Keywords: kratom, adverse effects, poison center data (PubMed Search)
Kratom (Mitragyna speciosa) has been used for centuries in Southeast Asia to manage pain and opium withdrawal. It is increasingly being used in the U.S. for similar purpose. The U.S. DEA lists Kratom as a “drug of concern”.
Effects of Kratom leaves
A study reviewed National Poison Data System (2011 to 2017) to evaluate the clinical effects/outcomes of Kratom exposure.
Finding: (N=1807; single-substance: 1174; multiple-substance: 633])
Sara Post, Henry A. Spiller, Thitphalak Chounthirath & Gary A. Smith (2019): Kratom exposures reported to United States poison control centers: 2011–2017, Clinical Toxicology, DOI: 10.1080/15563650.2019.1569236
Keywords: physostigmine, anticholinergic toxicity, adverse effects (PubMed Search)
Physostigmine is a cholinergic agent that can be administered to reverse delirium associated with anticholinergic toxicity. However, it is infrequenly used since the reports of cardiac arrest in patients with TCA overdose.
A recently published study reviewed 161 articles – involving 2299 patients – to determine the adverse effects and their frequency after the administration of physostigmine.
Adverse effects were observed in 415 patients (18.1%)
Specific adverse effects
Of 394 TCA overdose, adverse effects occurred in 14 patients (3.6%)
Arens AM et al. Adverse effects of physostigmine. J Med Toxciol. Feb 11. doi: 10.1007/s13181-019-00697-z. [Epub ahead of print] Review.
Keywords: tramadol, seizure, risk factors (PubMed Search)
Therapeutic use or overdose of tramadol has been associated with seizure. However, it is unknown if there are any specific predisposing factor that increases a patient’s risk of seizure after tramadol use/overdose.
In a recently published study, eighty patient data with single ingestion of tramadol were reviewed.
Risk of seizure
In this small study, Asian patients and patients with abuse/misuse were at higher risk of developing seizure compared to patients who overdose tramadol.
Murray, BP et al. Seizures in tramadol overdoses reported in the ToxIC registry: predisposing factors and the role of naloxone. Clin Toxicol. 2018 DOI: 10.1080/15563650.2018.1547826
Keywords: take home naloxone, opioid overdose (PubMed Search)
Take home naloxone (THN) programs have been expanded to help reduce the opioid overdose-related deaths. A study was done in Australia to characterize a cohort of heroin overdose deaths to examine if there was an opportunity for a bystander to intervene at the time of fatal overdose.
235 heroin-overdose deaths were investigated during a 2 year study period in Victoria, Australia.
Stam NC et al. Challenges with take-home naloxone in reducing heroin mortality: a review of fatal heroin overdose cases in Victoria, Australia. Clin Toxicol 2018 Nov 17:1-6. doi: 10.1080/15563650.2018.1529319. [Epub ahead of print]
Keywords: double-dose of single medication (PubMed Search)
Taking a double-dose of a single medication is presumed to be safe in most cases. However, there is limited data to support this assumption.
A retrospective study of the California Poison Control System was performed to assess adverse effects of taking double dose of a single medication. During a 10-year period, 876 cases of double-dose ingestion of single medication were identified.
Adverse effects were rare (12 cases). However, medication classes that were involved in severe adverse effects included:
Correia MS et al. A 10-year review of single medication double-dose ingestions in the nation's largest poison control system. Clin Toxicol 2018 Nov 28:1-5. doi: 10.1080/15563650.2018.1493205. [Epub ahead of print]
Keywords: Bupropion, TCAs, adolescents (PubMed Search)
Selective serotonin reuptake inhibitors are the most common anti-depressant used today. However, the use bupropion in adolescents is increasing due the belief that it has fewer side effects than TCAs.
Using the National Poison Data System (2013 – 2016), the adverse effects of bupropion were compared to TCA in adolescents (13 – 19 years old) with a history of overdose (self harm).
Common clinical effects were:
TCA: n=1496; Bupropion: n=2257
Bupropion overdose results in significant adverse effects in overdose; however, death is relatively rare.
Sheridan DC et al. Suicidal bupropion ingestions in adolescents: increased morbidity compared to other antidepressants. Clin Toxicol. 2018;56:360-364.
Keywords: alcohol withdrawal syndrome, phenobarbital (PubMed Search)
Alcohol withdrawal syndrome is frequently treated with benzodiazepines following CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol scale). There are other medications that are used as either second line or as adjunctive agents along with benzodiazepines. A retrospective study compared the clinical outcomes between phenobarbital vs. benzodiazepines-based CIWA-Ar protocol to treat AWS.
The primary was ICU length of stay (LOS); secondary outcome were hospital LOS, intubation, and use of adjunctive pharmacotherapy.
Study sample: 60 received phenobarbital and 60 received lorazepam per CIWA-Ar.
Adjunctive agent use
Phenobarbital therapy appears to be a promising alternative therapy for AWS. However, additional studies are needed prior to adapting phenobarbital as first line agent for AWS management.
Tidwell WP et al. Treatment of alcohol withdrawal syndrome: phenobarbital vs. CIWA-Ar protocol. Am J Crit Care. 2018 Nov;27(6):454-460. PMID: 30385536.
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: 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: 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: 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: 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: 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)
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: nystagmus, toxic (PubMed Search)
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.