1) 2CB
2) 2CI
3) 2CD
4) 2CT-2
5) 2CT-7
6) 2CE
7) 2CP
8) 2CN
9) 2CT-8
10) 2CT-9
11) 2CT-21
12) 2CF
13) 2CC
14) 2C-TFM

1) DOB
2) DOC
3) DOI
4) DOM
5) DON
6) DOEF
7) DOET
8) DOPR
9) DOTFM
10) Aleph-1
11) Aleph-6
12) Aleph-7
13) Ariadne
14) Beatrice
15) G3
16) G5

1) PMA
2) PMMA
3) 4-MTA
4) TMA
5) TMA-2
6) 2MA
7) 3MA

1) Hyperthermia may be life threatening, and has been contributory to death (Iwersen & Schmoldt, 1996). Core temperatures above 42 degrees C may develop, and indicate a need for aggressive cooling measures and control of agitation (Chadwick et al, 1991; Screaton et al, 1992; Henry et al, 1992; Campkin & Davies, 1992; Logan et al, 1993; Tehan, 1993; Mueller & Korey, 1998).
2) ETIOLOGY: Hyperthermia is a frequent clinical feature of MDMA toxicity with signs/symptoms similar to malignant hyperthermia which is biochemically caused by a rise of calcium ions in the myoplasm (Denborough & Hopkinson, 1997). An in-vitro muscle contracture study revealed a corresponding elevation of calcium within the cells following exposure to MDMA.
3) INCIDENCE/FATALITY: In a retrospective chart review of 191 cases of MDMA exposure, 7 cases experienced hyperthermia with 1 death due to hyperthermia reported (Rella et al, 2000).
4) COADMINISTRATION OF THC: In a study of 16 volunteers, the effects on heart rate and temperature were observed following MDMA (alone) or THC (alone) or a combination compared to placebo. Temperature was significantly higher in the MDMA-alone and MDMA + THC combination compared to THC alone and placebo. The addition of THC appeared to delay the onset and prolong the duration of temperature elevation compared to MDMA-alone. It was also found that epinephrine and norepinephrine levels were higher in MDMA + THC combination compared to THC-alone (Dumont et al, 2009).

1) Systolic and diastolic hypertension are common (Davies et al, 2014; Lamberth et al, 2008; Gee et al, 2005; Chang et al, 2005; Melian et al, 2004; Russell et al, 1992; Henry et al, 1992; Logan et al, 1993).

1) CASE SERIES: In a double-blind, placebo-controlled trial, 8 healthy adults with occasional MDMA use (described as once or twice per month) were given either MDMA (0.5 and 1.5 mg/kg) or placebo with regular measurement of heart rate and blood pressure and an echocardiographic evaluation. Each patient was also given dobutamine (5, 20 and 40 mcg/kg) in a preliminary session, and echocardiographic effects were measured. It was found that MDMA (1.5 mg/kg) and dobutamine (20 and 40 mcg/kg) increased heart rate by 28 beats/min, systolic and diastolic blood pressure by 25 mmHg and 7 mmHg, respectively, and cardiac output (an increase of 2 L/min {same finding as 20 mcg/kg/min of dobutamine}); a MDMA dose of 0.5 mg/kg had NO cardiac effect. The authors concluded that a modest dose of MDMA produced dose-dependent increases in heart rate and blood pressure and myocardial oxygen consumption with no measurable inotropic effect (Lester et al, 2000).
2) CASE REPORTS

1) PARAMETHOXY-AMPHETAMINE (PMA): A 20-year-old man was admitted unconscious after ingesting PMA (confirmed by laboratory analysis) with a blood pressure of 171/148 mmHg, temperature of 42.8 degrees C, heart rate 90 beats/min and respiratory rate of 40 breaths/min. His course was complicated by hyperthermia, persistent coma, shock, hyperkalemia and severe coagulopathy and he died 10 days after admission (Lamberth et al, 2008).

1) Tachycardia is common (Davies et al, 2014; Poon et al, 2010; Ovaska et al, 2008; Wood et al, 2007; Lamberth et al, 2008; Wood et al, 2008; Gee et al, 2005; Chang et al, 2005; Melian et al, 2004; Henry et al, 1992; Russell et al, 1992; Screaton et al, 1992; Jones et al, 1994; Engebretsen & Harris, 2001).

1) Tachycardia, sometimes severe (160 beats/min or more) has been reported in severe and fatal overdoses of MDMA and PMA (Caldicott et al, 2003; Refstad, 2003; Henry et al, 1992; Campkin & Davies, 1992; Screaton et al, 1992).
2) INCIDENCE: In a retrospective chart review of 191 cases of MDMA exposure, tachycardia (22%) was the most commonly reported symptom (Rella et al, 2000).
3) CASE REPORT/PEDIATRIC: An 8-month-old boy presented with generalized seizure activity, tachycardia (210 beats/min), hypertension (125/70 mm Hg), and hyperthermia (38.9 degrees C) after accidentally ingesting one Ecstasy tablet. Treatment with benzodiazepines, body cooling and fluids resulted in a resolution of all abnormal parameters 6 hours after admission (Eifinger et al, 2008).
4) COADMINISTRATION OF THC

1) Tachycardia and chest discomfort were reported in a 28-year-old man, with a history of substance abuse, after ingesting 1-(3-trifluoromethylphenyl)-piperazine (TFMPP; confirmed by laboratory analysis). Symptoms resolved spontaneously and the patient was discharged (Poon et al, 2010).

1) ADULT/ADOLESCENTS
2) PEDIATRIC

1) PARAMETHOXY-AMPHETAMINE: A 20-year-old man was admitted unconscious after ingesting PMA (confirmed by laboratory analysis) with hypertension, tachycardia and ECG showing a prolonged QRS interval of 160 ms (reference range: less than 100 ms). The patient had a complex course which included hyperthermia, persistent coma, shock, hyperkalemia, hypoglycemia, rhabdomyolysis and severe coagulopathy and he died 10 days after admission (Lamberth et al, 2008).

1) The first patient, a 20-year-old man, presented with chest pain 3 days after receiving 10 Ecstasy tablets. Laboratory results revealed a Troponin I of 0.22 mcg/L (reference less than 0.04 mcg/L) at 2 hours after onset of the chest pain and a peak of 1.3 mcg/L at 24 hours. His echocardiogram was normal and he recovered without further sequela. Another patient, a 22-year-old man, presented with a 12-hour history of severe crushing central chest pain, nausea, dyspnea, and clamminess, 48 hours after ingesting 2 Ecstasy tablets. His vital signs included a heart rate of 80 beats/min and a blood pressure of 128/70 mmHg. An ECG revealed an acute left bundle branch block and concordant ST elevation through the lateral leads. He was treated with supportive care, including aspirin, clopidogrel, heparin, and morphine. In another ECG, 45 minutes later, reversal of the left bundle branch block was observed, but the ST elevation in leads V2-V6 persisted. A primary coronary angiography revealed structurally normal coronary arteries with sluggish flow secondary to thrombosis. Laboratory results revealed a Troponin I peak of 10 mcg/L. His symptoms improved and he was discharged home on clopidogrel and diltiazem (Hoggett et al, 2012).
2) A 23-year-old woman, with a history of occasional Ecstasy and cocaine use, presented with insomnia and chest pain the day after ingesting 7 Ecstasy tablets over a 16-hour period with alcohol. Her vital signs included a heart rate of 123 beats/min and a blood pressure of 155/95 mmHg. He was treated with supportive care, including aspirin, diazepam, and sublingual nitrates and an ECG revealed sinus tachycardia. Laboratory results showed the Troponin I of 0.11 mcg/L. On day 2, normal wall motion with mild global ventricular systolic dysfunction were observed in an echocardiogram. On day 3, she developed severe central crushing chest pain and another ECG showed inferolateral ST segment elevation. She received aspirin, metoprolol, and ramipril at this time and her Troponin I peaked at 6.1 mcg/L. On day 4, she underwent coronary angiography after the recurrence of pain and ST elevation. Normal coronary arteries with no evidence of dissection was observed. She received aspirin, metoprolol, ramipril and was discharged home. On a 1-month follow-up, an echocardiogram was normal. Persistent inferior T wave inversion was observed on a follow-up ECG (Hoggett et al, 2012).

1) Pulmonary edema and ARDS may occur in severe intoxications (Lamberth et al, 2008; Chang et al, 2006; Curtis et al, 2003; Brown et al, 1986; Simpson & Rumack, 1981; Brown & Osterloh, 1987; Walubo & Seger, 1999) and has resulted in death (Albertson et al, 1995).

1) CASE REPORT: Hyponatremia (initial serum sodium 124 mmol/L) with secondary cerebral edema and acute lung injury developed in a 17-year-old boy following suspected MDMA use. Clinical findings included coma, increased oxygen demands, and a chest x-ray that showed marked fluffy infiltrates consistent with acute lung injury. Despite aggressive supportive care the patient did not improve and died following withdrawal of life support. Toxicology screen was positive for MDMA and chlorxylenol (Engebretsen & Harris, 2001).
2) CASE REPORT: A 23-year-old woman experienced generalized seizures and became comatose, necessitating mechanical ventilation, approximately 6 hours after ingesting 1 MDMA tablet while dancing at a discotheque. Following admission to the intensive care unit of the hospital, the patient developed severe hypoxemic respiratory failure diagnosed as acute respiratory distress syndrome. The patient became alert approximately 3.5 days postadmission and was discharged home with no sequelae (Ben-Abraham et al, 2003).

1) PARAMETHOXY-AMPHETAMINE: A 20-year-old man was admitted unconscious after ingesting PMA (confirmed by laboratory analysis) with hypertension, tachycardia and an ECG showing a prolonged QRS interval. Following intubation the patient had persistent hypoxia and an x-ray showed extensive bilateral airspace consolidation. The patient had an ongoing complex course which included hyperthermia, persistent coma, shock, hyperkalemia, rhabdomyolysis and severe coagulopathy. Five days after admission a head CT showed extensive cerebral edema. The patient died 10 days after admission (Lamberth et al, 2008).

1) A hospital in New Zealand reviewed 80 cases of 1-benzylpiperazine (BZP) exposures and found that agitation was reported in approximately 27% of cases (Gee et al, 2005).

1) Seizures are a common complication of severe toxicity (Vanden Eede et al, 2012; Patel et al, 2005; Barrett & Taylor, 1993; Henry et al, 1992; Woods & Henry, 1992; Singarajah & Lavies, 1992; Buhrich et al, 1983; Chadwick et al, 1991; Shulgin, 1981; Russell et al, 1992; Campkin & Davies, 1992; Watson et al, 1993; Lehmann et al, 1995; Ajaelo et al, 1998).
2) CASE REPORT/PEDIATRIC: Approximately 40 minutes after ingesting a portion of an ecstasy pill, a 14-month-old child developed a generalized convulsion with opisthotonos, hyperthermia (38 degrees Celsius), hypertension, tachycardia (130 beats/min), ventricular extrasystoles, tachypnea (50 breaths/min), and mydriasis. The urine levels of amphetamine/methamphetamine were greater than 16 mg/L 5 hours after ingestion. The serum level of MDMA was 0.591 mg/L 8 hours after ingestion. He continued to have hypertension, tachycardia and long periods of trigeminy, without hemodynamic repercussion during the first 12 hours. Following supportive care, the child recovered with no further sequelae (Melian et al, 2004).
3) CASE REPORT/PEDIATRIC: A 20-month-old child accidentally ingested a MDMA tablet and began seizing along with consciousness disturbances approximately 50 minutes later. In the ED, the infant was restless, febrile, hypertensive, and tachycardic. With cooling, hydration, and supportive treatment, he made a full recovery 2 days later (Chang et al, 2005).

1) CASE SERIES: After ingesting a "hallucinogen LSD-like" drug, 2 men developed a rapid onset of hallucinations (within 15 minutes), vomiting, and coma. The first subject, a 28-year-old (body mass 113 kg) survived but developed serious convulsions. The second subject, a 29-year-old man (body mass 65 kg) died 6 days postingestion after developing generalized convulsions and metabolic acidosis (pH 6.6). Although immunoassay for amphetamines was negative in urine specimens, GC-MS showed 2,5-dimethoxy-4-bromoamphetamines (DOB) in the gastric and urine samples of both individuals. DOB serum concentration was 13 ng/mL for the surviving patient and 19 ng/mL for the deceased patient, respectively (Balikova, 2005).

1) CASE REPORT: A 20-year-old man collapsed and had tonic-clonic seizures after presumably ingesting DOI (2,5 dimethoxy-4-iodoamphetamine) at a rave party. He required intubation in the field and was admitted comatose with a Glasgow Coma Score of 3/15. However, he had normal reflexes and a brain CT was normal. He also developed tachycardia (152 beats/min), metabolic acidosis, hypotension and an elevated creatine kinase (peak: 4924 International Units/L) with no evidence of renal failure. Following supportive care, including IV hydration and prophylactic antibiotics, the patient was extubated the next day and discharged to home with no permanent sequelae. Serum and urine samples confirmed the presence MDMA and DOC (2,5 dimethoxy-4-chloroamphetamine), which could not be quantified (Ovaska et al, 2008).

1) 1-(8-bromobenzo[1,2-b; 4,5-b']difuran-4-yl)-2-aminopropane: An 18-year-old man presented with hallucinations, agitation and 2 self-terminating seizures as a result of ingesting Bromo-dragonfly and an unknown white powder 8 hours prior to presentation. Shortly after arrival, the patient had a self-terminating seizure with apnea lasting over 1 minute, followed by another generalized seizure treated with lorazepam. The patient was intubated due to decompensating respiratory function; but was successfully extubated 24 hours later. Toxicological screen revealed a Bromo-dragonfly concentration of 0.95 ng/ml, ketamine and cannabis (Wood et al, 2009).

1) Coma may develop in severe cases (Vanden Eede et al, 2012; Lamberth et al, 2008; Campkin & Davies, 1992; Watson et al, 1993; Lehmann et al, 1995).

1) CASE REPORT: A 30-year-old man was found at home in a coma, apneic, and had symmetrical convulsions following a massive ingestion of 50 tablets of ecstasy along with oxazepam and alcohol. Treatment included gastric decontamination and supportive care; recovery was complete within 2 days of ingestion (Ramcharan et al, 1998).
2) CASE REPORTS: Coma was reported in 3 patients who ingested up to 3 MDMA tablets. The duration of coma ranged from approximately 1 to 3.5 days. The patients gradually recovered without neurologic sequelae (Ben-Abraham et al, 2003).
3) CASE SERIES: After ingesting a "hallucinogen LSD-like" drug, 2 men developed a rapid onset of hallucinations (within 15 minutes), vomiting and coma. The first subject, a 28-year-old (body mass 113 kg) survived, but developed serious convulsions. The second subject, a 29-year-old man (body mass 65 kg) died 6 days postingestion after developing generalized convulsions and metabolic acidosis (pH 6.6). Although an immunoassay for amphetamines was negative in urine specimens, GC-MS showed 2,5-dimethoxy-4-bromoamphetamines (DOB) in the gastric and urine samples of both persons. DOB serum concentration was 13 ng/mL for the surviving patient and 19 ng/mL for the deceased patient, respectively (Balikova, 2005).

1) PARAMETHOXY-AMPHETAMINE: A 20-year-old man was admitted unconscious after ingesting PMA (confirmed by laboratory analysis) with hypertension, tachycardia and an ECG showing a prolonged QRS interval. The patient had a complex course which included hyperthermia, persistent coma, shock, hyperkalemia, rhabdomyolysis and severe coagulopathy. Five days after admission, the pupils were sluggish and the gag and cough reflex were absent. Laboratory studies included an ammonia level of 219 micromol/L (reference range: 10 to 50). A head CT showed extensive cerebral edema and the patient died 10 days after presentation (Lamberth et al, 2008).

1) CASE REPORT/MDA and 2C-I: A 39-year-old-woman presented with rapidly diminishing mental status, agitation, hypothermia, emesis, urinary incontinence, severe hypertension, vasoconstriction and extensor posturing after ingesting MDA (3,4-methylenedioxyamphetamine) and 2C-I (2,5-dimethoxy-4-iodophenethylamine). Urinary drug concentrations were MDA 5.56 mg/L and 2C-I 0.311 mg/L. A head CT showed massive intraventricular hemorrhaging and underlying Moyamoya. One month after ingestion, the patient developed sympathetic storming and seizures. A tracheostomy was placed for long-term mechanical ventilation. After 4 months in the hospital, the patient was transferred to a skilled nursing facility with quadriplegia and had a modest improvement in mental status (ie, she could follow commands), but could not speak. She remained severely disabled and required total care (Drees et al, 2009).

1) CASE REPORT: A 25-year-old woman developed subarachnoid hemorrhage after taking 2.5 ecstasy tablets. Angiography revealed a left posterior communicating artery aneurysm (Gledhill et al, 1993).
2) Four patients developed intracerebral hemorrhage related to the ingestion of ecstasy or amphetamine, 3 of whom had normal intracranial vessels on angiography (Silve & Harries, 1992).

1) CASE REPORT: Parkinson-like symptoms (including postural instability and markedly abnormal gait) occurred in a 29-year-old man following ingestion of MDMA approximately 10 times over an 18 month period. Levodopa and pramipexole were tried unsuccessfully. It was speculated that the symptoms were a result of delayed neurotoxic effects of MDMA (Mintzer et al, 1999).

1) SUMMARY: Recent evidence suggests that MDMA use can result in alterations and potential damage to serotonin (5-HT) neurons (Milroy, 1999; Pham & Puzantian, 2001; Reneman et al, 2006). Further studies have indicated that the effects of MDMA on 5-HT neurons in the human cortex may be reversible in individuals who have stopped using MDMA, but the effects of MDMA on memory function may be long-lasting (Reneman et al, 2001).

1) Similar work has been done by McCann et al (1998) using quantitative PET studies with a ligand selective for 5-HT transporters. They found that abstinent MDMA users showed decreased global and regional brain 5-HT transporter binding compared with controls. Decreases in 5-HT transporter binding positively correlated with the extent of previous MDMA use (McCann et al, 1998).
2) In a small study by Obrocki et al (1999), positron emission tomography (PET) findings suggested that ecstasy use had lasting effects on central neuronal activity in humans (Obrocki et al, 1999).

1) Two cases of persistent neurobehavioral disturbance after MDMA ingestion have been reported (McCann & Ricaurte, 1992).
2) A young woman developed symptoms (hyperthermia, confusion, and tachycardia) similar to serotonin syndrome following ingestion of MDMA. Despite aggressive management, the patient died 5 hours after admission from complications of hyperthermia and cardiac dysfunction (i.e., hypotension, malignant dysrhythmias) (Mueller & Korey, 1998).
3) Ongoing interruption in serotonin transmission has been suggested in the role of discrete memory loss and learning deficits found in MDMA users (Klugman et al, 1999).

1) Gardner et all (2009) reported two cases of ecstacy ingestion that presented with tonic-clonic seizures, and MRI results showed hippocampal swelling that developed into sclerosis (Gardner et al, 2009).

1) MDMA given orally to rats demonstrated the same dose-related depletion of serotonin in the hippocampus (Finnegan et al, 1988). Battaglia et al (1988) found that brain serotonin levels in rats decreased 20% after only 2 doses of 10 mg/kg MDMA (Battaglia et al, 1988).

1) Nausea is common, with an onset of 30 minutes and lasting another 30 minutes (Hayner & McKinney, 1986). Vomiting may be protracted in some cases. Vomiting and diarrhea may also occur (Gee et al, 2010).

1) INCIDENCE: In a retrospective chart review of 191 cases of MDMA exposure, nausea and vomiting (12%) were frequently reported (Rella et al, 2000).

1) Hepatitis has developed in patients after recreational use of MDMA (Shearman et al, 1992; Gorard et al, 1992; Dykhuizen et al, 1995). Fatal fulminant hepatitis occurred in a young adult following MDMA exposure despite medical treatment (Colak et al, 2011).
2) ETIOLOGY: The potential risk for liver injury is likely multifactorial. Several possible explanations have been suggested in the literature: toxic hepatitis due to MDMA or its metabolites or to an unknown contaminant introduced during manufacture; idiosyncratic toxic hepatitis due to genetic predisposition; hemodynamic alteration in liver circulation; induction of isoenzymes of CYP450; or acute hyperthermic hepatotoxicity (Jones & Simpson, 1999; Garbino et al, 2001). Toxicity can produce asymptomatic hepatitis to acute hepatic failure (Colak et al, 2011).
3) ONSET: Signs of hepatic toxicity may develop a few days up to 1 to 2 weeks after exposure (Colak et al, 2011).
4) CASE REPORT: A 19-year-old man presented severely jaundiced 2 weeks after consuming 2 ecstasy tablets. He had an enlarged liver and spleen, but all serologic markers for liver diseases were negative. The patient had no other source or exposure to explain his acute hepatitis. With supportive care, he made a full recovery and was discharged on hospital day 20. All laboratory parameters normalized by 2 months (Brncic et al, 2006).

1) CASE SERIES: Six patients developed symptoms of hepatotoxicity with cholestatic jaundice following exposure to 4,4'-methylenedianiline (MDA). Although hepatic enzymes normalized over a period of 6 weeks in all patients, the authors suggested that, theoretically, the decline in acetylcholinesterase activity may result in severe liver damage leading to fulminant hepatic failure following recreational use (Tillman et al, 1997).

1) Hepatic failure may occur with severe exposure to these agents (Lamberth et al, 2008; Garbino et al, 2001; Kramer et al, 2003).

1) CASE REPORT: Necrotic toxic hepatitis developed in a 19-year-old man following ingestion of 1.5 tablets of ecstasy (MDMA) and alcohol. The patient reported an occasional use of recreational drugs. Symptoms progressed and the patient's condition deteriorated over a 3 week period resulting in fulminant hepatic failure which required auxiliary liver transplantation. The patient was discharged to home 20 days after surgery (Garbino et al, 2001).
2) CASE REPORT: Fulminant hepatic failure occurred in a 27-year-old man following injection of 0.5 g heroin, 1 g cocaine, and ingesting 3 MDMA tablets (300 mg). Liver transplantation was declined by the transplant surgeon due to the patient's history of illicit drug use. Initiation of experimental therapy using a fractionated plasma separation and adsorption system (FPSA/Promethus), a hemodialysis-based system, resulted in the gradual recovery of hepatic function (Kramer et al, 2003).

1) PARAMETHOXY-AMPHETAMINE: A 20-year-old man was admitted unconscious after ingesting PMA (confirmed by laboratory analysis) with hypertension, tachycardia and an ECG showing a prolonged QRS interval. The patient had a complex course which included hyperthermia, persistent coma, shock, hyperkalemia, rhabdomyolysis and severe coagulopathy. This was followed by renal and hepatic failure and extensive cerebral edema. Laboratory studies included a bilirubin of 412 micromol/L (reference range: 2 to 20) and ALT of 3961 Units/L (reference range: less than 55). He died 10 days after presentation (Lamberth et al, 2008).

1) Acute renal failure has been reported in patients who develop rhabdomyolysis and/or disseminated intravascular coagulation associated with BZP, MDA, MDEA, or MDMA (Davies et al, 2014; Alansari & Hamilton, 2006; Barrett & Taylor, 1993; Henry et al, 1992; Fahal et al, 1992; Watson et al, 1993; Walubo & Seger, 1999).

1) CASE REPORT: DIC and acute renal failure were reported in a 21-year-old man after taking 30 "hits" (a typical "hit" of MDMA is 100 mg, but can range from 50 to 250 mg) of ecstasy. The patient was extubated on day 25, but required daily hemodialysis, and permanent neurological impairment was present (Shannon, 2000).
2) PEDIATRIC EXPOSURE: A 2-year-old boy ingested an unknown amount of MDMA and presented with abnormal urine findings (ie, 1+ proteinuria, 2+ ketonuria, and 3+ occult blood with more than 100 red blood cells per high power field) and developed mild DIC and muscle injury. The patient tested positive for MDMA the morning after hospital admission; however, the length of time between MDMA exposure to clinical presentation was unknown (Feldman & Mazor, 2007).

1) Rhabdomyolysis is a common complication in patients who develop hyperthermia, or prolonged seizures, coma, or muscular hyperactivity (Ovaska et al, 2008; Lamberth et al, 2008; Brown & Osterloh, 1987; Campkin & Davies, 1992; Screaton et al, 1992; Singarajah & Lavies, 1992; Henry et al, 1992; Barrett & Taylor, 1993; Logan et al, 1993; Watson et al, 1993; Lehmann et al, 1995).

1) CASE REPORT: A 19-year-old man presented in a coma with seizures, and hyperthermia (temperature 42.5 degrees C) 2 hours after ingesting ethanol and 3 ecstasy tablets (total dose unknown). Physical examination revealed bilateral mydriasis, myoclonus, a systolic murmur, and a thrill over the femoral arteries. He had a heart rate of 95 beats/min and arterial blood pressure of 125/45 mm Hg. An ECG revealed broad QRS complexes with short QT interval and a long PR interval, indicating hyperkalemia. Despite supportive therapy, including treatment with active cooling measures, sedation with midazolam, IV calcium gluconate, sodium bicarbonate, glucose, and insulin, he developed bradycardia and a P wave asystole. During cardiopulmonary resuscitation, he developed ventricular fibrillation that was successfully defibrillated. Laboratory results revealed hyperkalemia (peak potassium, 9.4 mmol/L after 30 minutes in the ICU), rhabdomyolysis (peak CK, 12,509 Units/L), myocardial damage, and syndrome of inappropriate antidiuretic hormone. He experienced another cardiac arrest after arrival in the ICU. He had pulmonary edema and pulseless electrical activity, alternating with sinus bradycardia (30 beats/min). Resuscitation efforts were unsuccessful and he died 2 hours later. It was suggested that the cause of death was a rapidly evolving hyperkalemia due to rhabdomyolysis (Vanden Eede et al, 2012).
2) CASE REPORT: A 23-year-old man presented with tachycardia, hypotension, tachypnea, a Glasgow Coma Scale (GCS) of 12/15 and fever (rectal temperature of 108.9 degrees F; 42.7 degrees C) after ingesting 3 MDMA pills at a concert. He was also combative, tremulous, hypertonic and hyper-reflexic. Following supportive care, including ventilatory support, his temperature decreased to 99 degrees F (37.2 degree C) within 2 hours. He also received sodium polystyrene and calcium gluconate after laboratory results revealed hyperkalemia (potassium 6.2 mmol/L). Following further supportive care, including IV midazolam and propofol drips, his rigidity decreased and tachycardia improved. However, he developed severe rhabdomyolysis, multiorgan failure, and mild disseminated intravascular coagulopathy on day 2. Laboratory results revealed a peak CK of 130,350 Units/L, AST 3011 Units/L, ALT 314 Units/L, albumin 1.6 g/dL, creatinine 9.6 mg/dL, phosphate 8 mg/dL, platelet count 54 K/mcL, INR 1.44, activated partial thromboplastin time (aPTT) 42.7 and D-dimer concentrations of 1799 ng/mL. Following aggressive supportive care, including several sessions of hemodialysis (a total of 5 inpatient sessions and 2 outpatient sessions), he had a full recovery within 3 weeks (Davies et al, 2014).
3) CASE REPORT: Severe rhabdomyolysis as evidenced by an initial serum creatine kinase (CK) of 6,111 Units/L was observed in a 21-year-old man after ingesting ecstasy (7 tablets), amphetamine and alcohol. CK peaked at 122,341 Units/L on hospital day 10, remaining above 1000 until day 26, and returned to normal after 45 days. Progressive muscle damage was evidenced by severe weakness and ongoing ventilatory support (weaning attempts failed). After a complex hospital course, the patient was discharged to home doing well on hospital day 80 (Murthy et al, 1997).
4) CASE REPORTS: Rhabdomyolysis was reported in 3 people following ingestion of up to 3 MDMA tablets. The serum creatine kinase levels ranged from 800 Units/L on hospital day 1 (approximately 6 hours postingestion) to 225,000 Units/L on hospital day 3. All three patients completely recovered without sequelae (Ben-Abraham et al, 2003).
5) CASE REPORT/PEDIATRIC: An 8-month-old boy presented with generalized seizure activity, tachycardia (210 beats/min), hypertension (BP 125/70 mmHg), and hyperthermia (38.9 degrees C) after accidentally ingesting one ecstasy tablet. Creatine kinase (CK) level was also elevated and peaked 6 hours after admission at 1681 Units/L. Treatment with benzodiazepines, body cooling and fluids stabilized the child's clinical status within 6 hours of admission, and CK normalized 5 days after discharge (Eifinger et al, 2008).
6) PEDIATRIC EXPOSURE: A 2-year-old boy ingested an unknown amount of MDMA and presented with elevated creatine phosphokinase level of 2854 U/L. The patient tested positive for MDMA the morning after hospital admission; however, the length of time between MDMA exposure to clinical presentation was unknown. After supportive care, the patient recovered and was discharged (Feldman & Mazor, 2007).

1) PARAMETHOXY-AMPHETAMINE: A 20-year-old man was admitted unconscious after ingesting PMA (confirmed by laboratory analysis) with hypertension, tachycardia and an ECG showing a prolonged QRS interval. The patient had a complex course which included hyperthermia, persistent coma, shock, hyperkalemia, rhabdomyolysis and severe coagulopathy. Several days after admission, his laboratory studies included a creatine kinase of 58358 Units/L (reference range: 20 to 200), and a troponin I level of 85.8 (reference range: less than 0.06). Further multiorgan failure included renal and hepatic failure and extensive cerebral edema. He died 10 days after presentation (Lamberth et al, 2008).

1) CASE REPORT: A 20-year-old man collapsed and had tonic-clonic seizures after presumably ingesting DOI (2,5 dimethoxy-4-iodoamphetamine) at a rave party. He required intubation in the field and was admitted comatose with a Glasgow Coma Score of 3/15. However, he had normal reflexes and a brain CT was normal. He also developed tachycardia (152 beats/min), metabolic acidosis, hypotension and an elevated creatine kinase (peak: 4924 International Units/L) with no evidence of renal failure. Following supportive care, including IV hydration and prophylactic antibiotics, the patient was extubated the next day and discharged to home with no permanent sequelae. Serum and urine samples confirmed the presence MDMA and DOC (2,5 dimethoxy-4-chloroamphetamine), which could not be quantified (Ovaska et al, 2008).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

1) In a dog study where chlorpromazine 10 mg/kg was given intravenously immediately following a lethal dose of MDA (20 mg/kg intravenously), all dogs survived for 48 hours. Chlorpromazine protected against acidosis, seizures, and hyperthermia (Davis et al, 1986).

1) Haloperidol has been protective in mice against lethality and hyperthermia caused by some but not all hallucinogenic amphetamines (Nichols et al, 1975; Davis & Borne, 1984; Paton et al, 1975).
2) Dose: Up to 0.1 mg/kg
3) There are no data in humans. The mechanism of action is presumed to be dopaminergic blockade. Because haloperidol lowers seizure threshold and predisposes to hyperthermia, benzodiazepines are preferred.

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)

1) Consider if severe hypertension is unresponsive to short acting titratable agents such as sodium nitroprusside. Although labetalol has mixed alpha and beta adrenergic effects (Pearce & Wallin, 1994), it should be used cautiously if sympathomimetic agents are involved in the poisoning, as worsening hypertension may develop from alpha adrenergic effects.

1) INTRAVENOUS BOLUS: Initial dose of 20 mg by slow IV injection over 2 minutes. Repeat with 40 to 80 mg at 10 minute intervals. Maximum total dose: 300 mg. Maximum effects on blood pressure usually occur within 5 minutes (Prod Info Trandate(R) IV injection, 2010).
2) INTRAVENOUS INFUSION: Administer infusion after initial bolus, until desired blood pressure is reached. Administer IV at 2 mg/min of diluted labetalol solution (1 mg/mL or 2 mg/3 mL concentrations); adjust as indicated and continue until adequate response is achieved; usual effective IV dose range is 50 to 200 mg total dose; maximum dose: 300 mg. Prepare 1 mg/mL concentration by adding 200 mg labetalol (40 mL) to 160 mL of a compatible solution and administered at a rate of 2 mL/min (2 mg/min); also can be mixed as an approximate 2 mg/3 mL concentration by adding 200 mg labetalol (40 mL) to 250 mL of solution and administered at a rate of 3 mL/min (2 mg/min) (Prod Info Trandate(R) IV injection, 2010). Use of an infusion pump is recommended (Prod Info Trandate(R) IV injection, 2010).

1) INTRAVENOUS: LOADING DOSE: 0.2 to 1 mg/kg, may repeat every 5 to 10 minutes (Hari & Sinha, 2011; Flynn & Tullus, 2009; Temple & Nahata, 2000; Fivush et al, 1997; Fivush et al, 1997; Bunchman et al, 1992). Maximum dose: 40 mg/dose (Hari & Sinha, 2011; Flynn & Tullus, 2009). CONTINUOUS INFUSION: 0.25 to 3 mg/kg/hour IV (Hari & Sinha, 2011; Flynn & Tullus, 2009; Temple & Nahata, 2000; Fivush et al, 1997; Miller, 1994; Deal et al, 1992; Bunchman et al, 1992).

1) Common adverse events include postural hypotension, dizziness; fatigue; nausea; vomiting, sweating, and flushing (Pearce & Wallin, 1994).

1) Contraindicated in patients with bronchial asthma, congestive heart failure, greater than first degree heart block, cardiogenic shock, or severe bradycardia or other conditions associated with prolonged or severe hypotension. In patients with pheochromocytoma, labetalol should be used with caution because it has produced a paradoxical hypertensive response in some patients with this tumor (Prod Info Trandate(R) IV injection, 2010).
2) Use caution in hepatic disease or intermittent claudication; effects of halothane may be enhanced by labetalol (Prod Info Trandate(R) IV injection, 2010). Labetalol should be stopped if there is laboratory evidence of liver injury or jaundice (Prod Info Trandate(R) IV injection, 2010).

1) Monitor blood pressure frequently during initial dosing and infusion (Prod Info Trandate(R) IV injection, 2010).

1) REVIEW: In a systematic review of the literature, 71 case reports of MDMA-induced hyperpyrexia were reviewed to assess the safety and efficacy of dantrolene. In both groups, dantrolene (n=26) and no dantrolene groups (n=45), patients were young adults and there were no reports of cyproheptadine use. Overall, survival was higher in the dantrolene group (21/26) compared with no dantrolene group (25/45). In particular, survival rates were higher among patients with extreme (greater than or equal to 42 degrees C) and severe (greater than or equal to 40 degrees C) elevations in temperature in the dantrolene group (8/13 and 10/10 survived, respectively) compared with no dantrolene group (no survivors (n=4) and 15/27 survived, respectively). More severe sequelae was also reported in the no dantrolene group. The most common dose for dantrolene was 1 mg/kg or 80 mg IV and repeated as needed (Grunau et al, 2010).

1) Jackson (2005) suggested that the required dose of carvedilol to duplicate the above findings in clinical care might be considerably higher than that currently used for cardiovascular indications in humans (Jackson, 2005).

1) Consider if severe hypertension is unresponsive to short acting titratable agents such as sodium nitroprusside. Although labetalol has mixed alpha and beta adrenergic effects (Pearce & Wallin, 1994), it should be used cautiously if sympathomimetic agents are involved in the poisoning, as worsening hypertension may develop from alpha adrenergic effects.

1) INTRAVENOUS BOLUS: Initial dose of 20 mg by slow IV injection over 2 minutes. Repeat with 40 to 80 mg at 10 minute intervals. Maximum total dose: 300 mg. Maximum effects on blood pressure usually occur within 5 minutes (Prod Info Trandate(R) IV injection, 2010).
2) INTRAVENOUS INFUSION: Administer infusion after initial bolus, until desired blood pressure is reached. Administer IV at 2 mg/min of diluted labetalol solution (1 mg/mL or 2 mg/3 mL concentrations); adjust as indicated and continue until adequate response is achieved; usual effective IV dose range is 50 to 200 mg total dose; maximum dose: 300 mg. Prepare 1 mg/mL concentration by adding 200 mg labetalol (40 mL) to 160 mL of a compatible solution and administered at a rate of 2 mL/min (2 mg/min); also can be mixed as an approximate 2 mg/3 mL concentration by adding 200 mg labetalol (40 mL) to 250 mL of solution and administered at a rate of 3 mL/min (2 mg/min) (Prod Info Trandate(R) IV injection, 2010). Use of an infusion pump is recommended (Prod Info Trandate(R) IV injection, 2010).

1) INTRAVENOUS: LOADING DOSE: 0.2 to 1 mg/kg, may repeat every 5 to 10 minutes (Hari & Sinha, 2011; Flynn & Tullus, 2009; Temple & Nahata, 2000; Fivush et al, 1997; Fivush et al, 1997; Bunchman et al, 1992). Maximum dose: 40 mg/dose (Hari & Sinha, 2011; Flynn & Tullus, 2009). CONTINUOUS INFUSION: 0.25 to 3 mg/kg/hour IV (Hari & Sinha, 2011; Flynn & Tullus, 2009; Temple & Nahata, 2000; Fivush et al, 1997; Miller, 1994; Deal et al, 1992; Bunchman et al, 1992).

1) Common adverse events include postural hypotension, dizziness; fatigue; nausea; vomiting, sweating, and flushing (Pearce & Wallin, 1994).

1) Contraindicated in patients with bronchial asthma, congestive heart failure, greater than first degree heart block, cardiogenic shock, or severe bradycardia or other conditions associated with prolonged or severe hypotension. In patients with pheochromocytoma, labetalol should be used with caution because it has produced a paradoxical hypertensive response in some patients with this tumor (Prod Info Trandate(R) IV injection, 2010).
2) Use caution in hepatic disease or intermittent claudication; effects of halothane may be enhanced by labetalol (Prod Info Trandate(R) IV injection, 2010). Labetalol should be stopped if there is laboratory evidence of liver injury or jaundice (Prod Info Trandate(R) IV injection, 2010).

1) Monitor blood pressure frequently during initial dosing and infusion (Prod Info Trandate(R) IV injection, 2010).

1) Infuse 500 micrograms/kilogram (0.5 mg/kg) IV over 1 minute (Neumar et al, 2010).

1) Follow loading dose with infusion of 50 mcg/kg per minute (0.05 mg/kg per minute) (Neumar et al, 2010).
2) EVALUATION OF RESPONSE: If response is inadequate, infuse second loading bolus of 0.5 mg/kg over 1 minute and increase the maintenance infusion to 100 mcg/kg (0.1 mg/kg) per minute. Reevaluate therapeutic effect, increase in the same manner if required to a maximum infusion rate of 300 mcg/kg (0.3 mg/kg) per minute (Neumar et al, 2010).
3) The manufacturer recommends that a maximum of 3 loading doses be used (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
4) END POINT OF THERAPY: As the desired heart rate or blood pressure is approached, omit loading dose and adjust maintenance infusion as required (Prod Info BREVIBLOC(TM) intravenous injection, 2012).

1) Esmolol is a short acting beta-adrenergic blocking agent with negative inotropic effects. Esmolol should be avoided in patients with asthma, obstructive airway disease, decompensated heart failure and pre-excited atrial fibrillation (wide complex irregular tachycardia) or atrial flutter (Neumar et al, 2010).

1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

1) PREPARATION: Add 4 mL of 0.1% solution to 1000 mL of dextrose 5% in water to produce 4 mcg/mL.
2) INITIAL DOSE
3) MAINTENANCE DOSE

1) MAXIMUM RATE: Administer diazepam IV over 2 to 3 minutes (maximum rate: 5 mg/min).
2) ADULT DIAZEPAM DOSE: 5 to 10 mg initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
3) PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 mg/kg, repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
4) RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (not FDA approved), or lorazepam may be given intramuscularly.

1) MAXIMUM RATE: The rate of IV administration of lorazepam should not exceed 2 mg/min (Prod Info Ativan(R), 1991).
2) ADULT LORAZEPAM DOSE: 2 to 4 mg IV. Initial doses may be repeated in 10 to 15 minutes, if seizures persist (Prod Info ATIVAN(R) injection, 2003).
3) PEDIATRIC LORAZEPAM DOSE: 0.1 mg/kg IV push (range: 0.05 to 0.1 mg/kg; maximum dose 4 mg); may repeat dose in 5 to 10 minutes if seizures continue. It has also been given rectally at the same dose in children with no IV access (Sreenath et al, 2010; Chin et al, 2008; Wheless, 2004; Qureshi et al, 2002; De Negri & Baglietto, 2001; Mitchell, 1996; Appleton, 1995; Giang & McBride, 1988).

1) If seizures cannot be controlled with diazepam or recur, give phenobarbital or propofol.

1) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (15 to 25 mcg/mL).
2) ADULT PHENOBARBITAL LOADING DOSE: 600 to 1200 mg of phenobarbital IV initially (10 to 20 mg/kg) diluted in 60 mL of 0.9% saline given at 25 to 50 mg/minute.
3) ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 mg may be given every 20 minutes.
4) MAXIMUM SAFE ADULT PHENOBARBITAL DOSE: No maximum safe dose has been established. Patients in status epilepticus have received as much as 100 mg/min until seizure control was achieved or a total dose of 10 mg/kg.
5) PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 mg/kg of phenobarbital intravenously at a rate of 25 to 50 mg/min.
6) PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 mg/kg may be given every 20 minutes.
7) MAXIMUM SAFE PEDIATRIC PHENOBARBITAL DOSE: No maximum safe dose has been established. Children in status epilepticus have received doses of 30 to 120 mg/kg within 24 hours. Vasopressors and mechanical ventilation were needed in some patients receiving these doses.
8) NEONATAL PHENOBARBITAL LOADING DOSE: 20 to 30 mg/kg IV at a rate of no more than 1 mg/kg/min in patients with no preexisting phenobarbital serum levels.
9) NEONATAL PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 2.5 mg/kg every 12 hours may be given; adjust dosage to maintain serum levels of 20 to 40 mcg/mL.
10) MAXIMUM SAFE NEONATAL PHENOBARBITAL DOSE: Doses of up to 20 mg/kg/min up to a total of 30 mg/kg have been tolerated in neonates.
11) CAUTION: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.

a) Ingestion of a presumed "therapeutic" dose of 60 to 65 mg by an adult resulted in a severe, nearly fatal reaction (Hayner & McKinney, 1986). A similar severe reaction was noted in a 32-year-old woman who ingested 200 mg (Brown et al, 1986).
b) A 30-year-old man found at home survived a massive overdose of ecstasy (50 tablets), along with oxazepam 10 mg, and alcohol 5 units (Ramcharan et al, 1998).
c) A 23-year-old man presented with tachycardia, hypotension, tachypnea, a Glasgow Coma Scale (GCS) of 12/15 and fever (rectal temperature of 108.9 degrees F; 42.7 degrees C) after ingesting 3 MDMA pills at a concert. He was also combative, tremulous, hypertonic and hyper-reflexic. Despite supportive care, he developed severe rhabdomyolysis, multiorgan failure, and mild disseminated intravascular coagulopathy on day 2. Following further aggressive supportive care, including several sessions of hemodialysis (a total of 7 sessions), he had a full recovery within 3 weeks (Davies et al, 2014).

a) INFANT: A 13-month-old child developed hypertonia, muscular hyperactivity, seizures, hypertension, tachycardia, and hyperthermia after ingesting a single capsule of MDMA (Russell et al, 1992).
b) CASE REPORT: Approximately 40 minutes after ingesting a portion of an ecstasy pill, a 14-month-old child developed a generalized convulsion with opisthotonos, hyperthermia (38 degrees C), hypertension, tachycardia (130 beats/min), ventricular extrasystoles, tachypnea (50 breaths/min), and mydriasis. The urine levels of amphetamine/methamphetamine were greater than 16 mg/L 5 hours after ingestion. The serum level of MDMA was 0.591 mg/L 8 hours after ingestion. He continued to have hypertension, tachycardia and long periods of trigeminy, without hemodynamic repercussion during the first 12 hours. Following supportive care, the child recovered with no further sequelae (Melian et al, 2004).

1) A 19-year-old man developed coma, seizures, hyperthermia, rhabdomyolysis, and hyperkalemia after ingesting ethanol and 3 ecstasy tablets (total dose unknown). Serum toxicology results revealed an elevated MDMA concentration of 1.5 mg/L. Despite supportive care, he had a cardiac arrest. Resuscitation efforts were unsuccessful and he died 2 hours later (Vanden Eede et al, 2012).
2) In two cases of severe reactions, including hyperthermia, hypotension, coma, and pulmonary edema, serum MDMA levels were 6.5 to 7 mcg/mL (Brown et al, 1986; Hayner & McKinney, 1986).
3) Death occurred in a 16-year-old girl whose blood MDMA level was 0.424 mg/L (Chadwick et al, 1991).
4) A 30-year-old man survived a massive overdose at home of Ecstasy (50 tablets), oxazepam 10 mg, and alcohol 5 units. The patient's serum MDMA level 60 hours after ingestion was 0.8 mg/L (Ramcharan et al, 1998).
5) At necropsy, blood concentrations of MDMA were 4.56 mg/L and 0.36 mg/L for 3,4-methylenedioxyamphetamine with an ethanol level of 0.24 g/L in an adult following ingestion of 2.5 tablets of Ecstasy (total dose approximately 180 mg MDMA) and alcohol at a party. The authors speculated that ritonavir (recently added to the patient's drug regimen) increased serum concentrations of MDMA (Henry & Hill, 1998).
6) Postmortem serum concentrations were 3.05 mg/L in a 53-year-old man 5 days after ingesting an unknown quantity of MDMA (Walubo & Seger, 1999).
7) A postmortem plasma concentration of 3.65 mcg/mL was reported in a 19-year-old man following ingestion of 12 MDMA tablets (Ravina et al, 2004).
8) At more than 48 hours postingestion, postmortem serum concentration was 0.1 mg/L in a 29-year-old man after taking 1 Ecstasy tablet and a large amount of alcohol. At the time of autopsy, no alcohol or other agents were detected in the blood (Duflou & Mark, 2000).
9) The tissue distribution in a fatal acute overdose involving MDMA were as follows (Rohrig & Prouty, 1992)
10) Postmortem serum MDMA concentrations of an 18-year-old man and a 31-year-old man, obtained from peripheral blood samples, were 0.304 mcg/mL and 26.059 mcg/mL (via subclavian blood), respectively, and 13.508 mcg/mL (from the 31-year-old man via femoral blood). In contrast, the serum MDMA concentrations found in cardiac blood and various organs (lung lobes, liver, and stomach) were much higher, with right atrial blood concentrations of 0.416 mcg/mL and 57.297 mcg/ml, respectively, right lung upper lobe concentrations of 3.031 mcg/g and 79.225 mcg/g, respectively, liver concentrations of 4.867 mcg/g and 103.497 mcg/g, respectively, and the stomach contents concentration of 10.519 mcg/g and 2310.709 mcg/g, respectively.
11) A young man died of disseminated intravascular coagulation, induced by hyperthermia following the combined ingestion of amphetamines (3,4-methylenedioxymethylamphetamine, 3,4-methylenedioxyamphetamine, and paramethoxyamphetamine). Postmortem serum PMA, MDMA, MDA, AMP levels were as follows (Dams et al, 2003)
12) The authors proposed that blood sampled from femoral vein should be considered as the "gold standard" for blood sampling; however, if this sample is not available, iliac vein blood can also be used (Dams et al, 2003).
13) In 5 Ecstasy ingestion cases that all resulted in death, antemortem and postmortem MDMA and MDA blood samples were obtained. The mean antemortem concentrations for MDMA and MDA were 1.84 mg/L and 0.06 mg/L, respectively. Results from postmortem sampling were overall higher compared to antemortem values, and they also showed wide variation in concentration values dependent on anatomical site. Mean postmortem concentrations for MDMA and MDA from peripheral sites were 2.9 mg/L and 0.13 mg/L, respectively. The highest postmortem concentrations were measured in postmortem heart blood. The author concluded that MDMA and MDA postmortem concentrations are not directly comparable with antemortem findings, but it is clear that MDMA and MDA exhibit postmortem redistribution (Elliott, 2005).

1) A 20-year-old man died after insufflating 35 mg of 2C-T-7. Postmortem values were: heart blood 57 ng/mL; femoral blood 100 ng/mL; urine 1120 ng/mL; and liver 854 ng/g (Curtis et al, 2003).

1) Postmortem concentrations of Bromo-Dragonfly following ingestion of approximately 700 mcg in an 18-year-old girl were as follows: femoral blood 4.7 +/- 0.7 mcg/kg and urine 22 +/- 2 mcg/kg (Andreasen et al, 2009).

1) CASE SERIES: After ingesting a "hallucinogen LSD-like" drug, 2 men developed a rapid onset of hallucinations (within 15 minutes), vomiting, and coma. The first subject, a 28-year-old (body mass 113 kg) survived, but developed serious convulsions. The second subject, a 29-year-old man (body mass 65 kg) died 6 days postingestion after developing generalized convulsions and metabolic acidosis (pH 6.6). Although immunoassay for amphetamines was negative in urine specimens, GC-MS showed 2,5-dimethoxy-4-bromoamphetamines (DOB) in the gastric and urine samples of both persons. DOB serum concentrations were 13 ng/mL for the surviving patient and 19 ng/mL for the deceased patient (Balikova, 2005).

1) The ingestion of 5 tablets of MDA, in a 20-year-old man, resulted in hyperpyrexia, muscle rigidity, dilated pupils, opisthotonic posturing, profuse sweating, and tonic-clonic seizures. Serum and urine MDA levels were 1.51 and 48.6 mg/L, respectively (Woods & Henry, 1992).
2) In 5 Ecstasy ingestion cases that all resulted in death, antemortem and postmortem MDMA and MDA blood samples were obtained. The mean antemortem concentrations for MDMA and MDA were 1.84 mg/L and 0.06 mg/L, respectively. Results from postmortem sampling were overall higher compared to antemortem values, and they also showed wide variation in concentration values dependent on anatomical site. Mean postmortem concentrations for MDMA and MDA from peripheral sites were 2.9 mg/L and 0.13 mg/L, respectively. The highest postmortem concentrations were measured in postmortem heart blood. The author concluded that MDMA and MDA postmortem concentrations are not directly comparable with antemortem findings, but it is clear that MDMA and MDA exhibit postmortem redistribution (Elliott, 2005).
3) MDA and 2C-I: A woman developed a massive intraventricular hemorrhage and permanent quadriplegia after ingesting MDA and 2C-I. Liquid-chromatography tandem mass spectrometry method was able to detect and quantify both MDA (5.56 mg/L) and 2CI (0.311 mg/L) in urine. The exact toxic dose is unknown for 2C-I. However, the MDA concentration was within range of urine concentrations (2 to 175 mg/L; average 108 mg/L MDA) in 12 fatalities (Drees et al, 2009).

1) Caldicott et al (2003) at the time of article publication identified 32 cases of PMA-related deaths and blood concentrations ranged from 0.2 mg/L to 5.7 mg/L (Caldicott et al, 2003).
2) A postmortem serum concentration of 5.0 mcmol/L was reported in a 16-year-old boy who ingested 7 tablets of PMA (Refstad, 2003).
3) Postmortem blood concentrations of PMA and PMMA in a 20-year-old man, following ingestion of an unknown amount, were 3.4 mg/kg and 3.3 mg/kg, respectively. In a 24-year-old man, the postmortem blood concentrations of PMA and PMMA, following ingestion of an unknown amount, were 0.78 mg/kg and 0.68 mg/kg, respectively (Johansen et al, 2003).

1) The postmortem blood concentrations of PMA, PMMA, and other drugs were determined in 8 fatalities (age range: 14 to 25 years) associated with PMMA use. PMMA was found to be higher in postmortem blood and urine compared to PMA. The mean PMA and PMMA postmortem blood concentrations were 0.213 (+/- 0.144) and 4.312 (+/- 4.806) mcg/mL, respectively. Postmortem urine samples also contained high amounts of PMA and PMMA with the PMA-to-PMMA concentration ratios ranging from 0.019 to 0.237. Other agents detected included MDA, MDMA, ketamine, norketamine, hydroxymidazolam, methamphetamine, and pentobarbital (Lin et al, 2007).

1) Blood and urine levels in a fatal reported case were 21.3 and 12.3 mg/L, respectively. Autopsy reports showed pulmonary and cerebral edema (Davis & Brewster, 1988).

1) If within 2 hours of exposure, induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.
2) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
3) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).

a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

a) EMESIS/GASTRIC LAVAGE - Emesis may be initiated only if in the early period after ingestion, or if the animal is not overly stimulated. Lavage is preferred if the animal is stimulated (administer appropriate sedation) or if emesis is ineffective.
b) ACTIVATED CHARCOAL - Administer activated charcoal, 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
c) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.