High-dose Barbiturate Research Articles

Effect of hypothermia and cardiac arrest on outcome of near-drowning accidents in children

We conducted a retrospective review of 55 near-drowning victims (mean age 4.75 years) admitted to the intensive care unit during a 5-year period, to determine the factors that may influence survival both before and after hospital admission. All patients who remained comatose after resuscitation received ventilation for an initial 24 hour period, after which an assessment of central nervous system injury was made. Intracranial pressure was not monitored, and barbiturate therapy was used only for seizure control. Thirty-seven children survived and 18 died; five survivors had profound neurologic damage resulting in a persistent vegetative state: the remaining 32 (58%) survived intact. The major factors that separated intact survivors from those who died and from survivors in a persistent vegetative state were the presence of a detectable heartbeat and hypothermia (less than 33 degrees C) on examination in the emergency department. Thirteen patients with absent vital signs and a temperature of greater than 33 degrees C either died or survived in a persistent vegetative state. Fourteen patients had a combination of absent vital signs and hypothermia and were resuscitated; eight died, two survived in a persistent vegetative state, and four survived intact. All intact survivors had been submerged in cold water for prolonged periods, and all underwent prolonged cardiopulmonary resuscitation. All patients with a detectable pulse, regardless of temperature, survived without neurologic sequelae. The 58% intact survival rate in this series compares favorably with the 50% we reported previously when high-dose barbiturate therapy and hypothermia were used to control intracranial pressure; at the same time, the number of survivors with a persistent vegetative state has been reduced by 50%. We conclude that prolonged in-hospital resuscitation and aggressive treatment of near-drowning victims who initially have absence of vital signs and are not hypothermic either results in eventual death or increases the number of survivors with a persistent vegetative state.

Catecholamine and thyroid hormones in traumatic injury

During hyperthyroidism, hypothyroidism, and severe stress there is often an inverse relationship between plasma norepinephrine (NE) and thyroid hormones. We evaluated this relationship in patients who were severely burned, patients who had injury to both brain and body, patients with head injury, and patients receiving high dose barbiturates for head injury. Head-injured patients had a low thyroxine (T4), low triiodothyronine (T3), and high reverse T3. Phenytoin for control of seizures lowered T3 and T4 and increased thyroid-stimulating hormone. Burned patients had a strong negative correlation between NE and T3 (r = -.88, p less than .001). Patients with injury to both brain and body had a weak negative correlation between NE and T3 (r = -.5, p = .06). Patients with head injury showed no correlation between NE and T3. Severely injured patients had a close inverse relationship between elevated NE levels and depressed T3 levels. This relationship appears to depend on an intact CNS, as the relationship was disrupted by head injury and barbiturates.

Complications associated with barbiturate therapy

Fifty-six patients with elevated intracranial pressure caused by cerebrovascular accident, head injury, etc., were the subjects of this study. They were divided into three groups: low dose barbiturate therapy (15 patients), high dose barbiturate therapy (24 patients), and control group (17 patients). Barbiturate therapy was instituted using thiamylal, and the complications caused by barbiturate therapy were recorded. In the control group, complications occurred in the liver of two patients, but there were no renal or pulmonary complications. Pulmonary, renal, and hepatic complications were common in the barbiturate groups. Complications in the high dose therapy group were significantly more common than in the control group. Opportunistic infections occurred in ten patients, with seven patients having pneumonia. Only one patient, with pneumonia, was seen in the control group. The deaths of three patients were influenced by complications associated with barbiturate therapy, while the single death in the control group was not associated with the complication of barbiturate therapy.

High-Dose Barbiturate Control of Elevated Intracranial Pressure in Patients with Severe Head Injury

Comment The bottom line of this complex clinical study would seem to be that elevated ICP after severe head injury is a close correlate of mortality. Among the 25 patients in whom treatment (conventional, barbiturate, or conventionil crossover to barbiturate) successfully lowered ICP, 23 were alive at 30 days while among the 48 patients without ICP control 40 were dead at N days. This should not be too surprising to mo* physicians who deal with this type of patient On the other hand it emphasizes that an elevated ICP in itself is worthy of the most aggressive trert-ment available. Perhaps this is one time where beneficial alterations of a process variable, in mil case ICP, will predict a real change in the oat-come variable, survival. Richard F. Davis, M.D.

High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury

In a five-center study, 73 patients with severe head injury and elevated intracranial pressure (ICP) were randomly assigned to receive either a regimen that included high-dose pentobarbital or one that was otherwise similar but did not include pentobarbital. The results indicated a 2:1 benefit for those treated with the drug with regard to ICP control. When patients were stratified by prerandomization cardiac complications, the advantage increased to 4:1. A multiple logistic model considering treatment and selected baseline variables indicated a significant positive treatment effect of barbiturates, a significant effect of time from injury to randomization, and an interaction of treatment with cardiovascular complications. However, of 925 patients potentially eligible for randomization, only 12% met ICP randomization criteria. The results support the hypothesis that high-dose pentobarbital is an effective adjunctive therapy, but that it is indicated in only a small subset of patients with severe head injury.

The feasibility of low dose barbiturate administration by intra-carotid infusion to achieve EEG burst suppression--a preliminary report.

More than 10 years have elapsed since the introduction of high dose barbiturate administration in the management of patients with severe head injuries. Barbiturate therapy became an accepted method of treatment for increased intracranial pressure when other measures fail. One of the major limiting factors in the use of high dose barbiturate therapy is its significant hypotensive effect on the systemic arterial blood pressure. In seeking ways and means of minimising this hypotensive effect, we designed a study in which the systemic administration of barbiturates is avoided and replaced by selective perfusion of the concerned hemisphere with the drug utilising the intra-carotid route. Twenty-two rats, divided into two groups, were used in the study. Since monitoring of electroencephalographic (EEG) burst suppression serves as a good indicator of the lowest level of cerebral metabolic activity, we used this as the method for determining the desired endpoint of sodium amytal administration in both groups of animals. Group I, the intravenous group, consisted of eleven animals who received sodium amytal intravenously until burst suppression on the EEG was documented. Group II, the intra-carotid group, comprised eleven animals who received intra-carotid sodium amytal until EEG burst suppression was induced. In the intravenous group, a mean dose of 35 mg/kg of sodium amytal was administered before EEG burst suppression was achieved. This dose, however, was accompanied by an almost 50% reduction in systemic blood pressure compared to the pretreatment level. The intra-carotid group required a mean dose of 3.8 mg/kg sodium amytal and this was accompanied by only minor changes in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute epidural hematoma: an analysis of factors influencing the outcome of patients undergoing surgery in coma.

Mortality due to epidural hematoma is virtually restricted to patients who undergo surgery for that condition while in coma. The authors have analyzed the factors influencing the outcome of 64 patients who underwent epidural hematoma evacuation while in coma. These patients represented 41% of the 156 patients operated on for epidural hematoma at their centers after the introduction of computerized tomography (CT). Eighteen patients (28.1%) died, two (3.1%) became severely disabled, and 44 (68.8%) made a functional recovery. The mortality rate for the entire series was 12%, significantly lower than the 30% rate observed when only angiographic studies were available. A significant correlation was found between the final result and the mechanism of injury, the interval between trauma and surgery, the motor score at operation, the hematoma CT density (homogeneous vs. heterogeneous), and the hematoma volume. The patient's age, the course of consciousness before operation (whether there was a lucid interval), and the clot location did not correlate with the final outcome. The mortality rate was significantly higher in patients operated on within 6 hours or between 6 and 12 hours after injury than in those undergoing surgery 12 to 48 hours after injury. Compared with the patients operated on later, the patients undergoing surgery in the early period were, on the average, older and had more rapidly developing symptoms, more pupillary changes, lower motor scores at surgery, larger hematomas, a higher incidence of mixed CT density clots, more severe associated intracranial lesions, and higher postoperative intracranial pressure (ICP). The mechanism of trauma seems to influence the course of consciousness before and after surgery. Passengers injured in traffic accidents had a lower incidence of a lucid interval and longer postoperative coma than patients with low-speed trauma, suggesting more frequent association of diffuse white matter-shearing injury. The duration of postoperative coma correlated with the morbidity rate in survivors. Forty-eight patients (75%) had one or more associated intracranial lesions, and 70% of these required treatment for elevation of ICP after hematoma evacuation. An ICP of over 35 mm Hg strongly correlated with poor outcome; administration of high-dose barbiturates was the only effective means for lowering ICP in nine of 15 patients who developed severe intracranial hypertension after surgery. This study attempts to identify patients at greater risk for presenting postoperative complications and to define a strategy for control CT scanning and ICP monitoring.

Hemodynamic effects of high dose pentobarbital: studies in elective neurosurgical patients.

High dose barbiturate therapy has been used clinically for about 10 years. However, the hemodynamic consequences of such therapy have not been well defined in humans. We therefore examined the effects of a brief (30-minute), high dose (0.6 mg/kg/minute or 18 mg/kg total) infusion of pentobarbital in nine otherwise healthy patients (aged 20 to 30) scheduled to undergo operation for the removal of large or deeply seated arteriovenous malformations. Monitored variables included intravascular pressures, cardiac output, arterial and mixed venous blood gases and hematocrit, and the electroencephalogram (EEG). After a brief rest period and the collection of control data, pentobarbital infusion was begun, muscle relaxants were given, and normocarbia was maintained by mask ventilation. Because our primary intent was to examine the effects of the drug on the heart and arterial circulation, lactated Ringer's solution was infused continuously to keep pulmonary capillary wedge pressure (PCWP) at control values in an attempt to keep constant the ventricular "preload" (although PCWP is only an approximation of the true preload). Drug infusion resulted in progressive EEG suppression ending in a pattern of deep burst suppression (1 to 3 bursts/minute) at t = 30 minutes, with measured plasma pentobarbital concentrations (in four patients) of 34 +/- 4 micrograms/ml (mean +/- SD). There were no changes in PaO2, PaCO2, or pH, nor were there any changes in PCWP. The cardiac index did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Hypothermia, Barbiturate Therapy, and Intracranial Pressure Monitoring on Morbidity and Mortality After Near-Drowning

BOHN, D. J.; BIGGAR, W. D.; SMITH, C. R.; CONN, A. W.; BARKER, G. A. Author Information

Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning.

We retrospectively evaluated the clinical and pathologic effects of hypothermia and high-dose barbiturate therapy on hypoxic/ischemic cerebral injury after near-drowning in children. Of 40 near-drowned patients admitted to the ICU, 13 died, seven had permanent cerebral damage, and 20 survived. Twenty-four patients (group 1) were treated with a regime of hyperventilation, hypothermia, and high-dose phenobarbitone while intracranial pressure (ICP) was continuously monitored. Of ten who died in this group, three were diagnosed as having cerebral death shortly after admission; autopsy revealed severe cerebral edema with herniation. The remaining seven nonsurvivors had severe cerebral hypoxia without raised ICP and had the features of severe adult respiratory distress syndrome and hypoxic/ischemic damage to other organs. Six of these seven patients developed septicemia which was invariably associated with a profound neutropenia. Sixteen patients (group 2) were treated with a similar protocol but without hypothermia. Three of these patients died but only one developed septicemia. Neutropenia after resuscitation from near-drowning seemed to indicate a poor prognosis; the mean polymorphonuclear leukocyte count in nonsurvivors (1.9 +/- 0.5 X 10(9) cell/L) was significantly (p less than .01) lower than that in survivors (6.4 +/- 1.1 X 10(9) cell/L). Hypothermia was associated with a decreased number of circulating PMNs but did not increase the number of neurologically intact survivors. Similarly, although barbiturates may control ICP, their use did not improve outcome. Because severe cerebral edema and herniation after near-drowning is usually associated with irreversible brain damage, measures to control brain swelling such as hypothermia and barbiturates will be of little benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

In favor of intracranial pressure monitoring and aggressive therapy in neurologic practice.

There are several lively controversies regarding intracranial pressure (ICP) in acute neurologic practice, including its meaning in cerebral hemorrhage, ischemic brain edema, Reye's syndrome, global anoxia, and viral encephalitis. The value of measuring ICP, different methods of treatment, and the benefits of aggressive therapy each have supporters and detractors. Many subsidiary questions also beg answers, such as how to select patients for monitoring, treatment tailored to the patient's measured ICP as opposed to blind therapy with mannitol and hyperventilation, the place of high-dose barbiturate therapy or craniectomy in patients who have failed medical therapy, and the use of steroids. What is the neurologist, hampered by generations of passivity in therapeutics, to do? Monitor ICP or not? In my opinion, when this important problem is considered as a sequence of clinical problems, the answer is a compelling yes. My conclusions, based on personal experience and a biased reading of the

Effects of Naloxone During High Dose Barbiturate Anesthesia

TURNER, D. M.; KASSELL, N. F.; SASAKI, T.; COMAIR, Y. G.; BOARINI, D. J. Author Information

High Dose Barbiturate Therapy in Neurosurgery and Intensive Care

To assess the uses of high dose barbiturate therapy in neurosurgery and intensive care, the authors have undertaken a concise survey of relevant experimental investigations and a comprehensive review of published clinical experiences.

BARBITURATES IN BRAIN ISCHAEMIA

This review has indicated that barbiturates are useful in controlling ICP during anaesthesia in patients with intracranial hypertension. While laboratory data indicate that intraoperative administration of barbiturates during episodes of transient cerebral ischaemia, associated with surgical revascularization procedures, should be efficacious, current intraoperative results claiming benefit are anecdotal. Continuous high-dose barbiturate therapy (induced barbiturate coma) for occlusive stroke and persistently increased intracranial pressure is currently undergoing clinical trials. While it is clear that this therapy can often reduce increased ICP in head injured patients, its influence on neurological outcome remains to be determined by a multicentre trial at present in progress. Despite evidence that high-dose barbiturate therapy can reduce the area of infarction in occlusive stroke in the laboratory, organized clinical trials have not yet commenced. Until more definitive knowledge is available concerning the influence of high-dose barbiturate therapy in treating different forms of cerebral ischaemia, its application should be viewed sceptically and limited to centres willing to create an organized data base for inter-institutional evaluation of this form of treatment. If barbiturate therapy proves successful and the mechanisms involved are better understood, drugs with fewer side-effects and risks may become available to combat cerebral ischaemia.

Effects of naloxone during high dose barbiturate anesthesia

Effects of naloxone during high dose barbiturate anesthesia

Effects of naloxone during high dose barbiturate anesthesia.

This experiment was performed to investigate the ability of naloxone to reverse high dose barbiturate anesthesia or produce cerebrovasodilation or changes in cerebral metabolism in dogs neuronally depressed by high doses of barbiturate. Six dogs were deeply anesthetized with sufficiently high doses of sodium pentobarbital to produce and then maintain isoelectric activity or cerebral silence on the electroencephalogram (EEG). Blood flows were determined using the radioactive microsphere technique both before and after the intravenous bolus injection of naloxone (10 mg/kg), which failed to produce any significant changes in cerebral blood flow, the cerebral metabolic rate of oxygen, cerebrovascular resistance, or EEG activity. Cardiovascular parameters were also essentially unchanged. Naloxone in a dose of 10 mg/kg i.v. produced no changes in the cerebral or systemic circulations or in brain metabolism during high dose sodium pentobarbital anesthesia.

High dose barbiturate therapy in neurosurgery and intensive care

High dose barbiturate therapy in neurosurgery and intensive care

High dose barbiturate therapy in neurosurgery and intensive care.

To assess the uses of high dose barbiturate therapy in neurosurgery and intensive care, the authors have undertaken a concise survey of relevant experimental investigations and a comprehensive review of published clinical experiences.

Severe Acute Encephalitis–Improved Outcome after Barbiturate Treatment?

Six cases of severe encephalitis due to measles, varicellae, mononucleosis, influenza, rubella and pertussis were treated with high doses of barbiturates in combination with steroids and artificial hyperventilation. Four of the patients also received antiviral therapy. They all survived without neurological sequelae. The use of barbiturates in high doses may be of importance for an improved outcome in patients with severe encephalitis.

Barbiturate therapy in neurosurgery

Thirty patients with an acute midbrain syndrome were treated by high dose barbiturate therapy. Of these patients 19 had a severe head injury. In 8 patients the symptoms of acute midbrain syndrome developed after subarachnoid haemorrhage. In three patients these symptoms were caused by postoperative swelling or ischaemia. The results of those patients, who were treated with barbiturates after head injury were much better than in 16 other patients, who had no barbiturates. The indications for high dose barbiturate therapy in neurosurgery are discussed with reference to other publications and to the pathophysiological effects of barbiturates.