Blood Barbiturate Levels Research Articles

Spectrum of Poisoning Requiring Haemodialysis in a Tertiary Care Hospital in India

We report our experience in 66 cases of acute poisoning requiring haemodialysis (HD) in the last 17 years. Barbiturate poisoning was the commonest poisoning (30 cases). Mean blood barbiturate level was 8.9 mg%. Twenty four were in grade IV coma at the time of presentation. Twenty five required one HD and 5 cases needed 2 HD. Four died due to respiratory infection or hypotension. Copper sulphate poisoning was encountered in 19 cases. Common features in this group were: acute renal failure (ARF) (19), haematuria (3), gastrointestinal bleeding (7), intravascular haemolysis (9), jaundice (11), hepatocellular toxicity (8), methaemoglobinuria (8) and circulatory collapse (5). The indication for HD in all these cases was ARF. Seven patients died. There were 9 cases of mercuric chloride poisoning requiring 2-5 HD. Common features in this group were; ARF (9), gastrointestinal bleeding (9), anaemia (8), jaundice (2). Two patients died. Other patients had Mandrax, Naphthalene, Tincture Iodine, Ethylene Bromide and Lithium poisoning. Overall mortality in our study was 24.2%. It is concluded that HD is not the primary mode of therapy for drug intoxication. Adequate supportive management is most important in determining final outcome of these patients.

Declaration of brain death in neurosurgical and neurological practice.

A survey of neurosurgeons and neurologists assessed physician practices in the declaration of brain death. Ninety-four per cent of the respondents thought that the diagnosis of brain death was legitimate; most thought that it was justified by a failure of somatic survival after brain death. Fifty-four per cent of the respondents had made the diagnosis themselves 1 to 5 times a year. The criteria used to make the diagnosis varied significantly among the respondents. Most required the absence of a pupillary reflex (88%), the absence of a corneal reflex (85%), a lack of ventilatory effort with disconnection of the ventilator (84%), and the absence of eye movements with head turning (80%). Fewer required an absent cough reflex (61%) or gag reflex (69%), dilated pupils (59%), a body temperature under 90 degrees F (56%), or a blood barbiturate level of zero (43%). Over 65% required an isoelectric electroencephalogram; 29% required only one, and 36% required two electroencephalograms 24 hours apart. Twenty-six per cent required absent deep tendon reflexes. The time required for the declaration varied from 6 to 24 hours. There was wide variation in the response to a hypothetical situation in which the family of a patient fulfilling brain death criteria did not want death to be declared. Seventy-eight per cent of the respondents would continue ventilatory support, although about a third of these would declare the patient dead while doing so. Only 6% would stop the ventilator despite the family's wishes. These results substantiate a wide variation in the actions of neurologists and neurosurgeons in brain death declaration. This has important implications for decisions about death in neurology and neurosurgery.

The Use of Quantitative Structure-Activity Relationships as an Aid to the Interpretation of Blood Levels in Gases of Fatal Barbiturate Poisoning

The quantitative structure-activity relationships developed by Hansch and his co-workers have been applied to the blood barbiturate levels in fatal cases of poisoning for quinal-barbitone, pentobarbitone, amylobarbitone, butobarbitone and phenobarbitone in order to assess their potential usefulness in the interpretation of the results of toxicological analyses. Histograms and cumulative mortality curves were constructed from literature data and the blood levels of barbiturates causing death in 25%, 50%, 75% and 90% of the cited cases were determined. Regressions of fatal blood levels to n-octanoljwater partition coefficients gave correlation coefficients of between 0.726 and 0.976 showing that Hansch Analysis is applicable to problems in forensic toxicology. The use of Hansch Analysis to predict the likely fatal blood levels of a new drug was examined and the concept supported with reference to one of the barbiturates.

The outcome with aggressive treatment in severe head injuries. Part II: acute and chronic barbiturate administration in the management of head injury.

✓ 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.

Behavior Disturbance, Phenobarbital, and Febrile Seizures

Of 109 children treated daily with phenobarbital following the first fibrile convulsion, 42% developed a behavior disorder, usually hyperactivity. Daily phenobarbital therapy was prematurely discontinued in 54% of the children with behavior abnormality (20% of those treated). The behavior disturbance usually appeared within several months, was no correlated with high blood barbiturate levels, disappeared in 73%, and improved in all children when barbiturate therapy was discontinued. No characteristics of the child, the initial febrile seizure, or recurrence of febrile seizures were significantly correlated with the occurrence of the behavior disorder except for behavioral abnormality preceding the initial febrile convulsion. Eighteen percent of the children who received no phenobarbital developed behavior disorder, most often hyperactivity. The behavior disturbance spontaneously disappeared in 52%. Among these children not given phenobarbital, the group with normal behavior had a greater frequency of family history of seizures, especially febrile convulsions, and a lower frequency of preseizure behavior disturbance; abnormalities of pregnancy, labor, delivery, and neonatal period; delayed milestones; long seizures; abnormal results of neurological examination; abnormal EEG; and recurrent febrile seizures.

Acute Barbiturate Poisoning

This 370-page comprehensive monograph, Acute Barbiturate Poisoning , deals with the subject all of its aspects, including scientific information on biochemistry, pharmacology, and toxicology, as well as the diagnosis, specific treatment, prevention, and the psychosocial problems involved. The management includes special methods of therapy detail, with an important chapter on evaluation of these treatments. There is also a chapter devoted entirely to barbiturate poisoning children which will be useful and helpful to the pediatrician when this emergency arises. Intensive supportive therapy is emphasized throughout as the preferred treatment, with statements that alkaline diuresis is rarely needed, while peritoneal dialysis has a very limited role, with hemodialysis having a definite place only in a few very select cases. Assessment of the patient with acute barbiturate poisoning is based primarily on the clinical criteria, and the blood barbiturate level is considered secondary importance. It never takes precedence, because of

Blood barbiturate levels in a patient dependent upon amylobarbitone sodium.

SUMMARYIn a barbiturate dependent patient, the blood barbiturate was less than 0·2 mg% two and a half hours after an oral dose of 200 mg amylobarbitone sodium. Amylobarbitone was withdrawn, and the patient was maintained on phenobarbitone, with a blood barbiturate level that remained at about 4·0 mg% over several weeks. Themost likelyexplanation of the findings is that the oxidation of amylobarbitone, but not phenobarbitone, is accelerated in patients dependent on the former drug.

Barbiturate blood levels found at necropsy in proven cases of acute barbiturate poisoning.

In order to determine whether blood barbiturate levels could be used to ascertain that death had been caused by barbiturate overdose, samples of blood from 128 subjects of coroners' necropsies were examined for barbiturate content. Sixty of these were well authenticated cases of barbiturate overdosage, and barbiturates were implicated, together with other factors such as alcohol and carbon monoxide, in a further 16 cases. The remaining 52 cases were of an eliminatory nature, 10 of which had low barbiturate blood levels considered to be within the therapeutic range.The results indicate that when the accepted levels producing loss of consciousness are exceeded, and maintained, death will ensue if treatment is not given. These results may be of value in assessing findings in necropsies requested by the coroner, and are in no way applicable to the living patient in whom it is well established that recovery from higher blood levels may take place if adequate treatment is available.

Cerebral blood flow and oxygen consumption in barbiturate poisoning.

Abstract Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo2) have been determined by the nitrous oxide method in five cases of severe barbiturate poisoning (blood barbiturate level 2.2−15.2 mg/100 ml). All cases needed prolonged artificial ventilation (IPPV) to survive. Mean CBF was 30±9 ml/100 g/min and mean CMRo2 was 1.5±0.4 ml/100 g/min. Within the temperature range studied, 31.7°C−37.8°C, body temperature (BT) was correlated to CMRo2 according to the equation BT = 6.6 × CMRo2 + 25, the correlation coefficient being 0.96 (p<0.01). A similar correlation was found between CBF and BT (r=0.93, p<0.05). The cerebral arteriovenous oxygen difference was normal and rather constant in spite of generally low values for arterial Pco2. There was no indication of inadequate oxygen supply to the brain.

Toxic and depressant effects of alcohol given orally in combination with glutethimide or secobarbital

General central depressant and toxicologic effects were compared in dogs after oral administration of (a) alcohol alone, in a succession of three doses of 1 ml/kg of 50% ethanol at hourly intervals, (b) glutethimide (200, 300, or 500 mg/kg), either alone or with the third dose of alcohol, and (c) secobarbital sodium (25 mg/kg), either alone or similarly with alcohol. Blood alcohol and blood barbiturate levels after the various treatments were compared at hourly intervals, and blood glutethimide levels at 6-hourly intervals in some experiments. It was observed that the onset, intensity, and duration of central depressant effects and toxicity were strikingly enhanced in all experiments with alcohol-glutethimide or alcohol-secobarbital combinations, as compared with responses to similar doses of glutethimide or secobarbital alone. The changes in blood alcohol levels recorded hourly up to 6 hours were not significantly different in the three groups of experiments (alcohol alone, glutethimide or secobarbital alone, or either drug combined with alcohol), but subsequently blood alcohol levels declined significantly more slowly in the experiments with the combinations. Blood glutethimide and barbiturate levels also decreased significantly in the experiments with added alcohol. The exact mechanism or mechanisms involved in these changes are not established, but it is concluded that there is no evidence of increased absorption of alcohol under the conditions employed. It is, therefore, postulated that a rapidly increased absorption of glutethimide or secobarbital, due to the presence of alcohol in the stomach, might be one of the factors involved in the enhanced CNS depression induced by the combinations.

TREATMENT FOR BARBITURATE INTOXICATION.

To the Editor:— A communication in the Sept 21, 1963, issue ofThe Journal( 185 :936) by Drs. Myschetzky and Lassen reported the efficacy of alkalinization and osmotic diuresis for barbiturate coma. Their selection of patients whose blood barbiturate level was greater than 10 mg/100 ml may have biased the study, since levels are often much lower in deep coma induced by barbiturates having short or intermediate action. Likewise, to attribute shortened duration of coma to augmented renal elimination of the drug is not necessarily warranted. Acidosis potentiates the anesthetizing action of barbiturates, and, since respiratory acidosis occurs regularly in barbiturate coma, perhaps alkalinization per se was responsible for improvement of the treated group. The authors stated: Only severe cases involving the relatively slowly eliminated barbiturates were accepted for treatment. This is misleading, since nearly one half of the treated patients ingested phenobarbital or barbital. Of all barbiturates, these are

Chemical Findings in Patients with Acute Nonfatal Barbiturate Intoxication

Abstract 1. Clinical and chemical data on acutely intoxicated patients show a direct quantitative relationship of the patient's blood barbiturate levels to his clinical condition. 2. The "half-life" of phenobarbital, amobarbital, and pentobarbital was determined to aid in prognosis of an intoxicated patient with a given blood barbiturate level. 3. Urinary clearance studies showed that the clearance was directly proportional to the urine flow. 4. A patient's urine barbiturate level has no relation to his clinical condition.

Barbiturate studies. II. Correlation between clinical condition and blood barbiturate levels.

2, '• 8 Thus, rapid and reliable chemical data are available to corroborate the diagnosis of barbiturate intoxication. However, there are little available data on the correlation between the patient's clinical condition and his blood bar­ biturate level. It is difficult, therefore, to determine if a patient's clinical condi­ tion is due to barbiturate intoxication alone or whether other complicating factors are present. Fisher, 1 Wright, 9 Reed 5 and Roche 6 have presented data on blood barbiturate levels and the clinical condition of patients. Relatively few cases cited by these investigators were followed beyond the initial analysis and observation. This study concerns the clinical condition of barbiturate intoxicated patients as a function of their blood barbiturate levels. Where urine samples were avail­ able, renal excretion was studied. METHODS Blood samples were drawn at various intervals from patients admitted to several Cleveland hospitals with barbiturate intoxication. The samples were drawn upon admission, 12 hours after admission and at 24-hour intervals there­ after. The clinical condition of the patient was noted and categorized each time when blood was drawn for analysis. The blood samples were analyzed, using Goldbaum's technic, 2 which determines both the amount and type of barbiturate present. Whenever possible, 24-hour urine samples were also collected and analyzed to ascertain renal excretion.

Use of artificial kidney for removal of barbiturates in dogs.

SummaryAn artificial kidney of the Skegg-Leonards type was used successfully to lower blood barbiturate levels in dogs. Approximately 15 to 25% of the intravenously injected pentobarbital, 35% of intravenously injected amobarbital, and 40 to 70% of intra-peritoneally injected phenobarbital were recovered in the respective dialysates. This therapy was life saving in the phenobarbital experiments, of some value in the amobarbital intoxication, but of questionable value in pentobarbital poisoning.