hydroxocobalamin and Acidosis

Poisonings, adverse drug effects, and envenomations continue to be commonly encountered. Patients often present critically ill and warrant ICU admission. Many other patients who are initially stable have the potential for rapid deterioration and require continuous cardiopulmonary and neurologic monitoring. Given the potential for rapid deterioration, and because patients need continuous monitoring, ICU admission is frequently required. This article is the first of a three-part series to be published in CHEST; it discusses general management, laboratory tests, enhanced elimination, and emerging therapies. The second article will address the management of specific overdoses; the last will cover plants, mushrooms, envenomations, and heavy metals.

Topics: Acid-Base Equilibrium; Acidosis; Fat Emulsions, Intravenous; Humans; Hydroxocobalamin; Intensive Care Units; Naloxone; Narcotic Antagonists; Neuroleptic Malignant Syndrome; Osmolar Concentration; Poisoning; Renal Dialysis; Serotonin Syndrome; Therapeutic Irrigation; Xenobiotics

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

To report diagnostic, clinical and therapeutic aspects of cyanide intoxication resulting from ingestion of cyanogenic glucoside-containing apricot seeds.. Thirteen patients admitted to the Pediatric Intensive Care Unit (PICU) of Erciyes University between 2005 and 2009 with cyanide intoxication associated with ingestion of apricot seeds were reviewed retrospectively.. Of the 13 patients, four were male. The mean time of onset of symptoms was 60 minutes (range 20 minutes to 3 hours). On admission, all patients underwent gastric lavage and received activated charcoal. In addition to signs of mild poisoning related to cyanide intoxication, there was severe intoxication requiring mechanical ventilation (in four cases), hypotension (in two), coma (in two) and convulsions (in one). Metabolic acidosis (lactic acidosis) was detected in nine patients and these were treated with sodium bicarbonate. Hyperglycaemia occurred in nine patients and blood glucose levels normalised spontaneously in six but three required insulin therapy for 3-6 hours. Six patients received antidote treatment: high-dose hydroxocobalamin in four and two were treated with a cyanide antidote kit in addition to high-dose hydroxocobalamin. One patient required anticonvulsive therapy. All patients recovered and were discharged from the PICU within a mean (SD, range) 3.1 (1.7, 2-6) days.. Cyanide poisoning associated with ingestion of apricot seeds is an important poison in children, many of whom require intensive care.

Topics: Acidosis; Antidotes; Charcoal; Child; Child, Preschool; Coma; Cyanides; Eating; Female; Gastric Lavage; Hematinics; Humans; Hydroxocobalamin; Hyperglycemia; Insulin; Male; Poisoning; Prunus; Respiratory Insufficiency; Retrospective Studies; Seeds; Seizures; Sodium Bicarbonate; Turkey

Hydroxocobalamin is a new antidote approved by the FDA for the treatment of cyanide poisoning. Our report describes a patient with cyanide poisoning who survived after treatment with hydroxocobalamin and complications we encountered with hemodialysis. A 34-year-old female presented to the emergency department after a syncopal event and seizures. Her systolic blood pressure was 75 mmHg, her QRS complex progressively widened, and pulses were lost. She was intubated and resuscitated with fluids, sodium bicarbonate for her QRS widening and vasopressors. Venous blood gas demonstrated a pH of 6.36 with an O₂ saturation of 99%. Due to the acidemia with a normal pulse oximetry, simultaneous venous and arterial blood gases were obtained. Venous gas demonstrated a pH of 6.80 with a PO₂ of 222 mmHg, an O₂ saturation of 99%. The arterial blood gas showed a pH of 6.82, a PO₂ 518 mmHg, an O₂ saturation of 100%. Cyanide was suspected and hydroxocobalamin and sodium thiosulfate were given. Within 40 min of hydroxocobalamin administration, vasopressors were discontinued. Initially, nephrology attempted dialysis for metabolic acidosis; however, the dialysis machine repeatedly shut down due to a "blood leak". This was an unforeseen effect attributed to hydroxocobalamin. Cyanide level, drawn 20 min after the antidote was completed, was elevated at 22 mcg/dL. Her urinary thiocyanate level could not be analyzed due to an "interfering substance". Hydroxocobalamin is an effective antidote. However, clinicians must be aware of its effects on hemodialysis machines which could delay the initiation of this important treatment modality in the severely acidemic patient.

Topics: Acidosis; Adult; Antidotes; Bipolar Disorder; Cyanides; Female; Humans; Hydroxocobalamin; Renal Dialysis; Seizures; Syncope; Thiosulfates

To describe a case of severe accidental cyanide poisoning following a single ingestion of amygdalin with therapeutic intent.. A 68-year-old patient with cancer presented to the emergency department shortly after her first dose (3 g) of amygdalin with a reduced Glasgow Coma Score, seizures, and severe lactic acidosis requiring intubation and ventilation. The patient also ingested 4800 mg of vitamin C per day. She responded rapidly to hydroxocobalamin treatment. The adverse drug reaction was rated probable on the Naranjo probability scale.. Amygdalin and laetrile (a synthetic form of amygdalin) are commonly used as complementary or alternative medicine (CAM) for the treatment of cancer. Vitamin C is known to increase the in vitro conversion of amygdalin to cyanide and reduce body stores of cysteine, which is used to detoxify cyanide. Amygdalin has been used for decades by patients with cancer who are seeking alternative therapies, and severe reactions have not been reported with this dose. An interaction with vitamin C is a plausible explanation for this life-threatening response.. This case highlights the fact that CAMs can produce life-threatening toxicity. This case also adds a further note of caution, namely, the potential for serious interactions between CAMs, particularly where there is no tradition of concomitant use.

Topics: Acidosis; Aged; Amygdalin; Antineoplastic Agents, Phytogenic; Antioxidants; Ascorbic Acid; Complementary Therapies; Cyanides; Drug Interactions; Female; Glasgow Coma Scale; Hematinics; Humans; Hydroxocobalamin; Seizures

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

Methylmalonic acidaemia is an inborn error of metabolism characterized by recurrent episodes of life-threatening ketoacidosis. With improved and intensive treatment, these patients are living into adulthood, but many experience late-onset disease complications such as chronic renal failure, chronic pancreatitis and osteopenia. We report the successful delivery of a healthy baby to a 20-year-old woman with vitamin B12-unresponsive methylmalonic acidaemia who has these late-onset manifestations of the disease and had plasma methylmalonic acid concentrations of 1900 mumol/L during the first trimester of pregnancy.

Topics: Acidosis; Adult; Female; Humans; Hydroxocobalamin; Infant, Newborn; Male; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Vitamin B 12

A fifteen-year-old girl, with a clean medical history, was admitted to the intensive care unit 90 minutes after ingestion of 2.5 g potassium cyanide. She had typical signs of severe cyanide poisoning including deep coma, circulatory failure, and major metabolic acidosis. Gastric lavage and antidotal treatment with 4 g hydroxocobalamin and 8 g sodium hyposulfite was administered without delay together with supportive treatment consisting of mechanical ventilation with FIO2, blood alkalinisation and administration of beta-stimulants. These measures led to a rapid clinical improvement. The ventilatory support was discontinued after 24 hours and the patient left the intensive care unit on the fourth day with only slightly impaired mental status. She survived despite a very high blood cyanide concentration (494 mumol.l-1 on admission) probably because of the rapid symptomatic and antidotal treatment.

Topics: Acidosis; Adolescent; Autolysis; Coma; Cyanides; Female; Humans; Hydroxocobalamin; Oxygen Inhalation Therapy; Potassium Cyanide

Topics: Acidosis; Animals; Antidotes; Ferricyanides; Hydroxocobalamin; Infusions, Parenteral; Injections, Intravenous; Nitroprusside; Rabbits; Thiosulfates

Massive cyanide poisoning occurred in a 21-year-old man who had ingested 600 mg of potassium cyanide. The clinical course was marked by acute pulmonary edema and lactic acidosis. Because the poison was unidentified until nine hours after ingestion, the patient received only supported treatment which included diuresis, oxygen, bicarbonate, and assisted ventilation. A review of the literature shows that many case reports are poorly documented and do not provide a firm basis for evaluating therapy. To our knowledge, only four patients, including ours, have had blood levels of cyanide measured. In the absence of a suitable history, diagnosis of cyanide poisoning is difficult. A simple chemical test which can be performed on gastric aspirate is available. Hydroxocobalamin may be used as a nontoxic specific antidote. Nonspecific supportive therapy is of great importance.

Topics: Acidosis; Adult; Antidotes; Bicarbonates; Cyanides; Diuresis; Humans; Hydroxocobalamin; Lactates; Male; Oxygen Inhalation Therapy; Potassium Chloride; Pulmonary Edema

Topics: Acidosis; Adult; Cyanides; Cyanosis; Gastric Lavage; Gastrointestinal Hemorrhage; Humans; Hydrogen Cyanide; Hydrogen-Ion Concentration; Hydroxocobalamin; Hypotension; Liver; Middle Aged; Poisoning; Suicide; Time Factors; Vitamin B 12