Megadose steroids in severe head injury

1983 ◽  
Vol 58 (3) ◽  
pp. 326-330 ◽  
Author(s):  
Reinder Braakman ◽  
Hubert J. A. Schouten ◽  
Marijke Blaauw-van Dishoeck ◽  
Jan M. Minderhoud
Keyword(s):  
Head Injury ◽  
High Dose ◽  
Double Blind ◽  
Content Type ◽  
High Dose Dexamethasone ◽  
Double Blind Clinical Trial ◽  
Dexamethasone Phosphate ◽  
Significant Difference ◽  
High Doses ◽  
Injured Patients

✓ A prospective double-blind clinical trial was performed on 161 patients to determine the effectiveness of high-dose steroid therapy in patients admitted comatose after a non-missile-related head injury. Patients were randomized into a high-dose dexamethasone phosphate group and a placebo group. The initial dose of 100 mg of dexamethasone was administered within 6 hours of the accident. For statistical analysis, a sequential test was chosen, using survival at 1 month as a basic criterion of effectiveness. No significant difference was found in the 1-month survival rate or in the distribution of outcome after 6 months, either within the group as a whole, or in subgroups with varying severity of brain damage on admission. The authors conclude that dexamethasone in high doses has no statistically significant effect on morbidity or mortality in head-injured patients who are comatose on admission.

Influence of changes in arterial pCO2 on cerebral blood flow and metabolism during high-dose barbiturate therapy in dogs

1981 ◽  
Vol 54 (5) ◽  
pp. 615-619 ◽  
Author(s):  
Neal F. Kassell ◽  
Patrick W. Hitchon ◽  
Mary K. Gerk ◽  
Martin D. Sokoll ◽  
Todd R. Hill
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
High Dose ◽  
Sodium Thiopental ◽  
Arterial Pco2 ◽  
Content Type ◽  
Cerebral Vasoconstriction ◽  
Significant Difference ◽  
Before And After ◽  
High Doses

✓ In 13 dogs the response of the cerebral circulation to changes in PaCO2 ranging from 20 to 60 torr was studied before and after administration of high doses of sodium thiopental. Infusion of sufficient barbiturate to produce 30- to 60-second burst suppression in the electroencephalogram was associated with a profound degree of cerebral vasoconstriction, equivalent to that produced by hypocapnia with PaCO2 = 20 torr. Furthermore, once sodium thiopental was administered, no significant difference in cerebral blood flow (CBF) or vascular resistance (CVR) was noted between PaCO2 of 30 and 20 torr. However, changes of approximately 15% in CBF and 30% in CVR were noted between PaCO2 at 40 and 20 torr. These data suggest that hyperventilation of PaCO2 of less than 30 torr may not effectively increase the degree of cerebral vasoconstriction in these circumstances.

The outcome with aggressive treatment in severe head injuries

1979 ◽  
Vol 50 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Lawrence F. Marshall ◽  
Randall W. Smith ◽  
Harvey M. Shapiro
Keyword(s):  
Intracranial Hypertension ◽  
Head Injuries ◽  
High Rate ◽  
High Dose ◽  
Content Type ◽  
Diffuse Brain Injury ◽  
High Dose Dexamethasone ◽  
Brain Injured ◽  
Injured Patients ◽  
Fine Print

✓ In a series of 100 consecutive patients with severe head injuries, uncontrolled intracranial hypertension, which was defined as occurring when intracranial pressure (ICP) exceeded 40 mm Hg for 15 minutes or more, occurred in 25 patients. This was despite high-dose dexamethasone, hyperventilation, mannitol, normothermia, appropriate surgical evacuation, and cerebrospinal fluid drainage when possible. Persistently elevated ICP occurred in 19 patients with diffuse brain injury, and in six patients uncontrolled intracranial hypertension followed evacuation of a surgical mass. All of these patients received intravenous barbiturates to control the ICP. At the time of initial barbiturate administration, 11 of the 25 had bilaterally unreactive pupils and 12 were decerebrate. The initial pentobarbital loading dose (3 to 5 mg/kg) effectively reduced the ICP in 76% of the patients. Prolonged pentobarbital treatment with blood barbiturate levels from 2.5 to 3.5 mg% was associated with normalization of the ICP (ICP less than 15 mm Hg) in 13 patients. In those patients responding to barbiturates, the daily mannitol requirement was reduced from 4.5 to 0.5 gm/kg/day (p < 0.01). In six nonresponders to barbiturates, mannitol requirements increased to 5.9 gm/kg/day; five of these died and one remains vegetative. Ten of the 19 barbiturate responders have returned to a productive life, two remain moderately disabled, two are severely disabled, one is vegetative, and four are dead. The high rate of good quality survival in this series of severely brain-injured patients indicates that barbiturates are useful in the treatment of uncontrolled intracranial hypertension and that a broader investigation of the clinical application of barbiturates is indicated.

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.

Failure of the competitive N-methyl-d-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two Phase III clinical trials

1999 ◽  
Vol 91 (5) ◽  
pp. 737-743 ◽  
Author(s):  
Gabrielle F. Morris ◽  
Ross Bullock ◽  
Sharon Bowers Marshall ◽  
Anthony Marmarou ◽  
Andrew Maas ◽  
...  
Keyword(s):  
Head Injury ◽  
Demographic Data ◽  
Phase Iii ◽  
Double Blind ◽  
Content Type ◽  
Treatment Groups ◽  
Severity Of Injury ◽  
Significant Difference ◽  
Cgs 19755 ◽  
Fine Print

Object. Excessive activity of excitatory amino acids released after head trauma has been demonstrated to contribute to progressive injury in animal models and human studies. Several pharmacological agents that act as antagonists to the glutamate receptor have shown promise in limiting this progression. The efficacy of the N-methyl-d-aspartate receptor antagonist Selfotel (CGS 19755) was evaluated in two parallel studies of severely head injured patients, defined as patients with postresuscitation Glasgow Coma Scale scores of 4 to 8.Methods. A total of 693 patients were prospectively enrolled in two multicenter double-blind studies. Comparison between the treatment groups showed no significant difference with regard to demographic data, previous incidence of hypotension, and severity of injury. As the study progressed, the Safety and Monitoring Committee became concerned about possible increased deaths and serious brain-related adverse events in the treatment arm of the two head injury trials, as well as deaths in the two stroke trials being monitored concurrently. The Selfotel trials were stopped prematurely because of this concern and because an interim efficacy analysis indicated that the likelihood of demonstrating success with the agent if the studies had been completed was almost nil.Conclusions. Subsequently, more complete data analysis revealed no statistically significant difference in mortality rates in all cases between the two treatment groups in the head injury trials. In this report the authors examine the studies in detail and discuss the potential application of the data to future trial designs.

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.

scholarly journals Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the β-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects

2016 ◽  
Vol 60 (10) ◽  
pp. 6326-6332 ◽  
Author(s):  
David C. Griffith ◽  
Jeffery S. Loutit ◽  
Elizabeth E. Morgan ◽  
Stephanie Durso ◽  
Michael N. Dudley
Keyword(s):  
Plasma Clearance ◽  
Healthy Adult ◽  
Phase 1 ◽  
High Dose ◽  
Double Blind ◽  
Time Curve ◽  
Content Type ◽  
Multiple Doses ◽  
To Receive ◽  
Lactamase Inhibitor

ABSTRACTVaborbactam (formerly RPX7009) is a member of a new class of β-lactamase inhibitor with pharmacokinetic properties similar to those of many β-lactams, including carbapenems. The pharmacokinetics and safety of vaborbactam were evaluated in 80 healthy adult subjects in a first-in-human randomized, placebo-controlled, double-blind, sequential single- and multiple-ascending-dose study. A total of 10 dose cohorts were enrolled in the study, with 6 subjects randomized to receive 250 to 2,000 mg of vaborbactam and 2 subjects randomized to receive placebo in each cohort. Maximum concentrations for vaborbactam were achieved at the end of the 3-h infusion. Vaborbactam exposure (Cmaxand area under the concentration-time curve [AUC]) increased in a dose-proportional manner following multiple doses. There was no evidence of accumulation with multiple doses, consistent with the terminal half-life of ∼2 h. Both the volume of distribution (Vss) and plasma clearance were independent of dose. For the 2,000-mg dose, the plasma clearance was 0.17 ± 0.03 liters/h, the AUC from 0 h to infinity (AUC0–∞) was 144.00 ± 13.90 mg · h/liter, and theVsswas 21.80 ± 2.26 mg · h/liter. Urinary recovery was 80% or greater over 48 h across all dose groups. No subjects discontinued the study due to adverse events (AEs), and no serious AEs (SAEs) were observed. All AEs were mild to moderate and similar among the vaborbactam- and placebo-treated subjects, with mild lethargy as the only unique AE reported with the high dose of vaborbactam. Overall, this study revealed the safety, tolerability, and pharmacokinetic profile of vaborbactam and formed the basis for advancement into patient studies in combination with meropenem, including treatment of patients with carbapenem-resistantEnterobacteriaceae(CRE) infections. (This study is registered at ClinicalTrials.gov under identifier NCT01751269.)

Solumedrol Treatment for Severe Sepsis in Humans with a Blunted Adrenocorticotropic Hormone-Cortisol Response: A Prospective Randomized Double-Blind Placebo-Controlled Pilot Clinical Trial

2021 ◽  
pp. 088506662110388
Author(s):  
Divya Birudaraju ◽  
Sajad Hamal ◽  
John A. Tayek
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Adrenocorticotropic Hormone ◽  
Serum Cortisol ◽  
High Dose ◽  
Cortisol Response ◽  
Acth Stimulation ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive

Purpose To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, length of time in an intensive care unit (ICU), 14-day mortality, and 28-day mortality. The trial was prospective, randomized, and double-blind. As part of a larger sepsis trial, 54 patients with sepsis had an intravenous ACTH stimulation test using 250 µg of ACTH, and serum cortisol was measured at times 0, 30, and 60 min. Eleven patients failed to increase their cortisol concentration above 19.9 µg/dL and were excluded from the clinical trial as they were considered to have adrenal insufficiency. The remaining 43 patients had a baseline cortisol of 32 ± 1 µg/dL increased to 38 ± 3 µg/dL at 30 min and 40 ± 3 at 60 min. All cortisol responses were <12.9 µg/dL between time 0 and time 60, which is defined as a blunted cortisol response to intravenous ACTH administration. Twenty-one were randomized to receive 20 mg of intravenous Solumedrol and 22 were randomized to receive a matching placebo every 8 h for 7-days. There was no significant difference between the two randomized groups. Data analysis was carried out bya two-tailed test and P < .05 as significant. Results Results: The mean age was 51 ± 2 (mean ± SEM) with 61% female. Groups were well matched with regard to APACHE III score in Solumedrol versus placebo (59 ± 6 vs 59 ± 6), white blood cell count (18.8 ± 2.2 vs 18.6 ± 2.6), and incidence of bacteremia (29 vs 39%). The 28-day mortality rate was reduced in the Solumedrol treated arm (43 ± 11 vs 73 ± 10%; P < .05). There was no change in days in ICU, days on blood pressure agents, or days on ventilator. Seven days of high-dose intravenous Solumedrol treatment (20 mg every 8 h) in patients with a blunted cortisol response to ACTH was associated with an improved 28-day survival. This small study suggests that an inability to increase endogenous cortisol production in patients with sepsis who are then provided steroid treatment could improve survival.

A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery

1988 ◽  
Vol 69 (5) ◽  
pp. 687-691 ◽  
Author(s):  
Ross Bullock ◽  
James R. van Dellen ◽  
William Ketelbey ◽  
S. Gustav Reinach
Keyword(s):  
Controlled Trial ◽  
Prophylactic Antibiotics ◽  
Risk Of Infection ◽  
Broad Spectrum Antibiotic ◽  
Wound Sepsis ◽  
Double Blind ◽  
Content Type ◽  
Exact Test ◽  
Significant Difference ◽  
To Receive

✓ In this study, 417 patients undergoing “clean” elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis — a statistically significant difference (p < 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.

scholarly journals Propranolol versus topiramate in prophylaxis of migraines among children and adolescents: a randomized, double-blind clinical trial

2017 ◽  
Vol 5 (10) ◽  
pp. 4307 ◽  
Author(s):  
Ramakant Yadav ◽  
S. K. Shukla
Keyword(s):  
Clinical Trial ◽  
Children And Adolescents ◽  
International Headache Society ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Relative Reduction ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Significant Difference ◽  
Propranolol Group

Background: Migraine is a common health problem in children and adolescents. This study compares the efficacy and safety of propranolol and topiramate in preventing migraine among children and adolescents.Methods: Seventy-six patients (10-18 years of age) with migraine without auras defined by the 2004 International Headache society criteria were included in a prospective double blind clinical trial were allocated to receive propranolol (0.5-2mg/kg per day) or topiramate (1-2mg/kg per day). The primary outcome measure was reduction in 50 % or more headache days in comparison to baseline headache frequency per month. Secondary outcome measures were headache related disability, migraine intensity and duration. Efficacy measures were recorded at the baseline and at 12 weeks of prophylactic treatment.Results: In this study total of 76 patients with mean age of 12.43 years were evaluated, 40 in the propranolol group and 36 in the topiramate group. At the 12-week, the percentage of patients who had a relative reduction of 50% or more in the number of headache days were 67.5% patients in the propranolol group and 75.0% patients in the topiramate group. The monthly migraine frequency, headache related disability, intensity and duration were significantly decreased in both the propranolol and topiramate groups when compared to the baseline. No significant difference was observed between these two groups in term of reduction of frequency, headache related disability, severity and duration of attack. Fatigue, hypotension and exercise induced asthma were main side effects in propranolol group and weight loss, fatigue and loss of appetite, paresthesias in topiramate group.Conclusions: Propranolol and topiramate were found effective and safe for the prevention of paediatric migraines.

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