Clinical Presentation and Management of Acute Dystonia from Drug Abuse or Misuse in Adolescents and Young Adults: A Retrospective Cohort Study in Bangkok, Thailand.

Objectives: To describe the clinical presentation of acute dystonia (AD) from drug abuse or misuse, as well as the emergency department (ED) management and outcomes in adolescents and young adults. Methods: This was a retrospective cohort study of patients aged 10-25 years who were admitted to the ED for AD due to intentional abuse or misuse from January 1, 2014, to June 30, 2017. Data were collected from electronic medical records by three investigators with excellent interrater reliability (0.87). Results: Sixty-two cases met the criteria with male predominance (85.5%); the mean age was 16.7 years. Perphenazine was the most common cause of AD (38.7%), followed by haloperidol (32.2%). The most common AD manifestations were torticollis (51.6%), oromandibular dystonia (45.2%), and oculogyric crisis (22.6%). Intravenous (IV) diazepam combined with oral trihexyphenidyl and IV diazepam alone were the most frequently used first treatment in our ED (41.7% and 35.0%, respectively). Overall, the improvement rates from IV diazepam alone or combined with trihexyphenidyl ranged from 46.2%-75.0%. These rates were inferior to those observed with IV benztropine (100%) alone or combined with trihexyphenidyl. All patients were treated on an outpatient basis, except for one who was admitted to a pediatric ward. Conclusions: In recent years, drug-induced AD caused by intentional abuse among adolescents and young adults has become a concern in Thailand. The most common suspected drugs of abuse were first-generation antipsychotics, perphenazine, and haloperidol. The most effective treatment was benztropine.

Green Pit Viper Envenomations in Bangkok: A Comparison of Follow-Up Compliance and Clinical Outcomes in Older and Younger Adults.

We compared older and younger adults envenomated by the green pit viper (GPV) with regard to the following: follow-up compliance, elapsed time between envenomation and emergency department (ED) visit, and clinical/treatment outcomes. This was a two-site retrospective cohort study. We searched hospital electronic medical databases between January 2011 and December 2021. Patients aged 15 and above were eligible if they had a history of snakebite and had at least two VCT and/or platelet count results in their medical records. After the search, 1550 medical records were reviewed and 760 cases were found to be eligible for analysis. In total, 205 cases (27.0%) were ≥60 years old. The median ages in the younger and older groups were 40 (26-51) and 68 (64-75) years, respectively. The median elapsed times from bite to the ED were 47 (30-118) vs. 69 (35-150) min (p-value = 0.001). Overall, 91.3% of all cases were managed as out-patient cases and were eligible for follow-up appointments. The rate of out-patient follow-up at 72 ± 12 h in the older patients was significantly higher (43.2%) than in the younger adult patients (32.4%) (p-value = 0.01). Regarding the clinical/treatment outcomes, the rates of coagulopathy, antivenom administration, and hospital admission were not statistically different between both groups.

Diagnostic Tests for Hypofibrinogenemia Resulting from Green Pit Viper (Trimeresurus albolabris) Envenomation: A Simulated In Vitro Study.

INTRODUCTION: The green pit viper (GPV) Trimeresurus albolabris is found in Southeast Asia. Its venom has a thrombin-like activity that can cause hypofibrinogenemia. Fibrinogen measurement is not always available. We aimed to establish a more available diagnostic tool indicating hypofibrinogenemia caused by GPV envenomation. METHODS: This was an in vitro study, in which healthy subjects aged 20 to 45 y were enrolled. There were 2 experiments. In Experiment 1, blood samples from 1 subject had varying amounts of T albolabris venom added to determine its effect on the fibrinogen level (FL). In Experiment 2, 3 sets of blood samples were obtained from another 25 subjects. The 2 venom doses established in Experiment 1 were used on 2 sets of the samples to simulate severe (FL <1.0 g·L-1) and mild hypofibrinogenemia (FL 1.0-1.7 g·L-1). The third set of samples was venom-free. All samples were used for platelet counts, prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT), and 2 bedside clotting tests. Diagnostic parameters were calculated against the target FL of <1.0 g·L-1 and <1.7 g·L-1. RESULTS: Twenty-five subjects were enrolled in Experiment 2. On referencing normal cutoff values (platelet count >150,000 cells/mm3, venous clotting time <15 min, normal 20-min whole blood clotting time, INR <1.2, aPTT <30), we found abnormalities of 5, 0, 0, 3, and 22%, respectively. The highest correlation with hypofibrinogenemia was provided by PT/INR. For an FL of <1.0 g·L-1, PT and INR revealed the highest areas under the receiver operating characteristic curve, 0.76 (95% CI, 0.55-0.97) and 0.76 (95% CI, 0.57-0.97), respectively. The highest accuracy and the highest sensitivity were provided by PT/INR. CONCLUSIONS: PT/INR could be used as a diagnostic test for severe hypofibrinogenemia in GPV envenomation because of its high accuracy and area under the receiver operating characteristic curve.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Transient visual field loss after COVID-19 vaccination: Experienced by ophthalmologist, case report.

PURPOSE: The first reported case of bilateral transient visual field defect, experienced by an ophthalmologist, which developed shortly after COVID-19 vaccination (CoronaVac, Sinovac Biotech Ltd., Beijing, China) and confirmed by computerized automated perimetry. OBSERVATION: The patient is a 42-year-old Thai ophthalmologist. He developed blurred vision within an hour after the second dose of COVID-19 vaccination. We described his self-observed of sequential symptoms, chronologic events, and management steps. The visual field of left congruous hemianopia with respect to vertical midline was detected with computerized automated perimetry. The possible mechanism could be related to an acute vasospasm of the artery in the postchiasmatic visual pathway, triggered by COVID-19 vaccine, Corona Vac. CONCLUSION AND IMPORTANCE: With increasing use of the COVID-19 vaccine in the near future, it would be prudent for medical staff and ophthalmologists to be considered and aware of this associated condition.

Bacterial infection secondary to Trimeresurus species bites: A retrospective cohort study in a university hospital in Bangkok.

OBJECTIVES: Trimeresurus spp. (green pit viper [GPV]) inhabit several Southeast Asian countries. They account for more than 90% of snake envenomations in Bangkok. GPV venom causes coagulopathy from a thrombin-like effect and thrombocytopaenia. Envenomation can also cause local tissue reactions. The present study primarily aimed to determine the bacterial infection rate from GPV (Trimeresurus spp.) bites. Antibiotic use, microbiology report, and clinical course between those with and without infection were secondary objectives. METHODS: The present study took place at Vajira Hospital, Navamindradhiraj University. Medical records of patients more than 15 years old, bitten by GPV from our Toxicology Registry between 2015 and 2019, were reviewed by two chart extractors. Vital signs, pain scores, local reactions, time from bite to diagnosis of infection, use of antibiotics, bacterial culture samplings and complications were recorded. The infection rate was reported in percentages. Univariate analysis was utilised to determine risk factors for infection. RESULTS: The study included 123 patients over a 5-year period. The majority were male, 83 cases (67.5%). Overall, bacterial infection occurred in eight cases (6.5%). The median time from bite to infection diagnosis was 41.5 h (interquartile range 25.5-68.5). The antibiotic prescription rate was 12.2%. Haemorrhagic bleb was the only risk factor for infection (OR 22.4, 95% confidence interval 3.6-140.2). All bacterial culture samplings were negative. The non-infection group had a decreasing pain score throughout each follow-up visit. CONCLUSIONS: We found a low infection rate from GPV bites even without antibiotics suggesting prophylactic antibiotics should not be routinely prescribed in cases of GPV bite.

Patients with centipede bites presenting to a university hospital in Bangkok: a 10-year retrospective study.

INTRODUCTION: Centipede envenomation occurs commonly in tropical and subtropical countries. In most cases, centipede envenomation causes benign clinical manifestations. Serious complications are reported occasionally. Clinical studies regarding centipede envenomation are limited to case reports and case series. This study aimed to determine the prevalence and clinical characteristics of centipede bites in Bangkok, Thailand. METHODS: This was a retrospective medical record review study. We included patients who were clearly envenomated by a centipede presenting to the emergency department of a tertiary university hospital in Bangkok from January 1, 2006, to December 31, 2015. Data were collected on demographics, details of the exposure, signs, symptoms, treatment, and complications of envenomation. RESULTS: A total of 245 cases were included. The prevalence of centipede bite was 0.0367%. The majority were female (56.7%). The median age was 34.6 years (range: 1 month to 90 years). The number of envenomations was highest from October through December. Feet (38.3%) and hands (19.1%) were the parts of the body most often envenomated. Local effects were common with 99.5% of patients having localized pain and 87% having local swelling at the bite site. In terms of systemic effects, urticarial rash (5.7%) and fever (4.1%) were most frequently observed. Twelve cases (5%) had clinical pictures compatible with anaphylaxis. For pain management, all patients who had pain received analgesic drugs, while 29.7% were injected with local anesthesia. Antibiotics, antihistamines, and steroids were prescribed in 53.9%, 20.4%, and 10.2% of cases, respectively. No deaths occurred in this study. CONCLUSIONS: Even though the location of our hospital is in a metropolitan city in Thailand, there were centipede bites every month, especially during the last three months of each year. Nearly all patients had local effects. In contrast, serious complications such as anaphylaxis and systemic infection only occurred occasionally.

A study regarding follow-ups after green pit viper bites treated according to the practice guideline by the Ministry of Public Health of Thailand.

Introduction: For patients bitten by a Green Pit Viper (GPV), the Ministry of Public Health (MoPH) guideline suggests a physician order blood tests immediately after the ED arrival and repeat them 2 h later, if initial results are normal. If repeat tests remain normal, the patient can be discharged and scheduled for outpatient-follow-up at 24, 48 and 72 h.Objectives: To determine the probability of abnormal blood tests at the second draw (2 h after the first draw), and to determine the probability of adverse events within 24+/-12 h among those discharged home for outpatient-follow-up.Methods: This retrospective study included patients with a history of GPV (Trimeresurus albolabris or Trimeresurus macrops) bite who were 15 years or older presenting to our ED from 2008 to 2015. We excluded those with other types of animal bites or those with missing medical records.Results: 320 cases were included. The majority were male (56.3%) and median age was 44 years old. There were only 4 cases (1.3%) with abnormal venous clotting time (VCT) or platelet count (PC) at the second blood draws when the first test results were normal. Of those discharged after the second blood draws came back normal, and who had outpatient follow-up at 24+/-12 h, 3 had minor adverse events and none received antivenom.Conclusions: This study showed a very low probability of abnormal test results 2 h after initial tests. However, they were still needed if the first tests were done too early. This study also confirms the safety of the guideline's recommendation for outpatient follow-up, especially within the first 24 h, with a very low rate of minor adverse events, and instruction to seek immediate medical attention if symptoms worsen.

Guidelines for reporting case studies and series on drug-induced QT interval prolongation and its complications following acute overdose.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning.Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria.Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented.Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

Utility of QT interval corrected by Rautaharju method to predict drug-induced torsade de pointes.

INTRODUCTION: New QT correction formulae derived from large populations are available such as Rautaharju's [QTcRTH = QT * (120 + HR)/180] and Dmitrienko's [QTcDMT = QT/RR0.413]. These formulae were derived from 57,595 and 13,039 cases, respectively. Recently, a study has shown that they did not experience errors across a wide range of heart rates compared to others. OBJECTIVES: (1) To determine the best cut-off value of QTcRTH and QTcDMT as a predictor of torsade de pointes (TdP) and (2) to compare the sensitivity and specificity using the cut-off value of QTcRTH with those of the QTcBazett (QTcBZT), QTcFridericia (QTcFRD), and QT nomogram. METHODS: Data were derived from two data sets. All cases aged over 18 years with an exposure to QT-prolonging drugs. Group-1, all cases developed TdP. Data in Group-1 were obtained from systematic review of reported cases from Medline since its establishment until 10 December 2015. Group-2 is composed of those who overdosed on QT prolonging drugs but did not develop TdP. This data set was previously extracted from a chart review of three medical centers from January 2008 to December 2010. Data from both groups were used to calculate QTcRTH and QTcDMT. The cut-off values from QTcRTH and QTcDMT that provided the best sensitivity and specificity to predict TdP were then selected. The same method was applied to find those values from QTcBZT, QTcFRD, and QT nomogram. The receiver operating characteristic curve (ROC) was applied where appropriate. RESULTS: Group-1, 230 cases of drug-induced TdP were included from the systematic review of Medline. Group-2 (control group), which did not develop TdP, consisted of 292 cases. After applying all of the correction methods to the two datasets, the best cut-off values that provided the best accuracy (Ac) with the best sensitivity (Sn) and specificity (Sp) for each formula were as follows: QTcRTH at 477 milliseconds (ms), Ac = 89.08%, Sn = 91.30% (95%CI = 86.89-94.61), Sp = 87.33%(95%CI = 82.96-90.92); QTcDMT at 475 ms, Ac = 88.31%, Sn =91.30% (95%CI = 86.89-94.61), Sp = 85.96%(95%CI = 81.44-89.73); QTcBZT at 490 ms, Ac = 86.97%, Sn = 88.26% (95%CI = 83.38-92.12), Sp = 85.96% (95%CI = 81.44-89.73); QTcFRD at 473 ms, Ac = 88.89%, Sn = 89.13% (95%CI = 84.37-92.84), Sp =88.70% (95%CI = 84.50-92.09). We found a significant difference (p-value = 0.0020) between area under the ROC of the QTcRTH (0.9433) and QTcBZT (0.9225) but not QTcFRD (0.9338). The Ac, Sn, and Sp of the QT nomogram were 89.08%, 91.30% (95%CI = 86.89-94.61), and 87.33% (95%CI = 82.96-90.92), respectively, and they were all equal to those of QTcRTH. CONCLUSION: Rautaharju method not only produced minimal errors for QT interval correction but also at QTcRTH 477 ms, it could predict TdP as accurately as QT nomogram and was better than the QTcBZT.

Diospyros rhodocalyx (Tako-Na), a Thai folk medicine, associated with hypokalemia and generalized muscle weakness: a case series.

INTRODUCTION: Diospyros rhodocalyx (Tako-Na) is a Thai folk medicine purported to promote longevity, treat impotence, etc. We present patients with hypokalemia, weakness and hypertension after consuming Tako-Na tea. CASE SERIES: Case 1: A 61-year-old man was brought in nine hours after drinking 400-500 mL of Tako-Na tea. One handful of Tako-Na bark was boiled in water to make tea. He had vomiting and watery diarrhea six hours after drinking it. He took no medications and had no history of hypertension. The only remarkable vital sign was BP 167/90 mmHg. Physical examination revealed generalized muscle weakness. Laboratory findings were potassium 2.7 mmol/L, bicarbonate 24 mmol/L, and transtubular potassium gradient (TTKG) 5.6. He was discharged the next day with a BP 140/90 mmHg and potassium 4.2 mmol/L. Case 2: A 78-year-old man, a friend of case 1, also drank Tako-Na tea from the same pot at the same time as case 1. He also had vomiting and diarrhea six hours later. He took no medications despite past history of hypertension (baseline SBP 140-160). Initial BP was 230/70 mmHg. He also had muscle weakness. Laboratory findings were potassium 3.3 mmol/L, bicarbonate 24 mmol/L, TTKG 7.37 and normal thyroid function. He was also discharged the next day with a BP 148/70 mmHg and potassium 4.2 mmol/L. Case 3-7: These were patients reported to a poison center and their potassium concentrations were 1.4, 1.4, 3.3, 1.3 and 1.2 mmol/L, respectively. Three of them were intubated and case 3 died. CONCLUSIONS: Tako-Na contains betulin, betulinic acid, taraxerone, lupeol, and lupenone. Their structures are similar to glycyrrhetic acid, the active metabolite of glycyrrhizic acid found in licorice which is well known to cause pseudoaldosteronism. Glycyrrhetic acid is potent in inhibiting 11-beta-hydroxysteroid dehydrogenase, and causes pseudoaldosteronism. We hypothesize that the compounds in Tako-Na act in the same way as glycyrrhetic acid in producing pseudoaldosteronism.

Medical toxicologists' practice patterns regarding drug-induced QT prolongation in overdose patients: a survey in the United States of America, Europe, and Asia Pacific region.

OBJECTIVE: To describe practice patterns of medical toxicologists in the United States of America (USA), Europe, and Asia Pacific Region regarding management of drug induced QT prolongation and torsades de pointes in overdose. METHODS: A survey was developed to assess current practice patterns and consistency with guidelines published by the American Heart Association (AHA), American College of Cardiology (ACC), and European Society of Cardiology (ESC). It was reviewed by our department research committee and the American College of Medical Toxicology (ACMT). The ACMT, European Association of Poisons Centres and Clinical Toxicologists, and Asia Pacific Association of Medical Toxicology electronically disseminated the survey to their physician members in the USA, Europe and Asia Pacific Region. RESULTS: The overall response rate was 37% (229/617) (36% USA; 32% Europe; 52% Asia Pacific Region). Twelve toxicologists from Asia Pacific Region and Europe used the QT nomogram (Australia-5, New Zealand-1, United Kingdom-1) or QT alone (France-1, Russia-1, Romania-1, Germany-1, Philippines-1), in lieu of the corrected QT (QTc) to determine risks of developing torsades de pointes. Because only those who used QTc could proceed through the remainder of the survey, only 217 could do so. Approximately half of the respondents (52%) did not calculate QTc manually and based decisions on the electrocardiogram machines automated measurement. For those who corrected the QT interval themselves, the most common formula used was Bazett's (40%). There is great variation in the QTc value considered prolonged. Most responders considered QTc greater than 450 ms in men (28%) and 460 ms in women (25%) to be prolonged. Interestingly, approximately 15% of participants did not consider the QTc prolonged until it exceeded 500 ms in both men and women. Given an overdose scenario of a male patient with a QTc of 560 ms, heart rate of 90 beats/minute, 59% would not recommend administering intravenous magnesium sulfate. Forty-five percent and 36% believed magnesium could shorten QTc and prevent torsades de pointes, respectively. In addition, almost 90% believed administering 1-2 boluses of intravenous magnesium is safe, even when serum magnesium is not available. In regards to cardiac pacing of patients with QT prolongation and torsades de pointes, only 38% of the participating toxicologists' responses agreed with AHA/ACC/ESC recommendations. Furthermore, 21% would not pace a patient who developed torsades de pointes regardless of the scenario. DISCUSSION AND CONCLUSIONS: The results indicate that medical toxicologists have considerable heterogeneity in terms of management practices for overdose patients with QT prolongation and torsades de pointes. Medical toxicologists may benefit from developing evidence-based consensus guidelines for the management of this relatively common finding in overdose of QT-prolonging drugs.

Exotic venomous snakebite drill.

BACKGROUND: There were 900 exotic venomous snakebites reported from 2000 to 2009. The Association of Zoos and Aquariums' recommends institutions housing venomous reptiles have protocols for appropriate and timely transport of envenomed individuals to hospitals. The study objective was to evaluate functional aspects and potential problems of our emergency operation procedure designed for handling the response to an exotic venomous snakebite during implementation via a simulated drill. The emergency operation procedure consists of two protocols, the protocol for zoo personnel and exotic snakebite protocol for hospital personnel. METHODS: Before the exercise the poison center (PC), zoo, Emergency Medical Services (EMS), receiving hospital emergency department (ED), and pharmacy were contacted. The emergency operation procedure was reviewed to determine areas of deficiency. A checklist of all required actions for each participating institution was created for use during the exercise. The exercise was divided into four phases: zoo, EMS, PC, and ED. Each phase was evaluated by an independent observer. RESULTS: Review of the emergency operation procedure revealed sufficient and easy to follow information for zoo personnel. However, the exotic snakebite protocol for hospital personnel lacked details regarding signs and symptoms expected from each exotic venomous species in the zoo; and indications, dosing, and instructions on reconstitution for each of the antivenom carried by the zoo. Zoo, EMS, ED, and PC personnel completed 95%, 90%, 83%, and 25% of the required tasks, respectively. The PC encountered problems communicating the exotic snakebite protocol for hospital personnel to the ED due to phone and fax equipment failures. Creative solutions to the PC system issues were not identified in a timely manner. Despite the shortcomings, the time from simulated envenomation to antivenom (AV) administration was under an hour. CONCLUSIONS: This drill identified several issues leading to revision of our exotic snakebite protocol for hospital personnel. We also identified suboptimal PC response in the application of the emergency operation procedure. We encourage every poison center in cooperation with local zoos to perform a similar exercise.