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C Bismuth

Publications and source records attributed to C Bismuth.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Shock caused by poisoning. Use of cardiotropic agents].

At toxic doses, cardiotropic drugs may compromise cardiac output leading to circulatory shock. Specific treatment varies depending on the nature and the dose of the drugs ingested as well as causal mechanism including vasopegia, hypovolaemia, cardiogenic effects and sepsis. Progress in our understanding of the pharmacodynamic aspects of intoxication and the development of specific antidotes has led to reduced morbidity and mortality. In addition to the classical inotropes, mainly catecholamines and phosphodiesterase inhibitors, other therapeutic agents may have specific inotrope effects in such ad hoc situations. These include hypertonic alkaline saline solution, calcium, glucagon, hydroxocobalamine and other cobalt salts, oxygen and immunotoxicotherapy. Together with volum replacement, dobutamine at the dose of 7 to 20 micrograms/kg/min can usually restore cardiac performance in cases of carbamate-induced circulatory shock. In case of tricyclic antidepressant overdose, treatment should include respiratory assistance and infusion of alkaline sodium solutions to both reverse the extracellular acidosis and correct sodium balance. Catecholamines may be necessary in cases with severe hypotension. Major vasoplegia and impaired intraventricular conduction may be induced by overdoses of chloroquine and class I antiarrhythmic drugs. Signs of gravity are: ingested dose above 4 g, QRS > or = 0.12 s or systolic arterial pressure < or = 80 mmHg. Treatment with epinephrine, respiratory assistance and diazepam has been proven effective during the acute phase, but right catheterism is often required due to major haemodynamic instability during the first 72 first hours. Beta-blockers have both a bronchoconstrictor and respiratory depressor effects favouring cardiovascular failure by hypoemia. Symptoms occur in 30-40% of the cases of overdose. Shock results from the reduction in blood pressure and cardiac inotropism. Glucagon, isoprenaline and epinephrine, prescribed in that order, can considerably reduce mortality to less than 4%. Despite the development of specific molecules, the risk of mortality due to toxic shock caused by antiarrhythmics, chloroquine, colchicine, calcium inhibitors and paraquat remains high.

Cardiotonic Agents↗
PubMed1993

Clinical features and management of digitalis poisoning--rationale for immunotherapy.

The intensity of gastrointestinal and visual symptoms together with hyperkalemia and the characteristic ECG features make diagnosis of acute digitalis intoxication relatively easy. Death results mainly from ventricular fibrillation or from ventricular asystole or pump failure. Mesenteric infarct may also occur in elderly patients. Previous assessment of outcome has shown that mortality increases in patients exhibiting five prognostic factors: 1) advanced age; 2) heart disease; 3) male sex; 4) high-degree atrioventricular block; 5) hyperkalemia. Conventional treatment includes gastric lavage, activated charcoal and supportive care. First-line antiarrhythmic therapy is usually atropine, because of bradycardia-induced arrhythmia. Ventricular pacing is a toxicodynamic treatment that may be helpful in both bradycardia-induced arrhythmia and high-degree atrioventricular block. Pacing is difficult to handle and can result in serious adverse effects. Immunotherapy has two advantages. First, a strong toxicodynamic effect due to quick reversal of digitalis-induced dysrhythmias, hyperkalemia, and myocardial depression, by reactivation of membrane ATPases. Second, a toxicokinetic effect due to accelerated renal excretion of Fab-digitalis complexes. Since this therapy is well tolerated and efficient, we recommend early administration of Fab fragments as soon as poor prognostic factors are identified.

Animals↗
PubMed1993

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.

Adult↗
PubMed1993

Pathophysiology and management of self-poisoning with beta-blockers.

The prognosis of self-poisoning with beta-blockers is excellent, especially if medical management is started immediately but the wide variety of clinical symptoms and proposed treatments complicate the therapeutic strategy. Beta-blockers that are liposoluble or have marked anti-arrhythmic activity are more lethal (e.g. propranolol, sotalol). Similarly, pre-existing cardiac pathology or co-ingestion of psychotropic or cardioactive drugs increases mortality. The first-line symptomatic treatment is administration of atropine and volume-expanding fluids to treat bradycardia and hypotension, respectively. However atropine is often unsuccessful in reversing beta-blocker-induced bradycardia and repeated doses can provoke atropine poisoning. If symptomatic treatment fails, then antidotes should be administered in a precise order: first, high doses of glucagon, followed by isoproterenol, epinephrine, and the new inhibitors of phosphodiesterases. Mechanical ventilation should be started at the same time as pharmacological treatment in cases of severe collapse or prolonged QRS.

Adrenergic beta-Antagonists↗
PubMed1992

Pre-hospital strategy for therapeutic intervention of fire victims.

Fire victims are exposed to the triple threat of thermal injury (skin and lungs), smoke toxicity (toxic or irritant gases and soots) and even trauma whose occurrences are somewhat independent one from the other but whose addition does sharply increase the probability of death of the victims. As the different victims of the same fire may not suffer from the same injuries, this triple threat must be looked for in each fire victim.

Burns↗
PubMed1992

Toxicokinetics of colchicine in humans: analysis of tissue, plasma and urine data in ten cases.

1. A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2. Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 13 l h-1 and three-fold less than total body clearance (39 l h-1). The apparent volume of distribution was 21 l kg-1. 3. Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g-1); it was also found in the brain (125 ng g-1). 4. This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occurring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

Adolescent↗
PubMed1992

[Do antidotes have a future? The example of 4-methylpyrazole and hydroxocobalamin].

In all probability the future progress in the "molecular" approach of therapy in acute poisoning within the next 20 years or so will be more rapid than the "mechanistic" approach, which undoubtedly has brought considerable improvements in the overall survival of these patients in the past. Principally molecular antidotes can act on three different levels, a) prior to the cellular targets (e.g. through modifications of toxokinetics), b) at specific cellular receptors through competition for binding (e.g. naloxone and flumazenil), and c) after the receptor sites through unspecific counteraction of toxic effects (e.g. betablockers for intoxications with theophylline). Immune-antidotes act prior to cellular receptors. Examples are the digoxin antibodies and the anti-venoms as well as the very recently developed and not yet clinically tested antibodies against antidepressive drugs and against colchicine. Two newer antidotes, the 4-methylpyrazole and the hydroxocobalamin, act also prior the cellular targets of the corresponding toxic compounds. Thus, 4-Methylpyrazole decreases the degradation of ethylene-glycol by inhibiting alcohol dehydrogenase, which results in a higher excretion of unchanged ethylene-glycol in urine. Hydroxycobalamin complexes with cyanides to form the physiologic vitamin B12. In order to allow an equimolar neutralization of ingested cyanides a concentrated preparation containing 5 g of hydroxycobalamin was developed, the pharmacokinetic properties of which are discussed.

Antidotes↗
PubMed1991

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 patient's hospital admission, an elevated plasma lactate concentration is a useful indicator of cyanide toxicity in fire victims who do not have severe burns.

Adolescent↗
PubMed1991

Relationship between red blood cell potassium and plasma digitoxin concentrations in intoxicated patients.

After severe acute self-poisoning by cardiac glycosides, significant and persistent depletion of red blood cell K+ due to inhibition of Na+K+ ATPase is seen. Because of a delay between the time course of plasma digitalis concentrations and that of red blood cell K+ depletion, no direct relation exists between the two, and RBC K+ has hitherto not been considered useful as prognostic indicators of clinical outcome. In an effort to solve this problem, red blood cell K+ was measured by atomic absorption spectrophotometry and plasma digitoxin concentration assayed in six patients admitted to an intensive care unit after digitoxin self-poisoning. Using the effect compartment model of Sheiner, a relationship based on a sigmoid Emax model was able to relate the digitoxin concentration at the action site to red blood cell K+ depletion. Thus the duration of red blood cell K+ depletion could be predicted from two relative simple in vitro assays. Since RBC K+ is a marker of the inhibition of Na+K+ ATPase by digitoxin, this method could be of use for the management of patients self-poisoned with digitalis.

Adult↗
PubMed1990

Biological valuation of extra-corporeal techniques in acute poisoning.

The efficiency of dialysis methods a/o hemoperfusion in acute poisoning cannot be clinically estimated, because: a) Concomitant intestinal absorption, hepatic metabolism and urinary excretion must be taken into account. b) With supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of these methods can only be estimated biologically. Measuring the blood level at the beginning and the end of the treatment as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (from hourly differences of arteriovenous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge or measures in dialysis fluid. Plasma kinetics under dialysis a/o hemoperfusion should be compared with spontaneous toxicokinetic of the substance and not with pharmacokinetic data. The experience of toxicologists has shown dialysis a/o hemoperfusion to be ineffective for drugs with weak extra-cellular distribution (such as Digoxine, Tricyclic drugs, heavy Metals, Colchicine). In the case of intoxication with Paraquat or Paracetamol, there is a negative correlation between the amount of removed intoxicant and the survival: death is likely to occur when the procedure has been very productive. In the case of intoxication by hypnotic drugs, one hemodialysis a/o hemoperfusion allows the removal of an average of 4-12% of the ingested barbiturates, 7-17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life-saving of insignificant is largely a matter of personal standards.

Hemoperfusion↗
PubMed1990

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 (t1/2 alpha) of 5 h and a mean elimination half-life (t1/2 beta) 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.

Adult↗
PubMed1990

The cocaine body-packer syndrome: evaluation of a method of contrast study of the bowel.

The questionable reliability of the conventional procedures for detection of ingested drug packages triggered us to evaluate the accuracy of a method of contrast study of the bowel in 23 nonsurgically managed cocaine body-packers. A single dose (60 mL) of a water-soluble contrast compound (amidotrizoate + meglumine) was given orally after initial clinical examination and drug detection in urine. Thereafter, roentgenograms were performed daily after spontaneous passage until obtaining two packet-free stools and negative views. Roentgenograms showed packages when performed at least 3 h after the ingestion of the contrast compound. Sensitivity and specificity of the method with respect to the detection of residual packets in the body, assessed by subsequent examination of stools, was good and did not diminish as the number of packages decreased during the time spent in ward. No side-effects were observed. We conclude that oral administration of a water-soluble contrast compound is an easily performed, efficient, and safe method for the nonsurgical management of cocaine body-packers.

Cocaine↗