[Circulatory failure after bupropion overdose]. / Allt fler allvarliga förgiftningar med preparatet bupropion.

A case of massive overdose of sustained release bupropion tablets is described. The patient presented with GCS 3, tachycardic and in vasoplegic shock. ECHO and EKG were initially normal. The hemodynamic situation was stabilised with vasopressors, but 18 h after presentation the patient deteriorated with wide complex arrhythmias rapidly progressing to cardiac arrest. The patient was put on VA-ECMO after 35 minutes of CPR. Circulation could be stabilized and ECMO was discontinued after 36 h. The patient was extubated on day 6 and made a complete recovery on discharge two weeks after presentation. At 34h, with ongoing ECMO, 236 tablets (with visible print identifying them as bupropion) were evacuated from the patient's stomach by gastroscopy. The tablets were analysed by NMR (nuclear magnetic resonance) but no longer contained any active substance. Blood levels of bupropion and hydroxybupropion at 36h were 790 and 1300 µg/l. The case illustrates a worrying surge in serious bupropion poisonings as noted by the Swedish Poisons Information Centre during the last 5 years.

Neuropathy with Cerebral Features Induced by Nitrous Oxide Abuse-A Case Report.

Nitrous oxide abuse may cause functional cobalamin deficiency and subsequent damage to the peripheral nerves, the spinal cord, and the brain, a symptom complex best described by the term cobalamin neuropathy. Here, we report a case of cobalamin neuropathy with uncommon cerebral symptomatology following nitrous oxide intoxication and contextualize the symptomatology. A 22-year-old male with a history of mixed drug dependency presented at the emergency room after inhaling six 615 g cylinders, equal to ~1800 L, of nitrous oxide daily for two weeks. His main complaints were rapidly progressing paresthesias and gait difficulties, but he was also found to suffer from memory impairment and signs of extrapyramidal pathology in the form of dystonic posturing and athetosis. Neuroimaging demonstrated spinal cord hyperintensities consistent with subacute combined degeneration. The patient had low serum cobalamin and high plasma homocysteine, suggesting cobalamin neuropathy. After commencing treatment with parenteral hydroxocobalamin, plasma homocysteine normalized. The extrapyramidal symptoms disappeared during the first days of treatment, whereas the cognitive and peripheral symptoms only partially resolved over the following 20 days. This case highlights how neurological symptoms such as hyperkinetic movements and memory impairment may be associated with chronic nitrous oxide abuse. It is unclear to what extent these and other symptoms of cobalamin neuropathy are reversible, which underscores the public health concern.

[Severe neurologic and psychiatric symptoms after extensive use of nitrous oxide]. / Lustgasbruk gav pseudodemens.

We present a case of severe neurologic and psychiatric symptoms after extensive recreational use of nitrous oxide. The patient also had a transient pancytopenia that responded well to substitution with vitamins. Six months later the patient still had neurologic and psychiatric sequelae, due to the abuse.

[Improved access to test results for toxic alcohols can save lives]. / Bättre tillgång till provsvar för toxiska alkoholer kan rädda liv.

Acute poisoning involving toxic alcohols other than ethanol is not uncommon. Poisonings from drinking isopropanol are rarely life threatening, whereas methanol and ethylene glycol without prompt treatment cause severe metabolic acidosis, organ damage, and death, mainly due to toxic metabolites. Rapid identification of the type of alcohol responsible for the poisoning requires access to 24/7 toxicological service. The analysis of alcohols is usually done with gas chromatographic (GC) methods, which are not always available at smaller or medium-sized hospitals. As a complement to GC methods, reliable enzymatic oxidation procedures are now available for the analysis of ethanol, methanol, and ethylene glycol. The present study showed good agreement (r2 = 0.996) between the results of methanol analysis with a new enzymatic method (Catachem Inc.) and with GC over the clinically relevant concentration range (1-50 mmol/l). Moreover, high concentrations of ethanol (up to 80 mmol/l), ethylene glycol (to 40 mmol/l), isopropanol (to 100 mmol/l) or acetone (to 20 mmol/l) did not interfere with the analytical results for methanol. Toxicological analysis of the two most dangerous alcohols (methanol and ethylene glycol) can now be done with rapid and specific enzymatic methods, which makes it possible to diagnose and treat poisoned patients at smaller regional hospitals.

[Analysis of acid-base disturbances in the emergency department]. / ABC om Syra­bastolkning på akuten.

The analysis of acid-base disturbances contributes to the diagnostic work-up of critically ill patients. Most emergency departments are equipped with blood gas point-of-care analyzers that quantify within minutes pH, pCO2, standard bicarbonate, standard base excess, sodium and chloride levels. This article provides a pragmatic stepwise approach to the analysis of acid-base disturbances in the emergency department. Standard base excess is used to assess the adequacy of the secondary (compensatory) response. Calculation of the anion gap based on the actual bicarbonate is used to identify the coexistence of metabolic acidosis and metabolic alkalosis. The delta anion gap allows for the identification of measurement errors, such as falsely elevated lactate and chloride values, which in turn may provide diagnostic clues.

[Diethylene glycol poisoning - the first known Swedish case]. / Dietylenglykolförgiftning ­ första kända svenska fallet presenteras.

A woman in her sixties presented at the Emergency department with nausea, flank pain and profuse vomiting. She had an anion-gap metabolic acidosis, elevated liver enzymes and a pronounced renal failure with creatinine 1997 µmol/L (22,6 mg/dl). She was admitted and treated with haemodialysis. On hospital day 5 a bilateral facial palsy, blindness and a moderate generalized weakness rapidly developed. The patient now revealed that she had consumed about 2 dl of brake fluid with a high content of diethylene glycol about a week before hospital admission. Diethylene glycol poisoning typically causes irreversible kidney failure and demyelinating nerve damage in severe cases. The early and debilitating metabolic acidosis seen in ethylene glycol poisoning seems to be absent in diethylene glycol poisoning and patients often present late. This is the first known Swedish case of symptomatic diethylene glycol poisoning. Internationally, during the last century, several mass poisonings have been caused by diethylene glycol contaminated pharmaceutical products.

The unknown known: non-cardiogenic pulmonary edema in amlodipine poisoning, a cohort study.

Context: Amlodipine is the most common calcium channel blocker (CCB) on the Swedish market, and poison center (PC) consultations for amlodipine overdoses are increasing. The clinical picture is dominated by vasodilation with relative preservation of cardiac function. CCBs selectively dilate vessels on the afferent side of the capillary network which, in states of preserved or increased blood flow may lead to edema formation, including non-cardiogenic pulmonary edema (NCPE). This complication has been considered rare in CCB poisoning. In this cohort study of nineteen amlodipine poisonings with high amlodipine blood levels, the incidence and clinical significance of NCPE in severe amlodipine poisoning are explored.Methods: During 2017-2018 the Swedish PC prospectively encouraged the gathering of blood samples in amlodipine poisonings with symptoms requiring treatment with inotropes or vasopressors. Samples were sent by mail to the Forensic Toxicology Division at the Swedish National Board of Forensic Medicine for screening and quantification of relevant toxicants. Patients with blood amlodipine levels >0.25 µg/mL were included in a cohort whose case details were gathered from medical records and PC-case notes with a special focus on signs of NCPE.Results: Nineteen patients met the blood amlodipine inclusion criteria. Four (21%) died and one patient was treated with VA-ECMO. Nine patients developed NCPE defined as a need for positive pressure ventilation (PPV) while having an echocardiographically normal left ventricular function.Conclusion: In this prospective cohort study of consecutive and analytically confirmed significant amlodipine poisonings NCPE was a common finding occurring in 47% of the whole cohort and in 64% of patients who did not go on to develop complete hemodynamic collapse.

[Simplified N-acetylcystein treatment after paracetamol overdose - new recommendations from Swedish Poisons Information Centre]. / Ny förenklad motgiftsbehandling vid förgiftning med paracetamol - Giftinformationscentralen ändrar sin doseringsanvisning för N-acetylcystein.

Since the late 1970s N-acetylcystein has been used as an antidote after paracetamol intoxication. The treatment is traditionally given as three consecutive infusions for 20 hours and 15 minutes. The total dose given is 300 mg/kg. Half of this amount is given as a bolus during the first 15 minutes of treatment.  This regime has proven very efficient in avoiding liver injury. However, side effects, caused by histamine release, are common (10-15%). Symptoms as flush, urticaria and, in rare cases, bronchospasm, angioedema and circulatory shock typically appear during the bolus dose and may lead to interrupted and inadequate treatment. In addition, the regime is complicated leading to a risk of administration errors. During the last years several publications have described the use of a model with two infusions instead of three. The first and the second infusions are merged and given over four hours. The third infusion and the total dose are left unchanged. This modified regime has been shown to reduce side effects and seems not to increase the risk of liver injury. As of November 1, 2019, the Swedish Poisons Information Centre will change its recommendations to the new two-infusion protocol.

[High dose insulin euglycemia therapy ­ an important addition to the treatment arsenal in severe toxic myocardial depression]. / Högdos insulin­­euglykemiterapi vid svår ­toxisk myokard­depression - Ett viktigt tillskott i behandlingsarsenalen.

High dose insulin euglycemia therapy - an important addition to the treatment arsenal in severe toxic myocardial depression Fifty-nine patients who developed hemodynamic symptoms necessitating treatment with vasopressors or inotropes after poisoning with calcium channel blockers (CCB) and beta blockers (BB) between January 2010 and August 2016 were identified by a search of the Poisons Information Centre database. In-hospital circulatory arrest occurred in 16/59 (27 %) and the mortality rate was 7/59 (12 %). Two cases of analytically confirmed combined BB and CCB poisoning were treated with high dose insulin therapy (HIE) and are presented in detail. The outcome in both cases was good. They were the only cases in the study population treated with HIE, although signs of cardiac dysfunction was present in 55/59 (93%) and in all cases of circulatory arrest. Animal studies and international clinical cases indicate that HIE is a safe and effective method to improve cardiac function in CCB and BB poisoning, and its implementation in Sweden may improve the outcome for this at risk population.

[Goal-directed administration of antidote for reversal of dabigatran anticoagulation]. / Målstyrd antidotterapi vid reversering av dabigatran.

Goal-directed administration of antidote for reversal of dabigatran anticoagulation Idarucizumab is a monoclonal antibody fragment that acts as an antidote to dabigatran. Idarucizumab is indicated in dabigatran-associated serious bleeds and to reverse dabigatran anticoagulation before acute surgical interventions or invasive medical procedures. The recommended dose of 5 g idarucizumab is sufficient to achieve a lasting restoration of coagulation in most patients. In a number of cases however, notably in deliberate overdoses and in accumulation of dabigatran in renal failure, repeated doses of idarucizumab may be necessary to avoid persisting or rebound anticoagulation. This article gives a brief explanation of the mechanisms responsible for this phenomenon and argues that it should be anticipated. Serial monitoring of APTT or dTT in patients treated with idarucizumab should enable the early detection of treatment failure or rebound anticoagulation and, if clinically indicated, prompt administration of additional doses of antidote.

Characteristics of analytically confirmed 3-MMC-related intoxications from the Swedish STRIDA project.

BACKGROUND: 3-Methylmethcathinone (3-MMC) is a synthetic cathinone stimulant structurally related to the new psychoactive substance (NPS) mephedrone (4-methylmethcathinone, 4-MMC). We describe a case series of analytically confirmed intoxications involving 3-MMC presented to emergency departments in Sweden and included in the STRIDA project. STUDY DESIGN: Observational case series of consecutive patients with self-reported or suspected use of NPS presenting to hospitals in Sweden between August 2012 and March 2014. METHODS: NPS analysis was performed by a liquid chromatography-mass spectrometry (MS)/MS method that is updated with new substances as they appear. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. RESULTS: 3-MMC was detected in 50 (6.4%) of the 786 cases included in the STRIDA project during the 20-month study period, with the peak occurring in August 2013. The age range of patients testing positive for 3-MMC was 17-49 years (median 24) and 76% of them were men. The 3-MMC concentration in serum ranged between 0.002 and 1.49 µg/mL (median, 0.091) and between 0.007 and 290 µg/mL (median, 3.05) in urine. Co-exposure to other NPS and/or traditional drugs was very common, and 3-MMC mono-intoxication was found in only 4 (8%) cases. The most frequent clinical features were tachycardia (48% of cases) and agitation (42%). Other features included a reduced level of consciousness (32%), dilated pupils (24%), hallucinations (20%), diaphoresis (12%), seizures (8%), and hyperthermia (6%). Most patients (60%) needed hospital care for only 1 day but in 8% for 3 days or longer. CONCLUSION: The majority of patients with analytically confirmed 3-MMC exposure had sympathomimetic features similar to those associated with mephedrone intoxication. However, the high incidence of co-exposure to other drugs makes the clinical interpretation difficult. Nevertheless, 3-MMC was associated with a high admittance rate to intensive care (30%), and detected in two cases with a fatal outcome, suggesting that 3-MMC is a harmful drug.

[MT-45--a dangerous and potentially ototoxic internet drug]. / MT-45 - en livsfarlig och potentiellt ototoxisk internetdrog.

During the last years several synthetic opioids have been introduced on Internet sites selling new psychoactive substances (NPS). One of these, called MT-45, a piperazine derivative originally synthesized as a therapeutic drug candidate in the 1970s, has recently been detected in 21 deaths, according to unpublished data from the Swedish National Board of Forensic Medicine. We present clinical data from 12 analytically confirmed hospital cases of MT-45 poisoning. The cases demonstrate that MT-45, like other opioids, can induce potentially life threatening respiratory depression and loss of consciousness in users and that symptoms are usually reversed by standard doses of the opioid receptor antagonist naloxone. Significant auditory symptoms with transient tinnitus and hearing loss occurred in two cases and a pronounced sensorineural hearing loss still present at two weeks follow-up in one case. This indicates that MT-45 may be an ototoxic substance, illustrating the ubiquitous risk of unintended adverse effects NPSs pose to users.