Non-pharmaceutical fentanyl (NPF) is a major contributor to opioid overdoses and overdose fatality. In certain urban areas such as Vancouver, over 80% of heroin samples contain NPF. For isolated heroin overdose ED patients, they can be safely discharged after brief observation period (~2 hours). However, “safe” observation time for fentanyl is unknown.
Recently, a retrospective study evaluating the safe observation period in 1009 suspected (uncomplicated) fentanyl overdose ED visits (827 unique patients).
Results:
In the field:
In the ED:
Conclusion:
Bradycardias caused by poisoning are due to the toxin's effects on cardiovascular receptors and cellular channels and transport mechanisms and are often refractory to standard ACLS drugs. The most common drug classes responsible for bradycardias are calcium channel and beta blockers and digoxin (cardiac glycosides). Sodium channel blockers, clonidine, and opiates also can cause bradycardias. Antidotes are as follows:
** ILE is recommended only in life threatening poisonings where other accepted therapies have been use first or in cardiac arrest clinical scenarios.
Clonidine, (central alpha-2 receptor agonist) can produce opioid-like toxidrome in addition to its cardiac effects (bradycardia and hypotension). Previous studies have shown that naloxone has variable (~40%) success in reversing CNS/respiratory depression and cardiac effect.
A recent retrospective study (n=51) of pediatric poisoning showed that administration of 5 to 10 mg had improved reversal of clonidine toxicity.
Total of 51 somnolent patients: 5- 10 mg of naloxone reversed 40 patients
There was no adverse effect from naloxone administration.
Repeat administration of naloxone was required in some patients.
Bottom line
In the past couple of weeks, there have been reports from Illinois about patients using adulterated synthetic cannabinoids, resulting in elevated INR and bleeding. To date, there are approximately 70 cases including 3 fatalities. Brodifacoum, a long-acting vitamin K mediated anticoagulant (similar to warfarin) has been identified in 10 cases. Brodifacoum is frequently used as rodenticide.
This week, Maryland Poison Center received our first notification of a patient with bleeding and elevated INR due to suspected adulterated synthetic cannabinoid use.
When evaluating our patient population:
Patient management of suspected cases:
Patient can be discharged when INR < 2 is achieved with oral vitamine K regimen only (without recent FFP infusion).
Review of published cases highlights that most patients are started on a median doses of 100 mg/day (range: 15 - 600 mg) and stabilize on a PO regimen of 50-100 mg/day. Prolonged PO vitamin K course of 2 – 3 months or longer should be anticipated.
Pease call the Maryland Poison Center at 1-800-222-1222 as we are working with the Maryland Department of Health and CDC to track these cases.
Recently, an ex-Russian spy and his daughter were poisoned in Salisbury, England using a Soviet nerve agent called Novichok. He joins a list of defectors and ex-spies who's poisoning have been connected to Russia.
Nerve agents are organophosphate compounds, similar to the commercially available pesticides, but significantly more potent. Nerve agents such as VX take seconds to minutes to irreversibly inhibit acetylcholinesterase by “aging” and result in clinical toxicity.
Signs and symptoms
Treatment
Signs and symptoms of acute cyanide poisoning are not well characterized due to its rare occurrence. Commonly mentioned characteristics of bitter almond odor and cherry red skin have poor clinical utility.
Recently published review of 65 articles (102 patients) showed that most patients experienced following signs and symptoms:
There is no clear toxidrome for cyanide poisoning.
In a poisoned patient, health care providers should consider cyanide in their differential diagnosis in the presence of severe metabolic and lactic acidosis (lactic acid > 8 in isolated cyanide poisoning or > 10 in smoke/fire victim).
A leading cause of cardiac arrest in patients 40 years and younger is due to drug poisoning. Adverse cardiovascular events (ACVE) such as myocardial injury (by biomarker or ECG), shock (hypotension or hypoperfusion requiring vasopressors), ventricular dysrhythmias (ventricular tachycardia/fibrillation, torsade de pointes), and cardiac arrest (loss of pulse requiring CPR) are responsible for the largest proportion of morbidity and mortality overdose emergencies. Clinical predictors of adverse cardiovascular events in drug overdose in recent studies include:
Bottom line:
Obtain ECG and perform continuous telemetry monitoring in overdose patients with above risk factors. Patients with two or more risk factors have extremely high risk of in-hospital adverse cardiovascular events and intensive care setting should be considered.
Abnormal ocular movement (e.g. nystagmus) can often be observed in select CNS pathology.
Certain drugs/toxin overdose can also induce nystagmus.
In an "unknown" intoxication, physical exam findings such as nystagmus may help narrow the identity of the suspected ingestion/overdose.
Bupropion (Wellbutrin, Zyban) is unique monocyclic antidepressant and smoking cessation agent that is structurally similar to amphetamines. Bupropion blocks dopamine and norepinephrine reuptake and antagonizes acetylcholine at nicotinic receptors.
Bottom line:
Bupropion is a common cause of drug induced seizures but in severe overdose can also cause prolonged QTc and wide complex ventricular dysrhythmia that may be responsive to sodium bicarbonate. All patients with an overdose of bupropion should have an ECG performed and cardiac monitoring to watch for conduction delays and life-threatening arrhythmias.
47 year old woman presents with cough, headache, weakness, and low grade fever. Her symptoms have been present for several days. Vital signs are temperature 99.9 F, HR 96, RR 16, BP 140/88, Pulse Ox 98%. Physical exam is nonfocal. She is Influenza negative. She is treated with Ibuprofen and oral fluids. Upon discharge she mentions she is having difficulty hearing and feels dizzy. Upon further questioning she admits to ringing in her ears. What tests should you order?
Acute liver failure carries a high morbidity without liver transplantation. Liver support systems can act as “bridge” until an organ becomes available for the transplant procedure or until the liver recovers from injury. Artificial liver support systems temporally provide liver detoxification utilizing albumin as scavenger molecule to clear the toxins without providing synthetic functions of the liver (coagulation factors). One of the most widely used devices is the Molecular Adsorbent Recirculating System (MARS).This system has 3 different fluid compartments: blood circuit, albumin with charcoal and anion exchange column, and a dialysate circuit that removes protein bound and water soluble toxins with albumin.
Bottom Line
MARS therapy could be a potentially promising life saving treatment for patients with acute poisoning from drugs that have high protein-binding capacity and are metabolized by the liver, especially when concomitment liver failure. Consider consultation and transfer of patients to liver center.
Acetaminophen (APAP) overdose is the leading cause of liver failure in the U.S. and Europe. Large APAP ingestion can result in hepatotoxicity despite the early initiation of n-acetylcysteine (NAC).
A recently published study from Austrialia investigated the effect of activate charcoal and increasing the NAC dose for large APAP overdose patients (3rd bag: 100 to 200 mg/kg over 16 hours) during first 21 hours of NAC therapy
acetaminophen ratio (first APAP level taken between 4 to 16 hour post ingestion / APAP level on the Rumack nomogram line at that time point) was determined to compare APAP levels at different time points among study sample
e.g.
first APAP level at 4 hour post ingestion = 400
APAP level on the Rumack APAP nomogram at 4 hour post ingestion = 150
APAP ratio = 400/150 = 2.67
Findings:
Conclusion:
Note: Any increase in NAC dosing from the standard 21 hour therapy should be performed after consulting your regional poison center.
Loperamide (Imodium) is a common inexpensive over-the counter antidiarrheal agent. It acts peripherally at the mu opioid receptor to slow gastrointestinal motility and has no CNS effects at therapeutic doses due to it's low bioavailability and limited abillity to cross the blood brain barrier dependent on glycoprotein transport. In the past few years, reports of loperamide abuse causing serious cardio toxicity began to appear in the literature. Abused at daily doses of 25-200 mg to get high or and to treat symptoms of withdrawal. (therapeutic dose: 2-4 mg with a maximun of 8mg for OTC and 16mg for prescription). Loperamide has been called the "poor man's methadone".
At large doses, loperamide effects the cardiac sodium, potassium and calcium channels which prolongs the QRS complex and can lead to ventricular arrhythmias, hypotension, and death. Clinical features includes:
Take Home Point:
Consider loperamide as a possible cause of unexplained cardiac events including QT interval prolongation, QRS widening, Torsades de Pointes, ventricular arrhythmias, syncope, and cardiac arrest. Intravenouse sodium bicarbonate should be utilized to overcome blockade and may temporize cardiotoxic events. Supportive measures necessary may include defibrillation, magnesium, lidocaine, isoproternol, pacing, and extracorporeal life support.
Different chemical, food or pharmaceutical agent exposure can change the color of the urine.
What could cause this patient's urine to turn green?
Lithium salts have been used therapeutically for over a 150 years to sucessfully treat manic depressive symptoms, schizoaffective disorder, and cluster headaches. Lithium has a narrow therapeutic range (0.6-1.5 meq/L) and is 100% eliminated by the kidneys. Multisystem toxicity occurs however CNS toxicity is significant and consist of confusion, lethargy, ataxia, neuromuscular excitability (tremor, fasciculations, myoclonic jerks, hyperreflexia). Since there is a poor relationship between serum concentration and toxicity in the brain, serum blood levels may not reflect extent of toxicity . The goal of enhanced elimination is to prevent irreversible lithium-effectuated neurotoxcity which causes persistant cerebellar dysfunction with prolonged exposure of the CNS to high lithium levels.
Decision for hemodialysis is determined by clinical judgement after considering factors such as lithium concentration, clinical status of patient, pattern of lithium toxicity (acute vs. chronic), concurrent interacting drugs, comorbid illnesses, and kidney function. Strongly consider hemodialysis for the following:
Many medications are discovered from plants (quinine – cinchona trees) or organisms (penicillin – mold [penicillicum]).
Digoxin was isolated from foxglove (Digitalis lanata), a colorful floral plant often found in many gardens. There are other sources of cardioactive steroids (aka cardiac glycosides) that have similar effect as digoxin.
Non-digoxin cardioactive steroid exposure can result in a positive digoxin level due to cross reactivity. This confirms exposure; however, the “digoxin level” does not represent the true extent of the ingested dose or toxicity.
Non-digoxin cardioactive steroid toxicity
The cornerstone treatment of poisoning is removal of the toxin from the patient. This can be accomplished before absorption into the body by decontamination methods (dermal or gastrointestinal) or after absorption by blocking metabolism of parent compound, displacing drugs from receptors, binding toxins with neutralizing agents (chelators, Fab fragments), or enhancing elimination by dialysis. Toxins that are ideal candidates for dialysis include substances that are low molecular weight, have low volume of distribution (stay in the blood stream), or low protein binding. Toxins most commonly treated with dialysis are:
Her first book “The mysterious affair at Styles,” Agatha Christie introduced her lead detective in her novels, Hercule Poirot - the Belgian detective. She also described the death of Mrs. Emily Inglethorp by strychnine.
Strychnine is found in a disc-like seed of strychnos nux-vomica, a tree native to tropical Asia and North Australia.
It is currently used as rodenticide (moles and gophers), in Chinese herbal medicine and a traditional remedy in Cambodia.
Strychnine inhibits binding of glycine (a major inhibitory neurotransmitter in spinal cord) to Cl-channel resulting in identical clinical syndrome – seizure-like generalized muscle contraction with normal mental status – as tetanus toxin. Tetanus toxin inhibits the release of presynaptic glycine in the spinal cord.
Management
Goal: decrease muscle hyperactivity
Agatha Christie is an English crime novelist who frequently used poisons in her books to murder the victims. In her book, Murder is Easy, Ms. Christie uses arsenic/arsenic trioxide to kill several characters.
Primary source of arsenic in general population is contaminated food, water and soil. Arsenic exists in several forms: elemental, gaseous (arsine), organic and inorganic (trivalent or pentavalent).
Arsenic trioxide has also been used to treat acute promyelocytic leukemia in China; it’s use in other leukemia, lymphoma, and other solid tumors are currently being investigated.
Arsenic primarily inhibits the pyruvate dehydrogenase complex and multiple other enzymes involved in the citric cycle/oxidative phosphorylation, resulting in mitochondrial dysfunction.
Acute toxicity of arsenic after ingestion
Management
Cannabinoid hyperemesis is a syndrome (CHS) characterized by severe intractable nausea, cyclical vomiting, and abdominal pain associated with chronic marijuana abuse. It is often a underrecognized cause of cyclic vomiting syndrome. Despite well established anti-emetic properties of marijuana, paradoxical effects on the GI tract exist through cannabinoid receptors which exert their neuromodulatory properties in the central nervous system and the enteric plexus. Multiple theories of mechanism of CHS are in the literature. Diagnosis is based on the following clinical criteria:
Acute care goals are to treat dehydration and terminate nausea and vomiting. Administration of intravenous fluids, dopamine antagonists, topical capsaicin cream, and avoidance of narcotic medications are recommened treatment measures. Benzodiazepines followed by haloperidol and topical capsaicin are reported to be most effective. Capsaicin activates the transient receptor potential vanilloid 1 receptors (TRPV1) which impairs substance P signalling in the area postrema and nucleus tract solitarius similar to noxious stimuli, such as heat.
