Chantal Bismuth

Elevated Blood Cyanide Concentrations in Victims of Smoke Inhalation

BACKGROUND The nature of the toxic gases that cause death from smoke inhalation is not known. In addition to carbon monoxide, hydrogen cyanide may be responsible, but its role is uncertain, because blood cyanide concentrations are often measured only long after exposure. METHODS We measured cyanide concentrations in blood samples obtained at the scene of residential fires from 109 fire victims before they received any treatment. We compared the results with those in 114 persons with drug intoxication (40 subjects), carbon monoxide intoxication (29 subjects), or trauma (45 subjects). The metabolic effect of smoke inhalation was assessed by measuring plasma lactate at the time of admission to the hospital in 39 patients who did not have severe burns. RESULTS The mean (+/-SD) blood cyanide concentrations in the 66 surviving fire victims (21.6 +/- 36.4 mumol per liter, P less than 0.001) and the 43 victims who died (116.4 +/- 89.6 mumol per liter, P less than 0.001) were significantly higher than those in the 114 control subjects (5.0 +/- 5.5 mumol per liter). Among the 43 victims who died, the blood cyanide concentrations were above 40 mumol per liter in 32 (74 percent), and above 100 mumol per liter in 20 of these (46 percent). There was a significant correlation between blood cyanide and carbon monoxide concentrations in the fire victims (P less than 0.001). Plasma lactate concentrations at the time of hospital admission correlated more closely with blood cyanide concentrations than with blood carbon monoxide concentrations. Plasma lactate concentrations above 10 mmol per liter were a sensitive indicator of cyanide intoxication, as defined by the presence of a blood cyanide concentration above 40 mumol per liter. CONCLUSIONS Residential fires may cause cyanide poisoning. At the time of a patients hospital admission, an elevated plasma lactate concentration is a useful indicator of cyanide toxicity in fire victims who do not have severe burns.

Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole

THE toxic effects of ethylene glycol result from its metabolic conversion by alcohol dehydrogenase into glycolic acid — a process that causes metabolic acidosis. Glycolate is then metabolized to ox...

Prognosis and Treatment of Paraquat Poisoning: A Review of 28 Cases

Paraquat poisoning is very severe. When it is ingested, this herbicide may be responsible for causative lesions of the digestive tract, cytolytic hepatitis, renal tubular necrosis, circulatory failure, and/or pulmonary fibrosis. Since a very low dose (as little as one mouthful) is potentially lethal, it is important to understand why 11 of our 28 patients who entered our department for paraquat poisoning survived. The main prognostic factors appear to be the following: Route of administration. Of four patients who had inhaled paraquat aerosols and/or contaminated their skin with the herbicide, all survived. Ingested amount. Above 50 mg/kg, patients died of circulatory failure within 72 h; between 35 and 50 mg/kg, a progressive pulmonary fibrosis occurred. Delay between ingestion and the last meal. Paraquat is adsorbed and neutralized by foodstuffs. Caustic gastric lesions revealed by early endoscopic examination. The occurrence of an organic renal failure. The plasma paraquat concentrations within the first 24 h. Patients whose plasma concentrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg/L at 4, 6, 10, 16, and 24 h, respectively, are likely to survive. The different treatments that have been tested (fullers earth, forced diarrhea, furosemide, hemodialysis, hemoperfusion, artificial ventilation with hypoxic breathing mixtures) did not modify the initial prognosis. The 11 survivals are only linked to the circumstances of the poisonings (route of administration, ingested amount, delay between ingestion and the last meal, etc.). The treatments did not modify the outcome.

Toxicokinetics of paraquat in humans.

1 The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life (t ½ α) of 5 h and a mean elimination half-life (t ½ β) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2 Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3 Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.

4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man

4-Methylpyrazole (4 MP) is a strong inhibitor of alcohol dehydrogenase. Its use in acute ethylene glycol (EG) or methanol intoxication has been suggested in experimental studies about its efficacy and safety. We report three cases of accidental intoxication with ethylene glycol in man treated orally with 20 mg/kg/day of 4 MP. The treatment was maintained until plasma EG concentrations became unmeasurable. The patients were admitted early during the course of the poisoning. Their neurological status was good. A slight metabolic acidosis observed in two cases was easily corrected and did not recur. Renal function remained normal in all cases. No patient underwent hemodialysis. On admission plasma EG concentrations were 24.2 mmol/l, 13 mmol/l and 9.7 mmol/l respectively. Plasma EG half-lives were 14.5, 11.5 and 14.75 hours respectively. Plasma oxalate concentrations and the rate of urine oxalate elimination, determined in two patients, were high on admission but quickly returned to normal. Concerning possible side effects of 4 MP, a skin rash was observed in one patient and a possible eosinophilia in the others. These three cases suggest that 4 MP may decrease the metabolic consequences of EG poisoning in man and may be of therapeutic value when administered early during the course of the intoxication before coma, seizures and organic renal failure have occurred.

Acute Digitalis Intoxication — Is Pacing Still Appropriate?

Over a six year period, 92 patients intoxicated with either digitoxin or digoxin were admitted to our ICU. Fifty-one patients were treated with cardiac pacing and/or Fab fragments, and the mortality rate was 13% (14 were intoxications with digoxin, 36 with digitoxin, 1 was mixed). Forty-five cases were suicide attempts; six were accidental overdosages. Since cardiac pacing may trigger fatal arrhythmia or delay the administration of Fab fragments, we conducted a retrospective study to determine whether fatal outcomes could be related either to cardiac pacing or to unsatisfactory use of immunotherapy. In our study, prevention of life-threatening arrhythmia failed in 8% of cases with Fab and in 23% with pacing. Though Fab tended to be more effective, this difference was not significant. In our study, the main obstacles to the success of Fab were pacing-induced arrhythmias and delayed or insufficient administration of Fab. Iatrogenic accidents of cardiac pacing were frequent (14/39, 36%) and often fatal (5/39, 13%). In contrast, immunotherapy was not associated with any serious adverse effects (0/28, 0%) and was safer than cardiac pacing (p < 0.05). In conclusion, during digitalis intoxication, the pacemaker has limited preventive and curative effects, is difficult to handle, and exposes patients to severe iatrogenic accidents. Fab fragments act as a powerful antidote and are safer and much easier to use than pacing. These results encourage us to prescribe Fab fragments as first-line therapy during acute digitalis intoxication.

Treatment of acute chloroquine poisoning: A 5-year experience

OBJECTIVE To describe various aspects of prognostic and therapeutic importance in patients treated for acute chloroquine poisoning. DESIGN Retrospective study. SETTING Toxicology intensive care unit (ICU) of a university hospital. INTERVENTIONS None. PATIENTS One hundred sixty-seven consecutive patients with acute chloroquine overdose admitted to our toxicology ICU. MEASUREMENTS AND MAIN RESULTS The mean amount ingested by history was 4.5 +2- 2.8 g. and 43 (26%) of 167 patients ingested > 5 g. The mean blood chloroquine concentration on admission was 20.5 +/- 13.4 mumol/L The majority (87%) of our patients received at least one arm of a combination therapy regimen (epinephrine, mechanical ventilation, diazepam). cardiac arrest occurred in 25 patients before hospital arrival; In seven of these patients, cardiac arrest occurred immediately after injection of thiopental. The mortality rate was 8.4% overall, and was 9.3% in patients with massive ingestions (NS vs. the group as a whole). We did not find a meaningful correlation between the amount ingested as estimated by history and the peak blood chloroquine concentration; the latter was highly correlated with the mortality rate. CONCLUSIONS The mortality rate in patients with acute chloroquine poisoning, including those patients sick enough to be referred to a specialty unit such as ours, can be limited to < or = 10%. This finding appears to be true even in patients with massive ingestions. We were not able to correlate mortality with amount ingested by history, although the mortality rate does correlate with blood chloroquine concentration. While early use of diazepam, epinephrine, and mechanical ventilation in most of our patients may have contributed to the excellent overall results, these elements, either singly or in combination, do not appear to have a truly antidotal effect in acute chloroquine poisoning. Thiopental, on the other hand, should be used with great caution, if at all, in such cases.

Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning.

Objective:Despite administration of Fab fragments in digitalis poisoning, high mortality rates are consistently reported. A previous study suggested that Fab fragments prescribed as first-line therapy might improve mortality rate. Our objective was to evaluate this approach. Design:Retrospective chart review (January 1990 to January 2004). Setting:University hospital intensive care unit. Patients:Consecutive patients admitted for cardiac glycoside poisoning. Intervention:First-line therapy with Fab fragments (with or without atropine) in either curative or prophylactic doses. Measurements and Main Results:A total of 141 patients were admitted for digitalis poisoning of whom 66 received first-line Fab fragment therapy. Their median age was 74 years (25th to 75th percentiles: 51–83); 76% were women. Half were intoxicated by digitoxin and half by digoxin. Median serum concentration was 168 (108–205) ng/mL for digitoxin and 6.2 (4.3–13.5) ng/mL for digoxin. Conduction disturbances were reported in 45 cases (68%) and ventricular arrhythmia in six cases (9%). Fab fragments were administered as curative treatment in 21 patients (32%) and prophylactically in 45 patients (68%). The median cumulative dose was 4 (4–6) vials. No adverse effects were reported. Five patients (7.6%) died. Conclusions:First-line therapy with Fab fragments in patients with digitalis poisoning was associated with a low mortality rate.

Elimination of Paraquat

1 There is a striking discrepancy between the efficacy of the kidneys, haemodialysis and haemoperfusion in removing paraquat from the body and the poor prognosis of paraquat poisoning even when the blood and urine concentrations (which are good indices of concentrations in lung and other tissues) are very low. 2 Extracorporeal elimination techniques have been used world-wide in paraquat poisoning. Do they remove paraquat effectively? Certainly. Do they increase the survival rate? Probably not. The reason being that when these techniques of elimination are initiated, potentially lethal concentrations of paraquat have already been attained in the highly vascular tissues of vital organs and in pneumocytes. 3 The data presented here suggest that the successful treatment of paraquat poisoning will not be achieved by modification of toxicokinetics.

Chemical Submission: GHB, Benzodiazepines, and Other Knock Out Drops

AbstractWe leave to Sartre this sweeping generalization but the infliction of involuntary intoxication or chemical submission is clearly an attempt at annihilation or, at least, domination of the conscience of others. Chemical aggression is increasingly frequent and the popularization of gamma-hydroxybutyrate (GHB) as an uncontrolled intoxicant is expected to increase the diagnostic dilemmas of contemporary “knock out drops”1,2