sodium-nitrite and sodium-thiosulfate

Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies.. We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities.. We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients.. Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.

Topics: Adult; Aged; Antidotes; Female; Humans; Hypotension; Male; Middle Aged; Occupational Exposure; Poisoning; Sodium Azide; Sodium Nitrite; Suicide, Attempted; Thiosulfates

Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and, if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents (e.g., nitrites, dimethylaminophenol) or hydroxocobalamin (Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca (DTPA) or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca (DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany.

Topics: Antidotes; Carbon Monoxide; China; Germany; Humans; Hydrogen Cyanide; Hydroxocobalamin; Hyperbaric Oxygenation; Inhalation Exposure; Radiation Exposure; Radiography; Radioisotopes; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates

The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present.

Topics: Adenosine; Amyl Nitrite; Burns; Chelating Agents; Cyanides; Edetic Acid; Humans; Hydroxocobalamin; Hyperbaric Oxygenation; Oxygen Inhalation Therapy; Poisoning; Pteridines; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates

Topics: Amyl Nitrite; Antidotes; Cyanides; Humans; Hydroxocobalamin; Monitoring, Physiologic; Severity of Illness Index; Sodium Nitrite; Thiosulfates

Topics: Acute Disease; Adult; Aftercare; Amyl Nitrite; Antidotes; Cyanides; Decontamination; Emergency Medical Services; Emergency Nursing; Emergency Treatment; Humans; Hydroxocobalamin; Life Support Care; Male; Nurse's Role; Parkinsonian Disorders; Poisoning; Sodium Nitrite; Suicide, Attempted; Thiosulfates; Triage

The combination of sodium thiosulfate and sodium nitrite has been used in the United States since the 1930s as the primary antidote for cyanide intoxication. Although this combination was shown to exhibit much greater efficacy than either ingredient alone, the two compounds could not be used prophylactically because each exhibits a number of side effects. This review discusses the pharmacodynamics, pharmacokinetics, and toxicology of the individual agents, and their combination.

Topics: Animals; Antidotes; Biological Availability; Cyanides; Drug Therapy, Combination; Humans; Poisoning; Sodium Nitrite; Thiosulfates

The mechanism of cyanide intoxication has been attributed to the inhibition of cytochrome oxidase, thereby decreasing the tissue utilization of oxygen. One mechanism of cyanide antagonism is by sequestering cyanide with methaemoglobin to form cyanmethaemoglobin and another mechanism is detoxifying with a sulphur donor to thiocyanate. Questions have been raised with regard to these classical mechanisms. Oxygen with nitrite-thiosulphate antagonizes the lethal effects of cyanide. Theoretically, increased oxygen should serve no useful purpose, as it is the tissue utilization of oxygen which is inhibited. In the nitrite-thiosulphate antidotal combination, the proposal is made that the predominate antidotal action of nitrite is a vasogenic action, rather than methaemoglobin formation, because when methaemoglobin formation is inhibited by methylene blue the protective action of sodium nitrite persists. This suggests that methaemoglobin formation plays only a small part, if any, in the therapeutic antagonism of the lethal effects of cyanide. The roles and implications of sodium thiosulphate and non-rhodanese substrates in the detoxification mechanism are compared. Lastly, a new approach to cyanide antagonism has been initiated which involves the erythrocyte encapsulation of thiosulphate and sulphurtransferase as an antidote and prophylaxis against cyanide.

Topics: Animals; Antidotes; Biotransformation; Cobalt; Cyanides; Humans; Methemoglobin; Sodium Nitrite; Thiosulfates

To determine whether sodium thiosulfate (STS) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in an in-vitro model.. This was an in-vitro, controlled study where methemoglobinemia was induced by the addition of sodium nitrite (0.4 mg/mL) to 35-mL aliquots of blood obtained from ten healthy volunteers. Methemoglobin (MetHb) concentrations were measured at 5-minute intervals for 30 minutes by co-oximetry, and each aliquot was then subdivided into six 5-mL samples (time zero). Sample 1 served as control. The remaining samples received serial dilutions of STS (0.125 mg, 1.25 mg, 12.5 mg, 125 mg, 1,250 mg). MetHb concentrations were measured by co-oximetry at baseline, 0, 15, 30, 45, and 60 minutes. Areas under the MetHb concentration-time curve (AUC) between time zero and 60 minutes were compared using the Kruskal-Wallis test.. Methemoglobin concentrations increased from 0.07 g/dL (+/-0.06) at baseline to 8.42 g/dL (+/-0.69) at time 0 (the addition of STS). No significant difference was detected between baseline and time 0 hemoglobin concentrations (15.8 +/- 0.5 vs. 16.1 +/- 0.6 g/dL). There was no detectable difference found between the AUCs (measured in g min/dL) of any of the STS serial dilutions or control groups (0.125 mg STS = 576.01 +/- 42.53; 1.25 mg STS = 573.47 +/- 40.82; 12.5 mg STS = 583.68 +/- 42.29; 125 mg STS = 554.75 +/- 42.68; 1,250 mg STS = 566.95 +/- 38.08; p = 0.81).. Sodium thiosulfate was not found to be an effective reducing agent for the acute treatment of methemoglobinemia.

Topics: Antioxidants; Area Under Curve; Humans; In Vitro Techniques; Methemoglobinemia; Prospective Studies; Sodium Nitrite; Thiosulfates

This study was aimed to compare the efficacy of aqueous garlic extract, sodium nitrite (SNT), sodium thiosulfate (STS) and hydroxocobalamin against oral cyanide exposure in rabbits. For this purpose, forty two adult male rabbits were divided randomly into 7 groups of 6 animals (A-G) each. Rabbits in group A were offered feed only and served as negative control, while the rabbits in group B received feed plus potassium cyanide (KCN) at 3mg/kg orally and were kept as positive control. Animals in group C received feed, KCN and intraperitoneal injection (IP) of aqueous garlic extract at 500mg/kg. Rabbits in group D were given feed, KCN and IP injection of STS at 600mg/kg. Members in group E received feed, KCN and IP injection of both aqueous garlic extract at 500mg/kg and SNT at 20mg/kg. Animals in group F were given feed, KCN and IP injection of both STS at 600mg/kg and SNT at 20mg/kg, while the rabbits in group G received feed, KCN and IP injection of hydroxocobalamin at 300mg/kg. The treatments were given to respective groups for 40 days. The efficacy of the antidotes was measured on the basis of changes in biochemical profile of rabbits in each group. In this study, hydroxocobalamin was found to be significantly more effective cyanide (CNI) antidote than garlic, STS, SNT plus garlic extract, or SNT and STS, either alone or in combination. A combination of SNT and garlic extract was the second most effective CNI antidote. The efficacy of garlic alone was significantly higher than STS alone or in combination with SNT. The efficacy of combined SNT and STS was superior to STS alone in treating rabbits with CNI toxicity. In conclusion, aqueous garlic extract alone or in combination with STS can effectively be used against cyanide toxicity.

Topics: Administration, Oral; Alanine Transaminase; Alkaline Phosphatase; Animals; Antidotes; Aspartate Aminotransferases; Bilirubin; Creatinine; Garlic; Hydroxocobalamin; Plant Extracts; Potassium Cyanide; Rabbits; Serum Albumin; Sodium Nitrite; Thiosulfates; Thyroid Hormones

The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection.. We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy.. We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P<.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution-treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]).. We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care.

Topics: Animals; Antidotes; Cyanides; Disease Models, Animal; Injections, Intramuscular; Male; Mice; Rabbits; Random Allocation; Sodium Nitrite; Sus scrofa; Thiosulfates

Currently available cyanide antidotes must be given by intravenous injection over 5-10 min, making them ill-suited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramuscular injection. Here we show that adding sodium nitrite to cobinamide yields a stable derivative (referred to as nitrocobinamide) that rescues cyanide-poisoned mice and rabbits when given by intramuscular injection. We also show that the efficacy of nitrocobinamide is markedly enhanced by coadministering sodium thiosulfate (reducing the total injected volume), and we calculate that ∼1.4 mL each of nitrocobinamide and sodium thiosulfate should rescue a human from a lethal cyanide exposure.

Topics: Animals; Antidotes; Chlorocebus aethiops; Cobamides; COS Cells; Cyanides; Dose-Response Relationship, Drug; Injections, Intramuscular; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Rabbits; Sodium Nitrite; Structure-Activity Relationship; Thiosulfates; Time Factors

Sodium nitrite alone is shown to ameliorate sublethal cyanide toxicity in mice when given from ∼1 h before until 20 min after the toxic dose as demonstrated by the recovery of righting ability. An optimum dose (12 mg/kg) was determined to significantly relieve cyanide toxicity (5.0 mg/kg) when administered to mice intraperitoneally. Nitrite so administered was shown to rapidly produce NO in the bloodsteam as judged by the dose-dependent appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. It is argued that antagonism of cyanide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity rather than the methemoglobin-forming action of nitrite. Concomitant addition of sodium thiosulfate to nitrite-treated blood resulted in the detection of sulfidomethemoblobin by EPR spectroscopy. Sulfide is a product of thiosulfate hydrolysis and, like cyanide, is known to be a potent inhibitor of cytochrome c oxidase, the effects of the two inhibitors being essentially additive under standard assay conditions rather than dominated by either one. The findings afford a plausible explanation for an observed detrimental effect in mice associated with the use of the standard nitrite-thiosulfate combination therapy at sublethal levels of cyanide intoxication.

Topics: Animals; Antidotes; Cyanides; Electron Spin Resonance Spectroscopy; Electron Transport Complex IV; Hemoglobins; Humans; Injections, Intraperitoneal; Male; Methemoglobin; Mice; Nitric Oxide; Sodium Nitrite; Thiosulfates

Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate.. Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance.. Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar.. Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.

Topics: Acidosis; Animals; Antidotes; Blood Pressure; Cyanides; Disease Models, Animal; Drug Therapy, Combination; Female; Hydroxocobalamin; Hypotension; Lactates; Male; Monitoring, Physiologic; Sodium Nitrite; Sus scrofa; Thiosulfates; Time Factors

Topics: Animals; Cyanides; Drug Therapy, Combination; Humans; Hydroxocobalamin; Sodium Nitrite; Thiosulfates

Topics: Antidotes; Child, Preschool; China; Glasgow Coma Scale; Humans; Hydroxocobalamin; Male; Potassium Cyanide; Sodium Nitrite; Thiosulfates; Toes; Urinalysis

A case of poisoning with a Cotoneaster sp. is described in a llama (Lama glama). The clinical signs were dyspnea, with congested mucous membranes, chewing, recumbency, and opisthotonos. Several hours after ingestion of the plant, the llama died, despite treatment with sodium thiosulfate and nitrite. Necropsy revealed approximately 676 g of leaves and fruit of Cotoneaster in the first compartment of the stomach. The blood was light red and did not clot. Because Cotoneaster sp. contains low concentrations of cyanogenic glycosides, toxicosis occurs only following massive ingestion of plant material.

Topics: Animals; Antidotes; Camelids, New World; Dyspnea; Fatal Outcome; Poisoning; Rosaceae; Sodium Nitrite; Thiosulfates

Cyanide is a highly toxic cellular poison that requires immediate and aggressive treatments. Combination of sodium nitrite (SN) and sodium thiosulfate (STS) is the treatment of choice but oral treatment of alpha-ketoglutarate (A-KG) has also been shown to significantly antagonize cyanide poisoning in laboratory animals. This study reports the efficacy of various treatment regimens as: (i) repeated doses of A-KG after simultaneous treatment of A-KG and STS, (ii) repeated doses of A-KG after pre-treatment of SN, STS and A-KG, (iii) repeated doses of STS after pre-treatment of SN, STS and A-KG, and (iv) repeated doses of A-KG and STS after pretreatment of SN, STS and A-KG on mortality of female rats exposed to massive doses of potassium cyanide. A maximum of 40-folds protection was observed when A-KG at 1.0 g kg(-1) after 2 hr and 0.5 g kg(-1) after 4 hr was repeated following the pre-treatment of SN (0.025 g kg(-1); subcutaneous;-45 min), STS (1.0 g kg(-1); intraperitoneal; -15 min) andA-KG (2.0 g kg(-1); oral; -10 min). Similar protection was also conferred by repeating 0.5 g kg(-1) each of A-KG and STS 2 hr after pre-treatment of SN, STS and A-KG. Also, 38-folds protection after simultaneous administration of 20 g kg(-1) A-KG and 1.0 g kg(-1) STS, followed by 2.0 g kg(-1) A-KG after 2 hr was noteworthy The results indicate that repeated treatment of A-KG alone after simultaneous treatment of A-KG and STS or repeated treatment of A-KG alone or with STS after pre-treatment of A-KG, SN and STS have immense potential in challenging extremely high doses of cyanide as compared to the antidotes given once. The study has implications in the development of A-KG as an alternate treatment for cyanide poisoning.

Topics: Animals; Female; Ketoglutaric Acids; Poisons; Potassium Cyanide; Protective Agents; Rats; Rats, Wistar; Sodium Nitrite; Thiosulfates

Sodium azide poisonings occur very rarely. The mechanism of sodium azide toxic effect has not yet been fully explained. Despite the lack of an explicit procedure for the cases of sodium azide poisonings, in vitro tests and rare case reports suggest that treatment with antidotes for cyanide poisoning victims can be effective. This study describes two cases of suicidal sodium azide ingestion. Case 1. 30-year-old male ingested ca. 180 mg of sodium azide. On admission to hospital, within 4 hours from poisoning, the man complained of dizziness and anxiety. Physical examination revealed horizontal nystagmus, flapping tremor, HR 135/min. In laboratory tests, higher blood concentration of lactates (3 mmol/l) was detected, as well as lower potassium concentration (3.4 mmol/L) and increased transaminase activity (ALT 74 U/l, AST 90 U/l). Electrocardiographic tests showed a negative T wave in limb lead III. Other results were within normal. As the patient ingested a toxic dose of sodium azide, he was treated according to the therapy prescription for cyanide poisoning (amyl nitrite inhalation followed by intravenous administration of sodium nitrite and sodium thiosulphate). ECG record of the last day of hospitalization (7th day of treatment) showed negative T waves in lead III, V4-V6. He was discharged from hospital in good condition. Case 2.23-year-old male ingested 10 g of sodium azide 1.5 hours prior to admission to hospital. At the beginning, the patient's condition was good, but it changed to critical state within the first hours of hospitalization. He developed a deep coma, respiratory and circulatory insufficiency, metabolic acidosis, cardiac dysrrhythmias and anuria. Cardiac activity monitoring showed alternating tachycardia (140 beats per minute) and bradycardia (48 beats per minute), numerous additional supraventricular and ventricular extrasystoles and sinus dysrrhythmia. Cardiac arrest (asystolia) occurred twice, the second incident with fatal outcome. The patient received supportive therapy, he was also treated according to the therapy prescription for cyanide poisoning. Circulatory disturbances observed in both cases have been described in literature as symptoms of sodium azide poisoning. However, available literature data are scarce and lack systematization, most of them coming from several decades ago. The lack of patient's consent for detailed examination of circulatory system and liver made it impossible to gather further knowledge on the subject. T

Topics: Adult; Antidotes; Arrhythmias, Cardiac; Bradycardia; Clinical Protocols; Dose-Response Relationship, Drug; Electrocardiography; Fatal Outcome; Heart Arrest; Humans; Hydroxocobalamin; Hypokalemia; Lactates; Male; Monitoring, Physiologic; Nitrates; Pentanols; Poisoning; Sodium Azide; Sodium Nitrite; Suicide, Attempted; Thiosulfates; Transaminases; Treatment Outcome

Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD(50) for cyanide elicited by the antidotes. This required the use of high doses of cyanide following pre-treatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD(50) determinations: we developed a new test paradigm that allowed for maximal survival of cyanide-treated animals with greatly reduced numbers of animals. Symptoms of cyanide toxicity include disruption of neuromuscular coordination, i.e., the righting reflex. Therefore, to establish a dose-response curve, the times required for recovery of this righting reflex with increasing doses of cyanide were measured. A cyanide dose that disrupted this righting reflex for approximately 1h with minimal deaths was then selected. Using this paradigm, the current cyanide antidotes, viz., nitrite plus thiosulfate and hydroxocobalamin, as well as some potential cyanide antidotes that we developed, were evaluated pre- and post-cyanide. This allowed, for the first time, the assessment of the post-cyanide effectiveness of the current antidotes against cyanide poisoning in a live animal. In addition, some prototype compounds were found to exhibit antidotal efficacy not only when injected i.p. following cyanide, but also when administered orally 30 min before cyanide. Pre-cyanide oral efficacy suggests that such compounds have the potential of being administered prophylactically before exposure to cyanide. This new test paradigm was found to be a powerful tool for assessing the efficacies of some novel antidotes against cyanide and should be equally applicable for evaluating putative antidotes for other neurotoxins.

Topics: Animals; Antidotes; Drug Therapy, Combination; Hydroxocobalamin; Male; Mice; Neurotoxins; Reflex; Sodium Cyanide; Sodium Nitrite; Thiosulfates; Treatment Outcome

An 80-year-old diabetic patient was admitted to the hospital because of sudden unconsciousness and severe metabolic acidosis. His son reported the possibility of cyanide poisoning. Clinical data and the detection of cyanide in blood and gastric material confirmed this possibility. Supportive therapy and the following antidotes--sodium nitrite two doses 300 mg i.v., sodium thiosulfate 3 g i.v., and hydroxocobalamin 4 g in 24 hours--were administered immediately and the patient completely recovered in 48 hours. Our observations suggest that timely and appropriate use of antidotes for cyanide intoxication may prevent death, even in aged diabetic patients.

Topics: Acidosis; Aged; Aged, 80 and over; Antidotes; Cyanides; Hematinics; Humans; Hydroxocobalamin; Indicators and Reagents; Male; Sodium Nitrite; Thiosulfates; Treatment Outcome

A case of attempted homicide by cyanide ingestion is reported. The victim, a 19-year-old woman, unknowingly ingested cyanide and presented to the Emergency Department unresponsive, in shock, and in profound metabolic acidosis. The differential diagnosis of this presentation and the patient's successful treatment are reviewed. The important management issues surrounding the treatment of cyanide poisoning are discussed.

Topics: Acidosis; Acute Disease; Adult; Antidotes; Cyanides; Diagnosis, Differential; Electrocardiography; Emergency Treatment; Female; Fluid Therapy; Homicide; Humans; Respiration, Artificial; Shock; Sodium Nitrite; Spouse Abuse; Thiosulfates

Topics: Amyl Nitrite; Antidotes; Cyanides; Decontamination; Emergency Medical Services; Humans; Poisoning; Protective Clothing; Sodium Nitrite; Thiosulfates; Triage; United States; Violence

A 41-year-old woman ingested apricot kernels purchased at a health food store and became weak and dyspneic within 20 minutes. The patient was comatose and hypothermic on presentation but responded promptly to antidotal therapy for cyanide poisoning. She was later treated with a continuous thiosulfate infusion for persistent metabolic acidosis. This is the first reported case of cyanide toxicity from apricot kernel ingestion in the United States since 1979.

Topics: Acidosis; Acute Disease; Adult; Antidotes; Emergency Treatment; Female; Food, Organic; Fruit; Humans; Hydrogen Cyanide; Poisoning; Poisons; Seeds; Sodium Nitrite; Thiosulfates

Acetonitrile (methyl cyanide) is a common industrial organic solvent but is a rare cause of poisoning. We report the first recorded UK case. Acetonitrile is slowly converted to cyanide, resulting in delayed toxicity. We describe a case of deliberate self-poisoning by a 39-year-old woman resulting in cyanide poisoning 11 hours later which was successfully treated by repeated boluses of sodium nitrite and thiosulphate. The half-life of conversion of acetonitrile was 40 hours and harmful blood cyanide levels persisted for over 24 hours after ingestion. Departments treating or advising in cases of poisoning need to be aware of the delayed toxicity of acetonitrile. Monitoring in an intensive care unit of cases of acetonitrile poisoning should continue for 24-48 hours.

Topics: Acetonitriles; Adult; Antidotes; Cyanides; Female; Humans; Poisoning; Sodium Nitrite; Suicide, Attempted; Thiosulfates; Time Factors

Potassium cyanide (CN) intoxication in mice was found to be effectively antagonized by dihydroxyacetone (DHA), particularly if administered in combination with another CN antidote, sodium thiosulfate. Cyanide-induced convulsions were also prevented by DHA treatment, either alone or in combination with thiosulfate. Injection (i.p.) of DHA (2 g/kg) 2 min after or 10 min before CN (s.c.) increased LD50 values of CN(8.7 mg/kg) by factors of 2.1 and 3.0, respectively. Treatment with a combination of DHA and thiosulfate after CN increased the LD50 by a factor of 2.4. Pretreatment with a combination of DHA and thiosulfate (1 g/kg) increased the LD50 of CN to 83 mg/kg. Administration of alpha-ketoglutarate (2.0 g/kg), but not pyruvate, 2 min after CN increased the LD50 of CN by a factor of 1.6. Brain, heart and liver cytochrome oxidase activities were also measured following in vivo CN treatment with and without DHA. Pretreatment with DHA prevented the inhibition of cytochrome oxidase activity by CN and treatment with DHA after CN accelerated the recovery of cytochrome oxidase activity, especially in brain and heart homogenates. DHA is a physiological agent and, therefore, could prove to be a safe and effective antidote for CN, particularly in cases of fire smoke inhalation in which a combination of CN and carbon monoxide is present. In these cases the normally used antidote, sodium nitrite, to induce methemoglobin so as to trap the CN, is contraindicated because some of the oxygen-carrying capacity of the blood will have already been diminished by carbon monoxide.

Topics: Animals; Antidotes; Brain; Dihydroxyacetone; Electron Transport Complex IV; Ketoglutaric Acids; Lethal Dose 50; Liver; Male; Mice; Myocardium; Potassium Cyanide; Pyruvates; Pyruvic Acid; Sodium Nitrite; Thiosulfates

Thirty-seven employees were exposed to cyanide between 1956 and 1985. One was found dead. Thirty-six employees were treated; most were given nitrite and oxygen. Some received oxygen alone. All recovered completely. One-third of these employees were unconscious. One was convulsing. Most were discharged home at 6 h post-exposure. Some employees remained at the plant to work an additional shift. Amyl nitrite and/or oxygen were the only agents used with 33 employees. Forced oxygen was administered to the unconscious, apneic employees. Three employees were given sodium nitrite and sodium thiosulfate iv. Treatment generally began within 3 min. In 5 to 20 min all of the unconscious employees reacted positively to the use of forced oxygen and forced amyl nitrite or sodium nitrite. There were no residual effects except headache and transient loss of appetite. Amyl nitrite and oxygen have been effective tools in the treatment of cyanide intoxication at this plant site. There have been no intercurrent or residual drug effects that outweigh the life-saving capacity of these agents. Sodium nitrite should be employed if the use of oxygen and amyl nitrite fail to improve the cardiovascular status/level of consciousness in 5-10 min.

Topics: Amyl Nitrite; Antidotes; Cohort Studies; Cyanides; Hemoglobins; Humans; Methemoglobin; Occupational Exposure; Occupational Health; Oxygen Inhalation Therapy; Poisoning; Sodium Nitrite; Thiosulfates

Topics: 4-Aminopyridine; Antidotes; Humans; Hyperbaric Oxygenation; Nitriles; Occupational Exposure; Poisoning; Sodium Nitrite; Thiosulfates

Murine carrier erythrocytes containing bovine rhodanese and sodium thiosulfate are being explored as a new approach to antagonize the lethal effects of potassium cyanide in mice. Prior studies indicated that these carrier erythrocytes persist in the vascular system for the same length of time as normal erythrocytes and can enhance metabolism of cyanide to thiocyanate. The present studies demonstrate the ability of these carrier red blood cells containing rhodanese and thiosulfate to antagonize the lethal effects of cyanide either alone or in various combinations with sodium nitrite and/or sodium thiosulfate. Potency ratios are compared in groups of mice treated with sodium nitrite, sodium thiosulfate, and carrier erythrocytes containing rhodanese and sodium thiosulfate either alone or in various combinations prior to the administration of potassium cyanide. These results indicate that the administration of carrier erythrocytes containing rhodanese and thiosulfate alone can provide significant protection against the lethal effects of cyanide. These carrier erythrocytes potentiate the antidotal effect of sodium thiosulfate alone or the combination of sodium nitrite and sodium thiosulfate. The mechanisms of cyanide antagonism by these carrier erythrocytes and their broader conceptual significance to the antagonism of other chemical toxicants are discussed.

Topics: Animals; Antidotes; Cattle; Dose-Response Relationship, Drug; Drug Carriers; Drug Therapy, Combination; Erythrocytes; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Potassium Cyanide; Sodium Nitrite; Thiosulfate Sulfurtransferase; Thiosulfates

Propionitrile, a substituted aliphatic nitrile commonly used in the chemical manufacturing industry, is capable of generating cyanide. However, there are few reports of human intoxication involving propionitrile. We report two workers at an organic chemical manufacturing plant who were overcome by fumes while treating a waste slurry into which unreacted propionitrile was discharged by mistake. One victim was comatose, acidotic, and hypotensive; his blood cyanide level was later measured at 5.0 micrograms/ml. He responded to sodium nitrite/sodium thiosulfate therapy by regaining consciousness. Continued symptoms were treated with hyperbaric oxygen at 2 atmospheres for a total of 4 hours. The second victim, who complained only of nausea, dizziness, and headache and who never lost consciousness, was treated with sodium nitrite/sodium thiosulfate. His measured blood cyanide concentration was 3.5 micrograms/ml. The ambient concentration of propionitrile in air samples at the work site shortly after the exposure was 77.5 mg/m3. In occupational situations in which workers exhibit rapidly progressive symptoms of headache, dizziness, collapse, and coma, and where substituted nitriles are known to be on site, acute cyanide poisoning should be strongly considered. Because of continued endogenous generation of cyanide from the metabolism of the parent compound, hyperbaric oxygen may be a valuable adjunctive therapy to consider, in addition to the immediate use of the cyanide antidote kit, in cases of poisoning by propionitrile or other substituted nitrile compounds. We urge the Occupational Safety and Health Administration to adopt workplace standards for the maximum ambient air concentrations for propionitrile.

Topics: Adult; Antidotes; Coma; Combined Modality Therapy; Humans; Hyperbaric Oxygenation; Male; Neurologic Examination; Nitriles; Occupational Diseases; Respiratory Insufficiency; Sodium Nitrite; Thiosulfates

To evaluate serial cyanide, methemoglobin, and carbon monoxide levels in smoke inhalation patients.. Regional poison center and regional toxicology treatment center.. Seven critically ill smoke inhalation patients referred to the regional poison center.. Peak level and half-life were determined by obtaining serial carboxyhemoglobin, cyanide, and methemoglobin levels.. The mean observed half-life of cyanide was 3.0 +/- 0.6 hours. Methemoglobinemia was evaluated in four patients after sodium nitrite administration. The peak measured methemoglobin levels (mean, 10.5% +/- 2%; range, 7.9% to 13.4%) did not occur until a mean of 50 minutes (range, 35 to 70 minutes) following administration of sodium nitrite. The total oxygen-carrying capacity reduced by the combination of carboxyhemoglobin and methemoglobin was never more than 21% (range, 10% to 21%) in this series.. The administration of sodium nitrite to smoke inhalation patients in the presence of concomitant carbon monoxide poisoning may be relatively safe.

Topics: Adult; Antidotes; Carbon Monoxide Poisoning; Carboxyhemoglobin; Combined Modality Therapy; Cyanides; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Hyperbaric Oxygenation; Infusions, Intravenous; Male; Methemoglobin; Methemoglobinemia; Middle Aged; Poison Control Centers; Poisoning; Prospective Studies; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates; Time Factors

A new concept has been presented for the antagonism of cyanide and possibly other chemical toxicants. Until now, only a half dozen truly specific "antidotes" were known. There are many other "antidotes" which merely prevent the absorption or enhance the elimination of a toxic compound rather than specifically destroying the substance to prevent its toxic effect. This new approach has considerable conceptual significance in toxicology, as it suggests the encapsulating other enzymes to degrade various other chemical toxicants. There are many chemical toxicants for which there are no specific antidotes, and the conceptual approach of employing erythrocyte-encapsulated enzyme provides an innovative, specific approach to antagonize the toxic and lethal effects of these chemicals.

Topics: Animals; Drug Carriers; Erythrocyte Membrane; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Potassium Cyanide; Sodium Nitrite; Thiosulfate Sulfurtransferase; Thiosulfates

The in vivo effects of sodium cyanide and its antidotes, sodium nitrite, sodium thiosulfate and 4-dimethylaminophenol (DMAP), as well as the alpha-adrenergic blocking agent phentolamine, on rat brain cytochrome oxidase were studied. The course of inhibition was time-dependent and a peak of 40% was attained between 15 and 20 min after the s.c. injection of 1.3 LD50 (12 mg/kg) of cyanide. Pronounced dose-dependence was observed in the inhibition of the enzyme, at this relatively low, but lethal dose. Further observation was impossible because of rapidly lethal effects of cyanide. In animals artificially ventilated with room air, observation was possible up to 60 min. However, maximum inhibition was also 40%. When antidotes were applied 30 min after 20 mg/kg of cyanide, marked reactivation of cytochrome oxidase activity was observed with all antidotes (particularly with thiosulfate) except for phentolamine which had no effect. Prevention of methemoglobin forming with toluidine blue did not affect the reactivating ability of nitrite or DMAP, thus suggesting more complex protective mechanisms then simple methemoglobin formation. The high efficacy of thiosulfate may be attributed to its rhodanese catalyzed, direct binding to free blood cyanide, leading thus to its dissociation from cytochrome oxidase. The theory that cytochrome oxidase inhibition is a basic mechanism of cyanide toxicity could not be disproved.

Topics: Aminophenols; Animals; Antidotes; Brain; Electron Transport Complex IV; Male; Phentolamine; Rats; Rats, Wistar; Sodium Cyanide; Sodium Nitrite; Thiosulfates

Topics: Administration, Inhalation; Amyl Nitrite; Antidotes; Cyanides; Humans; Infusions, Intravenous; Nitroprusside; Poisoning; Sodium Nitrite; Thiosulfates

Cyanide poisoning is a life threatening condition. But specific antidotes exist and can be easily prepared from available substances in hospital. Administration of antidotes will produce methemoglobin, which itself causes hypoxia. Nitrite induced methemoglobin can be extremely dangerous and even lethal. Before administering the antidotes, the diagnosis should be confirmed. Nitrite should not be given if the poisoning is mild or diagnosis is uncertain, to avoid excessive methemoglobin, dosage of sodium nitrite must be adjusted according to hemoglobin level (Table 1). Usage of sodium nitrite and sodium thiosulfate in the recommended doses are safe and effective for cyanide poisoning.

Topics: Acute Disease; Adult; Antidotes; Humans; Male; Methemoglobinemia; Poisoning; Potassium Cyanide; Sodium Nitrite; Thiosulfates

Topics: Animals; Antidotes; Cyanides; Erythrocytes; Male; Mice; Mice, Inbred BALB C; Seizures; Sodium Nitrite; Thiosulfate Sulfurtransferase; Thiosulfates

Bitter cassava poisoning in 8 children is reported. The incidence of bright cherry-red blood is emphasized. These patients were in bad condition, but they survived although they received different therapies. Four of them were treated with sodium nitrite and thiosulfate and the remainder with hydroxocobalamin alone. This latter drug may be useful in less severe circumstances.

Topics: Antidotes; Child; Humans; Hydroxocobalamin; Intubation, Intratracheal; Male; Manihot; Oxygen; Sodium Nitrite; Thiosulfates

An investigation of "mysterious" disease due to hydrocyanic acid (HCN) poisoning in livestock in this state was carried out. Detailed clinicopathological and pathological studies were conducted. Characteristic signs of acute tympany followed with profuse frothing, convulsions and dyspnea were recorded. Cynosis of the mucosa with characteristic anoxemic tissue changes and a high concentration of HCN in rumen content, feed and skeletal muscles were recorded. These were sufficient to establish the diagnosis. Successful treatment with a specific antidote was achieved, and further morbidity and mortality was checked.

Topics: Animals; Antidotes; Cattle; Cattle Diseases; Drug Therapy, Combination; Hydrogen Cyanide; India; Sodium Nitrite; Thiosulfates

A 24-year-old woman ingested an unknown amount of potassium cyanide in a suicide attempt. Coma and metabolic acidosis developed. Administration of the Lilly Cyanide Antidote kit (Eli Lilly and Co, Indianapolis) resulted in prompt resolution of symptoms and full recovery. Whole blood cyanide level was 13 micrograms/mL approximately one hour after ingestion. The highest measured methemoglobin level after sodium nitrite administration was 9.2%, demonstrating that attaining a "therapeutic methemoglobin level" of 25% is unnecessary to insure a satisfactory clinical outcome. Because severe hypotension or excessive methemoglobinemia can be caused by the sodium nitrite component of the Lilly kit, only enough to produce an acceptable clinical response should be administered.

Topics: Acidosis; Adult; Amyl Nitrite; Antidotes; Coma; Cyanides; Drug Therapy, Combination; Female; Humans; Methemoglobin; Potassium Cyanide; Sodium Nitrite; Suicide, Attempted; Thiosulfates

Topics: Burns, Inhalation; Cyanides; Fires; Humans; Oxygen Inhalation Therapy; Sodium Nitrite; Thiosulfates

We report two cases of cyanide poisoning from accidental ingestion of an imported metal cleaning solution used by some Southeast Asians for shining coins. Both patients received specific therapy and recovered completely after a dramatic sequence of sudden collapse and severe cardiovascular compromise.

Topics: Accidents, Home; Adult; Amyl Nitrite; Asian; Child, Preschool; Combined Modality Therapy; Cyanides; Female; Hemoperfusion; Household Products; Humans; Male; Sodium Nitrite; Thiosulfates

In three patients with severe acute cyanide poisoning, a cyanosis was observed instead of the bright pink skin coloration often mentioned as a sign in textbooks. Treatment of cardiopulmonary insufficiency is as essential as antidotal therapy and the use of sodium nitrite and 4-DMAP is not without risk as, in practice, the methemoglobin-level induced is difficult to control.

Topics: Adult; Aminophenols; Coma; Cyanides; Humans; Male; Methemoglobinemia; Methylene Blue; Nitrites; Respiration, Artificial; Sodium Nitrite; Suicide, Attempted; Thiosulfates

A coincubation system composed of hepatocytes in primary monolayer culture and erythrocytes suspended in the culture medium was developed and used as a model for investigations of mechanisms of cyanide antidote action at the cellular level. Hepatocyte ATP was used as the cytotoxicity indicator. Treatment of rat hepatocytes in the coincubation system with KCN (1.0 mM) for 10 min at 37 degrees C selectively reduced hepatocyte ATP levels to 33 +/- 15% of control (no KCN added) levels. 4-dimethylaminophenol (DMAP), cobalt(II) chloride, sodium nitrite, sodium thiosulfate, or a combination of the last two antidotes added to the KCN-containing medium significantly reversed ATP depression and the response was concentration dependent. The relative effectiveness, on a molar basis, was estimated to be DMAP greater than CoCl2 much greater than NaNO2 congruent to Na2S2O3. NaNO2 and DMAP induced methemoglobin formation in the absence of cyanide and cyanmethemoglobin formation in its presence; erythrocytes were required in the medium for effectiveness. CoCl2 produced neither cyanmethemoglobin nor thiocyanate in appreciable quantities nor required erythrocytes for antagonism. Na2S2O3 converted cyanide to thiocyanate and reversed ATP depression without erythrocytes in the medium. The addition of erythrocytes increased these rates significantly and to a greater extent than albumin. The overall results are consistent with previously proposed modes of action for these antidotes. However, the enhancement in cyanide metabolism and ATP recovery with Na2S2O3 and erythrocytes in the system was unexpected and raises the possibility that erythrocytes may contribute to cyanide disposition and antagonism in vivo when this antidote is administered.

Topics: Adenosine Triphosphate; Aminophenols; Animals; Antidotes; Cell Survival; Cobalt; Cyanides; Erythrocytes; In Vitro Techniques; Liver; Male; Potassium Cyanide; Rats; Rats, Inbred Strains; Sodium Nitrite; Thiosulfates

A 34 year old, 73 kg man ingested a 1 gram potassium cyanide pellet in a suicide attempt. Within one hour, coma, apnea, metabolic acidosis, and seizures developed. Sodium nitrite and sodium thiosulfate were administered. Dramatic improvement in the clinical condition occurred by the completion of antidote infusion. Methemoglobin level was 2% immediately after nitrite administration. Serial whole blood cyanide levels were obtained, documenting a highest measured level of 15.68 mcg/mL. Estimations of toxicokinetic parameters including terminal half-life (t 1/2) (19 hours), clearance (163 mL/minute), and volume of distribution (Vd) (0.41 L/kg) were calculated. The nitrite/thiosulfate combination was clinically efficacious in this case and resulted in complete recovery.

Topics: Adult; Cyanides; Half-Life; Humans; Kinetics; Male; Nitrites; Potassium Cyanide; Sodium Nitrite; Thiosulfates

Cyanide intoxication in mice can be antagonized by the opiate antagonist, (-)naloxone HCl, alone or in combination with sodium thiosulfate and/or sodium nitrite. Potency ratios, derived from LD50 values, were compared in groups of mice pretreated with sodium nitrite (sc, 100 mg/kg), sodium thiosulfate (ip, 1 g/kg), and (-)naloxone HCl (sc, 10 mg/kg) either alone or in various combinations. These results indicate that naloxone HCl provides a significant protection against the lethal effects of potassium cyanide. The protective effect of sodium thiosulfate, but not sodium nitrite, was enhanced with (-)naloxone HCl. The combined administration of sodium nitrite and sodium thiosulfate was further enhanced with (-)naloxone HCl. This protective effect of naloxone HCl against the lethal effect of cyanide appears to be restricted to the (-)stereoisomer, as the (+)stereoisomer, the inactive opiate antagonist, is also inactive in protecting against the lethal effects of cyanide. The mechanism of antagonism is discussed.

Topics: Animals; Cyanides; Lethal Dose 50; Male; Mice; Naloxone; Potassium Cyanide; Receptors, Opioid; Sodium Nitrite; Stereoisomerism; Thiosulfates

It has been reported that compounds containing carbonyl groups can readily react with cyanide. Pyruvic acid, an alpha-ketocarboxylic acid, has been shown to antagonize the lethal effects of cyanide. It is suggested that its mechanism of action rests in its ability to react with or "bind" cyanide. In this study, alpha-ketoglutaric acid, also an alpha-ketocarboxylic acid, was evaluated for its ability to counteract the lethal effects of cyanide. alpha-Ketoglutaric acid increased the LD50 value of cyanide (6.7 mg/kg) by a factor of five, a value statistically equivalent to that ascertained in mice pretreated with sodium thiosulfate and sodium nitrite. The combination of alpha-ketoglutaric acid and sodium thiosulfate increased the LD50 value of cyanide to 101 mg/kg. Addition of sodium nitrite to the alpha-ketoglutaric acid/sodium thiosulfate regimen increased the LD50 value of cyanide to 119 mg/kg. Unlike sodium nitrite, no induction of methemoglobin formation was observed with alpha-ketoglutaric acid pretreatment. It is apparent from these studies that the administration of alpha-ketoglutaric acid in conjunction with sodium thiosulfate resulted in fewer animal deaths than sodium nitrite and sodium thiosulfate without the dangerous formation of methemoglobin.

Topics: Animals; Cyanides; Ketoglutaric Acids; Lethal Dose 50; Male; Methemoglobin; Mice; Potassium Cyanide; Sodium Nitrite; Thiosulfates

Topics: Acetylcysteine; Acrylonitrile; Animals; Antidotes; Cysteine; Humans; Nitriles; Sodium Nitrite; Thiosulfates

Previous reports from our laboratory indicated that prophylactic protection against cyanide intoxication in mice can be enhanced by administration of chlorpromazine when it is given with sodium thiosulfate. The mechanism of potentiation of sodium thiosulfate by chlorpromazine was studied alone and in combination with sodium nitrite. Although chlorpromazine was found to induce a hypothermic response, the mechanism of enhancement of the antagonism of cyanide by chlorpromazine does not correlate with the hypothermia produced. Various other possible mechanisms were investigated, such as rate of methemoglobin formation, enzymatic activity of rhodanese and cytochrome oxidase, and alpha-adrenergic blockade. The alpha-adrenergic blocking properties of chlorpromazine may provide a basis for its antidotal effect, since this protective effect can be reversed with an alpha-agonist, methoxamine.

Topics: Animals; Antidotes; Brain; Chlorpromazine; Cyanides; Drug Synergism; Electron Transport Complex IV; Male; Methemoglobinemia; Methoxamine; Mice; Nitrites; Potassium Cyanide; Sodium Nitrite; Thiosulfates

Topics: Adolescent; Antidotes; Cyanides; Edetic Acid; Humans; Male; Sodium Nitrite; Thiosulfates

Topics: Animals; Cyanides; Electron Transport Complex IV; Liver; Male; Mice; Oxygen; Potassium Cyanide; Sodium Nitrite; Thiocyanates; Thiosulfate Sulfurtransferase; Thiosulfates; Time Factors

Management of the acutely poisoned patient should start with decontamination of the skin and irrigation of the eyes, if necessary, and assessment of cardiorespiratory status, neurologic status, and pupils and eye movement. If a definable toxic syndrome is present, the specific "antidote" should be given. If no such syndrome is apparent and the patient is comatose, 50 ml of 50% glucose and 0.4 mg of naloxone (Narcan) intravenously should be tried. General measures, applicable in either situation, include induction of emesis or lavage and administration of charcoal and cathartics.

Topics: Acute Disease; Antidotes; Carbon Monoxide Poisoning; Consciousness; Cyanides; Depression, Chemical; Humans; Naloxone; Nitrates; Nitrites; Organophosphate Poisoning; Oxygen; Parasympatholytics; Poisoning; Pupil; Sodium Nitrite; Thiosulfates

Attempts were made to evaluate the effects of pretreatment with air and oxygen either alone or in various combinations with sodium nitrite and/or sodium thiosulfate on the physiological disposition of 14C-labeled sodium cyanide in mice. The radioactive respiratory excretion was studied by radiorespirometry, and the effects of various combinations of cyanide antagonists were compared. Oxygen either alone or in combination with sodium thiosulfate significantly enhanced the respiratory excretion when compared with air. Sodium thiosulfate accelerated the initial rate, but not the total amount of radioactivity excreted. The cumulative recovery of radioactive gases was significantly greater with groups receiving oxygen either alone or with sodium thiosulfate. When sodium nitrite was employed as an antidote either alone or with sodium thiosulfate, no difference in the respiratory excretion was noted between air and oxygen. The use of the sodium nitrite-sodium thiosulfate combination either with air or oxygen resulted in a marked decrease in the initial rate as well as the total amount of respiratory radioactivity excreted. No significant differences between various experimental groups were noted in the total amount of urinary radioactivity excreted or the total body retention of radioactivity.

Topics: Animals; Antidotes; Cyanides; Male; Mice; Nitrites; Oxygen; Sodium Cyanide; Sodium Nitrite; Thiosulfates; Time Factors

Male CD-1 mice were exposed for 60 min to toxic concentrations of acetonitrile, propionitrile, or n-butyronitrile and were maintained for the following 14 d. The LC50 values for acetonitrile, propionitrile, and n-butyronitrile were 2,693, 163, and 249 ppm, respectively. Pretreatment with Na2S2O3 or NaNO2, two common inorganic cyanide antagonists, can provide significant (p < 0.05) protection against the mortality associated with exposure to lethal concentrations of these nitriles. Administration of Na2S2O3 consistently provided a greater measure of protection than did NaNO2 against nitrile poisoning. Pretreatment with a heptatotoxic dose of CCl4 can protect mice against death from inhalation of lethal concentrations of these nitriles. The present results are compared with those of previous studies, and the conclusions support the rationale for administration of inorganic cyanide antagonists to individuals poisoned by inhalation of acetonitrile, propionitrile, or n-butyronitrile.

Topics: Acetonitriles; Animals; Carbon Tetrachloride; Humans; Lethal Dose 50; Liver; Male; Mice; Nitriles; Sodium Nitrite; Thiosulfates

Prophylactic protection against cyanide intoxication in mice can be enhanced by the administration of oxygen, especially when it is used in combination with the conventional cyanide antidotes, sodium nitrite and sodium thiosulfate. The LD(50) values were compared in groups of mice premedicated with sodium thiosulfate or sodium nitrite, or both, in air and in oxygen. These results indicate that oxygen alone provides only minimal protection. Although oxygen enhances the protective effect of sodium thiosulfate to a minor degree, it does not enhance the protection of sodium nitrite at all; and yet, it potentiates the effectiveness of a combination of these two antagonists against cyanide intoxication.

Topics: Animals; Drug Synergism; Lethal Dose 50; Male; Mice; Oxygen; Poisoning; Potassium Cyanide; Random Allocation; Sodium Nitrite; Thiosulfates

Topics: Antidotes; Cyanides; Humans; Nitrites; Sodium Nitrite; Thiosulfates