Sahaphume Srisuma

NBOMe and 2C substitute phenylethylamine exposures reported to the National Poison Data System

Abstract Background. Hallucinogenic designer drugs, especially NBOMe and the 2C substitute phenylethylamine series, have been increasing ubiquitous in past years. The purpose of this study is to characterize and compare clinical features of NBOMe and 2C exposures in humans. Method. This is a retrospective cohort study of all single agent exposures to NBOMe and 2C substitute phenylethlamine reported to the National Poison Data System (NPDS) from 1st September 2012 to 30th September 2014. Results. Over the study period, there were a total 341 cases including 148 NBOMe exposures and 193 2C exposures. The majority cases involved men (73.9%); median age was 18 years (Interquartile-range, 16–21). Similar clinical effects were reported in both groups including tachycardia (45.2%), agitation/irritable (44.3%), hallucination/delusion (32.0%), confusion (19.1%) and hypertension (18.5%). There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe exposures (40.5%, 8.8% and 50.0%respectively) than those of 2C exposures (25.4%, 3.1%, and 32.6% respectively). There were 2.3% death; no difference between two groups. Discussion. The higher rate of symptoms in NBOMe is consistent with the higher 5HT2A agonistic effects of NBOMe described in both molecular and animal studies. Conclusion. Common clinical effects of NBOMe and 2C exposures were tachycardia, agitation/irritable, hallucination/delusion, confusion, and hypertension. There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe.

Characterization of edible marijuana product exposures reported to United States poison centers

Abstract Context: Edible marijuana products are sold as brownies, cookies, and candies, which may be indistinguishable from counterparts without marijuana and are palatable to children and adults. The consumption of an entire product containing multiple dose-units may result in overdose. Objective: To characterize edible marijuana exposures reported to US poison centers with subgroup analysis by age. Methods: We analyzed single substance, human exposure calls coded to marijuana brownies, candies, cookies, beverages, or other foods reported to the National Poison Data System from January 2013 to December 2015. Calls were analyzed by state, age, gender, exposure route, clinical effect, therapies, and level of healthcare facility utilization. Results: Four-hundred and thirty calls were reported: Colorado (N = 166, 1.05/100,000 population/year) and Washington (96, 0.46) yielded the highest number of exposures. Three hundred and eighty-one (91%) calls occurred in states with decriminalized medical/recreational marijuana. The number of calls increased every year of the study. The most common age groups were: ≤5 years (N = 109, 0.15/100,000 population/year) and 13–19 (78, 0.09). The most frequent clinical effects were drowsiness/lethargy (N = 118, percentage = 43%), tachycardia (84, 31%), agitated/irritable (37, 14%), and confusion (37, 14%). Children ≤5 years have more drowsiness/lethargy, ataxia, and red eye/conjunctivitis. No deaths were reported. The most common therapies administered were intravenous fluids (85, 20%), dilute/irrigate/wash (48, 11 %), and benzodiazepines (47, 11%). Three patients (ages 4, 10, and 57 years) received intubation. 97 (23%), 217 (50%), and 12 (3%) calls were managed at home, treated/released, admitted to a critical care unit, respectively. Discussion: Although most clinical effects are minor, ventilatory support may be necessary for children and adults. We speculate the increasing exposures may be related to a combination of delayed absorption kinetics of Δ9-tetrahydrocannablnol, lagging packaging regulations, increased accessibility in decriminalized states, and increased familiarity of poison center specialists with edible product codes. Conclusions: Edible marijuana exposures are increasing and may lead to severe respiratory depression.

Clinical characteristics and outcome of toxicity from Amanita mushroom poisoning

Objective To describe and analyze the clinical characteristics and outcome of amatoxin poisoning cases. Methods We performed a retrospective cohort study of amatoxin poisoning cases from Ramathibodi Poison Center Toxic Exposure Surveillance System, from May 2013 to August 2015. Results There were 30 consultations with a total of 55 poisoning cases. Most cases were male and from the north-east region. Hepatitis, acute kidney injury, jaundice, and coagulopathy accounted for 74%, 46.3%, 44.7%, and 52.8% of the cases, respectively. Almost all of the patients were admitted to the hospital, and the median duration of hospital stay was found to be 4 days. Mortality rate was found to be 27.3%. Most patients (73%) received the treatment including multiple-dose activated charcoal (67.5%), intravenous N-acetylcysteine (87.5%), and benzylpenicillin (45%). In 60% of the cases, the treatment was initiated within 24 h after eating mushrooms. Exchange transfusion and liver transplantation were performed in one severe case. However, this patient died eventually. Because intravenous silybinin is not available in Thailand during the study period, 8 patients received oral silymarin instead. All 8 patients had hepatitis and were treated with high dosage of oral silymarin (5 patients with 4.48 g/day, 2 patients with 1.68 g/day, and 1 patient with 1.4 g/day) for a couple of days. One of these patients died as she received treatment very late; she was treated with silymarin at 1.68 g/day dosage. Thus, the fatality in oral silymarin treatment group was 12.5%. We performed the analysis between the dead and survival groups. We found that in hepatitis, initial and maximum serum aspartate transaminase, initial and maximum serum alanine transaminase, and acute kidney injury were significantly different between the two groups. Conclusion Amanita mushroom poisoning caused high fatalities. Serum transaminase and creatinine were the factors associated with death. Treatment with oral high dose silymarin should be investigated further as one of the principal therapies in amatoxin poisoning.

Proximal muscle weakness in severe lead poisoning from retained bullet fragments

Motor weakness in lead poisoning commonly affects distal upper limbs. This report describes a severe lead poisoning case from retained bullet fragments, presenting with predominated proximal motor weakness, GI symptoms, anemia, and encephalopathy. A 31-year-old male with retained bullet fragments had symptomatic lead poisoning 6 weeks after being shot by shotgun in his left chest. He developed abdominal pain and constipation without improvement with supportive care. His barium enema study was also normal. He developed muscle weakness at 10 weeks post injury. Examination at general hospital revealed proximal muscle weakness and microcytic anemia (hematocrit: 24%; mean corpuscular volume or MCV: 70 fl (80 – 100)) with basophilic stippling. Lead poisoning from the retained bullet fragments was suspected, and he was referred to a tertiary hospital. On arrival at tertiary hospital, the patient was agitated and restless with generalized weakness predominate in proximal limbs; motor power grade IV in all extremities except grade III in both elbow fl exion and both hips, and grade II in both shoulders. Deep tendon refl exes were absent. The physical examination was otherwise unremarkable. Pre-chelated whole blood lead level was 126 mcg/dl (0 – 5). He also had transient increased thyroxine (T4) level: 2.19 ng/dl (0.70 – 1.48) which spontaneously resolved in one week; free T3 and thyroid stimulating hormone levels were normal. Electrolyte, creatinine, liver function, and serum creatine phosphokinase (CPK) levels were normal. A chest X-ray (Fig. 1) and subsequent CT scan showed multiple metallic fragments in his left scapula, left upper lung, and left 4th and 5th ribs. Motor nerve conduction studies showed generalized small compound muscle action potentials (CMAP) without any change in conduction velocity, compatible with axonopathy without demyelination. Electromyography and sensory nerve study were not performed due to the patient ’ s critical condition. He got transfusion with packed red blood cell and was treated with dimercaprol (British anti-Lewisite or BAL) and calcium disodium ethylenediaminetetraacetic acid (EDTA). On the 4th day of chelation, the patient developed worsening encephalopathy and motor weakness despite ongoing chelation, and he was intubated for respiratory failure. Two days later, he regained his consciousness, but still had weakness with low negative inspiratory force of 3 cm H 2 O ( 15 suggests imminent ventilatory failure). On the 10th day of chelation, his blood lead level had decreased to 23 mcg/dL. Dimercaprol was stopped and calcium disodium EDTA treatment was continued. After 2 weeks of chelation, his motor power started to gradually improve, fi rst in distal musculature. Surgical debulking of the retained fragments in his lung, pleura, and ribs was performed on the 24th day. He was extubated on the 33rd day of chelation. Later, the chelator was switched to oral d-penicillamine, 750 mg/d. His clinical condition was gradually improved to totally independent active living with his blood lead level stabilized around 40 mcg/dl at the 6th month of chelation with continuing oral d-penicillamine. Peripheral neuropathy from lead poisoning typically affects distal upper limbs. 1 Lead neuropathy can be due to demyelination or axonopathy. Studies in human with asymptomatic chronic lead exposure report decrease in conduction velocity compatible with demyelination, while reports of overt lead neuropathy show decreases in CMAP compatible with axonopathy. 1 – 3 Proximal muscle weakness is rare, and may be found in cases with relatively abrupt and massive lead exposure. 4 – 6 In anemic cases, more lead dissolved in plasma may readily distribute to target organs. 6,7 In this setting, red blood cell transfusion has been recommended to bind free lead. 7

Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors.

Abstract Background. Although uncommon, severe ergotism continues to occur. The purpose of this study is to describe causes and clinical effects of ergotism in recent years. Methods. This is an observational case series with data obtained retrospectively from all patients with ergotism referred to Ramathibodi Poison Center in Bangkok, Thailand from January 2006 to August 2013. Result. Twelve cases of ergotism were identified. All cases involved ergotamine 1 mg/caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug–drug interactions with CYP3A4 inhibitors. The other cases involved suicidal attempt (2 cases) and pediatric unsupervised ingestion (1 case). Ten patients (83%) had signs of peripheral vascular insufficiency. Five of these patients initially had factitiously low or unmeasurable blood pressure using non-invasive technique and had paradoxical increase following intravenous vasodilator administration. Two patients required partial foot amputations due to gangrene. Two patients, including a 15-month-old boy with an unsupervised ingestion, died. Discussion. In this series, most cases of severe ergotism were associated with interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability. Factitious low blood pressure in these cases was likely caused by severe vasospasm. Conclusion. Critical ergotism continues to occur in Thailand, most commonly associated with the drug–drug interactions.

Missed opportunities? An evaluation of potentially preventable poisoning deaths

Abstract Introduction: Although most poisoning deaths are not preventable with current medical technology, in some cases different management decisions may have prevented fatal outcomes. Objective: This study aims to review reported poisoning-related deaths for preventability to provide insight to improve future care. Methods: Fatality abstracts published in the US National Poison Data System (NPDS) Annual Reports (2008–2012) were analyzed. Preventability was graded using a Likert scale of 1 (definitely non-preventable) to 6 (definitely preventable). Two medical toxicologists screened all cases. Cases deemed definitely not preventable (score 1) by both reviewers were excluded from further review and considered to be “non-preventable”. All cases considered at least possibly preventable by either screener were reviewed by a multidisciplinary panel of 5 physicians for preventability scoring. Differences were resolved by consensus. Cases determined to be “preventable” (scores 4–6) were characterized by type of improvement issue involved (diagnosis, treatment, monitoring, other) and recurring scenarios. Results: Of 390 published abstracts, 78 (20.0%) deaths were considered at least possibly preventable by at least one screener. Of these, 34 (8.7%) deaths were determined to be “preventable” by the panel. Inter-observer agreement by weighted kappa analysis was 0.58 for screening, 0.24 for preventability, and 0.44 for specific aspects of care. The most common toxicants were salicylates (n = 9), opioids (n = 4), toxic alcohols (n = 3), fluoride containing product (n = 3), and bupropion (n = 3). The most common improvement opportunities involved treatment and monitoring. Discussion: Most of the ingested substances in preventable deaths have delayed GI absorption or require metabolic activation to produce a delayed effect (such as salicylates, opioids, and toxic alcohols), and therefore provide an opportunity for early recognition and successful interventions. Most improvement opportunities are clearly described in the literature but may be not recognized. Conclusions: Based on an analysis of published NPDS data, a considerable number of poisoning-related deaths reaching medical attention may be preventable. The most common scenarios involved in potentially preventable poisoning fatalities related to monitoring and treatment. Salicylates and opioids were the most common agents involved in preventable deaths.

Krait envenomation in Thailand

Purpose Three species in the genus Bungarus inhabit Thailand. Among these, Bungarus candidus (Malayan krait) is the most common and deadliest. Currently, the clinical manifestations of patients envenomed by kraits, especially Bungarus fasciatus (banded krait), have not been thoroughly investigated. This study was performed to elucidate the clinical manifestations and outcomes of patients bitten by kraits in Thailand. Materials and methods The data of krait envenomation cases that occurred during a 9-year period were obtained from the Ramathibodi Poison Center Toxic Exposure Surveillance System and retrospectively analyzed. Results In total, 78 cases of krait envenomation were included. Most patients were male (59.0%) and the median age was 28 years. All had minimal local effects. The median duration from the bite to the onset of neurological manifestations was 3 hours (range, 0.5–8 hours). Besides neurological effects, the patients also developed high blood pressure (67.4%), tachycardia (61.7%), hypokalemia (55.3%), and hyponatremia (17.6%). Severe hyponatremia (<120 mEq/L) was noted in four pediatric patients. Other clinical manifestations were bradycardia, abdominal pain, and rhabdomyolysis. The mortality rate was 6.4%, and all deaths occurred from B. candidus bites. Eighty-six percent of patients received antivenom. Most patients (75.6%) were intubated and underwent assisted ventilation for a median of 6 days (range, 1–37 days). The median length of hospital stay was 7 days. Some patients developed complications during hospitalization; the most common was pneumonia. These in-hospital complications were significantly associated with death. Conclusion Although krait bites caused only minimal local effects, the mortality rate was still high, particularly from Malayan krait bites. Besides neurological effects, other clinical manifestations were high blood pressure, tachycardia, hypokalemia, and hyponatremia. Thus, vital signs and electrolytes should be frequently and closely monitored in these patients. Apart from antivenom treatment, adequate supportive care including management of complications might help to decrease the mortality rate.

Cyanide poisoning in Thailand before and after establishment of the National Antidote Project

Abstract Context: Antidote shortage is a global problem. In Thailand, the National Antidote Project (NAP) has operated since November 2010 to manage the national antidote stockpile, educate the healthcare providers on appropriate antidote use, and evaluate antidote usage. Objective: To evaluate the effect of NAP implementation on mortality rate and antidote use in cyanide poisoning cases arising from ingestion of cyanide or cyanogenic glycoside. Methods: This is a retrospective cohort of poisoning cases involving cyanide or cyanogenic glycoside ingestion reported to Ramathibodi Poison Center from 1 January 2007 to 31 December 2015. Mortality rate, antidote use, and appropriateness of antidote use (defined as correct indication, proper dosing regimen, and administration within 90 min) before and after NAP implementation were compared. Association between parameters and fatal outcomes was analyzed. Results: A total of 343 cases involving cyanide or cyanogenic glycoside ingestion were reported to Ramathibodi Poison Center. There were 213 cases (62.1%) during NAP (Project group) and 130 cases (37.9%) pre-NAP implementation (Before group). Implementation of NAP led to increased antidote use (39.9% in Project group versus 24.6% in Before group) and a higher rate of appropriate antidote use (74.1% in Project group versus 50.0% in Before group). All 30 deaths were presented with initial severe symptoms. Cyanide chemical source and self-harm intent were associated with death (OR: 12.919, 95% CI: 4.863–39.761 and OR: 10.747, 95% CI: 3.884–28.514, respectively). No difference in overall mortality rate (13 [10.0%] deaths before versus 17 [8.0%] deaths after NAP) was found. In subgroup analysis of 80 cases with initial severe symptoms, NAP and appropriate antidote use reduced mortality (OR: 0.327, 95% CI: 0.106–0.997 and OR: 0.024, 95% CI: 0.004–0.122, respectively). In the multivariate analysis of the cases with initial severe symptoms, presence of the NAP and appropriate antidote use independently reduced the risk of death (OR: 0.122, 95% CI: 0.023–0.633 and OR: 0.034, 95% CI: 0.007–0.167, respectively), adjusted for intent of exposure, cyanide source, age, and sex. Conclusions: After NAP implementation, both antidote use and appropriate antidote use increased. In cases presenting with severe symptoms, presence of the NAP and appropriate antidote use independently reduced the risk of mortality.