A 10-Year Retrospective Analysis of Medication Errors among Adult Patients: Characteristics and Outcomes.

Medication errors (MEs) are a global health problem. We conducted this study to clarify the clinical characteristics, outcomes, and factors associated with MEs that caused harm to adult patients (>15 years of age) who were managed in hospitals or healthcare facilities. We performed a 10-year retrospective study (2011-2020) by analyzing data from the Ramathibodi Poison Center (RPC) database (RPC Toxic Exposure Surveillance System). There were a total of 112 patients included in this study. Most were women (59.8%) and had underlying diseases (53.6%). The mean patient age was 50.5 years. Most MEs occurred during the afternoon shift (51.8%) and in the outpatient department (65.2%). The most common type of ME was a dose error (40.2%). Local anesthetic was the most common class of ME-related drug. Five patients died due to MEs. We analyzed the factors associated with MEs that caused patient harm, including death (categories E-I). The presence of underlying diseases was the single factor that was statistically significantly different between groups. Clinical characteristics showed no significant difference between patients aged 15-65 years and those aged >65 years. In conclusion, our findings emphasized that MEs can cause harm and even death in some adult patients. Local anesthetics were the most commonly involved in MEs. Having an underlying disease might contribute to severe consequences from MEs. Preventive measures and safety systems must be highlighted and applied to prevent or minimize the occurrence of MEs.

A Retrospective Cohort Study of Cobra Envenomation: Clinical Characteristics, Treatments, and Outcomes.

This study investigated the clinical characteristics, treatments, and outcomes of envenomation involving cobra species in Thailand (Naja kaouthia, Naja siamensis, and Naja sumatrana). Data of patients who had been bitten by a cobra or inoculated via the eyes/skin in 2018-2021 were obtained from the Ramathibodi Poison Center. There were 1045 patients admitted during the 4-year study period (bite, n = 539; ocular/dermal inoculation, n = 506). Almost all patients with ocular/dermal inoculation had eye involvement and ocular injuries, but none had neurological effects. Most of the patients bitten by a cobra had local effects (69.0%) and neurological signs and symptoms (55.7%). The median interval between the bite and the onset of neurological symptoms was 1 h (range, 10 min to 24 h). Accordingly, patients should be observed closely in hospitals for at least 24 h after a bite. Intubation with ventilator support was required in 45.5% of patients and for a median duration of 1.1 days. Antivenom was administered in 63.5% of cases. There were nine deaths, most of which resulted from severe infection. Neurological effects and intubation were significantly more common after a monocled cobra bite than after a spitting cobra bite. The administration of antivenom with good supportive care, including the appropriate management of complications, especially wound infection, might decrease fatality.

Poisoning from Ingestion of Fungus-Infected Cicada Nymphs: Characteristics and Clinical Outcomes of Patients in Thailand.

The current data regarding poisoning associated with ingestion of fungus-infected cicada nymphs are limited. We performed a retrospective cohort study of patients who ingested fungus-infected cicada nymphs and were referred to the Ramathibodi Poison Center for consultation from June 2010 to June 2022. Thirty-nine patients were included for analysis. Most were men (53.8%). Mean age was 40.2 ± 15.0 years. All nymphs were ingested as a health/food supplement. Thirty-one patients (79.5%) reported gastrointestinal symptoms. Median time from ingestion to symptom onset was 5 h. Twenty-nine patients (74.4%) reported neurological symptoms, including tremor, myoclonus, muscle rigidity, nystagmus/ocular clonus, drowsiness, dysarthria, seizure, and confusion. Some complained of dizziness, urinary retention, and jaw stiffness. Most patients (94.9%) were admitted to the hospital. Median hospital stay was 3 days. Ibotenic acid was detected in the blood and urine samples of one patient. All received supportive care. Four patients developed infectious complications. No deaths occurred. Consuming fungus-infected cicada nymphs may cause poisoning in humans. Gastrointestinal and neurological symptoms were common. Ibotenic acid might be the underlying cause. The main treatment is supportive care and appropriate management of complications. Education of the general public is advocated to prevent the incidence of this type of poisoning.

Clinical characteristics, treatment and outcomes of acute propanil poisoning in a 7-year retrospective cohort study.

The present study was a 7-year retrospective cohort study (2012-2018) of patients treated for acute propanil poisoning by ingestion, using data from Ramathibodi Poison Center, Thailand. The aim of this study was to describe the clinical characteristics, treatment, outcomes and factors associated with moderate to severe outcomes and death following acute exposure to propanil. The effect of administering multiple-dose activated charcoal (MDAC) on clinical outcomes was also evaluated. A total of 275 cases were included. The results show that two thirds of patients were male and mean age was 40 years. Patients ingested either propanil or a mixture of propanil and other herbicides. The majority (98%) of exposures was intentional. Most patients (65.5%) presented with gastrointestinal symptoms. Methemoglobinemia and hemolysis were observed in 108 patients (39.3%) and 25 patients (9.1%), respectively. Median time to onset of methemoglobinemia and hemolysis after propanil ingestion was 5.5 and 48 h, respectively. One hundred and forty-one patients (51.3%) were treated with MDAC, and some patients received methylene blue (21.5%), intubation (18.5%), or blood transfusions (8%). All patients were admitted to hospitals. The median length of hospital stay of patients who survived was 3 days. Multivariate analysis indicated that neurological symptoms at presentation, methemoglobinemia and acute kidney injury during admission, were associated with moderate to severe outcomes. Factors associated with mortality were older age, larger amount of ingestion, neurological symptoms at presentation and hypotension during admission. The overall mortality rate was 6.2%. The mortality rate was 3.6% in patients that received MDAC and 9% in patients that did not, although the difference was not statistically significant. Subgroup analysis of patients who developed methemoglobinemia or both methemoglobinemia and hemolysis found a statistically significant lower mortality rate in patients that received MDAC. In conclusion, methemoglobinemia and hemolysis contribute to poor outcomes in acute propanil poisoning. Age, amount of ingestion, neurological symptoms at presentation and hypotension during admission could prognosticate deaths, and patients with these factors should be closely observed and aggressively managed.

Early Adverse Reactions to Snake Antivenom: Poison Center Data Analysis.

Antivenom is an essential treatment for snake envenomation; however, early adverse reactions (EARs) are major limitations to its use. We performed a retrospective cross-sectional study using Ramathibodi Poison Center data (January 2016 to December 2017) to clarify the incidence and severity of EARs following different F(ab')2 antivenoms. Among 1006 envenomed patients, 684 (68%) received antivenom therapy with a total of 1157 doses, mostly green pit viper antivenom. The overall EAR incidence and rate were 22. 5% (154/684) and 15% (173/1157), respectively. The EAR rate following each type of antivenom was >10%, except for Russell's viper antivenom (2.9%); the severe reaction rate was 2.6% (30/1157). Malayan pit viper bites caused a high incidence of EARs (37.8%) and the highest EAR rate (22.3%). Fifty-two cases developed anaphylaxis. All EARs occurred within 2 h after treatment initiation. No deaths were attributed to EARs. The duration of administration was significantly different between doses of antivenom that induced EARs and those that did not. In conclusion, all types and every dose of antivenom should be infused for 30−60 min. Preparation of resuscitation equipment and continuous clinical observation are crucial for at least 2 h after administration, and prompt treatment should be provided when EARs occur.

Characteristics and Consequences of Medication Errors in Pediatric Patients Reported to Ramathibodi Poison Center: A 10-Year Retrospective Study.

Purpose: This study was performed to evaluate the clinical characteristics of, consequences of, and factors associated with medication errors (MEs) that cause harm to pediatric patients (<15 years of age) treated in the hospital setting. Patients and Methods: We performed a 10-year retrospective study (January 2011-December 2020) by analyzing data from the Ramathibodi Poison Center. MEs were classified into categories A to I according to the severity of the outcome. Results: In total, 121 patients were included in the study. Most (51.24%) patients were male. Their median age was 1 year (range, 1 hour-14 years). Infants, newborns, and toddlers were the three most common age groups in which MEs were reported. Most MEs occurred during the afternoon shift [n = 60 (49.59%)] and in the inpatient department (66.12%). The most common type of MEs was a dose error (64.46%). Antibiotics, sedative agents, and bronchodilators were the three most common classes of ME drugs. Four patients died. Three deaths occurred because of a dose error. One patient was a 1-year-old girl who received an iatrogenic intravenous phenytoin overdose of 10 times the normal dose, resulting in a phenytoin level of 72.4 mcg/mL. She died 22 hours after the ME occurred. The work shift was the only factor that significantly differed between patients with category C and D MEs and those with category E to I MEs. Conclusion: Small children were at highest risk for MEs. MEs induced harm and deaths in some patients. A preventive and safety system, including appropriate shift work administration, should be emphasized and implemented to prevent and/or decrease the occurrence of MEs.

Clinical effects and factors associated with adverse clinical outcomes of hymenopteran stings treated in a Thai Poison Centre: a retrospective cross-sectional study.

OBJECTIVE: To describe clinical effects and outcomes of hymenopteran stings and to explore the non-laboratory factors associated with adverse clinical outcomes, a composite outcome including death, respiratory failure requiring intubation, acute kidney injury (AKI) requiring dialysis and hypotension requiring vasopressor use. METHODS: A retrospective cross-sectional study was performed at the Ramathibodi Poison Center, a poison centre of a tertiary care hospital in Thailand. All cases of hymenopteran sting consultations from January 2015 to June 2019 were consecutively enrolled, and charts were reviewed. Demographics, initial clinical characteristics and outcomes were collected. Factors associated with adverse clinical outcome were explored. RESULTS: One hundred and fourteen hymenopteran stings cases (wasp 48%, bee 33%, hornet 14% and carpenter bee 8.8%) were included (median age, 36.5 years (interquartile range 9-55); male 63%). The prevalence of adverse clinical outcomes was 12.3% (95%CI 6.88-12.8). At initial presentation, 100% of cases had local skin reactions, 11.4% were clinical anaphylaxis, and 8% had red urine. Adverse clinical outcomes included death (n = 10), respiratory failure requiring intubation (n = 9), AKI requiring dialysis (n = 6) and hypotension requiring vasopressor use (n = 2). None of the patients with carpenter bee or hornet stings developed adverse clinical outcomes. In univariable analysis, urticaria, wheezing, red urine, wasp sting and sting number > 10 were significantly associated with adverse clinical outcomes. In multivariable analysis, red urine (adjusted OR 11.1 (95% CI 1.57-216)), wheezing (adjusted OR 16.7 (95% CI 1.43-402)) and a number of stings > 10 (adjusted OR 21.5 (95% CI2.13-2557)) were significant. CONCLUSIONS: Adverse clinical outcomes in hymenopteran stings were not uncommon among cases inquiring to a national Thai poison centre. At initial presentation, red urine, wheezing and a number stings >10 were significantly associated with adverse clinical outcomes. Larger epidemiologic studies are required to confirm these associations.

Malayan Pit Viper Envenomation and Treatment in Thailand.

INTRODUCTION: The Malayan pit viper (MPV; Calloselasma rhodostoma) is a hematotoxic snake found in all regions of Thailand and many countries in Southeast Asia. Treatment of MPV envenomation varies among facilities due to their capabilities. MATERIALS AND METHODS: This study was a retrospective review of patients with MPV envenomation who were reported to the Ramathibodi Poison Center from 1 July 2016 to 30 June 2018. RESULTS: Of the 167 patients (median age, 40.5 years; range, 1.3-87.0 years) bitten by an MPV, the most common bite site was the foot (29.3%). Most patients reached the hospital within 1 hour of being bitten. One-hundred fifty-six patients (93.4%) had local effects from envenomation; 17 patients (10.2%) had severe local complications including necrotizing fasciitis (3.0%) and compartment syndrome (7.2%). Systemic effects such as hemorrhage and abnormal hemostasis occurred in 147 patients (88.0%). Additional effects included abnormal venous clotting time in 123 patients (73.7%), unclotted 20-minute whole blood clotting time in 57 patients (34.1%), low platelet counts (<50,000/µL) in 29 patients (17.4%), prolonged international normalized ratio (>1.2) in 51 patients (30.5%), and systemic bleeding in 14 patients (8.4%). The median onset of bleeding disorder was 6 hours. Monitoring for 24, 48, and 49 hours after bite enabled detection of systemic effects in 94.2%, 99.3%, and 100.0%, respectively. Three hundred fifteen courses of antivenin were administered to 144 patients (86.2%). All the patients who received antivenin recovered from bleeding disorder. Only 7.0% of antivenin doses were administered without Thai Red Cross indications. Allergic reactions from antivenin occurred in 34.7% of the 144 patients. One hundred thirty patients (77.8%) received antibiotics, and 32 patients (19.2%) required surgical management, including debridement and fasciotomy. CONCLUSION: MPV envenomation results in local and systemic effects. Most systemic effects were abnormal clotting test results. Most patients reported onset of bleeding disorder within 48 hours.

Poisoning of Butanol-Containing Products: Clinical Characteristics and Outcomes.

BACKGROUND: Butanol (butyl alcohol) is a chemical which occurs naturally in some foods and is used in the manufacture of other chemicals. Current data on butanol poisoning in humans are limited. OBJECTIVE: This study describes clinical characteristics and outcomes of patients exposed to products containing butanol. METHODS: We performed a 5-year retrospective cross-sectional study by analyzing data from the Ramathibodi Poison Center Toxic Exposure Surveillance System for 2013-2017. RESULTS: There were 163 patients included in the study. All products containing butanol reported were agricultural adjuvant products. Most (67.5%) patients were males and had ingested butanol accidentally (75.5%). The median age was 42 years. Almost all patients had oral exposure to butanol. At presentation, most of our patients had normal vital signs and were conscious. Clinical presentations mostly included gastrointestinal symptoms (65%) and local irritation (28.8%). Fifty-four patients (33.1%) had no obvious clinical effects at presentation. Most patients had normal laboratory tests at presentation, although eight developed systemic effects including high anion gap metabolic acidosis (n=8), acute kidney injury (AKI; n=5), depression of consciousness (n=5), and hypotension (n=3). Of these eight patients, two with intentional ingestion developed altered consciousness, hypotension, AKI, severe metabolic acidosis, and eventually died. One of these died within 1 day after ingestion, while the other died later through complications during admission. Therefore, the mortality rate was 1.23%. Sixty-six patients (40.5%) were admitted to hospitals, with a median length of stay of 1 day. Most patients received only supportive treatment and fully recovered. CONCLUSION: Agricultural adjuvant products containing butanol or butanol itself caused only mild effects in most patients, but systemic effects occurred in some. The mortality from this poisoning was very low, and both fatalities were from intentional ingestion. Supportive care and proper management of complications should be the main treatment for this form of poisoning.

Development of a Physiologically Based Pharmacokinetic Model of Mitragynine, Psychoactive Alkaloid in Kratom (Mitragyna Speciosa Korth.), In Rats and Humans.

Mitragynine is a major psychoactive alkaloid in leaves of kratom (Mitragyna speciosa Korth.). To understand its disposition in organs, this study aimed to develop a physiologically based pharmacokinetic (PBPK) model that predicts mitragynine concentrations in plasma and organ of interests in rats and humans. The PBPK model consisted of six organ compartments (i.e. lung, brain, liver, fat, slowly perfused tissues, and rapidly perfused tissue). From systematic searching, three pharmacokinetic studies of mitragynine (two studies in rats and 1 study in humans) were retrieved from the literature. Berkeley Madonna Software (version 8.3.18) was used for model development and model simulation. The developed PBPK model consisted of biologically relevant features following involvement of (i) breast cancer-resistant protein (BCRP) in brain, (ii) a hepatic cytochrome P450 3A4 (CYP3A4)-mediated metabolism in the liver, and (iii) a diffusion-limited transport in fat. The simulations adequately describe simulated and observed data in the two species with different dosing regimens. PBPK models of mitragynine in rats and humans were successfully developed. The models may be used to guide optimal mitragynine dosing regimens.

Poisoning of glutaraldehyde-containing products: clinical characteristics and outcomes.

OBJECTIVE: This study describes the clinical characteristics, outcomes, and factors at presentation associated with death of cases poisoned by glutaraldehyde (GA)-containing products. METHODS: We performed a 5-year retrospective cohort study (July 2013-June 2018) using data from the Ramathibodi Poison Center. RESULTS: There were 244 cases included in this study. Most were men with a median age of 37 years. The GA-containing products were mainly used as farm disinfectants (99.2%), with a median concentration of 15%. Most products (76.2%) contained co-formulants such as cationic detergents and formaldehyde.Most circumstances were accidental (56.9%). The others were suicide attempts by ingestion, except one patient who intentionally injected GA subcutaneously. The most common route of exposure was ingestion (95.0%). Local symptoms in areas of exposure were common. Ingestion resulted in more severe local effects than other routes, and corrosive effects occurred in 23 cases (9.4%). Systemic signs and symptoms occurred in 149 patients (61.1%). Systemic effects included abnormal vital signs, desaturation, altered mental status, hypo/hypernatremia, hypokalemia, low bicarbonate/metabolic acidosis, acute kidney injury (AKI), hepatitis, and rhabdomyolysis. Systemic effects mostly resulted from ingestion. Most patients had mild severity, received only supportive treatment, and fully recovered. The median length of hospital stay was 2 days. The one case of subcutaneous injection developed both local and systemic effects but survived. The mortality rate was 3.7%. Multivariate analysis indicated that either neurological symptoms or AKI at presentation were associated with death. CONCLUSIONS: In our study, patients were exposed to GA-containing products that were mainly used as farm disinfectants and were generally co-formulated with other substances. Poisoning with these products commonly resulted in mild local irritative symptoms. However, some cases developed corrosive symptoms, systemic effects, or even died. As neurological symptoms or AKI could prognosticate deaths; physicians should look for these factors in patients with GA exposure at presentation for close monitoring and aggressive treatment.

Toad Poisoning: Clinical Characteristics and Outcomes.

OBJECTIVE: This study was performed to describe the clinical characteristics and outcomes of patients with toad poisoning in Thailand. METHODS: We carried out a retrospective study of patients with toad poisoning from the Ramathibodi Poison Center Toxic Exposure Surveillance System during a 5-year period (2012-2016). RESULTS: We studied 36 patients poisoned by toad toxin. The median age was 31 years. Most patients were male (66.7%) and had ingested toad meat (50%). The most common presentation was gastrointestinal (GI) symptoms with a median onset of 2 h after ingestion. Twelve patients presented with bradycardia; seven presented with shock and one with cardiac arrest. In the initial EKGs of all patients, the most common abnormality was sinus bradycardia.Two patients developed cardiac arrest early during management in the emergency room (within 15 minutes after ER arrival or within 4.5 h after ingestion). During admission, one patient developed sinus bradycardia, and two developed bradyarrhythmia; however, all three were stable. No tachyarrhythmias such as ventricular tachycardia were detected in any patient. Some patients (11.1%) presented with hyperkalemia. Serum digoxin was detected in five of seven patients tested, ranging from 0.43 to >8 ng/mL. Most patients (75%) were admitted to the hospital; the median duration of hospitalization was 2 d (range 0.5-5 d). The overall mortality rate was 8.3%, and all three patients that died ate toad meat and/or eggs and developed cardiac arrest. All patients received supportive with/without symptomatic care including GI decontamination, inotropic drugs, cardiac pacing, and management of hyperkalemia. One patient received intravenous calcium for hyperkalemia but did not develop dysrhythmia after calcium administration. One patient received digoxin-specific antibody fragments (DsFab), after which he clinically improved and was discharged. CONCLUSION: Toad poisoning commonly caused GI symptoms and bradycardia. However, in severe cases, death occurred. Tachyarrhythmia was not observed. Supportive, symptomatic care might be the main therapies for this poisoning, especially if DsFab is not available.

Myotoxic Mushroom Poisoning in Thailand: Clinical Characteristics and Outcomes.

PURPOSE: To describe the clinical characteristics and outcomes of myotoxic mushroom poisoning in Thailand. PATIENTS AND METHODS: We performed a retrospective cohort study of cases of myotoxic mushroom poisoning from the Ramathibodi Poison Center Toxic Exposure Surveillance System during a 5-year period (2012-2016). RESULTS: Forty-one cases were included. Most (53.7%) were male with the average age of 49 years. In three cases, the mushrooms were identified as Russula species by an experienced mycologist. Common presenting symptoms were gastrointestinal (GI) symptoms and myalgia. The median onset of GI symptoms and symptoms suggesting rhabdomyolysis after consuming mushrooms was 2 hours (0.17-24 hours) and 24-48 hours (2-120 hours), respectively. Eight patients who ate the mushrooms together with other patients with rhabdomyolysis had GI symptoms but did not develop rhabdomyolysis. For patients with rhabdomyolysis, acute kidney injury (AKI) and hyperkalaemia occurred in 51.5% and 33.3% of cases, respectively. Median initial and maximum creatine phosphokinase (CPK) levels in patients with rhabdomyolysis were 31,145 and 47,861 U/L, respectively. Fifteen of 17 patients who were investigated for troponin levels had elevated troponin. Three patients had a low ejection fraction. Most patients (95.1%) were admitted to hospital, with a median stay of 5 days. The mortality rate was 26.8%. Treatments included intravenous fluid, urine alkalinization, haemodialysis and peritoneal dialysis. Among patients with rhabdomyolysis, AKI, hyperkalaemia during hospitalisation, maximum CPK level, maximum creatinine level and initial and maximum potassium levels were the factors found to be significantly different between patients who died and those who survived. CONCLUSION: Myotoxic mushroom poisoning had a high mortality rate. Most patients had early or delayed onset of clinical symptoms after mushroom ingestion. Some patients developed severe cardiovascular effects. Early detection, close monitoring (especially serum potassium, creatinine, CPK and cardiac effect) and good supportive care were the main treatment modalities.

Acute Imidacloprid Poisoning in Thailand.

INTRODUCTION: Imidacloprid is the most commonly used neonicotinoid insecticide worldwide. Despite its reputation for safety, there is increasing evidence regarding its toxicity. This study characterized the clinical manifestations and outcomes of acute imidacloprid poisoning. METHODS: This was a retrospective study of patients with imidacloprid poisoning who were referred to the Ramathibodi Poison Center in Bangkok, Thailand between 2010 and 2018. RESULTS: A total of 163 patients with imidacloprid-only exposure were included. Most were exposed by ingestion (93.3%). The patients were predominantly male (55.8%), with a median age of 41.3 years. The common presenting features were gastrointestinal symptoms (63.8%) with no corrosive injuries and neurological effects (14.2%). The majority of medical outcomes was no (18.4%) to mild (76.1%) toxicity. One patient had symptoms mimicking cholinergic syndrome, three developed liver injury, and five died. Among the five deaths, two patients presented severe initial severity, and one presented moderate initial severity. Two of the patients who died initially presented only mild severity. The mortality rate was 3.1%. The estimated amount of ingestion, cardiovascular effects (especially tachycardia and cardiac arrest), central nervous system effects (especially coma), dyspnea, and diaphoresis were significantly associated with mortality. Patient management primarily included supportive and symptomatic care. CONCLUSION: Most patients with imidacloprid poisoning developed only mild toxicity. The mortality rate was low, but a few patients with mild initial severity died. Patients who ingest a large amount or show these warning signs including cardiovascular effects, central nervous system effects, dyspnea, and diaphoresis at the initial presentation should be considered for close observation and monitoring.

Clinical Characteristics of Acalypha indica Poisoning.

BACKGROUND: Acalypha indica is a tropical plant used as a herbal medicine in various parts of the world, including Thailand. In glucose-6-phosphate dehydrogenase (G6PD)-deficient patients, acute hemolysis has been reported following the ingestion of this plant. Methemoglobinemia was reported in the present study. PATIENTS AND METHODS: Descriptive data of patients who suffered from Acalypha indica toxicity reported from different hospitals to the Ramathibodi Poison Center were retrieved from 2011 to 2019. RESULTS: Eight patients were included, mostly male with a median age of 61.5 years. The plant was ground for fresh juice or boiled before consuming as herbal medicine. All patients presented with dark urine. Most had jaundice and fever, and all reported hemolysis. Seven out of eight patients were diagnosed as methemoglobinemia. Methemoglobin level was confirmed in five patients with the highest level of 23.9%. Early symptoms occurred within 24 hours of the last ingested dose. DISCUSSION: In previous case reports of Acalypha indica ingestion, acute hemolysis was mostly observed in G6PD-deficient patients, consistent with the current findings. However, our patients also demonstrated methemoglobinemia, with some constituents in this plant (quinine, 2-methyl anthraquinone and tectoquinone) implicated as the cause in previous studies. Further studies are crucial to validate these findings. CONCLUSION: We report a case series in which acute hemolysis and methemoglobinemia after Acalypha indica ingestion were observed. This study presents methemoglobinemia as the other toxicity caused by this plant.

Hematotoxic Manifestations and Management of Green Pit Viper Bites in Thailand.

INTRODUCTION: Green pit vipers (GPV) are widely distributed throughout Thailand and are responsible for significant morbidity. The primary objective of this study was to characterize clinical presentations and treatment methods for GPV bites. The secondary objective was to demonstrate the earliest and latest onset of hematotoxicity. METHODS: GPV bites reported to the Ramathibodi Poison Center between July 1, 2016, and June 30, 2018, were analyzed. RESULTS: There were 288 GPV cases within the study period. Patients were predominantly male (62.8%), and the median age was 40 years (interquartile range (IQR) 22.8-58). Median time from envenomation to hospital presentation was 1 hour (IQR 0.5-2). Patients were primarily bitten on the finger (27.4%). Most patients reported swelling (90.3%). Necrosis and compartment syndrome occurred in 13 and 9 cases, respectively. Systemic effects occurred in 190 cases (65.9%), with median onset 15 hours (IQR 6-28.3) post-bite. Venous clotting time (VCT) showed the highest percentage of abnormalities. Systemic bleeding occurred in 13 cases (4.5%). Monitoring patients for 24, 48, and 72 hours after bites detected 62.7%, 85.9%, and 96.5% of cases with systemic effects, respectively. In total, 184 patients (62.5%) were treated, sometimes repeatedly, with antivenoms (285 courses, 949 vials). The most common indication was prolonged VCT (144 courses, 50.5%). Recurrent systemic effects after antivenom occurred in 11 cases (6.1% of patients received antivenom). No recurrence presented as systemic bleeding. Adverse reactions to antivenom were reported in 44 courses (15.4% of 285 courses), being anaphylaxis in 19 courses (6.7%). Other treatments included antibiotics (192 cases, 66.7%), surgical intervention (10, 34.7%), and blood components (4, 1.4%). CONCLUSION: Most GPV bites result in envenomation. The most frequent local effect is mild swelling. Systemic bleeding is uncommon. The current recommendation of a 3-day follow-up can detect up to 96% of patients who may require antivenom. No severe morbidity or mortality is reported. Antivenoms are primarily indicated by prolonged VCT. Side effects of antivenom are minimal.

Utility of Thrombin Time in Management of Patients with Green Pit Vipers Bite.

OBJECTIVES: GGreen pit vipers (GPV) envenomation causes consumptive coagulopathy mainly by thrombin-like enzymes. Fibrinogen levels are generally investigated to help evaluate systemic envenomation. However, tests of fibrinogen levels may not be available in every hospital. This study aimed to determine the sensitivity, specificity and accuracy for a range of various coagulation tests (20 minute whole blood clotting test (20WBCT), prothrombin time, international normalized ratio and thrombin time (TT)), comparing to the two gold standards performed in patients with GPV bite. METHODS: This was the pilot study which we retrospectively reviewed fibrinogen level results including the hospital records of 24 GPV (Trimeresurus albolabris or macrops) bite patients visiting Ramathibodi Hospital, Thailand during 2013-2017 with 65 results of fibrinogen levels. The fibrinogen levels <164 and <100 mg/dL were used as the standard cut-off points or gold standards as the abnormal low and critical levels, respectively. RESULTS: Most were male. All had local effects. For fibrinogen levels <164 and <100 mg/dL, prolonged TT had the highest sensitivity of 57.1% and 82.4%; the negative predictive value of 74.5% and 93.6%; the accuracy of 81.0% and 92.1%; and the area under a receiver operating characteristic curve of 0.762 and 0.873, respectively. For fibrinogen levels <164, unclotted 20WBCT and prolonged TT had the highest specificity and positive predictive value of 100% all. For fibrinogen levels <100, unclotted 20WBCT had the highest specificity and positive predictive value of 100% both, while prolonged TT had the specificity and positive predictive value of 95.7% and 87.5%, respectively. One patient developed isolated thrombocytopenia without hypofibrinogenemia and coagulopathy. CONCLUSIONS: Among four coagulation tests, TT was the most sensitive and accurate test to indicate hypofibrinogenemia in GPV bite patients. In case of unavailable fibrinogen levels thrombin time might be investigated to help evaluate patients' fibrinogen status. Isolated thrombocytopenia could occur in GPV envenomation.

Recurrent neurotoxic envenoming of cobra bite.

Recurrent systemic envenomation in patients who sustained viper bites, and who previously responded to antivenom, is well described in the literature. However, cases of recurrent neurotoxic envenoming after antivenom treatment are rarely reported. We present three patients who were envenomed by a cobra (Naja kaouthia or N. siamensis) and experienced recurrent neurotoxic envenomation after they initially responded to antivenom treatments. These three patients, aged 13, 35 and 65 years, were consulted to the Ramathibodi Poison Centre. All were bitten by cobra snakes and developed neurotoxic signs and symptoms including ptosis, muscle weakness, and respiratory failure. All were treated with, and responded to, Fragment Affinity-Purified Secondary Antibody [F(ab')2] antivenom. Two cases underwent debridement and fasciotomy. One case required extensive wound dressing with bleb aspiration, in addition to usual wound care. Approximately 6-14 hours after these procedures, all three patients developed recurrent signs and symptoms of neurotoxicity. All received second doses of antivenom, after which their symptoms improved, and all were ultimately discharged. Each of these cases exhibited recurrent systemic envenomation that resulted from cobra bites after they exhibited antivenom responses. We believe that non-neutralized venom that remained at the bite site, was released, and re-entered the circulation after the wound was manipulated or the patient underwent surgery. This may explain these instances of recurrent envenomation. Future investigations should examine other potential mechanisms of recurrent envenomation, especially in patients without histories of aggressive wound manipulation. If neurological effects recur, prompt re-treatment with antivenom should be considered.

Clinical outcome of paraquat poisoning during pregnancy.

Objectives: We aimed to describe clinical characteristics and outcomes of paraquat poisoning in pregnant patients, their fetuses, and newborns. Methods: We performed a retrospective study of pregnant patients who were exposed to paraquat, from the Ramathibodi Poison Center Toxic Exposure Surveillance System, during a 5-year period. Results: Thirty-six patients, representing every trimester, were included. All experienced oral exposure with a mean age of 22.7 years and mean gestational age (GA) of 23.1 weeks. Most had gastrointestinal symptoms and signs. Systemic effects, which mainly comprised of acute kidney injury (AKI), were found in 13 patients (36.1%); obstetric complications were noted in five patients (13.9%). Medical treatment included intravenous dexamethasone and cyclophosphamide. Some patients received hemodialysis and endotracheal intubation. Nine patients delivered during hospitalization; four newborns (maternal GAs of 30-36 weeks with systemic effects) died after delivery. One patient with GA 26 weeks delivered and died, but her newborn survived. Mortality rates of pregnant patients and their offspring delivered in-hospital were 25% and 44.4%, respectively; all deaths occurred in patients with systemic toxicity. The median length of hospital stay was 6 days. Notably, AKI, hepatotoxicity, and maximum white blood cell count significantly differed between dead and surviving patients. We followed-up 15 surviving patients who were discharged before delivery to assess delivery outcomes. All 15 patients and newborns survived without reports of congenital anomalies. Conclusions: Paraquat poisoning during pregnancy caused high fatalities in pregnant patients, fetuses, and newborns who were delivered during hospitalization, especially among patients with systemic effects. The GA of the pregnancy affected fetal outcomes, both in utero and at birth. Selective, appropriate management is warranted and might be guided by poisoning severity and the GA of the pregnancy.

Improving access to antidotes and antivenoms, Thailand.

PROBLEM: Historically in Thailand, access to poison antidotes was limited and antivenom stock management was inefficient. APPROACH: In 2010, the country established a national antidote programme, which created national and subnational antidote stocks, managed their distribution and trained health-care providers on clinical management and antidote use. In 2013, the programme incorporated antivenoms to improve stock management and avoid wastage due to stock expiry. LOCAL SETTING: Before the programme, health-care providers consulted poison centres on clinical management of poisoning and some antidotes were not available. Individual hospitals stocked antivenoms, which often expired before use. RELEVANT CHANGES: Today, the National Health Security Office finances and manages the centralized procurement of antidotes and antivenoms and all Thai patients have a right to antidotes regardless of health insurance. National and subnational stock levels are determined based on demand, treatment urgency and cost. A web-based system, which incorporates geographical information, was introduced for requesting antidotes and antivenoms. Poison centres provide training, 24-hour consultation services and outcome monitoring. Antidotes and antivenoms are now readily available and used correctly and clinical management has improved. Moreover, better stock and distribution control has helped avoid antivenom wastage and reduced antivenom costs, from US$ 2.23 million United States dollars (US$) to US$ 1.2 million. LESSONS LEARNT: The programme's success depended on strong and sustained policy support, adequate funding, improved operational capacity, training for health-care professionals and the provision of 24-hour online consultation services. A web-based centralized procurement and distribution ensured these essential medicines were available, minimized costs, reduced waste and saved lives.