Clinical Presentation

history of sympathomimetic poisoning is that the onset of symptoms usually occurs within 2 hours post exposure

Life-threatening complications typically occur within 2-6 hours postexposure.

duration of action of illegal sympathomimetic agents differ based on their chemical structure. Methamphetamine has the chemical structure of amphetamine with an additional methyl group. The half-life of methamphetamine, however, is much longer (2-24 h) than that of amphetamine

The route of abuse also contributes to the duration of action of some of these illegal sympathomimetic agents.

the half-life of methamphetamine ranges from 10-20 hours, depending on the urine pH, history of recent use, and dosage.[11]

Metabolism occurs faster in acidic urine

The majority of methamphetamine is metabolized to amphetamine, which provides further CNS stimulation.

adverse effects of MDMA are not clearly dose related

some individuals developing life-threatening toxic syndromes after single doses of drug

MDMA-Induced Serotonin Neurotoxicity

Mortality/Morbidity

Acute methamphetamine overdose may result in sympathetic overdrive, cardiovascular collapse, rhabdomyolysis, ventricular tachyarrhythmia, and death.

Injuries from blunt and penetrating

trauma are common

 Clinical Presentation

Cardiovascular

Chest pain, aortic dissection, myocardial ischemia/infarction

Palpitations, tachyarrhythmia Dyspnea and edema Hypertension

Central nervous system manifestations

Agitation, violent behavior, self-harm Coma New-onset seizure, movement disorders Emotional lability, confusion, psychosis,

paranoia, hypersexuality, and hallucinations Headache

Headache and cerebrovascular accidents with focal neurologic deficits may be caused by hemorrhage or vasospasm, cerebral edema, and cerebral vasculitis

Coma may result from depletion of catecholamine stores

or concomitant ingestion of sedatives such as ethanol or narcotics

Gastrointestinal manifestations

Abdominal pain

Obstruction

Respiratory manifestations

Dyspnea Wheezing Pneumothorax

Renal failure

Hypoxemia Rhabdomyolysis Necrotizing angiitis Acute interstitial nephritis Cardiovascular shock with subsequent

acute tubular necrosis

nonlethal signs and symptoms

Mydriasis Tachycardia Diaphoresis Acute psychosis Paranoia Delirium Bruxism (amphetamines and bath salts)

Differential Diagnoses

Acute Coronary Syndrome Acute Respiratory Distress Syndrome Cardiomyopathy, Dilated Hypertensive Emergencies Hyperthyroidism, Thyroid Storm Seizures Subarachnoid Hemorrhage Toxicity, Anticholinergic Toxicity, Antihistamine

 Workup

CBC and chemistry test To assess renal and electrolyte function Creatine kinase and/or myoglobin levels To exclude rhabdomyolysis Serial troponin levels - If there is concern for

myocardial ischemia Pregnancy test - In women of childbearing age Toxicology screens - Useful for patients who

cannot or will not disclose drug use history and for pediatric patients with new-onset seizure

ECG for patients with chest pain, altered mental status, and tachycardia.

Procedures

Lumbar puncture may be indicated in patients with altered mental status

to rule out meningitis or subarachnoid hemorrhage.

Imaging Studies

chest radiograph for patients with pulmonary symptoms or chest trauma.

In patients with altered mental status, perform a head CT scan to exclude intracranial bleeding. Such bleeding may be the result of either methamphetamine-induced hypertension or associated head trauma.

Patients who are suspected body-packers, body-stuffers, should undergo abdominal imaging.

sympathomimetic toxicity

because no antidote exists. Assessment of the airway, breathing,

and circulation immediately is recommended.

close monitoring of the vital signs is recommended.

Sedation Protocol

Aim :control dangerous behaviour sufficiently

to facilitate accurate assessment and appropriate management

benzodiazepines are first line treatment agitated patients induced seizures cardiac toxicity

Acute Behavioural Disturbance

primary aim of management is to reduce the risk of harm to the patient, staff and other

people physical restraint alone is often not adequate may actually cause harm if agitation

increases.

Stimulant use risk factor for sudden death of individuals being physically restrained

Sedation Protocol

Oral diazepam 10-20mgs orally. If no clinical response at

30 MIN , an additional 10 mgs this regime until the patient is in a state

of drowsiness or a total dose of 60mgs

Sedation Protocol Intravenous diazepam 2.5-5mg to assess patients Sensitivity to

BZ Some patients will respond to this low dose.

If no clinical response at 10 min an Additional higher dose of 5-10 mg

Repeat this higher dose of 5-10mg every 10 min to a maximum dose of 60mg

if the patient is not sedated adequately. Consider alternate agent Midazolam 5 -10mg IM at 10 min or 2/5-5 IV (to a maximum dose of 25mg)

droperidol 2.5mg intravenously or olanzapine

10mg intramuscular (IM) if no response

Sedation ProtocolORAL DIAZEPAM

INTRAVENOUS DIAZEPAM

10-20mgs orally. If no clinical response at 30 min

, an additional 10 mgs should be administered. this regime until the

patient is in a state of drowsiness or a total

dose of 60mgs

2.5-5mg to assess patients Sensitivity to BZ Some patients will respond to this low dose.

If no clinical response at 10 min an Additional higher dose of 5-10 mg

Repeat this higher dose of 5-10mg every 10 min to a maximum dose of 60mg

if the patient is not sedated adequately. Consider alternate agent droperidol 2.5mg intravenously or

olanzapine 10mg intramuscular (IM) if no response

Observations

Patients should then be monitored for four hours,

Observations should be every 10 minutes for 30 minutes then every 15 minutes for 30 minutes , then every 30 minutes for 60 minutes then hourly for four hours or until awake.

Observations should include:

airway patient colour continuous oxygen saturation respiration rate blood pressure pulse temperature Glasgow Coma Scale score bedside BSL.

Cardiovascular Complications:

uncontrolled hypertension might be at risk for subarachnoid and intracerebral haemorrhage

chest pain benzodiazepines Sublingual nitroglycerine Beta-blockers, should be avoided

Serotonin Toxicity (including Hyperthermia)

Serotonin involved in a range of functions including:

mood, appetite and sleep regulation cognition; perception; motor activity;

temperature regulation; pain control sexual behaviour and hormone secretion

treatment of serotonin toxicity:

early recognition

prompt supportive care

treatment of serotonin toxicity

hyperthermia above 39.5OC intubation with deep intravenous sedation IV fluids/volume resuscitation for dehydration,

hypotension or rhabdomyolysis (ensure adequate urine output

in 1.5-2mls/kg/hr) mechanical ventilation for respiratory

compromise and sedation with IV benzodiazepines might be indicated

treatment of serotonin toxicity

5-HT2 antagonists such as olanzapine (24), chlorpromazine or

cyproheptadine (3) may be indicated (these specific antagonists should

only be used if the diagnosis of serotonin toxicity has been established

and anticholinergic agents have not been co-ingested)

paralysis and intubation may have a role in cases of severe intractable

rigidity management of secondary cardiac arrhythmias or

seizures involves standard measures

measure the core temperature of sympathomimetic poisoned patients.

If hyperthermia is present, standard cooling measures should be initiated.

Controlling agitation significantly helps in cooling a hyperthermic patient.

Hypertension unresponsive to sedation should be treated with a rapidly acting

and easily titrated agent (eg, sodium nitroprusside).

Seizures should be rapidly controlled with benzodiazepines and/or barbiturates.

Obtaining a CT scan of the brain for all sympathomimetic toxic patients who seize, develop a focal neurologic deficit, or experience a severe headache with or without accompanying hypertension is recommended

Prolonged critical care management often is required for the numerous complications that may occur with the severe overdose (eg, hyperthermia, seizures, advanced respiratory distress syndrome [ARDS], renal failure, rhabdomyolysis, CNS dysfunction).

A 19-year-old man was arrested after a traffic violation

and taken to the local jail. he had ingested 8 "balls" (8 g) of

methamphetamine

Personnel at the scene said that the man had had no seizures

but they did witness severe rigors with diaphoresis for approximately 30 minutes

Initially the patient was able to communicate

with difficulty. his last use was at least 10 hours earlier patient as red, cool, and diaphoretic, with severe shakes and incontinent of

urine His lungs were clear, and RR 60/min EKG revealed a sinus tachycardia of

200/min. Pulse oximetry 2.5 Llmin of oxygen was

91 %. blood glucose was 81 mg/dL

On arrival at the emergency department patient's rectal temperature was greater than 108°F,respirations were 45/min, pulse was 180/min , blood pressure was 186/96 mm Hg. Pulse oximetry on 10 Llmin of oxygen was 98% saturated. The patient displayed diffuse rigidity and tremulousness, his skin was hot and

diaphoretic, his pupils were dilated and he did not

respond to verbal or painful stimuli A Foley catheter returned minimal urine

output.

Ice packs on the patient's groin, axillae, and neck

lowered his temperature to 105.5°F. During resuscitation

he received sequential trials of lorazepam, labetalol, and 50% dextrose

in water. His blood pressure decreased to 86/44

mm Hg

After a trial of lidocaine for his tachycardia, the patient's heart rate decreased to 140 beats per minute.

Intravenous normal saline was rapidly infused. His respiratory status worsened, and pulse oximetry dropped to 63 % saturation on 10 Llmin of oxygen. He was intubated orally with difficulty because of

teeth clenching. Gastric lavage produced a string, but there were

no pill fragments. Sorbitol and activated charcoal were

administered, and the patient was given intravenous famotidine. rectal examination showed no pill fragments or other foreign bodies.

A chest radiograph CT scan of the head were negative

An electrocardiogram continued to show sinus tachycardia..

Initial chemistry and coagulation laboratory values were all essentially normal

Arterial blood gases indicated metabolic acidosis.

The patient was transferred to the critical care unit 3 hours after his arrest by police, when it is presumed that he had swallowed the

8 "balls" to avoid detection . A drug-screening test of blood drawn 8 hours

after admission was negative for alcohol. Cannabinoids were present. His blood was positive for amphetamines, with a serum value

of 3,500 ng/mL (3.5 mglL).

patient's liver function tests continued to worsen from day 2, with enzyme levels reaching their highest on day 4 at an AST level of 4,422

UIL and alanine aminotransferase (ALT) of2,786 UIL. The transaminase levels subsequently decreased rapidly with a delayed increase in total bilirubin. Serum creatine kinase levels exceeded 20,000

UIL on day 2

Dialysis was begun on day 4. His neurologic status never improved

during hospitalization Multiple cardiac arrests occurred

Management of amphetamine toxicity

start with the ARCs (airway, breathing, and circulation)

when apnea, cardiac arrest, dysrhythmias, or

seizures are the initial signs

Although urinary acidification can increase the elimination of amphetamines, is no recommended because of the

possibility of worsening renal insult from rhabdomyolysis. better to promote urine output with rapid, generous intravenous fluid

resuscitation to maintain an alkaline urine to alleviate

the effects of myoglobin on the kidneys

It is important to recognise that psychostimulant toxicity can occur among

both experimental and regular users of psychostimulants

If the Patient is Cooperative

type of psychostimulant used amount of psychostimulant used1 time of administration route of administration (intranasal, intravenous, oral, inhalation) frequency of use (e.g. regular daily use, binge pattern, recreational, experimental, etc) duration of current use and age of first use obtain a urine sample for a drug screen if possible. 2. Other drug use concurrent use of other drugs (particularly alcohol, benzodiazepines, opiates, party drugs), including criteria above concurrent use of antidepressant medication (e.g. TCAs, MAOIs, SSRIs, bupropion, venlaxafine) which may increase the serotonergic or catecholamine mediated effects of psychostimulants

If the Patient is not Cooperative

signs might indicate the patient has recently used

dilated pupils that react sluggishly to light clenched jaw or muscle rigidity restlessness, agitation, tremor or repetitive

movements rapid speech motor agitation or pacing hypertension tachycardia sweaty palms, flushed diaphoretic facial skin hypervigilance, paranoia.

Dantrolene was prescribed for temperatures of 104°F and higher.

Temperature decreased to 103.6°F with cooling measures and the paralytic. He remained comatose with a Glasgow score of 3 He began to ooze blood from various orifices His fibrinogen decreased from 128 mg/dL to 85 during the first 14 hours. His BUN and CR levels elevated on day 2 of

hospitalization. His AST level was elevated to 1,927 urine became positive for myoglobin

Managing the airway and controlling agitation are the two main prehospital treatment concerns.

any patients with sympathomimetic poisoning present in an agitated state.

In these cases, physical and/or chemical restraint may be required