Chen-Chang Yang

Taiwan National Poison Center: Epidemiologic Data 1985–1993

UNLABELLED The Taiwan National Poison Center has received more than 30,000 telephone calls since its establishment in July 1985. OBJECTIVE To obtain more information about poisoning exposures in Taiwan, a retrospective analysis was conducted of all telephone calls to the center concerning human poisoning exposures July 1985 through December 1993. METHODS The following data were tabulated: age, sex, intent of exposure, route of exposure, substances ingested and clinical severity. RESULTS During the eight years (1985-1993), 23,436 telephone calls concerning human poisoning exposure were recorded. Adults accounted for most cases (75.2%) and exposures involving males (54.2%) were somewhat more prevalent than female poisoning exposures (44.7%). Intentional poisonings (54.6%) were more common than unintentional poisonings (40.1%), with an inverse relationship in pediatric poisoning exposures. After amphetamines, the most frequently ingested poisons were pesticides, benzodiazepines, and cleaning products. Fatalities occurred most frequently following ingestion of pesticides. The mortality rate was 5.7% for all exposures. CONCLUSIONS Human poisoning is a serious problem in Taiwan. The reduction of suicide attempts is a major objective. Childhood poisonings are underreported and of high mortality.

Intermediate Syndrome Following Organophosphate Insecticide Poisoning

&NA; Acute organophosphate insecticide poisoning can manifest 3 different phases of toxic effects, namely, acute cholinergic crisis, intermediate syndrome (IMS), and delayed neuropathy. Among them, IMS has been considered as a major contributing factor of organophosphate‐related morbidity and mortality because of its frequent occurrence and probable consequence of respiratory failure. Despite a high incidence, the pathophysiology that underlies IMS remains unclear. Previously proposed mechanisms of IMS include different susceptibility of various cholinergic receptors, muscle necrosis, prolonged acetylcholinesterase inhibition, inadequate oxime therapy, downregulation or desensitization of postsynaptic acetylcholine receptors, failure of postsynaptic acetylcholine release, and oxidative stress‐related myopathy. The clinical manifestations of IMS typically occur within 24 to 96 hours, affecting conscious patients without cholinergic signs, and involve the muscles of respiration, proximal limb muscles, neck flexors, and muscles innervated by motor cranial nerves. With appropriate therapy that commonly includes artificial respiration, complete recovery develops 5–18 days later. Patients with atypical manifestations of IMS, especially a relapse or a continuum of acute cholinergic crisis, however, were frequently reported in clinical studies of IMS. The treatment of IMS is mainly supportive. Nevertheless, because IMS generally concurs with severe organophosphate toxicity and persistent inhibition of acetylcholinesterase, early aggressive decontamination, appropriate antidotal therapy, and prompt institution of ventilatory support should be helpful in ameliorating the magnitude and/or the incidence of IMS. Although IMS is well recognized as a disorder of neuromuscular junctions, its exact etiology, incidence, and risk factors are not clearly defined because existing studies are largely small‐scale case series and do not employ a consistent and rigorous definition of IMS. Without a clear understanding of the pathophysiology of IMS, specific therapy is not available. The prognosis of IMS, however, is likely to be favorable if respiratory failure can be promptly recognized and treated accordingly.

Acute pancreatitis following organophosphate intoxication.

BACKGROUND Acute pancreatitis as a complication of organophosphate intoxication has been infrequently addressed. Previous reports have suggested that acute pancreatitis may follow the oral ingestion of several organophosphates, including parathion, malathion, difonate, coumaphos, and diazinon, or after cutaneous exposure to dimethoate. No cases of acute pancreatitis following mevinphos (CAS 7786-34-71) poisoning have been reported to date. The possible pathogeneses of the pancreatic insult in organophosphate intoxication are excessive cholinergic stimulation of the pancreas and ductular hypertension. CASE REPORT We describe a patient presenting with painless acute pancreatitis following an intentional ingestion of large amounts of mevinphos. Serum amylase and lipase values were increased and determination of amylase isoenzymes confirmed a pancreatic origin. A computerized tomograph of the abdomen showed diffuse swelling of the pancreas. The patient was discharged after a seven week clinical course, complicated by a delayed neuropathy. CONCLUSIONS As acute pancreatitis in organophosphate intoxication may be more common than reported, serum pancreatic enzymes and appropriate imaging studies should be more liberally utilized. Early recognition and appropriate therapy for acute pancreatitis may lead to an improved prognosis.

Agricultural Avermectins: An Uncommon But Potentially Fatal Cause of Pesticide Poisoning

STUDY OBJECTIVE Avermectins have been used in the control of parasites and insects; however, human data concerning poisoning are lacking. This study investigated the clinical spectrum of avermectin poisoning. METHODS A retrospective study was conducted to evaluate patients with avermectin poisoning reported to a poison center from September 1993 through December 1997. RESULTS Eighteen patients with abamectin (Agri-Mek; 2% wt/wt abamectin) exposure and 1 with ivermectin (Ivomec; 1% wt/vol ivermectin) ingestion were identified. There were 14 male and 5 female patients, ranging in age from 15 to 83 years. Most patients were exposed as a result of attempted suicide (14). Oral ingestion (15) was the most common route of exposure. Four patients were asymptomatic, and 8 had minor symptoms after a mean ingestion of 23 mg/kg abamectin (4.2 to 67 mg/kg), or after dermal and inhalation contact. Seven patients manifested severe symptoms, such as coma (7), aspiration with respiratory failure (4), and hypotension (3), after a mean ingestion of 100.7 mg/kg avermectin (15.4 mg/kg for ivermectin and 114.9 mg/kg for abamectin). All 7 patients received intensive supportive care; 1 patient died 18 days later as a result of multiple organ failure. CONCLUSION Ingestion of a large dose of avermectin may be associated with life-threatening coma, hypotension, and subsequent aspiration.

Prolonged Severe Withdrawal Symptoms After Acute-on-Chronic Baclofen Overdose

INTRODUCTION Baclofen is frequently used to treat muscle spasticity due to spinal cord injury and multiple sclerosis. Baclofen overdose can lead to coma, respiratory depression, hyporeflexia, and flaccidity. An abrupt decrease in the dose of baclofen due to surgery or a rapid tapering program may result in severe baclofen withdrawal syndrome manifesting hallucinations, delirium, seizures, and high fever. Severe baclofen withdrawal syndrome secondary to intentional overdose, however, has not received mention. CASE REPORT A 42-year-old male receiving chronic baclofen therapy, 20 mg/d, attempted suicide by ingesting at least 800 mg of baclofen. He was found in coma 2 hours postingestion with depressed respirations, areflexia, hypotonia, bradycardia, and hypotension. Treatment with intravenous fluids, atropine, dopamine, and hemodialysis was associated with restoration of consciousness within 2 days but disorientation, hallucinations, fever, delirium, hypotension, bradycardia, and coma developed during the following week. Baclofen withdrawal syndrome was not diagnosed until hospital day 9, when reinstitution of baclofen rapidly stabilized his condition. Oral overdosage of baclofen causes severe neurological and cardiovascular manifestations due to its GABA and dominant cholinergic effects. Severe baclofen withdrawal syndrome is manifest by neuropsychiatric manifestations and hemodynamic instability. Caution should be exercised after a baclofen overdose in patients receiving chronic baclofen therapy.

Acute Toxicities of Betel Nut: Rare but Probably Overlooked Events

Background: Betel nut chewing has long been a social habit in Taiwan and other Asian and tropical countries. It produces various autonomic and psychoneurologic effects including tachycardia, flushing, warmth, cholinergic activation, alertness, and euphoria. Although the oral carcinogenic effects are well known, data concerning its acute toxicity are few. To better understand the toxicity of betel nut, cases reported to the Taiwan Poison Control Center as probable or possible betel nut–related toxicity (January 1988–June 1998) were reviewed. In the 17 cases suitable for review (14 males, 3 females, age 21 to 60 years), the most common manifestations were tachycardia/palpitations ; tachypnea/dyspnea ; hypotension and sweating ; vomiting, dizziness, and chest discomfort ; abdominal colic, nausea, numbness, and coma ; and acute myocardial infarction and related manifestations . The reported quantity of betel nut used was low (1 to 6 nuts), except an extract of 100 betel nuts was used in 1 case and 66 chewed in another. Most cases recovered within 24 hours after the exposure. One patient developed probable acute myocardial infarction and ventricular fibrillation and died despite repeated cardiac defibrillation. Although betel nut chewing is widespread, significant toxicity as reported to a poison center is rare. Because most betel nut–related effects are transient and mild in nature, the incidence of such events is likely to be underreported. Nevertheless, betel nut chewing can produce significant cholinergic, neurological, cardiovascular, and gastrointestinal manifestations. It is possible that it may aggravate cardiac diseases in susceptible patients but this hypothesis must be further investigated. Treatment is symptomatic. With timely support, rapid and complete recovery is anticipated but a small risk of major complications cannot yet be discounted.

The Clinical Significance of Hyperamylasemia in Organophosphate Poisoning

OBJECTIVE Hyperamylasemia with a presumptive diagnosis of acute pancreatitis has been reported following organophosphate poisoning but there are no large-scale studies incorporating more specific diagnostic criteria. METHODS Retrospective review of the medical records of 159 patients with a diagnosis of organophosphate poisoning over 3 years. Serum amylase, pancreatic amylase, salivary amylase, lipase and cholinesterase levels, and the clinical manifestations were analyzed. RESULTS Serum amylase data was available for 121 of the 159 study patients. Hyperamylasemia (amylase > or = 360 U/L) was found in 44 patients (36%). Lipase was measured in 28 patients with hyperamylasemia; 9 of 28 had hyperlipasemia (lipase > or = 380 U/L). The finding of hyperamylasemia was closely related to clinical severity and presence of shock. A presumptive diagnosis of painless acute pancreatitis was diagnosed by hyperlipasemia associated with hyperamylasemia, clinical severity, serum LDH, and leukocyte counts. Two patients with presumptive pancreatitis died. Shock, coma, and hypoalbuminemia were the factors predicting fatality. CONCLUSIONS Hyperamylasemia is frequent in severe organophosphate poisoning. However, hyperamylasemia is not synonymous with acute pancreatitis and pancreatic amylase is not a reliable parameter in the diagnosis of organophosphate-induced pancreatitis due to its low sensitivity and specificity. Lipase assay is indicated in patients with hyperamylasemia for early diagnosis of pancreatitis. Proper image studies and even pathological examination are also needed to confirm the extent of pancreatic injury. With prompt diagnosis and appropriate treatment, a complete recovery can be anticipated unless the patient has otherwise unrelated complications.

Tetramethylammonium hydroxide poisoning

Introduction. Tetramethylammonium hydroxide (TMAH) is widely used as a developer or etchant in semiconductor and photoelectric industries. In addition to alkalinity-related chemical burn, dermal exposure to TMAH may also result in respiratory failure and/or sudden death. The latter toxic effect has been of great concern in Taiwan after the occurrence of three fatalities in recent years. To better understand the toxicity following dermal exposure to TMAH, we analyzed all cases with TMAH exposure reported to the Taiwan Poison Control Center (PCC-Taiwan). Case reports. In total, there were 13 cases of such exposure, including three patients who died after being exposed to 25% TMAH. A worker also developed severe effects manifesting muscle weakness, dyspnea, hyperglycemia, and chemical burn (28% of total body surface area) shortly after an accidental exposure to 2.38% TMAH. He received endotracheal intubation with assisted ventilation for 2 days and survived. Conclusion. Skin corrosive injury related to the alkalinity of TMAH and the ganglionic toxicity of tetramethylammonium ion might contribute to the clinical manifestations that occurred after dermal TMAH exposure. Thorough skin decontamination followed by prompt respiratory support should be the mainstay in the management of dermal TMAH exposure. Preventive strategies are warranted as well to decrease future occupational TMAH exposures.

Neonicotinoid insecticides: an emerging cause of acute pesticide poisoning

Introduction. Neonicotinoids are a relatively new class of insecticides. They exhibit agonistic effects at postsynaptic nicotinic receptors in insects and are believed to have low toxicity in humans. Methods. We conducted a retrospective analysis of all neonicotinoid exposures reported to the Taiwan National Poison Center to better understand the toxicity profile of neonicotinoid insecticides. Results. A total of 70 patients were analyzed. Most exposures involved suicidal ingestions of imidacloprid alone. Clinical manifestations of neonicotinoid insecticide toxicity bear some resemblance to those of acute nicotine poisoning. Although most exposures were of mild-to-moderate severity, eight patients developed major effects and two died. Aspiration pneumonia and respiratory failure were the main cause of severe toxicity. Conclusion. Significant toxicity of neonicotinoids can occur following large amount of oral ingestion. Poisoned patients may present with cholinergic syndrome, and judicious use of atropine seems justified. Symptomatic treatment, especially ventilator support, remains most important in clinical management.

Risk factors associated with adverse drug events among older adults in emergency department

BACKGROUND Little is known about the emergency department (ED) visits from drug-related injury among older adults in Taiwan. This study seeks to identify risk factors associated with adverse drug events (ADEs) leading to ED visits. METHODS We prospectively conducted a case-control study of patients 65years and older presenting to the ED. ED visits between March 1, 2009 and Feb 28, 2010 identified by investigators for suspected ADEs were further assessed by using the Naranjo Adverse Drug Reaction probability scale. For each patient with an ADE, a control was selected and time-matched from the ED population of the study hospital. The association between the risk of adverse drug events and triage, age, gender, serum alanine transaminase (ALT), serum creatinine, number of medications, and Charlson Comorbidity Index scores were analyzed using logistic regression. RESULTS Of 20,628 visits, 295 ADEs were physician-documented in older adults. Independent risk factors for ADEs included number of medications (adjusted odds ratio [OR]=4.1; 95% confidence interval [CI] 2.4-6.9 for 3-7 drugs; adjusted OR=6.4; 95% CI 3.7-11.0 for 8 or more drugs) and increased concentration of serum creatinine (adjusted OR=1.5; 95% CI 1.1-2.2). Diuretics, analgesics, cardiovascular agents, anti-diabetic agents and anticoagulants were the medications most commonly associated with an ADE leading to ED visits. CONCLUSIONS This study suggests that prevention efforts should be focused on older patients with renal insufficiency and polypharmacy who are using high risk medications such as anticoagulants, diuretics, cardiovascular agents, analgesics, and anti-diabetic agents.