Hemodynamic abnormalities in sodium monofluoroacetate intoxication.

Hypotension is one of the most important predictors of mortality in sodium monofluoroacetate (SMFA) intoxication. This paper reports the hemodynamic response in one fatal and another survival case of SMFA intoxication. Despite correction of hypovolemia and with inotropic support, the patients remained in shock. Hemodynamic observations have provided evidence that shock after SMFA intoxication is due to diminished systemic vascular resistance and increased cardiac output. This is the first report in which such an invasive hemodynamic investigation has been recorded in a clinical case of SMFA intoxication.     

Effects of sodium monofluoroacetate on glucose,amino-acid,and fatty-acid metabolism and risk assessment of glucose supplementation

Sodium monofluoroacetate (SMFA; also known as compound 1080) is a highly toxic chemical; therefore, accidental exposure and intentional misuse are of great concern. SMFA intoxication is reportedly caused by the inhibition of aconitase. However, the pathogenesis underlying SMFA intoxication is not clear. This study was conducted to elucidate the acute effects of SMFA on glucose, amino-acid, and fatty-acid metabolism and to assess glucose supplementation as a possible alleviator or aggravator in SMFA intoxication. Rats were assigned to three groups: SMFA+saline, SMFA+glucose, and control (i.e., no SMFA), and blood samples were analyzed at 3 hours after SMFA or saline (control) administration. Additional rats were used for the monitoring of blood-glucose and lactate concentrations for 10 hour- and 14-day survival rates. SMFA increased the serum-citrate, serum-pyruvate, and blood-lactate concentrations. However, despite significant increases in these parameters when SMFA was administered with glucose, the effects on pH values were small and the survival rate was not changed. SMFA also increased the serum concentrations of free fatty acids, branched-chain amino acids, ammonia, urea, and calcium. The presence of glucose enhanced or suppressed these metabolic changes. Amphibolic intermediates in the tricarboxylic acid cycle might be supplied through the catabolism of proteins in SMFA intoxication. We conclude that other factors, in addition to the accumulation of lactate, citrate, and pyruvate, may affect survival rates, and that SMFA induces imbalances in glucose, amino-acid, and, fatty-acid metabolism. All these changes are inter-related and may contribute to SMFA intoxication.     

Respiratory Failure Following Isolated Ziprasidone Ingestion in a Toddler

Ziprasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar mania in adults and is used off label in children and adolescents. Despite increasing use of ziprasidone in both adult and pediatric populations, there remains a paucity of reports describing unintentional pediatric exposures. The following report describes a patient with isolated ziprasidone ingestion who required intubation secondary to respiratory failure. A 15-month-old previously healthy boy presented to the emergency department shortly after his father found him with approximately five partially dissolved 80-mg ziprasidone tablets in his mouth. The child was flaccid and lethargic with no eye opening, withdrawing from pain only. Two hours after arrival, he developed worsening CNS depression with inability to protect his airway and underwent endotracheal intubation. A serum ziprasidone level was 330 ng/mL by LC/MS. The patient was extubated approximately 14 h later and was discharged from the hospital shortly thereafter in good health without neurological sequelae. Isolated pediatric ingestion of ziprasidone resulting in the need for significant medical intervention has not been previously reported. We report a case of respiratory failure requiring intubation following accidental ziprasidone ingestion with confirmatory serum levels.     

Polyuria, Acidosis, and Coma Following Massive Ibuprofen Ingestion

Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5–49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.     

Seizures in a pediatric patient with a tiagabine overdose

Introduction

Tiagabine (TGB) is a novel antiepileptic that decreases GABA uptake. The literature contains one report of an adult with epilepsy who ingested up to 1 gram of TGB and developed status epilepticus. We reported on a pediatric patient who ingested significantly less TGB but still developed tonic-clonic seizures.

Case report

A previously healthy, 13 kg, two-year-old girl developed generalized tonic-clonic seizure activity at home approximately 1 hour after ingesting 90 mg of her grandmother’s TGB (forty five 2 mg tablets). At the hospital she had two 5 minute seizures at 1.5 and 3.5 hours post ingestion. Her serum TGB levels were 530 and 130 ng/ml approximately 5 and 11 hours post-ingestion (5–70 ng/ml trough levels with most probable range for seizure control). She was discharged 27 hours post ingestion, and she was in good condition.

Conclusion

An overdose of TGB, a novel anti-epileptic, can cause convulsive seizures.     

Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication

AIMS: Activated charcoal is now being recommended for patients who have ingested potentially toxic amounts of a poison, where the ingested substance adsorbs to charcoal. Combination therapy with gastric lavage and activated charcoal is widely used, although clinical studies to date have not provided evidence of additional efficacy compared with the use of activated charcoal alone. There are also doubts regarding the efficacy of activated charcoal, when administered more than 1 h after the overdose. The aim of this study was to examine if there was a difference in the effect of the two interventions 1 h post ingestion, and to determine if activated charcoal was effective in reducing the systemic absorption of a drug, when administered 2 h post ingestion. METHODS: We performed a four-limbed randomized cross-over study in 12 volunteers, who 1 h after a standard meal ingested paracetamol 50 mg kg(-1) in 125 mg tablets to mimic real-life, where several factors, such as food, interfere with gastric emptying and thus treatment. The interventions were activated charcoal after 1 h, combination therapy of gastric lavage followed by activated charcoal after 1 h, or activated charcoal after 2 h. Serum paracetamol concentrations were determined by h.p.l.c. Percentage reductions in the area under the curve (AUC) were used to estimate the efficacy of each intervention (paired observations). RESULTS: There was a significant (P<0.005) reduction in the paracetamol AUC with activated charcoal at 1 h (median reduction 66%, 95% confidence intervals 49, 76) compared with controls, and a significant (P<0.01) reduction for gastric lavage followed by activated charcoal at 1 h (median reduction 48.2%, 95% confidence interval 32.4, 63.7) compared with controls. There was no significant difference between the two interventions (95% confidence interval for the difference -3.8, 34.0). Furthermore, we found a significant (P<0.01) reduction in the paracetamol AUC when activated charcoal was administered 2 h after tablet ingestion when compared with controls (median 22.7%, 95% confidence intervals 13.6--34.4). CONCLUSIONS: These results suggest that combination treatment may be no better than activated charcoal alone in patients presenting early after large overdoses. The effect of activated charcoal given 2 h post ingestion is substantially less than at 1 h, emphasizing the importance of early intervention.     

How much is too much? Oligosymptomatic presentation after 11.5 g of diphenhydramine

We report the case of a 47-year-old male obese Caucasian patient presenting 2 hours after ingestion of 11.5 g of diphenhydramine. Despite this excessive overdose, he showed only a few hours of impaired consciousness and no further symptoms. A diphenhydramine plasma concentration of 15,352 nmol/L was measured 8 hours after the overdose ingestion. A heterogeneous CYP2D6 extensive metabolizer genotype excludes a pharmacokinetic explanation for this unusually oligosymptomatic presentation. However, the patient suffered from longstanding, refractory depression despite numerous treatment attempts with various drugs, pointing to the possibility of decreased pharmacodynamic responsiveness for therapeutic and toxic effects.     

Foxy methoxy: A new drug of abuse

Introduction

In 1999, a new synthetic tryptamine, 5-MeO-DIPT, became known as a street drug, with the street name of “Foxy” or “Foxy Methoxy”. By February 2003, the DEA reported law enforcement seizures and/or reports of abuse in 12 states. We report a case along with an analysis of poison center data on this new drug of abuse.

Case report

A 19-year-old male was brought to the emergency department following ingestion of a larger than his usual dose of Foxy. Upon arrival, he had hallucinations, hypertension, tachycardia, mydriasis, and catalepsy. Symptoms resolved within two hours after administration of lorazepam and he recovered uneventfully.

Discussion

The AAPCC TESS database contained 41 exposures to “Foxy” between April, 2002 and June, 2003; 26 had moderate or major effects, indicating this drug has significant toxic potential. Given the expanding use of this and other club drugs, the spectrum of toxicity from this new agent will continue to be elucidated.     

A Fatal Case of Thallium Toxicity: Challenges in Management

Background

Thallium is a highly toxic compound and is occasionally involved in intentional overdoses or criminal poisonings. Accidental poisonings also occur, but are increasingly rare owing to restricted use and availability of thallium. We report a fatal suicidal ingestion of thallium sulfate rodenticide in which multi-dose activated charcoal (MDAC) and Prussian Blue (PB) were both used without changing the outcome.

Case report

A 36 year old man ingested an unknown amount of thallium sulfate grains from an old rodenticide bottle. He presented to an emergency department (ED) 45 minutes later with abdominal pain and vomiting. On examination he was agitated with a blood pressure of 141/60 mmHg and a heart rate of 146 beats per minute (bpm). He received MDAC during his initial ED management and was started on PB 18 hours post arrival; he was intubated on the following day for airway protection. The patient continued to be tachycardic and hypertensive and subsequently developed renal failure. On hospital day three, the patient developed hypotension that did not respond to fluids. The patient required vasopressors and was transferred to a tertiary care center to undergo continuous renal replacement therapy (CRRT). The patient died shortly after his transfer. His last blood thallium concentration was 5369 mcg/L, a spot urine thallium >2000 mcg/L, and a 24- hour urine thallium was >2000 mcg/L.

Conclusion

Though extremely rare, thallium intoxication can be lethal despite early administration of MDAC and use of Prussian blue therapy. Rapid initiation of hemodialysis can be considered in cases of severe thallium poisoning, to remove additional thallium, to correct acid-base disturbance, or to improve renal function.     

Circadian changes in the bioavailability and effects of indomethacin in healthy subjects

Summary Nine subjects, 19 to 29 years old (2 females) synchronized with activity from 07.00 to 00.00 received a single daily oral dose (100 mg) of indomethacin at fixed hours: 07.00, 11.00, 15.00, 19.00 and 23.00, in random order and at weekly intervals. 1) Chronopharmacokinetics: Venous blood (sampled at: 0, 0.33, 0.67, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h post ingestion) was used for plasma drug determination. Circadian changes in peak height, time to peak, area under the concentration-time curve and the disappearance rate were used to characterize indomethacin chronopharmacokinetics. A circadian rhythm of both peak height and time to peak was validated. An evening ingestion led to smallest peak height and longest time to peak. 2) Circadian changes in a set of effects: Eleven physiologic variables were investigated (post absorption) at t=2 h. Circadian rhythms were detected: i) on control day and ii) with evening ingestion for ten of the eleven variables indicating that the subjects' temporal structure did not become altered by an evening ingestion, whereas it did become so by morning ones. Transient changes (n minutes post absorption) measured as T₂₄₀ min post absorption/T_{control day, same clock hour} ratio were also circadian rhythmic for most variables. Again, evening ingestion appeared least disturbing.     

Inorganic and organic fluoride concentrations in tissues after the oral administration of sodium monofluoroacetate (Compound 1080) to rats

Male rats were used to study the inorganic (ionic) and organic fluoride concentrations in plasma, liver, kidneys and stomach content after oral doses of 0, 2.2, 3.5, 4.0, 5.0 and 7.0 mg sodium monofluoroacetate (SMFA, Compound 1080)/kg body weight. Tissue and plasma ionic fluoride concentrations were observed to be higher in all rats given SMFA as compared to rats in the control group. This observation suggests in vivo defluorination of SMFA. Homogenates of liver obtained from SMFA poisoned rats showed significant increases in ionic fluoride concentration during a 6-day storage period at +4 degrees C, with the total fluoride concentration (ionic and organic) remaining constant. The average percentages of distribution of SMFA (organic fluoride) in plasma, liver, and kidneys were 7.05, 5.07 and 1.68, respectively. Plasma and tissue SMFA concentrations were generally lower than the corresponding stomach fluid SMFA concentrations for all dosage groups. Lethal concentration of SMFA in the liquid stomach content was in the range 84.9--189 micrograms/ml, corresponding to total (ionic and organic) fluoride concentrations in the range of 16.1--36 micrograms/ml.     

Fetal poisoning after maternal paraquat ingestion during third trimester of pregnancy: Case report and literature review

Introduction

Paraquat remains one of the common substances involved in intentional ingestions in Thailand. However, data on outcomes of paraquat ingestion during pregnancy is rarely available and the management is controversial.

Case report

A 17-year-old female in 36+ weeks of gestation attempted suicide by ingesting 1/2 a glass of Gramozone? (paraquat 27.6 % w/v) 5 hours prior to arrival to the hospital. Gastric aspiration and lavage was performed and she was given 50 g of activated charcoal and 150g of Fuller’s Earth suspension. A male infant, weighing 2,390g with an Apgar score of 7¹ 10¹⁰, was delivered via emergency caesarean section 7 hours after ingestion. Due to presence of paraquat in the gastric lavage fluid, the mother was placed on dexamethasone/cyclophosphamide therapy. She developed mild renal insufficiency 63 hours after the ingestion. The infant developed tachypnea immediately after birth that self-resolved. The infant developed tachypnea again on day 6 of life. A chest x-ray revealed right lower lobe infiltration that progressed to diffuse interstitial pattern; subsequent chest x-rays showed evidence of fibrosis. Both mother and infant survived and the infant was discharged and sent home with oxygen 0.5 LPM. Upon follow up at 10 months of age, he still had evidence of chronic lung disease clinically and on chest x-ray.

Conclusion

Paraquat ingestion during the third trimester of pregnancy usually carries a very poor prognosis. Review of reported literature suggests that this case report represents only the second survival of mother and child.     

Acute barium toxicity from ingestion of “snake” fireworks

Introduction

Ingestion of fireworks has been infrequently reported in the medical literature. We describe a case of acute barium poisoning following firework ingestion.

Case Report

A 35-year-old male with a history of severe mental retardation presented with vomiting and diarrhea following ingestion of 16 small fireworks (“color snakes” and “black snakes”). His condition rapidly deteriorated and he developed obtundation, wide complex dysrhythmias, and respiratory failure. Approximately 12 hours following ingestion, his serum potassium level was 1.5 mmol/L with a serum barium level of 20,200 μg/mL (reference range<200 μg/L). The patient eventually recovered with ventilatory support and potassium supplementation.

Discussion

Although firework ingestion is uncommon, clinicians should be prepared for potentially severe complications. In the case of barium poisoning, treatment consists of potassium supplementation, along with respiratory and hemodynamic support.     

A toxicokinetic analysis in a patient with acute glufosinate poisoning.

Incidents of poisoning in humans caused by the ingestion of the glufosinate ammonium containing herbicides are gradually increasing in Japan. This poisoning is characterized by various neurological symptoms such as disturbances of consciousness, convulsions and apnea which appear after an asymptomatic interval of several hours. We studied the toxicokinetics of glufosinate in a patient with this poisoning successfully treated without extracorporeal hemopurification. A 65-year-old male ingested BASTA, which contains 20% w/v of glufosinate ammonium, about 300 ml, more than the estimated human toxic dose. Four and a half hours after ingestion, he showed speech ataxia and systemic tremor. He was prophylactically intubated before the occurrence of serious respiratory failure. After 5 days of artificial ventilation he was extubated and discharged without any sequelae. We studied the serial change of serum glufosinate concentration every 3-6 h and assessed the urinary excretion of glufosinate every 24 h. The absorbed amount of glufosinate was estimated from the cumulative excreted in urine. Toxicokinetic analysis was performed using the two-compartment model. The changes in serum glufosinate concentration exhibited T1/2alpha of 1.84 and T1/2beta of 9.59 h. The apparent distribution volume at beta-phase and the total body clearance were 1.44 l/kg and 86.6 ml/min, respectively. Renal clearance was estimated to be 77.9 ml/min. The indication for extracorporeal hemopurification for this poisoning has been discussed.     

Determination of sodium monofluoroacetate (compound 1080) in biological tissues using oxygen combustion and a fluoride selective membrane electrode

Sodium monofluoroacetate (SMFA) was quantitated in plasma and liver homogenates after total fluoride analysis using an oxygen combustion method and fluoride selective electrode. The organic content of the samples were estimated by difference between total fluoride and inorganic fluoride. Recoveries (%±SD) of SMFA in aqueous samples, plasma and liver homogenates were 99.1 ± 2.3, 95.2 ± 3.3 and 95.3 ± 2.9, respectively. The within-run coefficient of variation in the 10.0-0.072 mg/ml (or mg/g) range for all samples was 4.7% or less. The method is suitable for quantitation of SMFA in biological materials and as a laboratory diagnostic aid in cases of acute SMFA intoxication.     

Vasoplegic Shock Treated with Methylene Blue Complicated by Severe Serotonin Syndrome

Introduction

Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. However, the patient subsequently developed severe Serotonin Syndrome (SS) as a result of an interaction between serotonergic drugs and MB.

Case Report

A 15-year-old male developed severe vasoplegic shock 1.5 hours after overdosing on several different medications including quetiapine slow release, quetiapine immediate release, desvenlafaxine slow release, venlafaxine, amlodipine, ramipril, fluoxetine, promethazine and lithium. His vasoplegic shock was resistant to high doses of noradrenaline and vasopressin. MB was administered 6.5 hours post ingestion and within 1 hour there was an improvement in his hemodynamic status and reduction of catecholamine requirements. Twelve hours post ingestion, he developed severe Serotonin Syndrome that lasted 5 days as a result of interaction between MB, a reversible monoamine oxidase inhibitor (MAO-I), and the antidepressants taken in overdose. MB had a calculated half-life of 38 hours.

Conclusion

MB is a useful additional strategy for severe drug induced vasodilatory shock and may be potentially life-saving. Clinicians should be aware that it can interact with other drugs and cause life-threatening Serotonin Syndrome. Lower doses or shorter durations may be wise in patients at risk of this interaction.

     

Acute quetiapine overdose in an eleven-year-old girl

We present a case of acute Quetiapine (SeroQuel) overdose in an 11-y-old girl who ingested 1,300 mg (22.2 mg/kg bw). Initial lethargy developed within I h followed by an episode of agitation and combativeness 3 h after ingestion. After treatment with lorazepam the patient experienced extended somnolence followed by return to normal mental status 16 h after ingestion. No cardiotoxic or laboratory abnormalities were found. This is the first report of acute Quetiapine overdose in an adolescent and suggests a relatively benign clinical course.     

Acute Hepatic Failure in a Dog after Xylitol Ingestion

Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1–2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-l-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.     

Whole bowel irrigation (WBI) in acute iron poisoning — case report

Objective: In theory, WBI (whole bowel irrigation) is indicated in iron poisoning, but the existing data are still insufficient to support or exclude its efficacy. Case report: A 46 year-old female admitted to the Toxicology Department due to suicidal ingestion of 5000 miligrams of elemental iron (57 mg/kg) in sustained-release preparation. WBI was instituted at 2 hours after ingestion, because abdominal X-ray showed mass of tablet material inside stomach and past pylorus. After 3-hour WBI subsequent X-ray revealed residual opacities in small intestine. Levels of serum iron were increasing 289 μg/dL on admission, (1,5 h post ingestion) 408 μg/dL (6 h after ingestion), 424 μg/dL (after 12 h). WBI was continued within 7 hours, until there was no radiographic evidence of toxin remaining in the gastrointestinal tract and clear rectal effluent was apparent. Subsequent serial serum iron concentrations were as follows: 389 μg/dL (after 14 h), 239 μg/dL (after 21 h), 119 μg/dL (after 36 h). Since the patient was asymptomatic did not undergo deferoxamine therapy. Patient recovered without sequelae. Conclusion: WBI seems to be beneficial in early stage of iron intoxication ensuring rapid and effective cleansing of gut, and decreasing toxin absorption. Authors believe that the use of early WBI allows to provide supportive care and avoid deferoxamine treatment.     

Zigadenus poisoning treated with atropine and dopamine

Introduction

Zigadenus (commonly known as “death camas” or “mountain camas”) is a common plant in the lilly family found throughout the United States. Its onion-like roots can be mistaken for an edible plant. Ingestion may cause hemodynamic instability which has successfully been treated with atropine. It has been suggested that vasopressors may be an effective therapy for this ingestion. We report the successful use of dopamine as therapy inZigadenus ingestion.

Case Report

A 45 year-old, previously healthy male presented to the ED with complaints of severe nausea and vomiting after ingesting two “wild onion” bulbs. He was noted to have marked hypotension and bradycardia in the ED, which initially responded to treatment with IV fluids and atropine. The plant was identified as a species ofZigadenus. After a second drop in heart rate and blood pressure in the ICU, hypotension and bradycardia were treated successfully with a dopamine infusion.

Discussion

Zigadenus ingestion presents with vomiting, hypotension and bradycardia. The hemodynamic instability responded well to atropine for 1–2 hours. Dopamine infusion was used to stabilize both heart rate and blood pressure. With supportive care, poisoned individuals become relatively asymptomatic within 24 hours of their ingestion. Patients may be discharged once asymptomatic, typically the day after ingestion, and do not have any known long term sequelae.

Conclusion

Zigadenus poisoning causes vomiting, hypotension and bradycardia. The hemodynamic instability may be treated with atropine administration and dopamine infusion.