Acute Barbiturate Poisoning Research Articles

Evaluating the detection of barbiturates in dried blood spots: A comparative analysis using gas chromatography-mass spectrometry, gas chromatography-tandem mass spectrometry, and liquid chromatography-tandem mass spectrometry with different extraction methods

Rapid and accurate characterization and quantitation of blood barbiturates and their combination drugs are very important for the clinical treatment of acute barbiturate poisoning. A comparison of dried blood spot (DBS) and traditional liquid-liquid extraction (LLE) in the pre-treatment stage, as well as a comparison of gas chromatography-mass spectrometry (GC–MS), gas chromatography-tandem mass spectrometry (GC–MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) as instrumental analysis methods, revealed differences in the analysis results of barbiturates and their combination drugs under different conditions. Based on these findings, we introduce a DBS-GC–MS/MS method. The developed and validated method showed good selectivity, sensitivity (LOD: 0.1 μg mL−1, LOQ: 0.2 μg mL−1), linearity (R2>0.9992), trueness (<15 %, except for carbamazepine, at 29.4 %), and precision (<15 %). Recovery was also good for most target compounds, but significant matrix effects were evident. Compared with the LLE method, the DBS method has the benefits of easy sample collection, storage, and transport, as well as simple pre-treatment and reduced reagent and energy consumption. Compared to LC-MS/MS, GC–MS/MS requires no switching between positive and negative ion modes and uses the MRM detection mode, meaning that more information about the sample compounds can be obtained in less analysis time. Using actual sample analysis, we have demonstrated the advantages of the DBS-GC–MS/MS method for the qualitative and quantitative analysis of barbiturates and poisoning events due to combinations of these drugs. Comparison of the three instruments and the two treatment methods revealed their analysis characteristics. From the perspective of practical application, the broad practical value and advantages of DBS should be embraced in more applications, and future analytical laboratory development should continue to recognize GC–MS/MS as a useful supplement to LC-MS/MS.

Acute poisoning with ваrbituric acid derivatves. Barbituric coma

Introduction. Aim of the study. To summarize the authors’ many years of experience in the diagnosis and treatment of acute poisoning with barbituric acid derivatives and to present the results of a detailed study of the clinic of barbituric intoxication, which prove a toxic damaging effect on the body, causing a deep inhibition of the functions of the central nervous system (CNS) with a predominant effect on the cortex and autonomic centers of the brain trunk. Material and methods. The analysis of 385 patients with acute poisoning with barbiturates of varying severity who were treated in the emergency toxicology department of the N.V. Sklifosovsky Research Institute for Emergency Medicine was carried out. The clinical and encephalographic picture of acute poisoning was assessed. The EEG data of two groups of patients were considered and analyzed, with the possibility of determining the type of bioelectric activity of the brain. The informative value of these types of EEG for a physician is in comparison with the characteristics of clinical and toxicological data. Results. Summarizing the obtained results of clinical and electroencephalographic changes in barbiturate poisoning, it was noted that the identified types of brain bioelectrical activity correspond to certain clinical symptoms and indicate different degrees of poisoning severity. This makes it possible for a practicing physician, after recording an EEG in a patient in a coma, to make a preliminary diagnosis of acute barbiturate poisoning, to purposefully conduct a toxicological study, and to begin specific treatment before receiving an analysis. Analeptic bemegrid causes a direct stimulating effect on the central nervous system. With the introduction of small doses of bеmegrid, a moderate activation of the bioelectrical activity of the brain was noted. Our experience in treating patients with this poisoning showed a negative effect of large doses of bemegrid on the central nervous system, which can lead to an inhibitory phase of parabiotic inhibition (according to N.E. Vvedensky). Conclusion. Poisoning with barbituric acid derivatives currently poses a serious danger to the life and health of patients. This makes the issue of timely diagnosis and treatment measures in the early stages of the disease relevant.

Enhanced elimination in acute barbiturate poisoning – A systematic review

Context. Despite a worldwide decline in barbiturate use, cases of acute poisoning with severe toxicity are still noted, particularly in developing countries. Severe poisonings often require prolonged admission to an intensive care unit, so enhanced elimination might be useful to hasten recovery. Information regarding the efficacy of these techniques for individual barbiturates is not available in standard textbooks. Objective. To determine the evidence supporting the effect of enhanced elimination and its role in the management of acute barbiturate poisoning. Methods. A systematic review was conducted using broad search criteria in three databases. All potentially relevant articles were obtained, and reference lists were manually reviewed. Ninety-four publications fulfilling inclusion criteria were located. Studies were classified as controlled or uncontrolled, and clinical and pharmacokinetic end points were manually extracted. If not directly stated, standard pharmacokinetic methods were used to calculate the clearance and efficiency of enhanced elimination techniques for each barbiturate and tabulated for direct comparison. Prospective controlled clinical trials. Two of the 94 publications were prospective controlled studies (only one stated that allocation was via blinded randomisation), and both assessed the effect of multiple-dose activated charcoal for acute phenobarbital poisoning. These studies demonstrated enhanced elimination with a decrease in elimination of half-life from approximately 80 to 40 h, but only one study reported clinical benefits. Uncontrolled series and single case reports. Sufficient data to determine the clearance due to enhanced elimination were available in only 52 of these papers. Barbiturate clearances by enhanced elimination varied markedly among studies. While extracorporeal modalities appeared to increase the direct clearance of many barbiturates, there was insufficient information to confirm a clinical benefit. Conclusions. There is limited evidence to support the use of enhanced elimination in the treatment of poisoning with most barbiturates. There is no role for urine alkalinisation, while multiple-dose activated charcoal may be useful for most phenobarbital and possibly primidone poisonings. Extracorporeal techniques appear to enhance elimination, but the clinical benefits, relative to the potential complications and cost, are poorly defined. Extracorporeal techniques such as haemodialysis and haemoperfusion can be considered for patients with life-threatening barbiturate toxicity such as refractory hypotension.

Management of Poisonings: Core Curriculum 2010

Management of Poisonings: Core Curriculum 2010

Coma Blister, Compressive Neuropathy and Rhabdomyolysis: Case Reports and Literature Review

Coma blister was first reported in 1965 as a bullous lesion in acute barbiturate intoxication. The etiology is debated and may be drug induced or caused by other factors. Regardless of causes, coma blisters have similar pathologic findings: epidermal-dermal separation with bullous formation and necrosis over all skin appendages, especially the sweat duct wall. In most patients, coma blisters are self-limited lesions without surgical indication. We present three cases of coma blister with diverse clinical presentations. Two patients with compartment syndrome and compressive neuropathy required fasciotomy to release the compartment pressure. Variable degrees of rhabdomyolysis were observed, and one patient developed acute renal failure requiring hemodialysis. Two other patients presented with self-limited rhabdomyolysis needing only supportive care. We review the literature on the relationship between compressive neuropathy, rhabdomyolysis, and coma blister.

Intensification of ammonium diffusion from rat gastrointestinal tract during acute barbiturate intoxication

In rats with acute sodium thiopental intoxication, ammonium concentration in the caecal contents was at the lower boundary of control values, while accumulation of ammonium in lavage solution injected intraperitoneally was 50-70% accelerated. Blood ammonium level did not change 3 h after sodium thiopental injection in a dose inducing sopor, but increased 3-fold during coma modeling. Intragastric administration of gentamicin (antibiotic poorly absorbed from the gastrointestinal tract) 2-fold reduced ammonium concentration in the caecal contents and prevented hyperammoniemia during induction of barbiturate coma. Hence, increased permeability of the gastrointestinal wall for ammonium promotes the development of hyperammoniemia in rats during induction of barbiturate coma.

Periodic EEG discharges in psychiatry.

Periodic EEG discharges are signs of severe CNS dysfunction. In psychiatry they usually indicate presenile dementia of the Jacob-Creutzfeldt type. Psychiatric patients are presented in whom the occurrence and EEG features of diffuse and lateralized periodic discharges are discussed. It appears that toxic conditions other than acute barbiturate intoxication, such as drug withdrawal states and psychotropic drug overdosage, represent important etiological factors for inducing periodic EEG discharges. Their relation to clinical signs such as epileptic symptoms, metabolic dysfunction, and disturbance of consciousness is particularly stressed and related to current literature data.

L'EEG dans le pronostic des comas toxiques: reflexions a propos de quelques donnees inhabituelles

During acute intoxications, the first EEG may show persistence or abolition of cerebral activity, but the possibility of recovery after isoelectric tracing in toxic comas must be emphasized. EEG patterns frequently suggest the probability of hypnotic tranquilizer poisoning; 4 types of EEG are encountered corresponding to different grades of toxic coma. Recurrent periods of electrical silence alternating with bursts of activity are habitually recorded in carus comas with hypothermia due to acute barbiturate intoxication, with good prognosis. The possibility of a neurological disturbance associated with drug overdose must be raised whenever an asymmetric tracing is encountered. Serial recordings may detect complications such as: a localized lesion, anoxia or, very rarely, typical paroxysmal abnormalities reappearing in comitial patients before emergence from a toxic coma. Paradoxical monomorphic delta activity corresponding to improvement must not be considered as an aggravation. Peculiar EEG findings occur after oral trichlorethylene poisoning, with temporary clinical deterioration and intermittent periods of electrical silence; recovery is possible. An alpha-like pattern after cardiac arrest of toxic origin has a poor prognosis. The appearance of alternating patterns suggests the development of irreversible brain damage.

Electrocardiographic Changes Associated with Hypothermia Due to Acute Barbiturate Intoxication

Summary: A patient with hypothermia due to acute barbiturate intoxication is presented. Features not usually present in the electrocardiograms of hypothermic patients suggested myocardial infarction. Hypothermia in temperate climates is uncommon but this diagnosis should be suspected when the characteristic electrocardiogram changes are seen.

Thyrotropin releasing hormone: antagonism of pentobarbital narcosis in the monkey

The effect of TRH on pentobarbital narcosis in 12 rhesus monkeys was examined. Vital signs monitored included respiration rate, heart rate, temperature, sleeping time, and time of reappearance of certain reflexes. Blood samples were obtained for pentobarbital assay. Two dose schedules for TRH administration were used. One group of 6 animals received a single dose of 20 mg/kg 30 min after barbiturate administration, while the other group received 3 injections of 20 mg/kg spaced at 30, 40 and 50 min after injection of pentobarbital. Both groups were sex balanced. TRH administration resulted in dramatically increased respiration and heart rates and arrested the progress of barbiturate induced hypothermia. The extended dose schedule prolonged increased respiration rate and a differential effect of TRH on pentobarbital induced hypothermia across sexes was observed. All animals regained reflexes sooner and sleeping time was reduced by 22%. No differences in pentobarbital blood levels with TRH were observed. These results extend earlier work in rodents to primates and suggest a possible use of TRH in cases of acute barbiturate intoxication.

Treatment of Common Acute Poisonings.

In his introduction to the British-neat minibook by Matthew and Lawson, Sir Derrick Dunlop, former Chairman on the Committee on Drug Safety of the United Kingdom, points out that poisoning has now become a common emergency, accounting for nearly 10% of all (acute) medical admissions to many general hospitals. As new drugs and chemical and botanical mind-rattlers, food additives, and pesticides increasingly penetrate our culture, new kinds of poisoning appear. Lithium, tetrahydrocannabinols, chlorinated hydrocarbons, and phenols are examples. The incidence of poisoning has gone up astronomically since 1950. Poison control centers have risen to combat its intended and unintended ravages. The one at Edinburgh has developed experience for 80 years. Diagnosis, the very difficult key to proper treatment, is discussed rather briefly. Certain basic principles of proper therapy make the difference, for example, between saving upward of 99% of cases of acute barbiturate poisoning and losing 25% of them.

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

The EEG in acute barbiturate intoxication, with particular reference to isoelectric EEGs : S. Sament and A. D. Huott (Boston, Mass., U.S.A.)

The EEG in acute barbiturate intoxication, with particular reference to isoelectric EEGs : S. Sament and A. D. Huott (Boston, Mass., U.S.A.)

Acute barbiturate intoxication. Concepts of management

Deep coma resulting from barbiturate overdose was studied in 50 patients. The length of coma correlated with depth of coma and serum barbiturate level except in those patients with drug addiction and hepatic or renal disease. The complications of pneumonia, bleeding of the gastrointestinal tract, urinary tract infections, and thrombophlebitis were common; however, all patients survived. Treatment was instituted on a rotation basis with supportive care alone, mannitol diuresis, or peritoneal dialysis. Using length of coma, the slope of disappearance of serum barbiturate value, and clearance data as indicators of the effectiveness of treatment, we found that the three treatment forms did not differ. Supportive care alone was associated with less local and systemic morbidity and appears to be the best method of reducing morbidity and mortality in patients with barbiturate overdose.

Acute Barbiturate Poisoning. Treatment with Modern Methods of Resuscitation

Acute Barbiturate Poisoning. Treatment with Modern Methods of Resuscitation

Value of forced diuresis in acute barbiturate poisoning.

The therapeutic usefulness of forced diuresis in severe barbi turate poisoning has yet to be evaluated by a controlled clinical trial. In the absence of such a trial its usefulness can be judged only indirectly from urinary barbiturate excretion rates. Unfortunately, however, the rate of apparent barbiturate excre tion varies with the method of its measurement. The usual clinical laboratory procedures (Varley, 1967) depend on chloroform or ether extraction of barbiturate fol lowed by spectrophotometric estimation. When applied to bio logical fluids they estimate not only unchanged barbiturate hypnotic but also a proportion of the metabolic derivatives (Bloomer, 1967). The resultant error is small when plasma is extracted, for the concentrations of unchanged barbiturate hypnotic and metabolites are of the same order in plasma. When urine is extracted, however, the error may be large, for the concentrations of metabolites may be several times greater than the concentration of unchanged barbiturate. Using more selective methods, Bloomer (1965, 1966) found that the urinary excretion of unchanged pentobarbitone and quinalbarbitone during forced diuresis was only a minor factor in the elimination of these driigs. Linton, Luke, and Briggs (1967) described the results of forced diuresis in 110 patients with severe barbiturate poisoning. They concluded that the barbiturate excretion rates justified forced diuresis in cases of poisoning by long-acting barbiturates and by cyclobarbitone. They also concluded that forced diuresis was useful in cases of poisoning by intermediate-acting barbi turates if the blood level had reached 4 mg./100 ml. and that mannitol had no practical advantages over frusemide. How ever, these conclusions were based on a method of barbiturate estimation which is not specific for unchanged hypnotic. The present report describes the pattern of barbiturate excre tion in four pairs of patients poisoned by pentobarbitone, amylobarbitone, butobarbitone, and phenobarbitone. Forced diuresis was induced with mannitol and frusemide, and the following were determined: (1) the rate of excretion of speci fically identified unchanged barbiturate hypnotic; (2) the extent to which the excretion rate was exaggerated by a less specific assay technique; (3) the rate of excretion of derivatives of barbituric acid, both unchanged barbiturate hypnotic and metabolites; and (4) the relative effects of frusemide and mannitol on the urinary excretion of unchanged barbiturate hypnotic.

Acute Barbiturate Poisoning. Treatment with Modern Methods of Resuscitation.

Acute Barbiturate Poisoning. Treatment with Modern Methods of Resuscitation.

OCCURRENCE OF BULLOUS LESIONS IN ACUTE BARBITURATE INTOXICATION.

OCCURRENCE OF BULLOUS LESIONS IN ACUTE BARBITURATE INTOXICATION.

UREA-INDUCED, OSMOTIC DIURESIS AND ALKALIZATION OF URINE IN ACUTE BARBITURATE INTOXICATION.

The use of urea-induced diuresis and alkalization of the urine is described for the treatment of severe barbiturate intoxication with compounds of slow spontaneous elimination. These patients represented only a small percentage of the total number with acute barbiturate intoxication hospitalized during the 2 years of this study. An average diuresis of 12.1 liters of alkaline urine per 24 hours was obtained in 57 patients; the average duration of treatment was 42 hours, with a calculated reduction of duration of coma to about one-third. Diuretic treatment was found to reduce mortality and frequency of tracheostomy to 50% of those in an untreated control group. The treatment, relatively simple and with few complications, can be considered a valuable adjunct to the fundamental supportive therapy in severe cases of barbiturate poisoning.

TREATMENT OF ACUTE BARBITURATE POISONING

SummaryAfter a short survey of the pharmacological properties of barbiturates and of the clinical signs of acute barbiturate intoxication, the authors review the different methods of treatment in use.Gastric lavage and administration of classical central analeptics are actually abandoned. The use of bemegride is limited to a few rare cases of respiratory depression of central origin.The modern treatment of acute barbiturate intoxication is essentially based on the Scandinavian method of reanimation and of the alkalinisation of plasma and urine by the method of Mollaret.The aim of the reanimation is to maintain within physiological limits of respiratory, cardiovascular and renal functions until the patient awakes, to prevent secondary infection and to ensure an adequate intake of liquids, calories and electrolytes. The primordial importance of the reanimation is actually everywhere admitted. The introduction of this symptomatic treatment has permitted to reduce the mortality of acute barbiturate intoxication to less than 3 %.Plasma and urine alkalinisation accelerates the renal output of the barbiturate. The duration of the coma is therefore significantly reduced.