sodium-nitrite and Acidosis

More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the survival of cyanide-poisoned mice.. To evaluate the effectiveness of isosorbide dinitrate compared with that of sodium nitrite in cyanide poisoning.. A comparative animal study was performed using 18 rabbits, randomized into 3 study groups. Animals were poisoned intravenously with potassium cyanide (1 mg/kg). The first group was not given any further treatment. The second and third groups were treated intravenously 1 min after poisoning with sodium nitrite (6 mg/kg) and isosorbide dinitrate (50 μg/kg), respectively. The primary outcome was short-term survival of up to 30 min. Secondary outcomes included time to death, a clinical score, mean blood pressure, pulse, blood pH, and lactate and methemoglobin levels.. Rabbits treated with isosorbide dinitrate or sodium nitrite survived while only one untreated rabbit survived. Median time to death of the 5 poisoned and untreated animals was 10 min. All the animals collapsed soon after poisoning, exhibiting rapidly disturbed vital signs and developed lactic metabolic acidosis; average peak blood lactate levels were 15.5-19.1 mmol/L at 10 min after poisoning. The treated animals improved gradually with practically full recovery of the clinical scores, vital signs, and blood gas levels. Sodium nitrite administration raised methemoglobin to an average peak of 7.9%, while isosorbide dinitrate did not change methemoglobin levels.. Early administration of isosorbide dinitrate improved the short-term survival of cyanide-poisoned rabbits. Isosorbide dinitrate shows potential as an antidote for cyanide poisoning and may exert its effect using a nitric-oxide-dependent mechanism.

Topics: Acidosis; Administration, Intravenous; Animals; Isosorbide Dinitrate; Male; Methemoglobin; Poisoning; Potassium Cyanide; Rabbits; Sodium Nitrite

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

A 49-year-old man lost consciousness after being accidentally exposed to what was probably hydrogen sulfide gas while performing maintenance on a machine producing feather meal. He was immediately taken to the hospital. Upon admission, his consciousness level was 14 (E4V4M6) on the Glasgow Coma Scale (GCS), but it subsequently decreased, and the patient was intubated when his respirations became depressed as well. About 5 hours after the initial incident, he was transferred to our department. His consciousness level was GCS 9 (E2V2M5), his blood pressure was 95/78 mmHg, and his heart rate was 90 beats per min. There was no metabolic acidosis. Mechanical ventilation was begun and 10% sodium nitrite was intermittently administered intravenously, with the goal of lowering arterial blood methemoglobin saturation to 20%. Two days following admission, the patient regained full consciousness and sodium nitrite administration was stopped. The following day mechanical ventilation was also discontinued. This patient exhibited severe recurring neurologic symptoms without metabolic acidosis; thus, the manifestations of toxicity in this case might have been due to the direct neurologic toxicity of hydrogen sulfide, hypoxia, or delayed post-ischemic cerebral hypoperfusion syndrome. The patient made a full recovery without any sequelae; therefore we would like to hypothesize that repetitive intravenous administration of sodium nitrite is effective in cases of hydrogen sulfide exposure.

Topics: Accidents, Occupational; Acidosis; Gases; Humans; Hydrogen Sulfide; Infusions, Intravenous; Male; Methemoglobinemia; Middle Aged; Occupational Exposure; Respiration, Artificial; Sodium Nitrite; Treatment Outcome; Unconsciousness

Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 muM and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite (maximum nitrite concentration of approximately 35 muM) independent of perfusate Po(2). Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO.

Topics: Acidosis; Animals; Breath Tests; Dose-Response Relationship, Drug; Erythrocytes; Hemoglobins; Hypoxia; Lung; Nitric Oxide; Perfusion; Pulmonary Circulation; Rats; Rats, Sprague-Dawley; Sodium Nitrite; Time Factors; Vasoconstriction; Xanthine Oxidase

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

The fundamental, yet poorly understood, physiological mechanism known as 'acidic-metabolic' vasodilation, contributes to local blood flow regulation during hypoxia/ischaemia and increased metabolic activity. The vasodilator nitric oxide (NO) has been suggested to be involved in this event. Besides enzymatic production by NO synthases, a novel mechanism for generation of this gas in vivo was recently described. This involves non-enzymatic reduction of inorganic nitrite to NO, a reaction that takes place predominantly during acidic/reducing conditions. We have studied the effects of physiological amounts of nitrite on NO generation and relaxation of rat aorta in vitro in a situation where environmental pH was reduced to levels seen in tissues during hypoxia/ischaemia. The relaxatory effect of nitrite was increased in an acidic buffer solution (pH 6.6) compared with neutral pH; EC50 for nitrite was reduced from 200 to 40 microM. Nitrite-evoked relaxation was effectively prevented by coadministration of an inhibitor of soluble guanylyl cyclase. The relaxation was further potentiated by the addition of ascorbic acid. In parallel, NO was generated from nitrite in a pH dependent manner with even larger amounts seen after addition of ascorbic acid. NO generation from nitrite correlated to the the degree of relaxation of rat aorta. These results illustrate non-enzymatic release of NO from nitrite at physiological concentrations. This may be an important auto-regulated physiological mechanism involved in the regulation of vascular tone during hypoxia/ischaemia.

Topics: Acidosis; Animals; Aorta; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hypoxia; In Vitro Techniques; Indicators and Reagents; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Donors; Oxadiazoles; Penicillamine; Quinoxalines; Rats; Rats, Wistar; Regional Blood Flow; Sodium Nitrite; Vasodilation

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

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

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

Acute hypoxemia was produced in chronically catheterized sheep fetuses to determine the response time necessary to increase plasma immunoreactive erythropoietin (Ep) concentration. Sodium nitrite (0.2 mM) was infused via a fetal vein to induce fetal hypoxemia. The resultant fetal methemoglobinemia was associated with a predictable, incremental decrease in arterial oxygen content. Twelve nitrite infusions were performed in eight fetal sheep preparations (gestational ages 115-146 days). Mean methemoglobin level increased to 33% of total Hb after 1-2 h of NaNO2 infusion. These results were compared to those obtained in nine control studies in eight fetuses in which no change was observed for plasma Ep, arterial oxygen content, PaO2, pHa, or whole blood lactate. In the nitrite infused group, however, a significant and progressive increase in mean plasma Ep level over baseline levels was observed during the 4th and 5th h of hypoxemia (p less than 0.01). This change in Ep was significantly greater compared to the control group. These results, however, were confounded by the concomitant development of a lactic acidemia secondary to the fetal hypoxemia. To examine the theoretic possibility that lactic acidemia may primarily affect fetal Ep levels, an additional group of five fetuses was infused with L-lactic acid for the same time period. Although the decrements in pHa and whole blood lactate levels achieved in these fetuses were in excess of those observed during the nitrite infusions, this possibility was ruled out since no change in fetal plasma Ep levels occurred. We conclude that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis; Animals; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Hemodynamics; Lactates; Lactic Acid; Methemoglobinemia; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Sodium Nitrite