Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants.

Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42) years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10,000 IU/L) for each of the four groups was synthetic cathinone with 5/19 (26 %), methamphetamine with 2/55 (3.6 %), cocaine with 1/9 (11 %), and other with 0/6 (0 %). Median maximal CK (range) by groups was as follows: synthetic cathinone, 2638 (62-350,000+) IU/L; methamphetamine, 665 (61-50,233) IU/L; cocaine, 276 (87-25,614) IU/L; and other, 142 (51-816) IU/L. A statistically significant difference (p = 0.004) was found when comparing maximal CK among the four groups. Exposure to a synthetic cathinone compared with other sympathomimetics was associated with increased risk of developing rhabdomyolysis and severe rhabdomyolysis with odds ratios of 3.09 and 7.98, respectively. In this cohort of patients with sympathomimetic toxicity, 42 % developed rhabdomyolysis. Synthetic cathinones were associated with an increased risk of rhabdomyolysis and severe rhabdomyolysis compared with other stimulants.

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.

Mephentermine dependence with psychosis.

Mephentermine misuse or dependence has been rarely reported in the literature. This is surprising as mephentermine bears a close structural similarity to methamphetamine. Here we report a case of mephentermine dependence with induced psychosis. A 23-year-old professional weightlifter used to administer mephentermine (60 mg) for improving performance in tournaments. The patient became dependent on mephentermine in 2009, and his consumption increased to 100-150 mg every 2-3 days since August 2012 until his presentation in clinic in mid-October 2012. He developed psychosis and had persecutory delusions. Remission of psychosis was seen with stopping use of mephentermine and use of antipsychotic medication.

Toxidromes.

The critical care physician is often called to care for poisoned patients. This article reviews the general approach to the poisoned patient, specifically focusing on the utility of the toxidrome. A toxidrome is a constellation of findings, either from the physical examination or from ancillary testing, which may result from any poison. There are numerous toxidromes defined in the medical literature. This article focuses on the more common toxidromes described in clinical toxicology. Although these toxidromes can aid the clinician in narrowing the differential diagnosis, care must be exercised to realize the exceptions and limitations associated with each.

Phenylpropanolamine toxicosis in dogs: 170 cases (2004?2009).

OBJECTIVE: To evaluate signalment, clinical signs, dose ingested, treatment requirements, duration of hospitalization, and outcome of dogs exposed to phenylpropanolamine. DESIGN: Retrospective case series. ANIMALS: 170 dogs with potential PPA toxicosis evaluated between 2004 and 2009. PROCEDURES: Dogs with potential PPA toxicosis were identified by reviewing the electronic database of an animal poison control center. RESULTS: 66 of the 170 (39%) dogs reportedly did not develop any clinical signs. Clinical signs reported in the remaining 104 (61%) dogs included agitation (n = 40), vomiting (27), mydriasis (19), lethargy (17), tremor or twitching (16), panting (15), bradycardia (13), tachycardia (12), hypertension (11), and erythema (8). Median dose ingested for all dogs was 29 mg/kg (13.2 mg/lb). Dogs developing clinical signs had a significantly higher median dose ingested (373 mg/kg [170 mg/lb]) than did dogs that did not develop clinical signs (18 mg/kg [8.2 mg/lb]). Likewise, median dose ingested for the 123 dogs treated as inpatients (36.9 mg/kg [16.8 mg/lb]) was significantly higher than the median dose for the 14 dogs treated as outpatients (20.5 mg/kg [9.3 mg/lb]). Median duration of hospitalization was 18 hours (range, 4 to 72 hours), and hospitalization time increased as the dose ingested increased. Survival rate was 99.4% (169/170); the dog that died had ingested a dose of 145 mg/kg (65.9 mg/lb). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that with supportive care, the prognosis for dogs that had ingested an overdose of phenylpropanolamine was excellent.

Dissociative and sympathomimetic toxicity associated with recreational use of 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1-benzylpiperzine (BZP).

INTRODUCTION: There is emerging evidence of increasing use of legally available synthetic compounds as recreational drugs. While there are some changes to legislation relating to these synthetic compounds, often the emergence of the agents outpaces the effect of the legislation to curb their use, and the legal status of these agents may change as more information on their toxicity becomes known. TFMPP [1-(3-trifluoromethylphenyl) piperazine] was initially temporarily controlled under Schedule I of the Controlled Substances Act in 2002 in the US, but following further review and lack of published information on toxicity, it was removed from this control in 2004. In addition, there are very few "user reports" of effects when TFMPP is taken alone or in combination with BZP [1-benzylpiperazine]. CASE REPORTS: Three patients presented to our emergency department after ingesting 4 tablets thought to be 3,4-methylenedioxy-N-methylamphetamine (MDMA, street name "Ecstasy") over the course of an evening. They presented with dissociative-type symptoms, nausea, and signs consistent with sympathomimetic toxicity. All 3 improved with conservative management and observation, within 12 hours of presentation. Serum analysis demonstrated the presence of TFMPP and BZP at concentrations of 263 +/- 5.8 ng/mL (range 260-270 ng/mL) and 46.7 +/- 15.3 ng/mL (range 30-60 ng/mL), respectively. No other recreational drugs were detected in an extended toxicological screen of blood and urine samples. DISCUSSION: This is the first case series of confirmed toxicity associated with recreational use of TFMPP in combination with BZP, with clinical features not consistent with BZP toxicity. In our view, the current legal status of TFMPP should be reviewed.

Case files of the medical toxicology fellowship at the toxikon consortium in Chicago: cocaine-associated wide-complex dysrhythmias and cardiac arrest - treatment nuances and controversies.

A 19-year-old woman was brought by ambulance to the emergency department (ED) from a police holding cell. Less than 3 hours earlier, the patient had been a passenger in a car stopped for a traffic violation. As the police officer approached the car, the patient was noted to hurriedly stuff 2 plastic bags containing a white powdery substance into her mouth. On questioning, it was reported that the packets contained cocaine. Less than an hour after being taken to the police station, the patient was witnessed to have a generalized seizure. What is the pharmacological basis of acute cocaine intoxication? What are the cardiovascular manifestations of acute cocaine intoxication? What is the basis for using sodium bicarbonate in cocaine-induced wide-complex dysrhythmias? What is the basis for the use of lidocaine in cocaine-induced wide-complex dysrhythmias? Is there any evidence for the use of amiodarone to treat cocaine-induced wide-complex dysrhythmias?

"Parachuting" meth: a novel delivery method for methamphetamine and delayed-onset toxicity from "body stuffing".

BACKGROUND: Methamphetamine is an illicit stimulant that is typically smoked, insufflated, or injected. We report an unusual method of ingesting methamphetamine called "parachuting" and its implications for the treatment of "body stuffers." CASE REPORT: A 25-year-old man wrapped methamphetamine into a plastic baggie and ingested it in an attempt to "parachute." He presented to an Emergency Department 10 hours after his ingestion because he realized that he forgot to puncture the baggie. He had no complaints and had a transient tachycardia. He was treated with activated charcoal and whole bowel irrigation, observed for 24 hours, and discharged. He returned 42 hours after his ingestion with tachycardia (220 bpm), agitation, hypertension (179/74 mmHg), and rhabdomyolysis (CPK 7771 U/L), requiring mechanical ventilation and a midazolam drip (10 mg/hr). CONCLUSION: "Parachuting" is a novel method of ingesting methamphetamine. We report a case of a single-packet "body stuffer" with severe symptom onset that was delayed over 36 hours. Treatment protocols for "body stuffers" using this technique may require more prolonged observation and/or imaging studies to determine the absence of gastrointestinal packets.

[Sympathomimetic syndrome caused by autointoxication with methylphenidate]. / Sympathicomimetisch syndroom door auto-intoxicatie met methylfenidaat.

A 31-year-old man claimed that he had ingested more than 100 tablets of methylphenidate (10 mg), 20 tablets ofibuprofen (400 mg) and 2 bottles of wine. At admission, signs of sympathomimetic syndrome were observed, including agitation, hallucinations, mydriasis and sinus tachycardia. The patient was treated with activated charcoal and an oral laxative. Given the possibly lethal dose of methylphenidate, the patient was admitted to the intensive care unit for observation. He made a full recovery and was discharged 36 hours after admission. Toxicological analysis indicated a plasma-ethanol concentration of 0.27% and a maximum serum-methylphenidate concentration of 176 microg/l (therapeutic range: 5-40 microg/l). The active metabolite ethylphenidate was also present at toxic concentrations. Treatment of potentially lethal methylphenidate poisoning includes prevention of absorption, careful observation and support of vital functions as necessary.

Management of drug-induced hyperthermia.

PURPOSE OF REVIEW: To review the current literature describing drug-induced hyperthermia and its treatment. Specifically, five syndromes will be discussed: malignant hyperthermia, neuroleptic malignant syndrome, anticholinergic poisoning, sympathomimetic poisoning, and serotonin syndrome. RECENT FINDINGS: The most recent findings in the literature are the recognition of previously undescribed drugs or drug combinations that have lead to hyperthermia. Recent literature also attests to the potential morbidity and mortality of drug-induced hyperthermia. SUMMARY: Although the recognition of causative agents is increasing, the treatment of drug-induced hyperthermia remains unchanged and continues to be primarily supportive.

Drug-induced hyperthermia and muscle rigidity: a practical approach.

Body thermoregulation can be violently offset by drugs capable of altering the balance between heat production and dissipation. Such events may rapidly become fatal. The drugs that are involved in the eruption of such syndromes include inhalation anaesthetics, sympathomimetic agents, serotonin antagonists, antipsychotic agents and compounds that exhibit anticholinergic properties. The resultant hyperthermia is frequently accompanied by an intense skeletal muscle hypermetabolic reaction that leads to rapidly evolving rigidity, extensive rhabdomyolysis and hyperkalemia. The differential diagnosis should, however, rule out non-drug-induced causes, such as lethal catatonia, central nervous system infection or tetanus, strychnine poisoning, thyrotoxic storm and pheochromocytoma. Prompt life-saving procedures include aggressive body temperature reduction. Patients with a suspected drug (or non-drug) hypermetabolic reaction should be admitted into an intensive care area for close monitoring and system-oriented supportive treatment. We present six conditions, in decreasing order of gravity and potential lethality, in which hyperthermia plays an essential role, and suggest a clinical approach in such conditions.

Accidental injection of epinephrine from an autoinjector: invasive treatment not always required.

BACKGROUND: Individual case reports of accidental injection with epinephrine appear in the literature and seem to represent the worst case scenarios. We present a case series of 28 exposures to epinephrine via autoinjector. METHOD: All accidental parenteral injections of epinephrine by autoinjector reported to two regional poison information centers over a 2-year period were included. RESULTS: Injection sites included digits (23 cases), palm (4 cases), and thigh (1 case). Symptoms included swelling, pallor, pain, and erythema. Four patients reported no effect, and 9 required no treatment. Ten patients obtained relief with warm soaks, 1 patient had massage only, and 2 patients were lost to follow-up. Fourteen were examined in the emergency department, and 14 were treated at home. CONCLUSION: Although some injection injuries must be treated in an emergency facility, many can be treated at home. Immediate referral to a health care facility is not needed in all cases and at times is unwarranted.

Herbal and alternative medicine.

An extensive range of herbal and dietary supplements is now available, and use of these products by ED patients is fairly common. Emergency physicians should be familiar with some of the products used more frequently for common complaints. Emergency personnel also should be vigilant for toxic syndromes resulting from ingestion of certain of these products and be wary of possible toxicity from any of these supplements owing to their minimal quality control and absence of FDA regulation.

Myocardial infarction associated with phenylpropanolamine.

Phenylpropanolamine is a sympathomimetic agent widely used in over-the-counter and prescription decongestant medications. We describe a young woman without cardiac risk factors who sustained myocardial infarction after unintentional overuse of a nasal decongestant containing phenylpropanolamine. The pathophysiology of myocardial injury and current management strategies as related to this agent are discussed. Although serious adverse reactions to phenylpropanolamine are uncommon, potentially serious harm may be caused by this widely available drug in healthy individuals.