Keywords: hydrocarbon ingestion, pediatric poisoning (PubMed Search)
The management of pediatric hydrocarbon ingestion has not changed significantly over the past several decades. One of the earlier study that helped established the management approach is by Anas N et al. published in JAMA, 1981.
It was a retrospective study of 950 children who ingested household hydrocarbon containing products.
Discharged patients: n=800
Admitted patients: n=150
This study recommended that hospitalization is required in patients…
Anas N. et al. Criteria for hospitalizing children who have ingeted products containing hydrocarbons. JAMA 1981;246:840-843
Keywords: Hyperemesis, Cannabinoid (PubMed Search)
Bottom line: Patient education should be provided on the paradoxical and recurrent nature of the symptoms of CHS to discourage relapse of use often stemming from false preception of beneficial effects of cannabis on nausea.
Cannabinoid hyperemesis: a case series of 98 patients. Simonetto DA, Oxentenko AS, et al,Mayo Clin Proc. 2012;87(2):114–9
Cannabinoid hyperemesis syndrome: potential mechanisms for the benfit of capsaicin and hot water hydrotherapy in treatment. Richards JR, Lapoint JM, et al. Clin Tox(phila) 2018 Jan :56(1): 15-24.
Cannabinoid Hyperemesis Syndrome: Public Health Implications and Novel Model Treatment Guidelines. West J Emerg Med. 2018 Mar:19(2):380-386.
Keywords: Anticholinergic, Plant (PubMed Search)
A 19 year old male presents confused and very agitated complaining of seeing things and stomach pain. His friends report he ingested a naturally occurring plant to get high a few hours ago but is having a "bad trip". His physical exam :
Temp 100.3, HR 120, RR 14, BP 130/88. Pulse Ox 98%.
Skin: Dry, hot , flushed
HEENT: Marked mydriasis 6mm
Abdomen: Distended tender suprapubic with absent bowel sounds,
Neuro: Extremely agitated pacing, no muscular rigidity.
What has he ingested and what is the treatment?
Datura stramonium, aka: Jimson Weed, flowers in the summer with white to violet trumpet petals, green irregular toothed leaves, and a green thorny round walnut sized seed pod (aka: thorn apple) the base of the stem. In the fall, the seed pods turn brown and split open to reveal chambers that are packed with dozens of small black seeds containing the anticholinergic tropane alkaloids, atropine, hyoscyamine, and scopolamine.
All parts of the plant are toxic and it has long been used in traditional medicine. Toxicity consists of anticholinergic toxidrome: Delirium and agitation, visual hallucinations, dry flushed skin, hyperthermia, mydriaisis, tachycardia, absent bowel sounds, urinary retention, remembered by the pneumonic "Red as a beet, hot as a hare, dry as a bone, blind as a bat, mad as a hatter, the bowel and bladder lose their tone, and the heart runs alone" . Toxicity is usually 12 hours but can be quite prolonged.
Treatment consists of :
-Gastric decontamination with activated charcoal and whole bowel irrigation for seed ingestion (seeds get caught up in gastric folds prolonging toxicity)
-IV Physostigmine, a reversible short acting acetylcholinesterase inhibitor increases acetylcholine at the synaptic clef, crosses the blood brain barrier, and is antidotal. Physostigmine has been demonstrated to be more effective and without significant complications when compared with benzodiazepines for the diagnosis and treatment of anticholinergic agitation and delirium. Usual dose is 0.5-2 mg with repeat dosages as needed.
Keywords: anaphylactoid reaction, IV NAC (PubMed Search)
Analphylatoid reaction is caused by non-IgE mediated histamine released. Intravenous N-acetylcysteine (NAC) infusion is well known to cause analphylatoid reaction. However, it’s incidence is unknown.
Recently, a large retrospective study of all patients who received 21-hour IV NAC in 34 Canadian hospitals (1980 to 2005) was performed.
Anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses
Over 90% patients developed analphylatoid reaction within 5 hours.
Onset of reaction:
Administered medication for treatment
Patient characteristics that were associated with higher incidence of Anaphylactoid reaction includes
Yarema M et al. Anaphylactoid reactions to intravenous N-acetylcysteine during treatment for acetaminophen poisoning. J Med Toxicol 2018: Jun;14(2):120-127. doi: 10.1007/s13181-018-0653-9. Epub 2018 Feb 8.
Keywords: Weakness (PubMed Search)
A 68 year old male presents to the ED complaining of weakness to his legs. He states today his yard chores took him over 2 hours to complete instead of the usual 15-20 minutes due need to take frequent breaks for rest due to leg pain. He denied any chest pain or shortness of breath. Past medical history included hypercholesteremia, HTN, and CAD. He is taking aspirin and recently started on rosuvastatin.
His physical exam was unremarkable.
Results showed normal EKG and CBC. Bun was 70, Creatinine was 3.4, and CPK of 1025.
This patient has statin induced rhabdomyolysis and acute renal failure.
Take Home Points:
Keywords: naloxone dose, recurrence of opioid toxicity (PubMed Search)
Various intial doses of naloxone (0.4 to 2 mg) are administered to reverse the signs and symptoms of opioid toxicity. However, there is limited data regarding the duration of action of naloxone is correlated to the administered dose.
A recently published retrospective study investigated whether initial naloxone doses (IV), low-dose (0.4 mg) vs. high-dose (1-2 mg), lead to different time to recurrence of opioid toxicity.
Study sample: 274 patient screened but 84 patients were included.
Higher rate of adverse effects (withdrawal symptoms - vomiting, agitation, tachycardia, etc.) were observed in high-dose group (41% vs. 31%) but this was not statistically signficant.
Wong F et al. Comparison of lower-dose versus higher-dose invetravenous naloxone on time to recurrence of opioid toxicity in the emergency department. Clin Toxicol (Phila) 2018 Jul 23:1-6. doi: 10.1080/15563650.2018.1490420. [Epub ahead of print]
Keywords: transaminitis, delayed acetaminophen toxicity, rhabdomyolysis (PubMed Search)
Elevated transaminases are found in both rhabdomyolysis and delayed acetaminophen (APAP) toxicity. Establishing the cause of elevated transaminase can be difficult when there is unclear history of acetaminophen ingestion.
A retrospective study of patients with delayed acetaminophen toxicity or rhabdomyolysis from 2006 to 2011 was recently published.
The authors compared AST/ALT, CK/AST and CK/ALT ratio of
Keywords: Sulfonylureas, Octreotide (PubMed Search)
Sulfonylureas are commonly used oral hypoglycemic agents for type II diabetes. Agents on the market include glipizide (Glucotrol), glyburide (Micronase, Glynase, Dibeta) and glymepiride (Amaryl). These agents exert their effect by stimulation of insulin release from the pancreatic beta islet cells. Following overdose, hypoglycemia is usually seen within a few hours of ingestion and can be prolonged and profound. First line treatment for rapid correction of severe hypoglycemia is administration of an intravenous bolus of concentrated dextrose. However, use of dextrose infusion in attempt to maintain euglycemia is problematic as it can cause further release of insulin and rebound hypoglycemia. Octreotide ia a long acting synthetic somatostain analogue, blocks insulin secretion and has been shown to prevent recurrence of hypogylcemia better than placebo.
Comparison of Octreotide and standard therapy versus standard therapy alone for treatment of sulfonylurea-induced hypoglycemia, Fasano CJ, O’Malley, et al. Ann Emerg Med. 2008 Apr;51(4): 400-406.
Octreotide for the treatment of sulfonylurea poisoning. Glatstein M. et al. Clin Toxicol 2012;50:795-804.
Keywords: antimuscarinic/anticholinergic toxicity, reversal of delirium (PubMed Search)
From 1960s to 1970s, physostigmine was routinely administered as part of the "coma cocktail." Since the publication of two cases by Pentel (1980) that resulted in asystole after administration of physostigmine in TCA poisoned patient, its use has declined significantly.
However, physostigmine still possess limited but clinically useful role in the management of patients with antimuscarinic/anticholinergic induced delirium.
Recently, a prospective observational study was performed in the use of physostigmine when recommended by a regional poison center.
In 1 year study period, physostigmine was recommended by a regional poison center in 125 of 154 patients with suspected antimuscarinic/anticholinergic toxicity.
common exposures were
57 of 125 patients received physostigmine per treating team.
Of the remaining patients,
Adverse events (physostigmine group vs. non-physo group) - no statistically significant difference.
Physostigmine can safely control antimuscarinic/anticholinergic-induced delirium.
Boley SP et al. Physostimgine is superior to non-antidote therapy in the management of antimuscarinic delirium: a prospective study from a regional poison center. Clin Toxicol 2018 Jun 29:1-6. doi: 10.1080/15563650.2018.1485154. [Epub ahead of print]
Keywords: acute agitation, midazolam, antipsychotics, (PubMed Search)
Acutely agitated patients in the emegency room receive single or combination of benzodiazepine (lorazepam vs. midazolam) and antipsychotic (e.g. haloperidol) agents. Recently, use of ketamine has also been advocated to sedate agitated patients.
A recently published article compared IM administration several medications to treat acutely agitated patients in the ED. According to established protocol, each medication was administered in predetermined 3 week blocks:
N=737 with median age of 40 years, 72% men.
Midazolam resulted in greater proportion of patients with "adequate" sedation (altered mentatl status scale <1) compared to antipsychotics at 15 min post administration. Among antipsychotics, olanzapine resulted in greater proportion of patient with sedation.
Adverse effect were limited
Midazolam 5 mg IM achieve more effective sedation at 15 min in agitated ED patients than antipsychotics.
Klein LR et al. Intramuscular midazolam, olanzapine, ziprasidone or haloperidol for treating acute agitaion in the emergency department. Ann of Emerg Med 2018 June 6. pii: S0196-0644(18)30373-1. doi: 10.1016/j.annemergmed.2018.04.027. [Epub ahead of print]
Keywords: Methylene Blue (PubMed Search)
Methylene Blue Used in the Treatment of Refractory Shock Resulting From Drug Poisoning. Fisher J, et al. Clin Toxicol 2914 Jan;52:63-65.
Calicum channel antagonist and beta blocker overdose: antidotes and adjunct therapies. Graudins A, et al. British Journal of Clin Pharm. 2016;81(3):453-461.
Keywords: Factor Xa inhibitor, reversal agent, adexanet alfa, andexxa (PubMed Search)
On May 3, the FDA approved adexanet alfa, the reversal agent for factor Xa inhibitors - apixaban and rivaroxaban. It received both U.S. Orphan Drug and FDA Breakthrough Therapy designations.
Unlike indarucizumab (a monoclonal antibody fragment) to reverse dabigatran (direct thrombin inhibitor) associated bleeding, adexanet alfa is a recombinant modified human factor Xa decoy protein.
A phase 3 study showed that adexanet alfa decreased the anti-factor Xa activity of rivaroxaban by 92% from baseline and by 94% in apixaban treated participants.
ANNEXA-4 study involving participants with acute major bleeding (GI and intracranial) showed a significant decrease in the anti-factor Xa activity after the bolus dose of adexanet alfa and "effective" hemostasis was noted in 79% of the participants at 12 hours post infusion.
Andexanet alfa is expected to become available in June 2018.
Keywords: Intralipid Emulsion (PubMed Search)
Despite initial excitement for the use of intravenous lipid emulsion (ILE) therapy as an antidote for serious poisonings due to lipohphilic drugs there remains an absence of evidence combined with an incomplete understanding of its efficacy, mechanisms of action, safety, and analytical interferences to recommend its use except in a few clinical scenarios.
The lipid emulsion workgroup performed a comprehensive analysis of four systematic reviews and based recommendations from consensus of expert panelists from the American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists, the American College of Medical Toxicology, the Asia Pacific Association of Medical Toxicology, the American Association of Poison Control Centers, and the Canadian Association of Poison Control Centers. Toxins evaluated had to have a minimum of three human cases reported in the literature.They concluded that ILE could be indicated for the following clinical situations:
The Bottom Line:
The use of Intravenous Lipid Emulsion in severe poisoning is recommended only for a few poisoning scenarios and was based on very low quality of evidence, and consideration of risks and benefits, adverse effects, laboratory interferences as well as related costs and resources.
Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Goseslin S. Hoegeberg L, Hoffman R, et al. Clinical Toxicology, 54:10, 899-923.
Intravenous Lipid Emulsion Therapy and VA-ECMO rescue therapy for Massive Venlafaxine and Clonazepam Overdose. Thomas A, Ovakim D, et al. J Clin Toxicol 2017 7: 368.
Keywords: fentanyl overdose, observation period (PubMed Search)
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).
In the field:
In the ED:
Scheuermeyer FX et al. Safety of a brief emergency department observation protocol for patients with presumed fentanyl overdose. Ann Emerg Med 2018 (PMID: 29530654)
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.
Toxic Bradycardias in the Critically Ill Poisoned Patient. Givens M. Emergency Medicine International. Vol 2012.
The safety of high-dose insulin euglycaemia therapy in toxin-induced cardiac toxicity.Page CB, Ryan NM, et al. Clin Toxicol. 2017 Oct 26:1-6
Keywords: clonidine toxicity, high-dose naloxone (PubMed Search)
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.
Seger DL, Loden JK. Naloxone resersal of clonidine toxicity: dose, dose, dose. Clin Toxicol (Phila) 2018 Mar 16:1-7. doi: 10.1080/15563650.2018.1450986. [Epub ahead of print]
Keywords: adulterated synthetic cannabinoid, elevated INR, brodifacoum (PubMed Search)
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.
Gunja N, Coggins A, Bidny S. Management of intentional superwarfarin poisoning with long-term vitamin K and brodifacoum levels. Clinical Toxicology. 2011;49(5):385-390. doi:10.3109/15563650.2011.587126.
Keywords: nerve agents, organophosphate compounds (PubMed Search)
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
Keywords: cyanide, signs and symptoms (PubMed Search)
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).
Parker-Cote JL et al. Challenges in the diagnosis of acute cyanide poisoning. Clin Toxicol 2018 Feb 8:1-9. doi: 10.1080/15563650.2018.1435886. [Epub ahead of print]
Keywords: QTc, Dysrhythmias, drug overdose (PubMed Search)
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:
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.
Clinical risk factors for in-hospital adverse cardiovascular events after acute drug overdose. Manini AF, Hoffman RS, et al. Acad Emerg Med. 2015:22(5):499-507.
Incidence of adverse cardiovascular events in adults following drug overdose. Manini AF, Nelson LS, et al. Acad Emerg Med. 2012;19:843–9.