related to the dose and rate of administration of mannitol. 3~

Several investigators have reported beneficial results with regard to intracranial pressure and oxygen delivery from resuscitative measures using dimethyl sulfoxide and hypertonic saline.3< 35 Dimethyl sulfoxide has numerous potential clinical effects including free radical scavenging, diuresis, improved cerebral perfusion pressure, and decreased platelet aggregation. > Hypertonic saline improves coronary perfusion pressure by augmenting intravascular volume and improves oxygen delivery at the microcirculatory level, possibly independent of its effects on intravascular volume. 35

Hyperventilation reduces intracranial pressure through reduction of cerebral blood volume via constriction of pial and cerebral arterioles. The hydrogen ion is a potent smooth muscle relaxant and decreasing its concentration results in rapid vasoconstriction. 36 Several studies have shown that hyperventilation provides only temporary reduction in cerebral blood vessel diameter. Prolonged hyperventilation with maintenance of hypocapnia fails to prevent vasorelaxation over prolonged periods due to

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return of brain interstitial pH to normal levels.36, 3r Prolonged hyperventilation increases vessel reactivity rela- tive to changes in Paco 2 due to loss of brain interstitial buffering capacity. 3s Finally, prolonged hyperventilation may result in cerebral ischemia secondary to a shift in the oxygen hemoglobin dissociation curve with increasing pH. 3 Experimental studies suggest that hyperventilation and hypocapnia should be used only as a temporizing measure for control of intracranial pressure.

RECOMMENDATIONS FOR PATIENT CARE

The treatment approach in patients with severe head injury includes maintenance of coronary perfusion pres- sure and control of intracranial pressure through hyper- ventilation, head-of-bed elevation, osmotic diuretics, cerebral spinal fluid drainage, and, in certain cases, barbi- turates. The rationale for intracraniai pressure control has been discussed previously. ~3 Coronary perfusion pressure can be manipulated through control of mean arterial pres- sure and intracranial pressure. The primary aim of coronary perfusion pressure control is to maintain levels adequate for autoregulatory responses by the cerebral vascular bed. Recent data suggest that although manipulation of systemic blood pressure does not alter cerebral oxygen utilization, a positive correlation was found between coronary perfu- sion pressure and the intracranial pressure-volume index in patients with intact autoregulation. 30 Lowering of systemic blood pressure resulted in marked increases in intracranial pressure due to autoregulatory vasodilation to maintain cerebral blood flow. The data support mainte- nance of coronary perfusion pressure and mean arterial pressure but do not necessarily argue in favor of induced hypertension, which some investigators have advocated. 19 Patients with impaired autoregulation vary intracranial pressure with coronary perfusion pressure and obtain only a modest decrease in intracranial pressure with mannitol dosing. 19,3~

Head-of-bed elevation traditionally has been used to decrease intracranial pressure. Recently, several investiga- tors have questioned its usefulness. Rosner and colleagues emphasized maximizing coronary perfusion pressure by placing patients in a horizontal position, although this results in an increase in intracranial pressure. 19,29 However, Feldman et al have shown that head-of-bed elevation from zero to 30 degrees results in decreased intracranial pressure without a statistically significant change in cerebral perfusion pressure, cerebral blood flow, cerebral metabolic rate for oxygen, or cerebral vascular resistance.39

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Dosing of mannitol should be individualized on a per- patient basis. Small, frequent doses (0.25 to 0.50 g/kg every two to four hours) are as effective as single large doses (1.0 g/nag every four to six hours). 4o Smaller doses of mannitol result in fewer side effects related to electrolyte shifts. 4°

Continuous IV infusions of mannitol are not recom- mended for treatment of head injury as they negate the immediate hemodynamic benefit of mannitol in patients with marginal autoregulation. Continuous infusion of mannitol may lead to equilibration of mannitol across an altered blood-brain barrier with resultant attenuation of the dehydrating effects of mannitol, which requires at least a 10-mOsm change to affect intracranial pressure. 4o

Other measures for manipulation of intracranial pres- sure include drainage of cerebral spinal fluid and control of agitation, fever, electrolyte imbalance, and seizure activity. Patients unresponsive to hyperventilation and osmotic diuretics usually benefit from serial or continuous drainage of cerebral spinal fluid against a pressure of 15 to 20 mm Hg. ~1 Agitation may result in marked increases in intracranial pressure and can be controlled through judi- cious use of sedatives and paralyzing agents. 4a Seizure activity results in local loss of autoregulation with concomitant increases in cerebral blood flow and tissue lactacidosis, which may aggravate intracranial pressure.4~ Electrolyte imbalance and fever also may contribute to elevation of intracranial pressure and should be avoided.42, 44

The use of barbiturates has been a topic of recent debate. In a prospective, randomized comparison of mannitol versus pentobarbital in patients with a GCS of 7 or less, Schwartz et al found that pentobarbital was less effective than mannitol in lowering intracranial pressure. 5 In contrast, more selective studies indicate that in a subset of patients refractory to aggressive therapy that included cerebral spinal fluid drainage, hypervendlation, and mannitol use, high-dose barbiturates were effective.~5, 46 Marshall et al noted that addition of high-dose barbiturates reduced intracranial pressure in 75% of 25 patients who were refractory to maximized conservative therapy 46 In a multicenter, prospective randomized study, gisenberg et al found that one third of patients who failed to respond to maximal medical therapy had their intracranial pressure controlled after the addition of high-dose pentobarbital. 45 Barbiturates do not appear to be effective when given as initial therapy in patients with severe head injury4r A pulmonary artery catheter is used in conjunction with high-dose barbiturates because prolonged use can result in depression of cardiac function. 47

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CONCLUSION

The approach to severe closed-head injury (GCS of 3 to 8) entails manipulation of the physiologic parameters that will allow the cerebral vasculature to maximize oxygen delivery to damaged and ischemic tissue, clear vasoactive metabolites, improve cerebral blood flow, and decrease intracranial pressur e. Aggressive management of intra- cranial pressure coupled with maintenance of cerebral perfusion pressure relies on intracranial pressure monitor- ing, control of ventilation, head-of-bed elevation, use of osmotic diuretics, and occasional judicious use of barbitu- rates. Appropriate management of electrolyte and volume status impacts overall success. Clinical studies suggest that the greatest benefit of intensive management is in patients whose raised intracranial pressure is reducible with aggressive hemodynamic management.

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37. McDowall DG, Harper AM: Cerebral blood flow and cerebrospinal fluid pH in the monkey during prolonged hyperventilatien. J Lab Cfin Invest1968;(suppl):102.

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46. Marshall LF, Smith RW, Shapiro HM: The outcome with aggressive treatment in severe head injuries. Part 2. Acute and chronic barbiturate administration in the management of head injury. J Neurosurg 1979;50:26-30.

47. Ward JD, Beckar DP, Miller JD, et ah Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg 1985;62:383-388.

Address for reprints: Fernando G Diaz, MD, PhD

Department of Neurological Surgery

6EUHC

4201 St Antoine

Detroit, Michigan 48201

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