Recurrent convulsions and cardiac conduction disturbances after propafenone overdose.

Propafenone is a class Ic antiarrhythmic agent which also exhibits beta-adrenergic and fast sodium channel blockade. We report a case of severe poisoning in a 24-y-old woman who suffered a seizure 1 h after the intentional ingestion of 2.7 g propafenone, and had a recurrence of convulsion on arrival at the hospital. She also developed severe arrhythmia during her hospital course. She recovered uneventfully with supportive treatment.     

Orthotopic liver transplants necessitated by acetaminophen-induced hepatotoxicity.

BACKGROUND: Acetaminophen-induced hepatotoxicity has been recognized since 1966. Patients experiencing a massive hepatic insult due to acetaminophen (APAP) may recover with minimal residual complications or develop fulminant hepatic necrosis. We report 3 patients with hepatic failure due to an APAP overdose who received orthotopic liver transplants and survived. CASE REPORTS: An 18-y-o female ingested 60 500 mg APAP tablets (30 g). She presented with tachycardia and lethargy stating that she had taken amoxipine, carbamazepine, and lorazepam. She began to recover but on day 2 experienced an upper gastrointestinal bleed and became hypotensive and hyperpyrexic. She developed hepatic encephalopathy and it was then determined she had ingested APAP. Her APAP level was 13 micrograms/ml 96 h post-ingestion. She was successfully transplanted 19 d post-ingestion with recovery. A 40-y-o female was admitted for flu-like symptoms persisting for 7 d. She was jaundiced, hyperventilating and hypotensive. She admitted ingesting approximately 17 g APAP over 36 h. Her APAP level was 12.2 micrograms/ml. Her condition worsened and on day 3 she was in grade IV coma. She was successfully transplanted 4 d post-arrival with recovery. A 16-y-o female ingested an unknown amount of APAP. She presented approximately 24 h post-ingestion with a serum APAP level of 130 micrograms/ml. Her condition deteriorated and she became encephalopathic with grade IV coma. She was successfully transplanted on day 7 post-arrival. DISCUSSION: Hepatotoxicity can occur as a result of either acute or chronic APAP overdose. Although n-acetylcysteine (NAC) is effective antidotal therapy, it must be used within 8-12 h post-ingestion to be optimally effective. Inaccurate patient histories may prevent NAC administration resulting in hepatotoxicity. CONCLUSION: Liver transplantation is a viable option to be considered in those APAP overdose patients who experience rapidly progressing encephalopathy, hemolysis, and hepato-renal failure.     

Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine

Case Report

We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 × 10-mg olanzapine tablets, 7 × 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient’s own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state.

Conclusion

To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.     

Serotonin Syndrome Associated with Metaxalone Overdose

Introduction

Serotonin syndrome is a potentially life-threatening entity associated with pro-serotonergic medications in therapeutic use, in overdose, or when co-administered with other drugs. A broad range of drugs and drug combinations have been associated with serotonin syndrome. Metaxalone overdose associated with serotonin syndrome has not been previously reported.

Case Report

(Case 1) A 23-year-old female overdosed on tramadol and metaxalone. She developed dysautonomia, diaphoresis, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, and hyperthermia 5 h after ingestion. Her course was complicated by status epilepticus. (Case 2) A 56-year-old female overdosed on metaxalone and was found unresponsive. She developed dysautonomia, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, rhabdomyolysis, acute renal failure, and hyperthermia. Non-depolarizing neuromuscular blockade and cooling blankets were required to control hyperthermia in both cases. Serum metaxalone levels were markedly elevated in both cases.

Conclusion

These are the first reported cases of metaxalone overdose associated with serotonin syndrome, which may be related to monoamine oxidase inhibition.     

Therapeutic Plasma Exchange for Refractory Hemolysis After Brown Recluse Spider (Loxosceles reclusa) Envenomation

Introduction

The brown recluse spider (BRS) (Loxosceles reclusa) envenomation can lead to multiple complications, including hemolysis. We present a case of refractory hemolysis after a BRS bite treated with therapeutic plasma exchange (TPE).

Case Report

A 17-year-old female presented with fever, fatigue, and dyspnea. She was diagnosed with sepsis and received intravenous (IV) fluids, inotropic support, and antibiotics. On hospital day 1 she was noted to have skin lesion consistent with a BRS bite and developed hemolysis. Systemic loxoscelism with hemolysis was then suspected and methylprednisolone IV was initiated. She was discharged with a stable HGB on hospital day 3 on oral prednisolone. She was re-admitted 24 h later, with signs of worsening hemolysis. Methylprednisolone was restarted and she was transfused 4 units of packed red blood cells. TPE was initiated due to the refractory hemolysis. Shortly after the TPE session, her clinical and laboratory status improved. She required no further transfusions and was discharged on a steroid taper.

Discussion

TPE is an extra-corporeal method to remove substances from the blood by separating plasma from cellular blood components and replacing it with physiologic fluids. TPE has been used for snake envenomation but there are no reports detailing its use for BRS envenomations. Improvement was associated with TPE initiation and may have been due to removal of complement components activated by the spider venom. This report suggests that TPE could be a possible treatment modality for systemic loxoscelism with refractory hemolysis due to BRS envenomation. Further investigation is warranted.     

Case Report: Dabigatran-Associated Gynecologic Bleeding

Purpose:

The case of a patient who experienced major gynecological bleeding after initiation of dabigatran therapy for atrial fibrillation is reported.

Summary:

A 33-year-old Hispanic female with multiple medical problems presented to the emergency department (ED) with a 5-day history of menorrhagia and a 3-day history of dizziness, fatigue, and weakness. Prior to ED presentation, she had been initiated on dabigatran 150 mg twice daily for atrial fibrillation. Four days later, she began having profuse vaginal bleeding. She discontinued all of her home medications including dabigatran, and her bleeding subsided the next day. Upon presentation to the ED, her hemoglobin was 7.1 g/dL, for which she was transfused 2 units of packed red blood cells, increasing her hemoglobin to 9.6 g/dL. Because the patient was in atrial fibrillation, warfarin was initiated once she was clinically stable and she was never restarted on dabigatran. Her hemoglobin was stable throughout admission with no further bleeding. She was discharged on warfarin and closely followed without incident.

Conclusion:

A 33-year-old Hispanic female with no pre-existing gynecologic abnormalities had a major gynecological bleed shortly after starting dabigatran that resolved after discontinuation.     

Which Xenobiotic(s) Could be Responsible for the Radiologic Findings Below?

Background

The proconvulsive properties of tramadol, bupropion, and nortriptyline have been well documented. Spinal fractures secondary to drug-induced seizures have been rarely reported.

Case Report

A 39-year-old female presented with a chief complaint of back pain. She went to bed feeling well in a separate room from her husband. During the previous night, he heard a noise and went into her room, finding her confused and twisted in an awkward position on her bed. Later she complained to him of severe back pain, prompting transport to a hospital. Shortly after arrival in the emergency department, staff witnessed a generalized convulsion. Following a one-hour post-ictal period, she complained of worsened back pain. Lab studies were normal, including a urine tox screen for drugs of abuse. No alcohol was implicated. ECG showed sinus rhythm, HR 113 beats/min, QRS 108 ms, QTc 389 ms. Brain magnetic resonance imaging (MRI) was normal. X-ray and an MRI of the thoracic spine confirmed four contiguous vertebral compression fractures, from T2 through T5. EEG showed diffuse changes consistent with a metabolic or toxicologic process. She denied taking any drugs other than prescribed doses of her medications, which included tramadol, bupropion, and nortriptyline. She had no previous history of seizures, head injury, or CVA. Bupropion and tramadol were discontinued, and seizures did not recur.

Case Discussion

This patient's history, EEG findings, and brain imaging all point to a metabolic or toxic cause. It is likely that her three proconvulsant medications—even at therapeutic doses—synergistically lowered her seizure threshold or even precipitated her seizures. Retrospective studies and case reports portray these drugs as potentially offending agents.

Conclusions

Sudden onset of back pain during sleep can be an important clue to a seizure complicated by vertebral compression fractures, even in the absence of trauma. Toxicology consultation in seizures of unclear etiology can help discern drugs that offend even in therapeutic doses.     

Continuous intravenous flumazenil infusion for benzodiazepine poisoning

This is the first US report of continuous iv flumazenil infusion for benzodiazepine poisoning. A MEDLINE search from 1966 to 1999 revealed no similar reports in the US literature. A 24-y-o woman ingested 50, 2 mg (=100 mg) flunitrazepam tablets in a suicide attempt. She presented 30 min after ingestion with a temperature of 36.5 C, blood pressure of 90/36 mmHg, pulse of 84/min, and shallow respirations of 8/min. Her Glasgow coma scale (GCS) was 8. Her ECG showed sinus rhythm at 80/min, a QRS axis of 30 with no terminal 40 msec deviation, and a QRS interval of 84 msec. She received 0.2 mg flumazenil iv and her GCS improved to 15. She was orogastrically lavaged and given 50 g of activated charcoal. Resedation to a GCS of 8 recurred twice, requiring additional 0.3 mg and 0.5 mg boluses of flumazenil iv, totaling 1.0 mg over 1 h. Then, a continuous flumazenil infusion was started at 1.0 mg/h, maintaining her GCS at 15. Fourteen h later, the continuous flumazenil infusion was terminated, resulting in resedation and clinical hypoventilation. Flumazenil infusion was restarted at 1.0 mg/h with resolution of sedation and hypoventilation. Thirty h after overdose flumazenil infusion was terminated without resedation or hypoventilation. Continuous iv flumazenil infusion is not US Food and Drug Administration approved, and further study is necessary in carefully selected patients to determine its safety and efficacy.     

Diltiazem and metoclopramide overdose

A fatality resulting from the suicidal ingestion of diltiazem and metoclopramide is described. The decedent was a 25-year-old female with a history of alcoholism and cocaine abuse who overdosed on her mother's medications. On admission she was bradycardiac with severe hypotension and third-degree heart block which progressed to asystole. She was resuscitated but remained comatose until her death four days later. Serum samples from the first 15 h of hospitalization were analyzed for diltiazem and metoclopramide by gas chromatography with nitrogen-phosphorus detection. Diltiazem levels 1 hour post admission were 8.49 mg/L. Diltiazem elimination followed zero-order kinetics with an elimination rate of 0.68 mg/L/h. Metoclopramide levels 1 hour post admission were 4.4 mg/L. Data indicated a biphasic elimination curve for metoclopramide with an initial half-life of 1.3 h and a terminal half-life of 20 h.     

Severe Hypertension and Bradycardia Secondary to Midodrine Overdose

The objective of this case is to describe the pharmacokinetics and toxicity of midodrine in overdose. A 20 year old female ingested up to 350 mg midodrine while recovering in hospital from another overdose. She developed vomiting and severe hypertension (blood pressure [BP], 210/100 mmHg). Remarkable findings included a heart rate with a range of 43–60 beats/min, spontaneous respirations (20 breaths/min), and oxygen saturations of >95 % on FiO2 25 %, and a GS of 8. She was admitted to intensive care and had a normal non-contrast CT brain. She was treated with a glyceryl trinitrate patch (5 mg) and observed for 36 h with subsequent BP reduction to 124/81 mmHg and improved in conscious state. Midodrine and desglymidodrine concentrations were measured with liquid chromatography tandem mass spectrometry and were detected with 2-h post-ingestion at concentrations of 158.4 and 169.7 ng/mL, respectively. The parent drug concentrations rapidly decreased with an elimination of half-life of 1.6 h, and the metabolite initially increased and then decreased. The peak in blood pressure appeared to coincide with peak metabolite concentrations. Midodrine in overdose can potentially cause severe hypertension and reflex bradycardia but given its short half-life treatment with vasodilator agents and supportive care is sufficient.     

Acute on Chronic Ivabradine Overdose: a Case Report

Ivabradine is a newly approved medication which reduces the heart rate by antagonizing the I_f channel. We report a case of intentional overdose on ivabradine. A 26-year-old female presented after taking 250 mg ivabradine. On arrival, her vital signs and neurologic exam were unremarkable. Within 30 min, her heart rate decreased to 31 bpm, but she remained normotensive with no change in mentation. Her bradycardia resolved after treatment with atropine. She experienced two further bradycardic episodes responsive to atropine; the second episode was associated with hypotension, responsive to a fluid bolus. For the remainder of her hospitalization, she remained hemodynamically stable without further interventions. She was dispositioned to the psychiatry service approximately 36 h post-ingestion with a heart rate of 67 bpm. Laboratory analysis confirmed a serum ivabradine concentration of 525 ng/mL, greater than 50 times the mean level in therapeutic trials. Proposed treatments for ivabradine include activated charcoal, atropine, isoproterenol, and intravenous pacing. Further study is needed to identify ideal treatment modalities.     

Deliberate Fingolimod Overdose Presenting with Delayed Hypotension and Bradycardia Responsive to Atropine

Introduction

Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability.

Case report

A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 μg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes.

Discussion

Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.     

Clinical Effects and Toxicokinetic Evaluation Following Massive Topiramate Ingestion

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 µg/ml (reference range, 5–20 µg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.     

Use of benzylglycinamide by a HIV-seropositive polysubstance user: The changing pattern of novel psychoactive substance use among youths

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology.     

Detoxication treatment for carbamazepine and lithium overdose

This article reports detoxication treatments of a case of combined overdose of carbamazepine and lithium in a 38-year-old female with bipolar disorder. She was brought to the emergency unit after the family found her unresponsive and lying near empty packages for carbamazepine (corresponded to 7.7 g) and lithium carbonate (corresponded to 6.6 g) tablets. On admission, her blood pressure, heart rate and respiratory rate were 80/55 mmHg, 90 per minute and 13 per minute, respectively. Her GCS was 3 (E1, M1, V1). She received gastric lavage after intratracheal intubation, followed by administration of activated charcoal via gastric tube, and a large volume (800 ml/h) of lactate Ringer's solution by intravenous infusion. The serum levels of carbamazepine and lithium approximately 5 h after ingestion were 56.0 mug/ml and 3.56 mEq/l, respectively. The carbamazepine overdose was mainly treated by a 3 h charcoal hemoperfusion (CHP). The CHP treatment decreased serum carbamazepine levels by approximately 30-40% as compared with the levels simulated by Bayesian analysis using 1-point or 2-points serum level(s) (without detoxication treatment). For lithium overdose continuous infusion of Ringer's solution was effective, which increased serum sodium gradually and facilitated the elimination of lithium. In conclusion, the treatments with CHP and continuous infusion of Ringer's solution were considered to be effective for detoxification of carbamazepine and lithium overdose, respectively, when compared with those drug levels without detoxication treatment that simulated by Bayesian analysis method.     

Phenelzine-Induced Myocardial Injury: a Case Report

Introduction

Phenelzine is an irreversible monoamine oxidase inhibitor (MAOI). Hypertensive reactions after ingestion of tyramine-rich foods such as cheese are well known. However, a review of the available medical literature found no previous reports of myocardial infarction resulting from the ingestion of cheese by a patient taking a MAOI.

Case Report

A 34-year-old female taking phenelzine for depression developed severe chest pain 1 h after eating cheese. She was hypertensive and the electrocardiography showed ischemic changes in the antero-lateral chest leads. The chest pain and elevated blood pressure were relieved with intravenous morphine and nitroprusside. The initial serum troponin I level was normal, but serial repeat levels showed a rising trend with a peak at 4.89 ug/L (reference range <0.05 ug/L) 6 h after the initial blood draw, suggestive of a non-ST elevation myocardial infarction. The patient subsequently developed hypotension 4 h after another therapeutic dose of phenelzine was served to the patient 4 h after her admission to the ED. This was corrected with at least 2 L of intravenous normal saline boluses. Subsequent EKGs and Sestamibi scan showed no evidence of cardiac ischemia. She was discharged home after a hospital stay of 3 days.

Discussion

We believe this to be the first reported case of myocardial infarction resulting from ingestion of cheese in a patient taking a MAOI. It might be expected that hypertensive crisis could lead to a myocardial infarction, but a review of the medical literature found no such cases reported.     

Serum copper elevation from estrogen effect, masquerading as fungicide toxicity

Introduction

Copper toxicity has previously been reported from the wood preservative, copper naphthenate. Serum copper levels may be elevated by estrogen. Reported here is a case of a woman who was initially diagnosed with elevated serum copper levels from copper naphthenate exposure. She was later found to have a normal RBC copper level with resolution of her elevated serum copper level following discontinuation of estrogen.

Case Report

A previously healthy 44-year-old Caucasian female was referred for toxicology consultation due to persistently elevated serum copper levels following copper naphthenate applied in her home. She had initial nausea, nasal congestion and headache from the fumes but then remained asymptomatic. No evidence of underlying systemic disease or organ injury was found. Despite this and no further exposure, her serum copper remained elevated by 30% above normal over 9 months, peaking at 2301 μg/L (36 μmol/L). Review of the literature confirmed that oral contraceptive use will routinely elevate serum copper levels to the extent noted in this case. Her RBC copper level was normal. Cessation of the oral contraceptive for 2 months returned the serum copper levels to normal.

Discussion

This patient’s elevations in serum copper were probably unrelated to her chemical exposure to copper naphthenate. Serum levels of copper were falsely elevated as a result of concomitant estrogen use, and were returned to normal when estrogen was discontinued.     

High‐dose buprenorphine for treatment of high potency opioid use disorder

A 29‐year‐old woman presented to detox for treatment of an opioid use disorder with illicit fentanyl. While in detox, she was started on opioid agonist treatment with buprenorphine/naloxone. Unfortunately, she continued to have withdrawal symptoms despite being optimised to a dose of 32 mg. She was given additional PRNs of buprenorphine/naloxone to a total daily dose of 40 mg, which helped to alleviate her symptoms of withdrawal and cravings. She was stabilised on buprenorphine/naloxone 40 mg daily without any side effects and was discharged to a rehabilitation centre.     

Evolution of the NBOMes: 25C- and 25B- Sold as 25I-NBOMe

Introduction

The NBOMes (N-benzyl-oxy-methyl derivatives of known 2C phenylethylamines) are a new and growing class of potent synthetic stimulants. Case reports provide the bulk of available safety and clinical data for clinicians. We report two cases of NBOMe intoxication with 25C-NBOMe (the first lab-confirmed US case) and 25B-NBOMe, respectively, both confirmed via triple quadrapole mass spectrometry.

Case Reports

Case 1: A 16-year-old girl had a generalized seizure after reported use of 25I-NBOMe. She presented with altered mental status, lower extremity rigidity, and elevated CPK (6042 U/L). Despite treatment with benzodiazepines, her lower extremity rigidity persisted and CPK peaked at 47,906 U/L. She was discharged on hospital day 8. Serum and urine specimens confirmed presence of 25C-NBOMe. Case 2: A 15-year-old boy developed bizarre behavior after reported use of 25I-NBOMe. In the ED, he had two generalized seizures and persistent muscle rigidity. CPK peaked at 429 U/L. Seizures were managed with benzodiazepines, and he was discharged within 24 h. Serum specimens revealed 25B-NBOMe.

Discussion

NBOMes are amphetamine derivatives and highly potent 5-HT_2A receptor agonists. Clinical manifestations are a product of enhanced central sympathetic and serotonergic tone. We report two cases of NBOMe intoxication in patients who believed they used 25I-NBOME, while lab confirmation proved otherwise. Whether unique clinical manifestations are specific to the NBOMe variant, dose, route of administration, or other factors is unknown. Laboratory confirmation may play a role in identifying unexpected NBOMe variants, while contributing to the epidemiologic data on these novel substances.