Steroids in severe head injury

1981 ◽  
Vol 54 (5) ◽  
pp. 596-600 ◽  
Author(s):  
Thomas G. Saul ◽  
Thomas B. Ducker ◽  
Michael Salcman ◽  
Eric Carro
Keyword(s):  
Head Injury ◽  
Steroid Therapy ◽  
Severe Head Injury ◽  
Randomized Study ◽  
Treatment Protocol ◽  
Rational Approach ◽  
Content Type ◽  
Coma Scale ◽  
Significant Difference ◽  
Injured Patients

✓ This is a prospective randomized study of the efficacy of steroid therapy in patients with severe head injury. One hundred patients were randomized into two equal groups: the steroid group received 5 mg/kg/day of methylprednisolone, and the nonsteroid group received no drug. The groups were similar in their clinical features. All patients received a standardized therapeutic regimen. The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration, on the basis of change in Glasgow Coma Scale score during the first 3 days of admission. There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months. Of the responders who were on steroids, 74% had good outcomes or were disabled, compared with 56% of the responders who did not receive steroids. In the nonresponder group, the patients on steroids were actually associated with a worse outcome than those who did not receive steroids: 75% of the nonresponders who received steroids were dead or vegetative, compared to 56% of those who were not receiving steroids. The data suggest that: 1) the effect of steroids may be different for different patient groups; 2) in order to identify these patients, a sensitive coma scale is needed; and 3) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids, but to discontinue their use in patients identified as not benefiting from steroid therapy.

Effect of THAM upon outcome in severe head injury: a randomized prospective clinical trial

1993 ◽  
Vol 78 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Aizik L. Wolf ◽  
Lion Levi ◽  
Anthony Marmarou ◽  
John D. Ward ◽  
Paul J. Muizelaar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Head Injury ◽  
Adverse Effects ◽  
Glasgow Coma Scale ◽  
Severe Head Injury ◽  
Prospective Clinical Trial ◽  
Content Type ◽  
Coma Scale ◽  
Significant Difference ◽  
Fine Print

✓ Although mortality and morbidity rates from head injury have been reduced substantially by improved prehospital interventions, intensive care, and aggressive management of intracranial pressure (ICP), successful treatment of the primary brain injury has been elusive. In experimental models, tromethamine (THAM) has been effective in treating head injury; this drug acts by entering the cerebrospinal fluid compartment, reducing cerebral acidosis and ICP, and reversing the adverse effects of prophylactic hyperventilation on early recovery. In this randomized prospective clinical trial, THAM was studied to determine if it had beneficial effects in the early management of severe head injuries and if the adverse effects of hyperventilation could be prevented. A total of 149 patients with severe head injury (Glasgow Coma Scale scores of ≤ 8) were randomly assigned to either a control or a THAM group. Both groups of patients matched in terms of clinical parameters, including age, sex, number of surgical mass lesions, number in each Glasgow Coma Scale stratum, and first ICP measurement. All patients were treated by a standard management protocol, intubated, mechanically ventilated, and maintained in the pCO2 range of 32 to 35 mm Hg for 5 days. Tromethamine was administered as a 0.3-M solution in an initial loading dose (body weight × blood acidity deficit, average 4.27 cc/kg/hr) given over 2 hours, followed by a constant infusion of 1 ml/kg/hr for 5 days. Outcome was measured at 3, 6, and 12 months postinjury. Although analysis indicated no significant difference in outcome between these two groups at 3 months, 6 months, and 1 year, there was a difference regarding ICP. The time that ICP was above 20 mm Hg in the first 48 hours postinjury was less in patients treated with THAM (p < 0.05). Also, the number of patients requiring barbiturate coma was significantly less in the THAM group (5.48% vs. 18.4%, p < 0.05). The authors conclude that THAM ameliorates the deleterious effect of prolonged hyperventilation, may be beneficial in ICP control, and warrants further study as to the dosage and timing of administration.

Impairment of helper T-cell function and lymphokineactivated killer cytotoxicity following severe head injury

1991 ◽  
Vol 75 (5) ◽  
pp. 766-773 ◽  
Author(s):  
Keith B. Quattrocchi ◽  
Edmund H. Frank ◽  
Claramae H. Miller ◽  
Asim Amin ◽  
Bernardo W. Issel ◽  
...  
Keyword(s):  
T Cell ◽  
Head Injury ◽  
Severe Head Injury ◽  
Cell Cytotoxicity ◽  
Content Type ◽  
Lak Cell ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ Infection is a major complication of severe head injury, occurring in 50% to 75% of patients who survive to hospitalization. Previous investigations of immune activity following head injury have demonstrated suppression of helper T-cell activation. In this study, the in vitro production of interferon-gamma (INF-γ), interleukin-1 (IL-1), and interleukin-2 (IL-2) was determined in 25 head-injured patients following incubation of peripheral blood lymphocytes (PBL's) with the lymphocyte mitogen phytohemagglutinin (PHA). In order to elucidate the functional status of cellular cytotoxicity, lymphokine-activated killer (LAK) cell cytotoxicity assays were performed both prior to and following incubation of PBL's with IL-2 in five patients with severe head injury. The production of INF-γ and IL-2 by PHA-stimulated PBL's was maximally depressed within 24 hours of injury (p < 0.001 for INF-γ, p = 0.035 for IL-2) and partially normalized within 21 days of injury. There was no change in the production of IL-1. When comparing the in vitro LAK cell cytotoxicity of PBL's from head-injured patients and normal subjects, there was a significant depression in LAK cell cytotoxicity both prior to (p = 0.010) and following (p < 0.001) incubation of PBL's with IL-2. The results of this study indicate that IL-2 and INF-γ production, normally required for inducing cell-mediated immunity, is suppressed following severe head injury. The failure of IL-2 to enhance LAK cell cytotoxicity suggests that factors other than decreased IL-2 production, such as inhibitory soluble mediators or suppressor lymphocytes, may be responsible for the reduction in cellular immune activity following severe head injury. These findings may have significant implications in designing clinical studies aimed at reducing the incidence of infection following severe head injury.

Cell-mediated immunity in severely head-injured patients: the role of suppressor lymphocytes and serum factors

1992 ◽  
Vol 77 (5) ◽  
pp. 694-699 ◽  
Author(s):  
Keith B. Quattrocchi ◽  
Claramae H. Miller ◽  
Franklin C. Wagner ◽  
Sally J. DeNardo ◽  
Gerald L. DeNardo ◽  
...  
Keyword(s):  
Head Injury ◽  
Cellular Immunity ◽  
Severe Head Injury ◽  
Normal Subjects ◽  
Lymphocyte Function ◽  
Serum Factors ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ Severe head injury results in suppression of cellular immunity associated with defective in vitro functioning of effector lymphocytes, such as helper T cells and cytotoxic T cells. It is not known whether this suppression in effector lymphocyte function is due to intrinsic lymphocyte dysfunction, to suppressor peripheral blood mononuclear cells (PBMC's) such as suppressor lymphocytes or suppressor monocytes, or to serum factors capable of inhibiting effector lymphocyte function. The purpose of this study was to determine whether a subpopulation of PBMC's and/or serum factors) are responsible for this observed suppression in cell-mediated immunity. Cell-mediated immune activity was determined measuring in vitro lymphokine-activated killer (LAK) cytotoxicity following incubation of PBMC's from 15 head-injured patients with those from 15 heterologous normal subjects. The PBMC's were separated into lymphocyte-enriched and monocyte-enriched subpopulations by plastic adherence techniques, and the effect of each population on LAK cytotoxicity was determined. Additionally, the effect on cytotoxicity of serum from the head-injured patients was determined in a dose-response fashion. There was significant depression in LAK cytotoxicity when: 1) PBMC's from normal subjects were incubated with PBMC's from head-injured patients (p < 0.001); 2) lymphocytes (PBMC's depleted of monocytes) from head-injured patients were incubated with PBMC's from normal subjects (p < 0.001); and 3) PBMC's from normal subjects were incubated with serum from head-injured patients (p < 0.001). No suppression in cellular immunity was noted when lymphocytes from normal subjects were incubated with monocytes from head-injured patients. The results indicate that lymphocytes rather than monocytes actively inhibit cellular immunity following severe head injury. The detection of immmunosuppressive serum factors suggests a mechanism by which lymphocytes might be modulated by severe head injury.

A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury

1998 ◽  
Vol 89 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Lawrence F. Marshall ◽  
Andrew I. R. Maas ◽  
Sharon Bowers Marshall ◽  
Albino Bricolo ◽  
Michael Fearnside ◽  
...  
Keyword(s):  
Placebo Group ◽  
Head Injury ◽  
Severe Head Injury ◽  
Treated Group ◽  
Good Recovery ◽  
Content Type ◽  
Significant Difference ◽  
Tirilazad Mesylate ◽  
Gcs Score ◽  
Fine Print

Object. The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries. Methods. A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4–8) and 15% (163) had sustained a moderate head injury (GCS score 9–12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p = 0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p = 0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p = 0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups. Conclusions. Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents.

Failure of high-dose steroid therapy to influence intracranial pressure in patients with severe head injury

1979 ◽  
Vol 51 (3) ◽  
pp. 301-306 ◽  
Author(s):  
Steven K. Gudeman ◽  
J. Douglas Miller ◽  
Donald P. Becker
Keyword(s):  
Head Injury ◽  
Intracranial Pressure ◽  
Steroid Therapy ◽  
Severe Head Injury ◽  
High Dose ◽  
Content Type ◽  
High Dose Steroid ◽  
Negative Results ◽  
High Incidence ◽  
Mass Lesions

✓ 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 of ICP 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.

Failure of prophylactic barbiturate coma in the treatment of severe head injury

1985 ◽  
Vol 62 (3) ◽  
pp. 383-388 ◽  
Author(s):  
John D. Ward ◽  
Donald P. Becker ◽  
J. Douglas Miller ◽  
Sung C. Choi ◽  
Anthony Marmarou ◽  
...  
Keyword(s):  
Head Injury ◽  
Severe Head Injury ◽  
Controlled Trial ◽  
Neurological Status ◽  
Treated Group ◽  
Control Group ◽  
Barbiturate Coma ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients

✓ In certain subgroups of severely head-injured patients, the mortality rate remains unacceptably high. The authors describe a randomized, controlled trial of prophylactic pentobarbital therapy in a group of these patients. Pentobarbital was started as soon as possible after the head injury, regardless of the intracranial pressure (ICP), and was continued for a prescribed period of time. The study included 53 consecutive head-injured patients over the age of 12 years, who had either an acute intradural hematoma (subdural and/or intracerebral, large enough to warrant surgical decompression), or no mass lesion but whose best motor response was abnormal flexion or extension. All patients in the study were randomly assigned to a control group (26 cases) or a pentobarbital-treated group (27 cases) once the diagnosis had been made and informed consent obtained. All patients were treated with the same protocol of aggressive resuscitation, prompt diagnosis and treatment of mass lesions, and intensive care, with close follow-up monitoring. The randomization was effective in producing a close match between the control and treated groups with respect to age, sex distribution, cause of injury, neurological status, intracranial lesions, prevalence of early systemic insults, midline shift, and initial ICP. Outcome was essentially the same in each group. There was no difference between groups in the incidence of elevated ICP, the duration of ICP elevation, or the response of ICP elevations to treatment. Arterial hypotension occurred in 14 patients (54%) in the treated group and only two patients (7percnt;) in the untreated group. Based on these data the authors cannot recommend the prophylactic use of pentobarbital coma in the treatment of patients with severe head injury. They also believe that its use is accompanied by significant side effects which can potentially worsen the condition of a patient with severe head injury.

Outcome following severe head injuries in children

1978 ◽  
Vol 48 (5) ◽  
pp. 679-688 ◽  
Author(s):  
Derek A. Bruce ◽  
Luis Schut ◽  
Leonard A. Bruno ◽  
James H. Wood ◽  
Leslie N. Sutton
Keyword(s):  
Head Injury ◽  
Severe Head Injury ◽  
Head Injuries ◽  
Good Recovery ◽  
Content Type ◽  
Coma Scale ◽  
High Incidence ◽  
Low Incidence ◽  
Mass Lesions ◽  
Child's Brain

✓ The outcome in 53 children following severe head injury is presented. All children were graded using the Glasgow Coma Scale; 90% made a good recovery or were moderately disabled, and 8% died or were left vegetative. All patients were treated with controlled ventilation and steroids; mannitol, and, if necessary, Nembutal (pentobarbital) were used to maintain the intracranial pressure below 20 torr. With this regimen, only one death occurred due to uncontrollable intracranial hypertension. All patients with a coma scale of 5 or greater recovered well. The worst prognostic sign was the presence of flaccidity: 33% of these patients died or were vegetative. Five of seven patients who were decerebrate or flaccid with bilateral fixed pupils and absent caloric responses made a good recovery or were moderately disabled. The relatively low incidence of mass lesions (23%) and high incidence of diffuse cerebral swelling (34%) suggest a different pathophysiological response of the child's brain to injury, which may play a role in the improved survival of children following severe head injury when compared to adults.

Pulmonary shunt as a prognostic indicator in head injury

1979 ◽  
Vol 50 (6) ◽  
pp. 768-772 ◽  
Author(s):  
Elizabeth A. M. Frost ◽  
Carlos U. Arancibia ◽  
Kenneth Shulman
Keyword(s):  
Head Injury ◽  
Glasgow Coma Scale ◽  
Severe Head Injury ◽  
Prognostic Indicator ◽  
Respiratory Arrest ◽  
Respiratory Pattern ◽  
Pulmonary Shunt ◽  
Content Type ◽  
Coma Scale ◽  
Fine Print

✓ Severe head injury may cause momentary respiratory arrest. Resultant hypoxia would increase cerebral edema and adversely affect the quality of survival. This study examines the effect of hypoxemia on outcome. Pulmonary shunt was calculated as a convenient measurement of respiratory insufficiency in 86 severely head-injured patients who underwent surgery. All samples were taken shortly after induction into anesthesia when controlled ventilation with high inspired-oxygen concentration had been established. In 39 patients who improved, mean pulmonary shunt was 8.9%. Twelve patients who survived with deficit showed a mean shunt of 13.6%, and in 35 patients who died, the mean initial shunt was 15.6%. No significant correlation was found between abnormal chest x-ray findings or the occurrence of hypertension and shunt percentage. The American Society of Anesthesiologists at-risk classification correlated grossly with the outcome. Early pulmonary shunt is a prognostic indicator in severe head injury and should be used in conjunction with the Glasgow Coma Scale in assessing outcome. Despite an apparently adequate respiratory pattern, all patients with severe head injury must be assumed to be hypoxic until proven otherwise. While hypoxemia may prove to be refractory in overwhelming injury, patients who score low on the Glasgow Coma Scale but who have relatively normal oxygen exchange may still survive with little deficit.

Influence of the type of intracranial lesion on outcome from severe head injury

1982 ◽  
Vol 56 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Thomas A. Gennarelli ◽  
Gerri M. Spielman ◽  
Thomas W. Langfitt ◽  
Philip L. Gildenberg ◽  
Timothy Harrington ◽  
...  
Keyword(s):  
Head Injury ◽  
Severe Head Injury ◽  
Acute Subdural Hematoma ◽  
Good Recovery ◽  
Content Type ◽  
Injury Group ◽  
Lesion Type ◽  
Severity Of Injury ◽  
Gcs Score ◽  
Injured Patients

✓ Recent studies attempting to define the outcome from severe head injury have implied, directly or indirectly, that the severity of injury (as determined by the Glasgow Coma Scale (GSC)) is the sole determinant of outcome. Little attention has been focused on the type of lesion that causes the low GCS score, and there exists an unstated hypothesis that the lesion type is not an important determinant of outcome. No attempt has been made to determine whether patients who have the same GCS score caused by different lesions have the same or different outcomes. Since this is impossible to test without a large number of cases, data were obtained from seven head-injury centers on patients who fulfilled the Glasgow criteria for severe head injury (GCS ≤ 8 for at least 6 hours). Patients were categorized according to a simple classification system comprising seven lesion types, each of which was further subdivided into two GCS score ranges (3 to 5 and 6 to 8). Of 1107 patients, the overall mortality was 41%, but ranged from 9% to 74% among the different lesion categories. Conversely, 26% had good recovery (at 3 months), but among the different lesion groups the range was 6% to 68%. Acute subdural hematoma with GCS scores of 3 to 5 was uniformly the worst problem (74% mortality and 8% good recovery), whereas diffuse injury coma of 6 to 24 hours with GCS scores of 6 to 8 had 9% mortality and 68% incidence of good recovery. Results of this study demonstrate marked heterogeneity within this severe head-injury group and point out that patients with the same GCS score have markedly different outcomes, depending on the causative lesion. The type of lesion is thus as important a factor in determining outcome as is the GCS score, and both must be considered when describing severely head-injured patients.

The favorable effect of early parenteral feeding on survival in head-injured patients

1983 ◽  
Vol 58 (6) ◽  
pp. 906-912 ◽  
Author(s):  
Robert P. Rapp ◽  
D. Pharm ◽  
Byron Young ◽  
Diana Twyman ◽  
Brack A. Bivins ◽  
...  
Keyword(s):  
Head Injury ◽  
Enteral Nutrition ◽  
Parenteral Nutrition ◽  
Favorable Effect ◽  
Controlled Clinical Trial ◽  
Content Type ◽  
Significant Difference ◽  
Head Injured ◽  
Injured Patients ◽  
Fine Print

✓ This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p < 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p < 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.

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