J Neurosurg 51:301-306, 1979
Failure of high-dose steroid therapy to influence intracranial pressure in patients with severe head injury STEVEN K. GUDEMAN,M.D., J. DOUGLAS MILLER,M.D., PH.D., F.R.C.S., AND DONALD P. BECKER, M . D .
Division of Neurological Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia While corticosteroids in standard neurosurgical dosage do not appear to influence recovery from severe head injury or elevated intracranial pressure (ICP), some reports claim that a much higher dose is effective. A resultant hypothesis is that an abrupt increase in corticosteroid dosage in patients with severe head injury should cause a detectable reduction in ICP and in cerebral elastance within 48 hours. To test this hypothesis, 20 consecutive patients with severe head injury, 12 of whom had had surgical decompression of mass lesions, were studied. All patients were artificially ventilated, and had continuous monitoring of ICP and intermittent testing of elastance by measurement of the volume-pressure response (VPR). For the first 12 hours after admission, patients received methylprednisolone, 40 mg every 6 hours. The dose was then increased abruptly by giving a single dose of 2 gm and 500 mg every 6 hours for the next 24 hours, then tapering rapidly. No significant change in ICP or VPR could be detected after 24 or 48 hours of high-dose steroid therapy. Of the 20 patients, 50% had good recovery or were moderately disabled, 15% were severely disabled or vegetative, and 35% had died. The course oflCP and the outcomes in these patients were not significantly different from those observed in a previous group of 262 patients managed in the same way for the high-dose regimen. There was, however, a high incidence of gastric hemorrhage (50%) and of hyperglycemia with glucosuria (85%) in these 20 patients. These negative results in patients with head injury stand in marked contrast to our experience of the benefit of methylprednisolone in patients with brain tumors. KEY WORDS high-dose steroids volume-pressure response 9
I
N the past 10 years glucocorticoid therapy has come to be used routinely in the management of patients with severe head injury. This has happened despite a disconcerting lack of evidence of its beneficial influence on outcome or on intracranial pressure (ICP) in such patients. This is in marked contrast to the application of steroid therapy in patients with chronic focal lesions, such as brain tumors or abscesses, that are associated with spreading, perifocal edema2 a~ In such patients clinical improvement ensues within hours of starting steroid therapy, accompanied by reduction in the extent and frequency of waves of increased ICP. This is paralleled by a reduction in periventricular elastance as measured by the immediate response of ICP to the injection of 1 ml of fluid in the lateral ventricle in 1 second? T M After 48 hours of treatment the baseline level of ICP descends into the normal range? ,8
J. Neurosurg. / Volume51 / September, 1979
9 head injury
9 intracranial pressure
9
In certain instances, notably where increased ICP has recurred in brain tumor patients previously controlled on the usual dosage of glucocorticoids, ICP may respond only to considerably higher doses of steroids. This has led to the suggestion that in cases of severe head injury a higher-dose regimen of steroid therapy may be beneficial. This has been supported by two studies in which high-dose therapy was associated with improved outcome and reduced incidence of intracranial hypertension. 5,6 It has been the policy of this neurosurgical department to monitor ICP in all patients with severe head injury, and to treat all patients with 10 mg dexamethasone on admission (within 6 hours of injury in over 90% of cases), followed by 4 mg every 6 hours, la,13 In addition, intracranial mass lesions are evacuated by immediate craniotomy, and all patients are artificially ventilated. Despite this aggressive ap301
S. K. Gudeman, J. D. Miller and D. P. Beeker TABLE 1
Clinical features, lesions, and outcome in two groups of patients with severe head injury Factors
Present Study
sex female (7o) 25 male (~o) 75 age mean (yrs) 28 range (yrs) 7-65 decerebrate (~o) 40 bilateral fixed pupils (7o) 30 impaired/absent oculocephalic response (7o) 60 mass lesions, operative (70) 60 lesions acute epidural hematomas (~o) 20 acute subdural hematomas (~o) 15 acute intracerebral mass lesions (7o) 25 outcome good recovery/moderate disability (~o) 50 severe disability/vegetative (7o) 15 dead (7o) 35
Previous Series 26 74 27 4-72 36 23 43 40 7 16 15 57 11 32
proach to management, intracranial hypertension presents an important problem in these patients? Based on experience in 262 cases, elevated ICP (> 20 mm Hg mean) recurs or persists in 40% of patients and is the cause of death in 15% or half of the fatalities. 1~ In certain subgroups of patients, notably those with acute subdural hematomas and acute intracerebral mass lesions, the incidence of persistent or recurrent and of fatal intracranial hypertension is much higher (70% incidence and 64% mortality). If high-dose steroid therapy is to influence eventual outcome from head injury, this effect ought to be manifest first in the reduction of the incidence and severity of posttraumatic intracranial hypertension. We have therefore studied the acute effects of abrupt changes from "low- to high-dose" steroid therapy in a well documented group of patients with severe head injury. This communication reports the results of this pilot study. Clinical Material and Methods A consecutive series of 20 patients with severe head injury was studied. The criteria for entering this study were that following admission to the hospital, resuscitation, and evaluation, all patients were unable to obey commands, and unable to utter formed words. All patients were immediately intubated, started on 40 mg methylprednisolone every 6 hours, and referred for immediate computerized tomography (CT). In 12 patients the CT scan disclosed an intracranial mass le302
sion requiring surgical decompression. These patients received a bolus of 1 gm/kg body weight of mannitol and were transferred immediately to the operating room where a wide decompressive craniotomy was performed with removal of clot, liquid blood, and/or resection of frontal or temporal lobes as indicated. A ventricular catheter for ICP monitoring was inserted at the end of the procedure. The eight patients in whom the CT scan failed to reveal a mass lesion were referred directly to the intensive care unit where a ventricular catheter was inserted for ICP monitoring. In the intensive care unit all patients were artifically ventilated to a PaCO2 of 20 to 25 mm Hg, and had continuous monitoring of heart rate, blood pressure, and ICP, and frequent intermittent neurological evaluations. This consisted of assessment using the Glasgow Coma Scale (eye opening, motor response, verbal response), measurement of oculocephalic or oculovestibular response, pupillary size, and light response and limb power. 1,15 After a stable recording of ICP had been obtained, three to five measurements of the volume-pressure response (VPR) were made. This was done by injecting 1 ml of normal saline into the ventricular catheter in 1 second and measuring the resultant rise in ICP as described previously. 12When these measurements had been completed, the dose of methylprednisolone was abruptly increased to 2000 mg in a single dose followed by four doses of 500 mg every 6 hours, four of 250 mg every 6 hours, then 40 mg every 6 hours. Assessments of ICP, VPR, and neurological status were repeated after 24 and 48 hours of high-dose therapy, and CT scans were repeated after 72 hours of therapy. Assessment of the effects of high-dose steroid therapy was made by comparing initial ICP and VPR values with those made after treatment. Also the incidence of intracranial hypertension on high-dose steroid treatment was compared with the known incidence of raised ICP in similar patients taken from our previous series of 262 cases. Changes in neurological status, in CT scan appearance, and in outcome from head injury were compared with the expected outcomes for similar patients in our previous series of patients who had been managed on a "normal-dose" steroid regimen. Finally, all patients on the high-dose steroid regimen were carefully screened for secondary complications such as gastrointestinal bleeding, electrolyte abnormalities, and infections. Results
Patient Population, Status, and Outcome The clinical features of this series and the earlier group of 262 patients are shown in Table 1. The mean age of the patients in this series was 28 years with a range of 7 to 65 years. Mean age in the previous series was 27 years with a range of 4 to 72 years. The sex J. Neurosurg. / Volume51 / September, 1979
F a i l u r e o f h i g h - d o s e s t e r o i d t h e r a p y in s e v e r e h e a d i n j u r y THERAPY
ratio was 75% male and 25% female (previous series 74% and 26%). Sixteen (80%) patients scored 8 or less on the Glasgow Coma Scale on admission. Seven (35%) were posturing or flaccid as the best motor response. Impaired oculocephalic responses were present in 12 patients (60%). The following lesions were noted on CT scan: acute subdural hematoma in four, acute epidural hematoma in two, intracerebral hematoma in five, and mixed intra- and extracerebral lesions in five. Three patients had diffuse brain swelling, implied by symmetrically small ventricles. Only one patient had a normal CT scan. Twelve patients (60%) underwent surgical decompression of an intracranial mass lesion. The incidence in our previous series was 40%. The overall outcome was assessed at 3 months by the scale devised by Jennett and Bond. + There was good recovery or moderate disability in 50% or 10 patients, severe disability in 15% or three patients, and seven patients (35%) died. This compares to our previous series of 57%, 11%, and 32%, respectively. Thus, no difference in outcome could be discerned.
INITIATED
+
30
I I I
~' 25 E
E "' rr 2 0
I I L
O3 Ld
a:
o_
15
_.J
z < cr Io (..9
20 mm Hg) recurred or persisted in 40% or eight patients, and was the mode of death in 15% or three. This is exactly the same incidence as in our previous series, u
THERAPY I N I T I A T E D
60
"I"-
E E
50
/
W rr
co 4 0 U3 bJ n~ (3-
d
30
Volume-Pressure Tests
rr
~
zo
I--Z
I0
iI HOSPITAL
DAYS
FIG. 2. Graph showing intracranial pressure (ICP) in 20 patients. High-dose steroid therapy does not alter the individual ICP course of each patient.
lowest ICP recorded before the change in steroid therapy was 6.3 • 4.5 mm Hg, and of the highest recorded ICP was 22.9 + 20.7 mm Hg. On Day 2 (first posttreatment day) the overall mean ICP was 15.6 + 12.4 mm Hg, with a low mean ICP of 6.7 + 4 . 8 mm Hg, and a high mean ICP of
25 E E
20
w oc
THERAPY INITIATED
t I I I
_c c I N T R A C R A N I A L PRESSURE 9 ........ 9VOLUME PRESSURE RESPONSE
d
Z
Failure of high-dose steroid therapy to influence intracranial pressure in patients with severe head injury STEVEN K. GUDEMAN,M.D., J. DOUGLAS MILLER,M.D., PH.D., F.R.C.S., AND DONALD P. BECKER, M . D .
Division of Neurological Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia While corticosteroids in standard neurosurgical dosage do not appear to influence recovery from severe head injury or elevated intracranial pressure (ICP), some reports claim that a much higher dose is effective. A resultant hypothesis is that an abrupt increase in corticosteroid dosage in patients with severe head injury should cause a detectable reduction in ICP and in cerebral elastance within 48 hours. To test this hypothesis, 20 consecutive patients with severe head injury, 12 of whom had had surgical decompression of mass lesions, were studied. All patients were artificially ventilated, and had continuous monitoring of ICP and intermittent testing of elastance by measurement of the volume-pressure response (VPR). For the first 12 hours after admission, patients received methylprednisolone, 40 mg every 6 hours. The dose was then increased abruptly by giving a single dose of 2 gm and 500 mg every 6 hours for the next 24 hours, then tapering rapidly. No significant change in ICP or VPR could be detected after 24 or 48 hours of high-dose steroid therapy. Of the 20 patients, 50% had good recovery or were moderately disabled, 15% were severely disabled or vegetative, and 35% had died. The course oflCP and the outcomes in these patients were not significantly different from those observed in a previous group of 262 patients managed in the same way for the high-dose regimen. There was, however, a high incidence of gastric hemorrhage (50%) and of hyperglycemia with glucosuria (85%) in these 20 patients. These negative results in patients with head injury stand in marked contrast to our experience of the benefit of methylprednisolone in patients with brain tumors. KEY WORDS high-dose steroids volume-pressure response 9
I
N the past 10 years glucocorticoid therapy has come to be used routinely in the management of patients with severe head injury. This has happened despite a disconcerting lack of evidence of its beneficial influence on outcome or on intracranial pressure (ICP) in such patients. This is in marked contrast to the application of steroid therapy in patients with chronic focal lesions, such as brain tumors or abscesses, that are associated with spreading, perifocal edema2 a~ In such patients clinical improvement ensues within hours of starting steroid therapy, accompanied by reduction in the extent and frequency of waves of increased ICP. This is paralleled by a reduction in periventricular elastance as measured by the immediate response of ICP to the injection of 1 ml of fluid in the lateral ventricle in 1 second? T M After 48 hours of treatment the baseline level of ICP descends into the normal range? ,8
J. Neurosurg. / Volume51 / September, 1979
9 head injury
9 intracranial pressure
9
In certain instances, notably where increased ICP has recurred in brain tumor patients previously controlled on the usual dosage of glucocorticoids, ICP may respond only to considerably higher doses of steroids. This has led to the suggestion that in cases of severe head injury a higher-dose regimen of steroid therapy may be beneficial. This has been supported by two studies in which high-dose therapy was associated with improved outcome and reduced incidence of intracranial hypertension. 5,6 It has been the policy of this neurosurgical department to monitor ICP in all patients with severe head injury, and to treat all patients with 10 mg dexamethasone on admission (within 6 hours of injury in over 90% of cases), followed by 4 mg every 6 hours, la,13 In addition, intracranial mass lesions are evacuated by immediate craniotomy, and all patients are artificially ventilated. Despite this aggressive ap301
S. K. Gudeman, J. D. Miller and D. P. Beeker TABLE 1
Clinical features, lesions, and outcome in two groups of patients with severe head injury Factors
Present Study
sex female (7o) 25 male (~o) 75 age mean (yrs) 28 range (yrs) 7-65 decerebrate (~o) 40 bilateral fixed pupils (7o) 30 impaired/absent oculocephalic response (7o) 60 mass lesions, operative (70) 60 lesions acute epidural hematomas (~o) 20 acute subdural hematomas (~o) 15 acute intracerebral mass lesions (7o) 25 outcome good recovery/moderate disability (~o) 50 severe disability/vegetative (7o) 15 dead (7o) 35
Previous Series 26 74 27 4-72 36 23 43 40 7 16 15 57 11 32
proach to management, intracranial hypertension presents an important problem in these patients? Based on experience in 262 cases, elevated ICP (> 20 mm Hg mean) recurs or persists in 40% of patients and is the cause of death in 15% or half of the fatalities. 1~ In certain subgroups of patients, notably those with acute subdural hematomas and acute intracerebral mass lesions, the incidence of persistent or recurrent and of fatal intracranial hypertension is much higher (70% incidence and 64% mortality). If high-dose steroid therapy is to influence eventual outcome from head injury, this effect ought to be manifest first in the reduction of the incidence and severity of posttraumatic intracranial hypertension. We have therefore studied the acute effects of abrupt changes from "low- to high-dose" steroid therapy in a well documented group of patients with severe head injury. This communication reports the results of this pilot study. Clinical Material and Methods A consecutive series of 20 patients with severe head injury was studied. The criteria for entering this study were that following admission to the hospital, resuscitation, and evaluation, all patients were unable to obey commands, and unable to utter formed words. All patients were immediately intubated, started on 40 mg methylprednisolone every 6 hours, and referred for immediate computerized tomography (CT). In 12 patients the CT scan disclosed an intracranial mass le302
sion requiring surgical decompression. These patients received a bolus of 1 gm/kg body weight of mannitol and were transferred immediately to the operating room where a wide decompressive craniotomy was performed with removal of clot, liquid blood, and/or resection of frontal or temporal lobes as indicated. A ventricular catheter for ICP monitoring was inserted at the end of the procedure. The eight patients in whom the CT scan failed to reveal a mass lesion were referred directly to the intensive care unit where a ventricular catheter was inserted for ICP monitoring. In the intensive care unit all patients were artifically ventilated to a PaCO2 of 20 to 25 mm Hg, and had continuous monitoring of heart rate, blood pressure, and ICP, and frequent intermittent neurological evaluations. This consisted of assessment using the Glasgow Coma Scale (eye opening, motor response, verbal response), measurement of oculocephalic or oculovestibular response, pupillary size, and light response and limb power. 1,15 After a stable recording of ICP had been obtained, three to five measurements of the volume-pressure response (VPR) were made. This was done by injecting 1 ml of normal saline into the ventricular catheter in 1 second and measuring the resultant rise in ICP as described previously. 12When these measurements had been completed, the dose of methylprednisolone was abruptly increased to 2000 mg in a single dose followed by four doses of 500 mg every 6 hours, four of 250 mg every 6 hours, then 40 mg every 6 hours. Assessments of ICP, VPR, and neurological status were repeated after 24 and 48 hours of high-dose therapy, and CT scans were repeated after 72 hours of therapy. Assessment of the effects of high-dose steroid therapy was made by comparing initial ICP and VPR values with those made after treatment. Also the incidence of intracranial hypertension on high-dose steroid treatment was compared with the known incidence of raised ICP in similar patients taken from our previous series of 262 cases. Changes in neurological status, in CT scan appearance, and in outcome from head injury were compared with the expected outcomes for similar patients in our previous series of patients who had been managed on a "normal-dose" steroid regimen. Finally, all patients on the high-dose steroid regimen were carefully screened for secondary complications such as gastrointestinal bleeding, electrolyte abnormalities, and infections. Results
Patient Population, Status, and Outcome The clinical features of this series and the earlier group of 262 patients are shown in Table 1. The mean age of the patients in this series was 28 years with a range of 7 to 65 years. Mean age in the previous series was 27 years with a range of 4 to 72 years. The sex J. Neurosurg. / Volume51 / September, 1979
F a i l u r e o f h i g h - d o s e s t e r o i d t h e r a p y in s e v e r e h e a d i n j u r y THERAPY
ratio was 75% male and 25% female (previous series 74% and 26%). Sixteen (80%) patients scored 8 or less on the Glasgow Coma Scale on admission. Seven (35%) were posturing or flaccid as the best motor response. Impaired oculocephalic responses were present in 12 patients (60%). The following lesions were noted on CT scan: acute subdural hematoma in four, acute epidural hematoma in two, intracerebral hematoma in five, and mixed intra- and extracerebral lesions in five. Three patients had diffuse brain swelling, implied by symmetrically small ventricles. Only one patient had a normal CT scan. Twelve patients (60%) underwent surgical decompression of an intracranial mass lesion. The incidence in our previous series was 40%. The overall outcome was assessed at 3 months by the scale devised by Jennett and Bond. + There was good recovery or moderate disability in 50% or 10 patients, severe disability in 15% or three patients, and seven patients (35%) died. This compares to our previous series of 57%, 11%, and 32%, respectively. Thus, no difference in outcome could be discerned.
INITIATED
+
30
I I I
~' 25 E
E "' rr 2 0
I I L
O3 Ld
a:
o_
15
_.J
z < cr Io (..9
20 mm Hg) recurred or persisted in 40% or eight patients, and was the mode of death in 15% or three. This is exactly the same incidence as in our previous series, u
THERAPY I N I T I A T E D
60
"I"-
E E
50
/
W rr
co 4 0 U3 bJ n~ (3-
d
30
Volume-Pressure Tests
rr
~
zo
I--Z
I0
iI HOSPITAL
DAYS
FIG. 2. Graph showing intracranial pressure (ICP) in 20 patients. High-dose steroid therapy does not alter the individual ICP course of each patient.
lowest ICP recorded before the change in steroid therapy was 6.3 • 4.5 mm Hg, and of the highest recorded ICP was 22.9 + 20.7 mm Hg. On Day 2 (first posttreatment day) the overall mean ICP was 15.6 + 12.4 mm Hg, with a low mean ICP of 6.7 + 4 . 8 mm Hg, and a high mean ICP of
25 E E
20
w oc
THERAPY INITIATED
t I I I
_c c I N T R A C R A N I A L PRESSURE 9 ........ 9VOLUME PRESSURE RESPONSE
d
Z
