The pharmacokinetics and pharmacodynamics of severe aldicarb toxicity after overdose

Abstract

Objective. To describe the clinical effects, pharmacokinetics, and pharmacodynamics of plasma and acetylcholinesterase in an aldicarb overdose. Case Report. A 57-year-old female was found unconscious and incontinent of urine after ingesting aldicarb. She was bradycardic, hypotensive, hypersalivating, clammy, had small pupils, and generalized weakness. She was intubated, ventilated, and treated with large atropine doses (50 mg and 20 mg/h infusion) and adrenaline. She improved hemodynamically over 24 h, but remained comatose for another 24 h, before recovering without sequela. Aldicarb concentration at admission was 2.18 μg/ml and concentration–time data best fitted a two compartmental model with first order absorption and a time of ingestion 4.5 h preadmission. The half-life of distribution was 0.4 h and half-life of elimination, 13 h. Plasma cholinesterase concentration at admission was 0.3 kU/L (Reference range[RR]:4.3–10.6 kU/L) and red cell cholinesterase was 10 U/gHb (RR:38–66 U/gHb). The IC₅₀ was 0.15 μg/ml and 0.26 μg/ml for plasma and red cell cholinesterase, respectively. Discussion. Aldicarb poisoning causes rapid onset severe toxicity with muscarinic and nicotinic excess, seizures, and decreased consciousness. Cholinesterases rapidly recover once aldicarb concentrations decrease and precede clinical recovery.     

Failed rescue therapy with rapamycin after paraquat intoxication

Introduction. Ingestion of large quantities of paraquat leads to irreversible, often fatal pulmonary fibrosis. Case presentation. A 50-year-old man (body weight of 78.6 kg) ingested 500 mL Gramoxone® containing 200 g/L of paraquat in a suicide attempt. The patient did not seek medical attention until 15 h after ingestion. Initial treatment consisted of the administration of intravenous methylprednisolone, 250 mg once daily. Seventy-two hours after ingestion the patient was transferred to our tertiary care center. Paraquat concentration was 0.2 mg/L in the serum and urinary concentration was 4.42 mg/L. Antioxidative therapy including the administration of acetylcysteine and an anti-inflammatory therapy employing methylprednisolone (1 g/day) was started. Extended daily dialysis was initiated. As the high plasma concentration of paraquat indicated a 100% predicted mortality, we expanded treatment strategies by using the antiproliferative agent rapamycin. A dose of 8 mg/day was started 72 h after the intoxication. Maximum rapamycin concentrations amounted to 12.9 μg/L. Despite these efforts, the patient died on day 18 after intoxication from respiratory failure caused by severe pulmonary fibrosis. Conclusion. Despite theoretical considerations suggesting the use of rapamycin in paraquat poisoning, the substance failed to halt the progression of pulmonary fibrosis in this case.     

Pharmacokinetics of four metabolites of DA-125, a new anthracycline antineoplastic agent after single and multiple intravenous administration to rats

The tissue distribution, and biliary and urinary excretion of four metabolites (M1-M4) of a new anthracycline antineoplastic agent (DA-125) were compared after single and multiple (7 consecutive days) intravenous (i. v.) administration to rats. The mean pharmacokinetic parameters of M1, such as area under the plasma concentration-time curve (AUC: 56.4 μg min/ml vs. 69.0 μg min/ml), terminal half-life (t_1/2: 3.51 h vs. 3.01 h), total body clearance (CI: 70.9 ml/min/kg vs. 58.0 ml/min/kg), renal clearance (CI_R: 0.193 ml/min/kg vs. 0.336 ml/min/kg) and nonrenal clearance (CI_NR: 70.7 ml/min/kg vs. 57.7 ml/min/kg); of M2, such as plasma AUC (39.4 μg min/ml vs. 41.9 μg min/ml), t_1/2 (6.15 h vs. 7.34 h) and CI_R (10.5 ml/min/kg vs. 13.8 ml/min/kg); and of M4, such as plasma AUC (4.82 μg min/ml vs. 6.54 μg min/ml) and t_1/2 (3.33 h vs 4.02 h), were comparable between single and multiple administrations of DA-125. M3 was detected in plasma for up to 1–5 min, and M3 and M4 were below the detection limit in 24-h urine after both single and multiple administrations of DA-125. M2 was the main metabolite of DA-125 excreted (among M1-M4) in 24-h urine after both single and multiple administrations of DA-125; approximately 12.3% and 20.1% (P<0.01) of i. v. dosage (expressed in terms of DA-125) was excreted as M2 after single and multiple administrations of DA-125, respectively. Corresponding values for MI were 0.326% and 0.694% (P<0.05). The mean levels of M1 (229 μg vs. 175 μg) and M2 (1330μg vs. 1120μg) excreted in 24-h bile after single and multiple administrations of DA-125 were not significantly different; the percentages of i. v. dosage excreted in 24-h bile as M1 (expressed in terms of DA-125) were 4.83% and 3.58% after single and multiple administrations, respectively. The corresponding values for M2 were 27.8% and 22.5%. M3 and M4 were below the detection limit in 24-h bile after both single and multiple administrations of DA-125. Mean AUA, s (area under the amounttime curves from time zero to last measurement time t) (or AUC, s-area under the plasma concentration-time curves from time zero until the last measurement time t) of M1-M4 in each tissue after single and multiple administrations of DA-125 were also comparable except in the bone marrow and thymus. The data suggest that 7 consecutive days of i. v. administration of DA-125 (4 mg/kg) to rats does not lead to considerable accumulation of M1-M4 in the tissues, except in the bone marrow and thymus.     

Management of thallium poisoning in patients with delayed hospital admission

Objective. To describe the clinical features and management of thallium poisoning in patients with delayed hospital admission. Methods. Fourteen patients (median age 36 years) were admitted 9–19 days after ingesting food poisoned with thallium. Clinical and laboratory data, including blood and urine thallium concentrations, were collected. Patients were treated with oral Prussian blue, a chelating agent sodium dimercaptosulfonate, and hemodialysis. Results. All patients experienced a triad of symptoms of acute gastrointestinal upset, painful combined polyneuropathy, and hair loss after consuming poisoned food. Fatigue and skin pigmentation were observed in all patients. Abnormal liver function tests were found in 6 (42.9%) and delirium and coma were identified in 4 (28.6%). Two weeks after the poisoning, the blood and urine thallium concentration ranged from 219.0 to 1414.4 μg/L (median: 535.3) and 956.5 to 11285.0 μg/L (median: 7460.0), respectively. One patient (7.1%) with a previous history of pulmonary fibrosis died of respiratory failure in hospital. Symptoms were improved and blood or urine thallium levels were normalized in the remaining 13 patients before discharge. After a 6.5 ± 1-month follow-up, 1 patient (7.1%) developed deep venous thrombosis in the left lower limb. In another patient (7.1%), numbness in the lower limbs remained. Conclusion. Acute thallium poisoning is commonly manifested by gastrointestinal upset, painful polyneuropathy, and significant hair loss. Treatment strategies included Prussian blue and hemodialysis, which were associated with a good outcome in this case series.     

Methylene blue used in the treatment of refractory shock resulting from drug poisoning

Background. Methylene blue inhibits the nitric oxide–cyclic guanosine monophosphate (NO–cGMP) pathway, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in distributive shock from various causes including septicaemia and post-cardiac surgery. Reports of use in overdose are limited. We describe the use of methylene blue to treat a case of refractory distributive shock following a mixed drug poisoning. Case details. A 41-year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlled-release carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate and 375 mg oxazepam. He was comatose and intubated on presentation. Progressive hypotension developed. Echocardiogram revealed a hyperdynamic left ventricle, suggesting distributive shock. The patient remained hypotensive despite intravenous fluid boluses, escalating vasopressor infusions. Arterial blood gas revealed metabolic acidaemia and high lactate. Methylene blue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 h, then 0.75 mg/kg/h for 12 h) resulting in rapid improvement in haemodynamic parameters and weaning of vasopressors. Serum quetiapine concentration was 18600 ng/mL (30–160 ng/mL), collected at the time of peak toxicity. Conclusion. Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Methylene blue may have utility in the treatment of distributive shock resulting from poisoning refractory to standard vasopressor therapy.     

Hemoperfusion-Hemodialysis Ineffective for Paraquat Removal in Life-Threatening Poisoning?

Abstract

We report on a patient treated with hemoperfusion-hemodialysis (HP-HD) for severe paraquat poisoning. This procedure was adopted since the combination of adsorption and dialysis may improve overall drug removal. On admission blood paraquat was 15.8 μg/ml. He received conventional treatment and combined HP-HD which started within 3 hours after ingestion of the chemical and lasted 5 hours. Blood samples were obtained during and after HP-HD. The samples during HP-HD were taken before the charcoal column, between the charcoal column and the artificial kidney and after the artificial kidney. Blood clearances of paraquat were 116 ± 32 ml/min (n=6) for the charcoal column (HP), 90 ± 54 ml/min (n=6) for the artificial kidney (HD) and 151 ± 37 ml/min (n=6) for the combined systems (HP-HD). After HP-HD a limited rebound of blood paraquat level was seen. One day after admission renal and hepatic failure had developed, and the patient died after 5 days. Tissue paraquat levels (μg/g wet tissue) were: skeletal muscle 9.4, pancreas 6.0, prostate 5.6, thyroid 4.2, lungs 4.0, bone marrow 4.0, kidney 3.1, spleen 2.9, adrenal 2.9, heart 2.8, liver 2.3, stomach and testis below 1.0.

Measurements of blood levels demonstrated the efficient clearances of paraquat with HP-HD from the central (plasma) compartment. However, the present results confirmed those previously reported which suggest that the efficiency of short HP-HD in treating severe paraquat poisoning is questionable since paraquat levels in the peripheral (tissue) compartment remain elevated.     

Accidental poisoning with Veratrum album mistaken for wild garlic (Allium ursinum)

Introduction.?Veratrum album (white or false hellebore) is a poisonous plant containing steroidal alkaloids that cause nausea, vomiting, headache, visual disturbances, paresthesia, dizziness, bradycardia, atrioventricular block, hypotension, and syncope. It is regularly mistaken for Gentiana lutea (yellow gentian). We report accidental poisoning with V. album mistaken for Allium ursinum (wild garlic), a wild plant used in soups and salads in Central Europe. Case series.?Four adults (24–45 years) accidentally ingested V. album mistaken for A. ursinum in self-prepared salads and soups. Within 15–30?min of ingestion they developed nausea, vomiting, and abdominal pain. At the same time dizziness, tingling, dimmed and jumping vision, transient blindness, and confusion appeared. On arrival at the ED, all patients had sinus bradycardia and hypotension. Following treatment the patients were discharged well 24–48?h after ingestion. Conclusion.?In patients presenting with gastrointestinal, neurological, and cardiovascular symptoms a history of wild plant ingestion suggests possible poisoning with V. album mistaken for wild garlic.     

Acute Elevation of Blood Lead Levels Within Hours of Ingestion of Large Quantities of Lead Shot

Background: Ingestion of elemental lead foreign bodies is felt to have a low risk of clinically significant lead absorption unless gastrointestinal pathology and/or prolonged transit time are present. We present a case of ingestion of a large quantity of small diameter lead shot accompanied by rapid elevation of blood lead levels. Case Report: A 5½-year-old previously healthy girl was found eating the pellets from an ankle weight. She vomited and complained of abdominal pain. In the emergency department, she had no complaints and normal vital signs. An abdominal X-ray showed thousands of small, round, metallic density objects in the stomach. Her white blood cell count was 14,700/mm³, and the hemoglobin, mean corpuscular volume, free erythrocyte protoporphyrin, zinc protoporphyrin, biochemistry panel 21, and urinalysis were normal. She had no prior lead level for comparison. Whole-bowel irrigation was begun and she passed over 11 stools with pellets as well as other foreign bodies (erasers, bead, etc.) in the first 24 hours. Pellets were still seen on X-ray the following day so she received a high-fiber diet and bisacodyl tablets 10 mg/d. On hospital day 2, her admission blood lead (drawn 13 hours after ingestion) was reported as 57 μg/dL (2.7 μm/L) and chelation was begun with oral 2,3-dimercaptosuccinic acid 10 mg/kg 3x/d for 5 days, then 2x/d for 14 days. Her peak measured lead level was 79 μg/dL approximately 36 hours after ingestion. She excreted 2273 μg lead in the urine during her first 24 hours of chelation. Her blood lead dropped to 14.3 μg/dL by the end of chelation. She did not develop any apparent signs of lead poisoning. Conclusion: Acute elevations of blood lead concentrations may occur rapidly after ingestion of multiple small elemental lead objects.     

Management of diethylene glycol ingestion

Context. Diethylene glycol is a toxic alcohol used as an industrial solvent in various products. Human exposure to diethylene glycol has resulted in multisystem organ dysfunction and death in cases of acute intentional ingestions as well as epidemics of mass poisoning. Debate remains as to whether the parent compound or metabolite, 2-hydroxyethoxyacetic acid, is responsible for the majority of the toxicity seen in diethylene glycol poisoning. Therefore, cases of diethylene glycol poisoning create management dilemmas when deciding whether to administer alcohol dehydrogenase inhibitors, hemodialysis, or both. Case details: A 35-year-old male was presented to the emergency department reporting that he intentionally ingested brake fluid containing diethylene glycol 8 hours prior to arrival. The patient complained only of epigastric abdominal pain, had a normal physical exam, with a serum bicarbonate of 22 mmol/L, serum creatinine of 0.9 mg/dL, and an undetectable serum ethanol. The management dilemma in this case was whether to initiate fomepizole therapy, administer hemodialysis, or both given the high risk circumstances of the presentation. The decision was made not to administer any therapy other than usual supportive care. Serial basic metabolic panels were sent showing the development of no acidosis or renal dysfunction until his serum diethylene glycol concentration returned undetectable. Discussion. Diethylene glycol ingestion can be life threatening. This case highlights the difficulty regarding management of these cases while attempting to balance resource utilization, diagnosis, monitoring, and therapy. Due to continued debate, these decisions remain practitioner specific. Keywords Toxic alcohols; fomepizole; hemodialysis     

The determination of paraquat (1,1′-dimethyl-4,4′-bipyridylium cation) in urine

Three methods of paraquat analysis have been examined and a suitable procedure for clinical laboratory use is recommended. The method is rapid and can determine down to 0.01 μg paraquation/ml in a 250-ml aliquot of urine. A rapid spot test with visual sensitivity of 1–1.5 μg ion/ml is also described. Some urine levels following oral ingestion of paraquat are reported, but it was not possible to correlate the levels found with severity of poisoning.     

Benzonatate Overdose Associated with Seizures and Arrhythmias

Abstract

Background: Benzonatate is an antitussive with a unique chemical structure. It can contain as many as 8 structural analogs. Therefore, laboratory analysis of benzonatate is difficult. We report 2 cases of benzonatate poisoning with seizures and cardiac arrest and an analytical method to identify and quantify benzonatate in human plasma. Case Reports: Case 1: A 12-month-old male presented to the emergency department of a rural hospital following ingestion of an unknown amount of benzonatate. Upon arrival, the child was seizing and in full cardiac arrest. Resuscitative measures were unsuccessful and the child died shortly after arriving at the emergency department. Case 2: A 39-year-old male ingested 36 benzonatate capsules in a suicide attempt. Enroute to the health care facility, the patient experienced a seizure, had a cardiac arrest, and was cardioverted. Upon arrival at the emergency department, the patient was acidotic with a pH of 6.8. Gastric lavage was performed followed by the administration of activated charcoal. Six hours after arrival at the emergency department, the patient was alert, oriented, and hemodynamically stable. The patient was observed for 24 hours and subsequently discharged. Laboratory confirmation of benzonatate in the plasma of the patient was performed using high-pressure liquid chromatography with tandem mass spectrometry (MS/MS). The benzonatate concentration was estimated to be 2.5 μg/mL. Conclusion: Seizures and cardiac arrest are possible following an acute ingestion. Quantitative analysis of benzonatate is possible using high-pressure liquid chromatography with tandem mass spectrometry. Routine analysis for benzonatate is not common.     

Octreotide for the treatment of sulfonylurea poisoning

Background. Sulfonylureas are used extensively for treating type-2 diabetes mellitus. Sulfonylurea poisoning can produce sustained and profound hypoglycemia refractory to IV dextrose, particularly in children and the elderly. Objective. To review the use of octreotide, a long-acting somatostatin analog, in the treatment of sulfonylurea-induced hypoglycemia. Methods. A computerized search of U.S. National Academy of Medicine, Embase, PubMed and Toxline databases was undertaken using the keywords “octreotide”, “sulfonylurea”, “poisoning”, “intoxication”, “overdose” and “children”. Textbooks of Clinical Toxicology and Pharmacology and the articles cited in their bibliographies were also searched. Twenty-four publications (19 articles and five conference abstracts) were identified; no publication was excluded. Pharmacology of octreotide. Octreotide, a synthetic peptide analog of somatostatin, binds to G protein-coupled somatostatin-2 receptors in pancreatic beta-cells, resulting in decreased calcium influx and inhibition of insulin secretion. Octreotide markedly inhibited insulin secretion and decreased the number of hypoglycemic events and supplemental dextrose requirements in animal studies. In humans octreotide markedly inhibited insulin release, increased serum glucose concentration, reduced dextrose requirement, prevented recurrent hypoglycemia and was superior to IV dextrose and diazoxide after administration of sulfonylureas. Efficacy of octreotide in pediatric sulfonylurea poisoning. Fourteen pediatric patients were reported; 13 ingested second-generation sulfonylureas, with time to hypoglycemia of 1.5–16 hours. IV dextrose (10–25%) was administered before and after octreotide therapy. Octreotide was given after failure to correct hypoglycemia with IV dextrose in doses of 0.51–2 μg/kg IV or SC; two also required an IV octreotide infusion. Seven patients (50%) had recurrent hypoglycemia and received IV dextrose and additional octreotide. Efficacy of octreotide in adult sulfonylurea poisoning. Fifty-three patients were reported in prospective controlled (n = 22) and retrospective (n = 9) studies, case series (n = 6) and case reports. Fifty-one ingested second-generation sulfonylureas with time to hypoglycemia of 1–13 hours. All received IV dextrose (10–50%) before and after octreotide treatment. Octreotide 40–100 μg SC or IV was administered followed by additional doses in most patients; three patients also required an IV infusion. Octreotide significantly increased serum glucose concentrations, decreased dextrose requirement and recurrent hypoglycemic events compared with IV dextrose. Recurrent hypoglycemia was recorded in 22–50% of the patients treated with octreotide. Therapeutic recommendations. Based on the published clinical and pharmacokinetic data of sulfonylureas and octreotide, we suggest the following dose regimens: in children, octreotide 1–1.5 μg/kg IV or SC, followed by 2–3 more doses 6 hours apart. In adults, octreotide 50 μg SC or IV, followed by three 50 μg doses every 6 hours. During this treatment IV dextrose infusion should be gradually tapered off. Adverse events. Hypertension and apnea were recorded in one pediatric patient 30 minutes after IV octreotide; the relationship to octreotide is unclear. One adult patient with chronic renal failure treated with atenolol developed severe hyperkalemia. Conclusions. Although relatively limited, the available data suggest that octreotide should be considered first-line therapy in both pediatric and adult sulfonylurea poisoning with clinical and laboratory evidence of hypoglycemia. Maintenance doses of octreotide may be required to prevent recurrent hypoglycemia.     

分光光度法检测血清百草枯质量浓度及意义

目的 评价分光光度法测定血清百草枯(paraquat,PQ)质量浓度的可靠性及其临床意义。方法 验证普通分光光度法和二阶导数分光光度法测定血清PQ质量浓度的检测波长后,采用二阶导数分光光度法测定血清PQ质量浓度,确定其线性范围并评价其准确性;采用该法测定8例PQ中毒患者血清PQ质量浓度并与高效液相色谱法测定值比较分析其可靠性;对上海市第十人民医院肾病免疫科2008年10月至2010年9月收治的口服PQ4h以上人院的21例急性PQ中毒患者的资料行回顾性统计分析,根据该法测定患者入院时血清PQ质量浓度是否大于1.8 μ.g/mL分为两组,采用成组t检验和Fisher精确概率法对两组患者的临床特征进行统计分析。结果 (1)普通分光光度法检测含PQ血清样本时在257 nm波长处未见明显吸收峰;(2)二阶导数分光光度法测定血清PQ质量浓度在0.4～8.0 μg/mL范围内呈现良好的线性关系,相关系数为0.996;回收率为95.0％～99.5％,相对标准差(RSD)为1.35％～5.41％ (n=6),检出下限为0.05 μg/mL;(3)8例PQ中毒患者血清PQ质量浓度二阶导数分光光度法测定值与HPLC法检测值相吻合,r=0.995,P＜0.01;(4)血清PQ质量浓度＞1.8 μg/mL组患者存活率为22.2％,酸中毒和少尿发生率55.6％,纵膈气肿发生率77.8％,与血清PQ质量浓度＜1.8 μg/mL组比较差异均有统计学意义(P＜0.05)。结论 (1)普通分光光度法用于测定血清PQ质量浓度不能采用257 rn为检测波长;(2)二阶导数分光光度法用于检测血清百草枯质量浓度可靠性高;(3)二阶导数分光光度法测定值可用于中毒患者的临床严重程度判断,口服PQ中毒4h后血清质量浓度＞1.8 μg/mL是患者预后不良的重要指标。     

A Reply to “Carnitine” and “Role of Carnitine in Valproic Acid Toxicity”

Background. Amatoxin‐containing species are responsible for the most severe cases of mushroom poisoning, with high mortality rate. Therefore, this poisoning should be ruled out in all patients presenting gastrointestinal symptoms after wild mushroom ingestion. Objective. To determine sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficacy (DE) of urinary amanitin analysis in cases of suspected mushroom poisoning. Methods. All cases of mushroom ingestion referred to a Poison Center during a one‐month period were analyzed. Amanitin measurements were performed by ELISA method (functional least detectable dose 1.5 ng/ml; cut‐off value not clearly established). Gastrointestinal symptoms latency and initial clinical assessment were considered alternative diagnostic tools. Definitive diagnosis was used as the reference standard. Results. Among 61 patients included in the study, amatoxin poisoning was diagnosed in 10 cases. Urine samples were collected 5.5 to 92 hours after mushroom ingestion. Urinary amanitin DE was 91.8%, 93.4%, and 80.3%, based on the cut‐off value considered (1.5, 5.0, and 10.0 ng/ml, respectively). Symptoms latency longer than 6 hours and initial clinical assessment DE were 70.5% and 67.2%, respectively. To identify amatoxin poisoning, initial clinical assessment resulted more sensitive and urinary amanitin analysis more specific. Conclusions. Urinary amanitin analysis is a valuable diagnostic tool and may significantly contribute to the management of suspected mushroom poisoning. At present, the best diagnostic accuracy can be obtained taking advantage of both the high sensitivity and negative predictive value of the clinical assessment performed by an experienced toxicologist, and the high specificity and positive predictive value that characterize urinary amanitin analysis.     

Acute human self-poisoning with bispyribac-containing herbicide Nominee®: a prospective observational study

Introduction.?Self-poisoning with herbicides is an important reason for hospital admission and death in Asia. Although some herbicides have a well-described toxicity profile in humans, many of the newer compounds rely on extrapolation from animal results as no published literature on clinical outcomes of human self-poisoning has been described. One example of these compounds is bispyribac, a selective herbicide used in rice and wheat cultivation that is marketed in two containers, one containing bispyribac 400 g/L with a solvent and the other the surfactant, polyethylene glycol. We present the first case series of acute human self-poisoning with an herbicide product containing bispyribac.?Methods.?Clinical data for all patients who presented with acute poisoning from a bispyribac-containing herbicide (Nominee®) to two general hospitals in Sri Lanka from June 2002 to January 2009 were collected prospectively. Admission and serial blood samples were collected from consenting patients to confirm exposure and to study the toxicokinetics of bispyribac, respectively. Results.?One hundred ten patients with a history of bispyribac ingestion presented after a median time of 4 h post-ingestion. There were three deaths at 15, 6, and 5 h post-ingestion because of asystolic cardiac arrest. All three patients had reduced Glasgow Coma Score (GCS) (3, 12, and 13, respectively) of whom the former two had co-ingested ethanol and developed tonic-clonic seizures. Admission blood sample was obtained from the former two of these patients but bispyribac was detected in only one of these patients. The other patient presented 2.5 h post-ingestion with a GCS of 12 but bispyribac was not detected. Excluding the patient with undetectable bispyribac, a conservative estimate of the case fatality ratio at 1.81% (95% confidence interval 0.32–5.8) can be made. The majority of the remaining patients had self-limiting upper gastrointestinal symptoms and eight patients had an abnormal GCS on presentation to hospital. The overall median hospital stay was 3 days. Bispyribac was not detectable on admission in 21 patients; in the remaining patients, the median plasma concentration was 50.55 μg/mL (interquartile range 1.28–116.5; n = 32). The peak concentration was noted around 3 h post-ingestion and plasma bispyribac concentration did not predict the severity of poisoning.?Conclusion.?The majority of patients developed self-resolving symptoms and were successfully managed in rural general hospitals without transfer to larger tertiary hospitals. Patients who died developed significant poisoning within 6 h and plasma bispyribac concentrations did not appear to predict mortality. The lack of correlation between bispyribac outcomes and the available plasma concentrations may be because of exposure to nonbispyribac components or other undefined factors. Clinical outcomes from acute self-poisoning with bispyribac-containing herbicides appear to be relatively more favorable than other commonly used herbicides.     

Asymptomatic congenital lead poisoning – case report

Context. Congenital lead poisoning is uncommon and there is no consensus on the management of the newborn. Case Details. A female infant was born to a lead-burdened woman identified by screening just prior to delivery. Maternal blood lead level (BLL) was 58 μg/dL. The infant's BLL on the second day of life was 72 μg/dL with a free erythrocyte protoporphyrin level of 175 μg/dL. The child was managed by an exchange transfusion followed by chelation. The BLL 6 h after exchange transfusion was 11.4 μg/dL. Follow-up 2 years later showed a BLL of 9 μg/dL and normal development. Discussion. We present the details of a case of congenital lead poisoning treated aggressively which appears to have resulted in a favorable outcome.     

Methemoglobinemia associated with metaflumizone poisoning

Context. Metaflumizone is a voltage-dependent sodium channel blocker insecticide, which is chemically similar to indoxacarb. Although indoxacarb poisoning is known as a cause of methemoglobinemia, the effect of metaflumizone poisoning in humans is still unknown. Case details. A 57-year-old man presented with a decreased mentality following ingestion of 100 ml of metaflumizone, 150 ml of glyphosate and alcohol. Although initial methemoglobin (MetHb) level was slightly higher than the normal limit, it gradually rose to reach a maximum level of 27.8%, on the 19 h after ingestion. After hemodialysis, MetHb level was reduced to 15.8%, which decreased further to the level of 6%, following methylene blue administration. Discussion. Metaflumizone shares a similar chemical structure to indoxacarb, which is known to be a cause of methemoglobinemia. Physicians should be alert for the development of methemoglobinemia in symptomatic patients when facing potential pesticide poisoning such as metaflumizone poisoning.     

Compatibility and stability of fentanyl admixtures in polypropylene syringes

Objective: To determine the physicochemical stability of fentanyl in combination with midazolam and either hyoscine butylbromide or metoclo- pramide, and stored in 30 ml polypropylene syringes. Methods: Solutions containing approximately 40 μg/ml of fentanyl in combination with midazolam (approximately 600 μg/ml) and either metoclopramide (approximately 700 μg/l) or hyoscine (approximately 850 μg/ml) were prepared from commercial ampoules of the drugs. The solutions were stored, in triplicate, in the dark at 32 °C (to simulate usage conditions) for 10 days, and the concentration of each constituent drug was periodically determined using a stability-indicating high-performance liquid chromatography assay. Results: The combinations were relatively stable, with all drugs maintaining over 90% of their initial chemical potency for at least 1 week. There were no evident changes in either the physical appearance or pH values of the solutions over the course of the study. Conclusions: On the basis of physicochemical stability, polypropylene syringes containing fentanyl with midazolam and either hyoscine butylbromide or metoclopramide can be safely prepared and stored at or below 32 °C for periods of up to 1 week prior to use by palliative care patients receiving the drugs via a portable subcutaneous infusion device.     

Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.