Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD50 was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD50=66.4 mg/kg) and SNP by intraperitoneal (LD50=16.7 mg/kg) and subcutaneous (LD50=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD50 ATCN. Order of cyanogens (0.75 LD50; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)

Pseudo-blood leak? A hemodialysis mystery.

Hydroxocobalamin is a treatment for cyanide toxicity with few side effects. We report a case of a hemodialysis patient whose treatment was compromised by hydroxocobalamin interference with the blood leak detector.

A series of hospital homicides.

Patient deaths in hospitals due to medical staff are very rare. In the autumn of 2006, preliminary proceedings were initiated against a nurse on account of an overdose of medication leading to death, administered during her care of the patient. In the course of these proceedings, exhibits relating to the deaths of a total of 13 patients who had died due to chemical-toxicological causes were reviewed. Nine of them were exhumed. On average, death had occurred 22 months prior to exhumation (range of 1-34 months). The average age of the deceased was 76 years (range of 65-92 years). In five of the cases, analysis results and an evaluation of the medical records confirmed that a final, undocumented dose of sodium nitroprusside or midazolam was administered. After administration of sodium nitroprusside, the active agent rapidly releases nitrogen monoxide, itself undetectable. Another indicator that can be detected, however, is the cyanide that is also released. In one of the exhumed patients, cyanide could still be detected 18 months after death. The nurse stated that her motive was sympathy towards seriously ill patients. She was sentenced res judicata to life imprisonment on five counts of causing the death of a patient.

A probable case of nitroprusside intoxication.

This article describes the clinical history of a patient admitted to the Emergency Room after severe infrascapular pain unaffected by breathing or postural changes. After thoracic CT a type B aortic dissection was diagnosed. On admission to the CCU, the patient's blood pressure was still high (210/120 mmHg). Sodium nitroprusside (1 microg/kg/min drip) was initiated. As blood pressure remained high after 24 h, the infusion rate was increased gradually up to 18 microg/kg/min. In the evening of the following day the patient was transferred to the operating room because acute renal failure (BUN 108 mg/dL, Cr 4.00 mg/dL) occurred and arterial pressure was still high (180/60 mmHg). A thoracic endoprosthesis was then inserted. During this procedure the patient was relaxed and his blood pressure was satisfactory (140/80 mmHg) without drugs. In order to further lower blood pressure and afterload before positioning the second prosthetic segment within the aortic arch, 1 microg/kg/min nitroprusside drip was continued. A few minutes initiation of the drip an abrupt rise in blood pressure (systolic 200 mmHg) was observed, which had to be controlled before continuing the procedure. Increased nitroprusside infusion and repeated boluses of 10 mg urapidil (3-4 boluses with an interval of 15 min) and 30 microg clonidine were unsuccessful. After 15 min with an increased nitroprusside infusion rate, the patient showed psychomotor agitation and O2 his saturation dropped to 91% while arterial pH was 7.2 and lactate concentration was 3.5 mmol/L. Nitroprusside infusion was discontinued, while 0.1 microg/kg/min fenoldopam (started when the patient arrived in the operating room) was continued without improvement. In order to complete the procedure, general anaesthesia with sevflurane (2 MAC) in air (FiO2= 40%) was induced. After successful reduction in blood pressure the procedure was completed. In the postoperative course the patient was admitted to the ICU.

A case of suicide by ingestion of sodium nitroprusside.

The study reports a case of suicide by ingestion of sodium nitroprusside which resulted in acute cyanide poisoning. Analyses carried out on body fluid yielded the quantitation of total (5.00 mg/L) and free (3.30 mg/L) cyanide in blood and of methemoglobin (blood = 10.5%). At the scene, some solid reddish-brown material was found in a glass, which on toxicological analysis was found to contain sodium nitroprusside; about 9 g of the same substance was identified in stomach contents. The detection and quantification of cyanide and methemoglobin in biological samples from the case indicated that the lethal effect was due to both metabolic products (cyanide and methemoglobin).

Cyanide toxicity in the surgical intensive care unit: a case report.

Hypertension is a widespread entity in the surgical intensive care unit. Not only is the clinical spectrum varied, but the armamentarium available to the clinician is also wide-ranging. Sodium nitroprusside, a potent vasodilator with a short half-life, is often used for hypertensive crisis and to deliberately maintain a low blood in certain clinical conditions. Cyanide toxicity is a known complication of sodium nitroprusside use. Herein is reported a case of probable cyanide toxicity in an elderly trauma patient. The pharmacology of sodium nitroprusside and the pitfalls of making the diagnosis of cyanide toxicity are discussed.

Prophylactic effect of methylene blue against neurotoxicity of sodium nitroprusside.

AIM: To examine the effect of methylene blue (MB) on cytotoxicities of sodium nitroprusside (SNP) and cyclic guanosine monophosphate (cGMP) in cultivated cerebellar neurons. METHODS: The cytotoxicities of xenobiotic SNP and cGMP on cultivated murine cerebellar neurons were examined according to Dessi's method. Toxicity of SNP i.c.v. to mice and the prophylactic effect of i.c.v. MB were investigated with respect to the incidence of seizure and the mortality of mice within 24 h. RESULTS: Ten min treatment of SNP 1 mmol.L-1 decreased the survival rate of murine cerebellar nerve cells from 92% of normal control to 35%. Incubation with cGMP 0.1 mmol.L-1 for 1 h declined the survival rate from 94% of normal to 40%. Injection i.c.v. SNP 20 nmol killed one tenth of the mice in 24 h, and SNP 30 nmol killed 11/13 of the mice. MB (100 nmol) i.c.v. injection protected 11/13 of the mice against seizure and death caused by SNP (30 nmol, i.c.v.), and completely eliminated the toxicity of SNP 20 nmol. CONCLUSION: SNP and cGMP inhibit the vitality of murine neurons in vitro. MB injection i.c.v. markedly antagonizes the dose-dependent neuron-toxic effect of SNP in respect of convulsion and mortality of mice.

Management of hypertensive emergencies: changing therapeutic options.

Rapid lowering of severe hypertension is essential to prevent irreversible damage to vital organs. The patient's clinical status should be evaluated, noting particularly cardiac, neurologic, and renal functions. Choice of treatment should be based on speed and efficacy of action and on hemodynamic, vascular, and renal consequences. It is also important to preserve circulatory homeostasis and vital organ function. Sodium nitroprusside, labetalol, diazoxide, and hydralazine have been used parenterally for rapid control of severe hypertension, but they do not always produce optimal, balanced hemodynamic effects. Calcium antagonists have been advocated because of their beneficial circulatory effects. Nicardipine, a new dihydropyridine calcium antagonist, produces significant antihypertensive effects, and when given intravenously, results in a rapid fall in blood pressure. Studies have confirmed that nicardipine is effective and safe in the management of severe hypertension and hypertensive crises. Because the aim of rapidly controlling severe hypertension is to prevent target organ dysfunction, nicardipine therapy offers a useful additional option in the clinical management of severe hypertension and hypertensive crises.

Importance of symptoms in recognizing nitroprusside toxicity.

Symptoms of nitroprusside toxicity may precede the commonly described physiologic derangements. A characteristic sequence of symptoms associated with thiocyanate toxicity was exhibited by a patient who received a seven-day infusion of nitroprusside. The recognition of symptoms of nitroprusside toxicity is especially crucial when nitroprusside is infused over a prolonged period, in high doses, or in the presence of renal failure.

The use of hydroxocobalamin in the prophylaxis and treatment of nitroprusside-induced cyanide toxicity.

The use of OHB12 in the prophylaxis of CN intoxication resulting from SNP infusions is well documented in the literature. However, data is lacking to support its use as an antidote once signs and symptoms have developed. Because of the efficacy of oxygen therapy combined with supportive therapy and nitrite/sodium thiosulfate administration, the use of OHB12 as an antidote cannot be recommended at this time. Further studies are needed to determine efficacy, dosing, mode of administration and comparative trials to other antidotes.

Sodium thiosulfate disposition in humans: relation to sodium nitroprusside toxicity.

Thiosulfate concentrations and pharmacokinetics were studied in relation to sodium nitroprusside before, during, and after anesthesia. Normal thiosulfate concentrations were 1.13 +/- 0.11 mg/dl and 0.28 +/- 0.02 mg/dl in plasma and urine, respectively. Cholecystectomy patients had similar concentrations during surgery, with bile thiosulfate concentration of 13.72 +/- 2.95 mg/dl. Fasting patients and children had significantly higher plasma and urine thiosulfate concentrations. Over 99% of endogenous filtered thiosulfate was reabsorbed by the kidney in the average case. Coronary bypass patients had decreased plasma thiosulfate levels and increased excretion postoperatively. Disappearance of injected thiosulfate was biphasic; the distribution phase was dependent on the initial rate of injection, and the elimination phase depended on extracellular fluid turnover and renal excretion. Cholecystectomy patients on diuretics had a markedly increased rate of excretion, 56% within 100 min, versus normal subjects who excreted less than 50% in up to 18 h. In children, plasma thiosulfate did not change significantly, while blood cyanide concentration increased significantly during sodium nitroprusside administration and surgery. Thiosulfate did not change during recovery while cyanide decreased. Normal production of thiosulfate in humans may be limited; hence, continuous thiosulfate infusion may be required during sodium nitroprusside administration.

Detoxification of cyanide in a new-born child.

A well-developed male baby was given infusions of 2-5 microgram/kg/min of sodium nitroprusside (SNP) in the first few days after birth on account of high arterial blood pressure. After 30 h of treatment, cyanide accumulation was found to have reached a life-threatening level. IV administration of 100 mg/kg of sodium thiosulphate promptly lowered the cyanide level. The mixed infusion of SNP together with thiosulphate, used in the subsequent course, was no longer toxic.

Effects of cyanide antidotes used with sodium nitroprusside infusions: sodium thiosulphate and hydroxocobalamin given prophylactically to dogs.

Cyanide antidotes were given to dogs before an infusion of sodium nitroprusside 1.5 mg kg-1 for 1 h. Dogs given thiosulphate 75 mg kg-1 had significantly lower plasma and red cell cyanide concentrations while plasma thiocyanate concentrations were significantly increased in comparison with control. These changes were associated with only minimal disturbance of tissue oxygenation. There was no effect on red cell cyanide or thiocyanate concentrations in dogs treated with hydroxocobalamin 1.5 mg kg-1, but plasma cyanide concentrations were significantly greater than in those receiving no antidote although there was less evidence of impaired oxygenation. There was no evidence of a synergistic action between thiosulphate and hydroxocobalamin. The vascular response to nitroprusside was unchanged in the thiosulphate-treated dogs, but was significantly greater in those given hydroxocobalamin. The implications for prophylaxis and treatment of cyanide poisoning following nitroprusside overdose are discussed.