Ethchlorvynol ingestion in San Diego County: a 14-year review of cases with blood concentrations and findings.

Cases of nonfatal (51) and fatal (38) ingestions involving ethchlorvynol over a 14-year period (1975 through 1988) were reviewed in order to evaluate the current status of ingestion of this drug. In both series of cases men and women were involved approximately equally. Sixty-three percent of cases in both series occurred during the period 1975 through 1980. Most (78% of nonfatal and 89% of fatal) ingestions involved other drugs in addition to ethchlorvynol. Physical findings for nonfatal ingestions and causes of death for fatal ingestions are presented. Blood ethchlorvynol concentrations are discussed, and a composite of the average patient for each series is presented. Although ethchlorvynol abuse appears to be decreasing with time, it still occurs, and a search for this sedative-hypnotic agent should be included in the so-called "toxicology screen."

Ethchlorvynol pharmacokinetics during long-term administration in a patient with hyperlipidemia and hypothyroidism.

A 33-year-old obese, hypothyroid, white male with several medical problems was admitted to University Hospital in September 1984 for treatment of drug intoxication. Admitting medications included ethchlorvynol in addition to other central nervous system depressants. Initial serum concentrations were reported at 70 micrograms/ml in this somnolent yet totally conscious adult. Established therapeutic concentrations are 2-8 micrograms/ml, with toxic exceeding 20 micrograms/ml. A tolerance phenomenon seemed evident. Serum ethchlorvynol concentrations were monitored daily during early hospitalization and continued to be substantially greater than reported toxic concentrations. Kinetic values were as follows: total body clearance 9.92 ml/min, volume of distribution 68.0 liters, and half-life 78 hours. These values are unique in that they were calculated from a patient who had not suffered an acute overdose, thereby differing markedly from previously published values. The influence of hypothyroidism and hyperlipidemia on these markedly different values appears to be significant. Ethchlorvynol should probably be added to the list of drugs influenced by thyroid disease.

Charcoal hemoperfusion for treatment of ethchlorvynol overdose.

Charcoal hemoperfusion is commonly employed to treat overdose of a number of drugs. There are varying reports of its efficacy in the treatment of ethchlorvynol overdose. Herein is reported a case of ethchlorvynol overdose successfully treated with charcoal hemoperfusion within 5 h of ingestion of 12.5 g of the drug. The patient was deeply comatose at that time but recovered consciousness at the end of 4 h of hemoperfusion. Ethchlorvynol clearance over the charcoal varied from 118 to 147 ml/min. There were no bleeding complications. Prompt charcoal hemoperfusion may be an effective mode of treatment in cases of ethchlorvynol intoxication.

Ethchlorvynol ingestion: interpretation of blood concentrations and clinical findings.

Thirty-eight patients who ingested ethchlorvynol were seen at our institution over an 8.7 year period. Eleven involved ethchlorvynol alone ("pure") while the remainder included at least one other drug ("mixed"). Twenty-three of the patients were women. Six patients required hospitalization. Five patients were chronic users of the drug. Admission ethchlorvynol blood concentrations ranged from 3 to 46 mg/L ("pure") and from 3 to 75 mg/L ("mixed"). For the "pure" cases the most common physical findings were depressed level of consciousness (10 cases), dysarthria (7), mydriasis (6), nystagmus (6), areflexia (4), tachycardia (4), and hypotension, ataxia, and respiratory depression (2 cases each). Following "pure" ingestion, ethchlorvynol concentrations greater than 19 mg/L were usually associated with dysarthria, mydriasis, nystagmus, and tachycardia. When concentrations exceeded 38 mg/L, coma, areflexia, hypotension, and respiratory depression were generally noted as well. All patients recovered with supportive care alone.

A comparative study of ethchlorvynol levels in blood versus bone marrow.

Bone marrow may be utilized as an alternative biological sample in cases where uncontaminated blood samples are not available for analyses. Bone marrow/blood ratios of ethchlorvynol as a function of time and dosage level were determined in 40 rabbits. A modified quantitative analysis that produced accurate and reproducible results was employed for the determination of ethchlorvynol levels. Further, ten blood and bone marrow samples containing ethchlorvynol were chosen to study the effects of storage for a period of 24 hours. Studies of blood and bone marrow ethchlorvynol levels with time showed no linear relationship. Bone marrow/blood ratios as a function of dose resulted in close mean averages with a wide range of values. Significant losses in both blood and bone marrow ethchlorvynol levels were evidenced in most of the samples subjected to the 24-hour storage study.

Resin hemoperfusion in ethychlorvynol overdose.

An 18-yr-old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD-4 resin hemoperfusion. Plasma ECV concentration declined 33% during a 3.5-hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/1/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (Cl = 270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (Cl = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 +/- 0.04 and fraction free in plasma, 0.38 +/- 0.02; neither changed as a function of blood concentration between 27 and 108 mg/1. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD-4 hemoperfusion may be clinically useful.

Resin hemoperfusion for treatment of ethchlorvynol overdose.

Hemoperfusion has been increasingly used to treat drug intoxication. Although efficient extraction rates have been reported with hemoperfusion devices, simultaneous measurements of drug adsorption on the columns and endogenous clearance rates have not been made. We studied three patients who ingested 12 to 22 g of ethchlorvynol (Placidyl). In each patient saline diuresis was induced, and Amberlite XAD-4 resin hemoperfusion was done. Resin extraction of ethchlorvynol was calculated hourly, and the recovery of drugs from each column was measured. Renal clearance of ethchlorvynol was simultaneously measured. The resin removed 100% of perfused ethchlorvynol measured by gas chromatography. Ethchlorvynol recovery from the columns agreed well with calculated extraction. Renal clearance was 1 to 6 mL/min, and estimated metabolic clearance was 16% to 31% of resin extraction rate. Complications included anemia, thrombocytopenia, hypocalcemia, and pancreatitis. Resin hemoperfusion substantially supplements endogenous clearance of ethchlorvynol and is a valuable therapy in ethchlorvynol intoxication.

Analysis of chlormethiazole, ethchlorvynol and trichloroethanol in biological fluids by gas-liquid chromatography as an aid to the diagnosis of acute poisoning.

A simple method has been developed whereby chlormethiazole, ethchlorvynol and trichloroethanol can be simultaneously detected and measured in biological fluids. The procedure is based upon the rapid extraction of a small (50-microliter) sample volume with an equal volume of chloroform containing an internal standard, followed by the gas-liquid chromatographic analysis of this extract. Specimens of blood plasma or serum, urine and gastric contents can be used, and no interference from either endogenous or exogenous sources has been observed. The method is suitable for the measurement of the plasma concentrations of these compounds attained after overdosage.

Ethchlorvynol intoxication.

Ethchlorvynol intoxication can be confusing because of the lack of correlation between blood levels of the drug and clinical status. In this case, the patient was in a coma for approximately one week although he had a blood level of ethchlorvynol (0.8 mg/100 ml) generally considered to be subtoxic.

Rapid micro-method for the measurement of ethchlorvynol in blood plasma and in urine by gas-liquid chromatography.

A rapid gas-liquid chromatographic method has been developed for use in the measurement of the hypnotic drug ethchlorvynol in small (50 microliter) volumes of either blood plasma or urine. Neither solvent transfer nor evaporation steps are used in the procedure and sources of interference have proved to be minimal. The method has been applied primarily to the analysis of specimens obtained from patients who had ingested an overdose of this drug. However with slight modification, the technique may be used in the measurement of the plasma concentrations of ethchlorvynol attained during therapy.

Analytical toxicology: Applications of element-selective electrolytic conductivity detection for gas chromatography.

We applied a commercially available microelectrolytic conductivity detector to toxicological problems of qualitative and quantitative analysis by gas chromatography. The detector can be used for the sensitive and selective detection of halogen-, nitrogen-, and sulfur-containing compounds. Relative response in different element-selective detector variables such as reaction gas, reaction catalyst, and furnace temperature can be used to further improve qualitative identification by gas chromatography.

The reduction of coma time in lipophilic drug overdose using castor oil.

A clinical trial of castor oil in overdoses of lipophilic drugs gave a strong clinical impression that it was effective in speeding up recovery. Therefore, animal experiments were undertaken to confirm that castor oil acts as a ligand in Ethchlorvynol poisoning and that its use reduces coma time. Serial serum levels of Ethchlorvynol were obtained from dogs given Ethchlorvynol 150 mg/kg alone, and the same dose dissolved in castor oil 15 ml/kg in a crossover fashion. The result was a reduction of peak serum levels and of the half-life of the drug when the castor oil solution was used. In order to mimic the clinical situation more closely, a further crossover study was undertaken using Ethchlorvynol 300 mg/kg alone and the same dose followed by castor oil 15 ml/kg repeated q12h. This showed no delay in reaching peak serum concentration and no reduction of peak levels. However, it did show a 31 per cent reduction in the half-life of the drug. This change is statistically significant, and supports the continued use of castor oil in lipophilic drug overdose.

Rate of decrease in serum ethchlorvynol concentrations after extreme overdosage-a case study.

Ethchlorvynol is a commonly abused sedative hypnotic. I report here a seven-day study of serum ethchlorvynol concentrations in a patient who had received an extreme overdose. These concentrations were correlated with the patient's response to stimuli. Serum ethchlorvynol concentrations were logarithmically related to time, a fact that can be useful in predicting when a patient's serum ethchlorvynol concentration will return to a therapeutic concentration. In this case the decrease was about 35% per 24h.