Cyanide is one of the deadliest known poisons causing immediate toxic effects and lethality within seconds to minutes. Exposures are rare, most commonly by inhalational route (HCN gas) from structural fires due to combustion of synthetic materials or from ingestion of cyanide salts. Cyanide toxicity can also occur from dermal or parental (sodium nitroprusside) exposure.
The preferred first line antidote is hydroxycobalamin (vitamin B12) available as Cyanokit, which has higher affinity for cyanide than cytochrome oxidase and binds to form harmless cyanocobalamin and is renally excreted. Limited studies reveal good survival rates in noncardiac arrest patients. Hydroxycobalamin has minimal side effects (red skin and urine, increased BP) and is well-tolerated with safer and simpler mechanism of action than Nithiodote (original antidote), containing sodium nitrite (CN preferentially binds methemoglobin to form cyanomethemoglobin) and thiosulfate (provides sulfur to convert cyanide to thiocynate for excretion). Sodium nitrite has numerous adverse effects causing hypotension and methemoglobin (contraindicated in smoke inhalation victims due to concern for carbon monoxide poisoning, G6PD deficiency, preexisting amenia), and hypersensitivity reactions. Sodium thiosulfate has less side effects and augments cyanide excretion but is considered less effective due to its slow onset, short half-life, low volume of distribution, and poor intracellular penetration.
As of August 2025, the American Society of Health -System Pharmacists (ASHP) Drug Shortage lists Cyanokit as “limited availability” in the U.S. as manufacturing was suspended due to investigation of ongoing quality defect with concern for sterility and endotoxin content. Impacted batches were released and their numbers are listed in an FDA bulletin (see references). Healthcare providers should weigh the potential benefit of using Cyanokit against the risk of infection. Infusion set with 0.2 micron in line filter can be temporarily used for administration of Cyanokit 5 mg hydroxycobalmin to prevent potential infection.
Carbon Monoxide Poisoning (COP) is a major toxicologic pathology and a common case in the Emergency Department and pre-hospital setting. History is a key component in assessment with the standard diagnostic test being blood gas analysis of Carboxyhemoglobin (COHb).
Standard pulse oximeter devices are not capable of differentiating oxyhemoglobin from carboxyhemoglobin, leading to the classic pearl that pulse ox may be falsely reassuring in COP.
In recent years, devices capable of differentiating oxyhemoglobin from COHb have been developed and are fielded in many hospitals and EMS agencies.
This meta-analysis reviews diagnostic accuracy of pulse CO-oximetry (spCO) devices in comparison to a reference standard COHb blood test. Six studies (1734 patients) were included.
This analysis found that spCO testing has a low sensitivity and high specificity.
Pooled sensitivity 0.65 (95% CI 0.44–0.81)
Pooled specificity 0.93 (95% CI 0.83–0.98)
Pooled LR+ 9.4 (95% CI 4.4 to 20.1)
Pooled LR- 0.38 (95% CI 0.24 to 0.62)
The authors conclude that the low sensitivity precludes use of spCO as an effective screening tool for COP or substitute for COHb. Conversely, we can recognize the utility of the high specificity in identifying patients who do have clinically significant toxicity. Indeed, the authors discuss potential applications for triage and transport to a hyperbaric oxygen chamber for those who are found to have elevated readings.
Technology advancement and refinement will be interesting to follow. In the meantime, don’t skip the COHb lab just because spCO measurement is reassuring.
This study looking at pre and post-phenobarbital order set use to treat inpatient alcohol withdrawal syndrome found:
“AWS symptoms resolved more rapidly after implementation, with a 4.2- to 5.0-point reduction in daily maximum CIWA-Ar scores at 24 to 96 hours from hospital presentation, 30.1-hour reduction in AWS treatment duration (95% CI, 16.7-43.5 hours), and 2.2-day reduction in time to hospital discharge (95% CI, 0.7-3.7 days). Safety outcomes did not significantly differ before and after implementation.”
Remember phenobarbital can be used for alcohol withdrawal for our ED patients as well.
Here is the protocol:
Nursing
Vital signs 10 minutes after phenobarbital loading dose
Clinical Institute Withdrawal Assessment for Alcohol Revised (CIWA-Ar) every 1-4 hours based on score
Loading Dose
Phenobarbital 15 mg/kg intravenous piggyback (recommended for most patients)
Phenobarbital 10 mg/kg intravenous piggyback (low risk or heavily pretreated with benzodiazepines)
As-Needed Doses
Phenobarbital 130 mg intravenous twice as needed for uncontrolled agitation or CIWA-Ar ?15
Phenobarbital 260 mg intravenous once as needed for uncontrolled agitation or CIWA-Ar ?15
This study from Australia reminds us that what patients think they ingested isn’t always what they did ingest. A high percentage of “cocaine” and other stimulants was actually fentanyl or other opiates. The authors do a nice job referencing similar studies in the United States. Any overdose could be a mixed picture due to impure street drugs.
This retrospective population cohort study looked at first time ED visits for adolescents and young adults comparing those with visits related to alcohol to those not related to alcohol. Patients in the alcohol related visit group had a threefold increased one year mortality rate. Cause of death was trauma, poisoning by drug and alcohol. Risk factors include being male, age 20-29, history of mental health and having a visit for withdrawal.
Adolescents and young adults presenting to an emergency department for an alcohol related complaint are high risk for one year mortality and deserve intervention and appropriate referral.
Bupropion associated cardiac toxicity widens the QRS complex by inhibiting the cardiac gap junction, not cardiac Na channel blockade. NaHCO3 is often administered when EKG changes are noted. But the effectiveness of NaHCO3 in bupropion toxicity is not well established.
A retrospective study between 2010-2020 showed, that administration of NaHCO3 only decreased QRS duration by 2 msec (median). The median NaHCO3 administered was 100 mEq. Although this study was limited by the fact that it only had a small sample size of 13, NaHCO3 administration may provide limited clinical benefit in patients with QRS widening from bupropion overdose.
Acetaminophen (APAP) is the leading cause of acute liver failure worldwide. Standard treatment for APAP overdose is with N-acetylcysteine (NAC), which is highly effective if given within 8 hours of ingestion. However, in delayed presenters or massive ingestions patients can still develop hepatotoxicity. Adjunctive therapies can be considered in these cases including augmented NAC dosing, renal replacement, and fomepizole.
A small amount of APAP is metabolized to N-acetyl-p-benzoquinone imine (NAPQI) by cytochrome 2E1. In therapeutic doses, the body is able to detoxify the NAPQI using glutathione. In overdose, glutathione stores get depleted and NAPQI can cause hepatotoxicity. Mitochondrial damage in APAP overdose is mediated by the c-Jun-N-terminal Kinase (JNK) pathway.
NAC works to replenish glutathione stores and detoxify NAPQI. In large overdoses, increased dosing of NAC may be necessary. Fomepizole is typically used for its alcohol dehydrogenase inhibitor property to treat methanol and ethylene glycol poisoning. Fomepizole is also a cytochrome 2E1 and JNK inhibitor and can be used in APAP overdose to block the formation of NAPQI and mitigate mitochondrial damage. Dialysis can be used to eliminate APAP from the body completely in massive overdoses or if significant acidosis or renal failure.
This study is a case series of 14 patients treated for APAP overdose between 2017 – 2021 at a tertiary hospital
Limitations of the study:
In summary:
Medical Cannabis is permitted in 39 states and Washington DC while 18 sates and Washington DC has legalized recreational cannabis use. As cannabis products become more available, pediatric exposure has also increased.
A retrospective study of National Poison Data System involving children < 6 years from 2017 and 2021 showed: Pre-COVID (2017-2019) & COVID (2020-2021)
Common Clinical effects
Disposition
Conclusion
Lithium toxicity can present acutely with gastrointestinal symptoms and chronically with neurologic symptoms such as tremor and ataxia. Diagnosis and treatment with normal saline hydration and/or dialysis depends on lithium levels in conjunction with signs and symptoms.
Lithium levels can be falsely elevated when blood samples are collected in green top tubes which contain lithium heparin, or if the blood collection volume is too small. Not recognizing that a lithium level may be falsely elevated can lead to misdiagnosis as well as unnecessary hospitalizations and treatments. The study by Wills et al found lithium levels as high as 4 mmol/L (therapeutic range 0.6-1.2 mmol/L) in lithium naïve volunteers collected in the wrong tube and with small blood volumes. If a patient has an elevated lithium level in the absence of lithium toxicity symptoms, consider a falsely elevated level and redraw using the appropriate tube and sample size.
In summary:
Calcium channel blocker (CCB) overdose can lead to severe shock/hypotension. A small study was conducted to compare the hemodynamic effects of high-dose insulin (HDI) for two classes of CCB (dihydropyridines vs. non-dihydropyridines) that work differently to manage hypertension.
Study design:
Study sample:
Result
Median number of maximum concomitant vasopressors (p=0.04)
Median difference in max concomitant vasopressors: 1 (95% CI: 0 – 2)
Median max epinephrine dosing
Use of rescue methylene blue (p=0.009)
Conclusion:
Flumazenil is a reversal agent for benzodiazepine overdose. Adverse events including seizure, agitation and cardiac arrhythmias have been reported but the frequency of adverse events is unknown.
AE and serious AEs were defined as:
AE:
Serious AE (SAE):
A systematic review/meta-analyses of 13 randomized controlled trials showed
Most common AEs
Most common SAEs
Conclusion
Xylazine is a central alpha-2 agonist (similar to clonidine) that is used as a veterinary tranquilizer. It also possesses analgesic, and muscle relaxant properties. Heroin/fentanyl is increasingly being adulterated with xylazine and resulting in severe adverse effects (CNS and respiratory depression, bradycardia, and hypotension), including deaths.
According to CDC, 0.1%-5.5% of IMF death in US between 2019 – 2020 involved xylazine.
In Philadelphia, PA:
The detection of xylazine in unintentional overdose death increased from
Approximately 25% of drug seizures in Philadelphia contained xylazine in 2019
There is no effective pharmacologic agent for xylazine toxicity. Similar to clonidine toxicity, high dose naloxone may be tried. But pediatric data show that approximately 50% of pediatric clonidine toxicity response to high-dose naloxone administration. Thus, naloxone administration may not reverse the CNS/respiratory depression, bradycardia and hypotension.
Conclusion
Substance use disorder contributes significantly to pediatric exposure/poisoning. There has been an increase in the opioid overdose deaths in the US, placing pediatric population to possible exposure. A retrospective study of fatal pediatric poisoning in the US was investigated using the National Violent Death Reporting System (NVDRS) from 2012-2017.
17 US states (AK, CO, GA, KT, MD, MA, NJ, NM, NC, OH, OK, OR, RI, SC, UT, VA, WI) reported to NVDRS from 2012-2017.
Age was limited to 0-9 years
Results
1850 violent deaths were identified: n=122 (7%) were poisoning related
Characteristics
Region
Most common exposure/etiology
Conclusion
There are several clinical scoring systems (SAPS II, SAPS III, SOFA, etc.) to assess the severity and/or risk of mortality in critically ill patients. However, the routinely used physiologic scoring systems are not always suitable for poisoned patient.
ICU requirement score (IRS) has been recently developed by investigators from Europe and a validation study (retrospective cohort) has been performed.
ICU requirement score (IRS) components (see inserted table)
Retrospective cohort
Results
N=1503
Area under the curve for IRS ROC: 0.736 (95% CI: 0.702-0.770)
IRS <6
Conclusion
Canada legalized recreational cannabis use in 2017. A retrospective study of children (0-18 years) who presented to pediatric ED with cannabis intoxication/exposure was performed between Jan 1, 2008 to Dec 21, 2019 to assess the trend/severity of intoxication.
Methods
Result
A total of 298 patients were identified
|
| Pre-legalization | Peri-post legalization | P value |
| Monthly ED visit | 2.1 (IRQ: 1.9-2.5) | 1.7 (IQR: 1.0-3.0) | 0.69 |
| ICU admission | 4.7% | 13.6% | 0.02 |
| Respiratory symptoms | 50.9% | 65.9% | 0.05 |
| Altered mental status | 14.2% | 28.8% | <0.01 |
| Age < 12 years | 3.0% | 12.1% | 0.04 |
| Unintentional exposure | 2.8% | 14.4% | 0.02 |
| Edible ingestion | 7.8% | 19.7% | 0.02 |
Respiratory symptoms: tachypnea/bradypnea, cyanosis, O2 sat < 92%, bronchospasm, oxygen requirement
Conclusion
What is the mechanism of action of N-acetylcysteine that is used to treat acetaminophen induced liver injury/toxicity?
There are three commonly household spices that can be abuse/misused or cause toxicity after exposure.
Pure vanilla extract contains at least 35% ethanol by volume per US Food and Drug Administration standards
Nutmeg contains myristicin – serotonergic agonist that possess psychomimetic properties.
Clinical effects:
Cinnamon contains cinnamaldehyde and eugenol – local irritants.
Diphenhydramine is commonly involved in overdose or misused. Although it is primarily used for its anti-histamine property, it also has significant antimuscarinic effect.
A recent retrospective study investigated the clinical characteristics associated with severe outcomes in diphenhydramine overdose using the multi-center Toxicology Investigators Consortium (ToxIC) Registry.
Severe outcomes were defined as any of the following:
Results
863 cases of isolated diphenhydramine ingestion were identified between Jan 1, 2010 to Dec 31, 2016
Most common symptoms:
Factors associated with severe outcome
Conclusion
