Keywords: methadone overdose, hypoglycemia (PubMed Search)
Methadone overdose produces classic signs and symptoms of opioid intoxication - CNS and respiratory depression with pinpoint pupils. However, methadone overdose has also been associated with hypoglycemia – a relatively uncommon adverse effect.
Several case reports have been published over the past years. Recently, a case of refractory hypoglycemia was reported in a woman, without a history of diabetes, after ingesting 250 mL of methadone (18.2 mg/kg).
She required, in additional to naloxone infusion for respiratory depression, dextrose infusion (initially D10 then D20) for 54 hours.
Incidence of hypoglycemia has also been observed in patient with rapid methadone dose escalation as well as in cancer patient who were started on methadone for pain control with dose-depedent association.
In a mice study, methadone induced a dose dependent hypoglycemia - 20 mg/kg methadone resulted in decrease in average glucose level of 172 +/- 7 mg/dL to 55 +/- 6 mg/dL. This effect was reversed by naloxone administration. morphine, fentanyl, oxycodone and levorphanol did not produce hypoglycemia.
However, in the case report published in Clinical Toxicology Nov 2016, naloxone infusion did not effect the hypoglycemia.
Keywords: salicylate poisoning (PubMed Search)
A small retrospective study of an acute poisoning cohort attempted to identify risk factors for severe outcome in salicylate poisoning.
Severe outcomes were defined as
A multivariate analysis of 48 patients showed that older age and increased respiratory rate were independent predictors of severe outcomes when adjusted for salicylate level.
Initial salicylate acid level was not predictive of severe outcome.
Elevated lactic acid level was also a good predictor of severe outcome in univariate analysis but not in multivariate analysis.
Shively RM et al. Acute salicylate poisoning: risk factors for sever outcome. Clin Toxicol 2017 Jan 9:1-6. doi: 10.1080/15563650.2016.1271127. [Epub ahead of print]
Keywords: cyanide toxicity, lactic acid (PubMed Search)
Smoke inhalation victims (house fires) are at risk of carbon monoxide (CO) and cyanide poisoning (CN). CO exposure/poisoning can be readily evaluated by CO - Oximetry but CN level can be obtained in majority of the hospital.
Lactic acid level is often sent to evaluate for CN poisoning.
In a manuscript published in 1991, N Engl J Med by Dr. FJ Baud is the source of this data.
CN blood levels were measured in 109 residetial fire victims in France prior to any treatment was initiated.
Baud FJ et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med 1991;325:1761-6.
Keywords: acetaminophen overdose, APAP levels (PubMed Search)
Recent study evaluated whether an acetaminophen (APAP) level obtained less than 4-hour post acute ingestion can predict which patient would not require n-acetylcysteine (NAC). APAP cutoff level of 100 ug/mL was used for analysis. This was a secondary analysis of the Canadian Acetaminophen Overdose Study database (retrospective study).
Table 2. Diagnostic accuracy of acetaminophen concentration obtained 2 to 4 hours post-ingestion to identify subsequent potentially toxic concentration measured 4 to 20 hours pos-ingestion.
Subsequent 4-hour equivalent [APAP]
[APAP] obtained 2 to 4 hours post-ingestion
< 150 ug/mL
Yarema MC, et al. Can a serum acetaminophen concentration obtained less than 4 hours post-ingestion determine which patients do not rquire treatment with acetylcysteine? Clin Toxicol 2016; online early: doi: 10.1080/15563650.2016.1247959
Keywords: heroin overdose, observation period, bystander naloxone (PubMed Search)
Recently a review paper was published regarding the duration of observation in heroin overdose patients who received naloxone.
It made several conclusions regarding heroin overdose:
It should be pointed out that this is a review paper of limited number of articles with variable quality. Additionally, the clinical history of “heroin use” may be unreliable as fentanyl and novel synthetic opioids are also sold as “heroin.” Providers should exercise appropriate clinical judgement when caring for these patients.
The paper attempted to answer following questions
Review conclusion (8 articles): Patients were safe to release if they had normal mentation and vital signs. Mortality from recurrent heroin toxicity was 0.13% - 0.49% within 24 to 48 hours after naloxone administration.
Review conclusion (5 articles): Wide range of observation period is reported. One study showed that 1-hour observation is sufficient when patients have normal ambulation, normal vital signs and GCS of 15 after 1-hour observation.
Review conclusion (15 articles): Rate of successful reversal ranged from 83% to 100% in the literature. Bystander and first responder naloxone administration is associated with minimum risk outside of mild opioid withdrawal symptoms.
The conclusion of this review paper only applies to heroin intoxication, a short-acting opioid. However, it can be difficult to discern clinically what type of opioid is causing the clinical toxicity as “heroin” may actually be other opioids such as fentanyl or other novel synthetic opioids (e.g. U-47700).
Keywords: buprenorphine exposure, pediatrics, retrospective study (PubMed Search)
Recently, a retrospective study of unintentional buprenorphine/naloxone exposure among pediatric population was published. All patients were evaluated by toxicologists at the time of initial hospital presentation (or transfer) at the study center.
A retrospective study of single center/referral center’s toxicology consultation service.
88 patients were included. (median age: 24 months [range: 10 to 77 months]). Majority were transferred from other hospitals.
Sources of the medication were
The median hospital stay was 22 hours (7 - 248 hours).
Keywords: CCB poisoning (PubMed Search)
US, Canadian and European critical care and toxicology societies recently published a consensus recommendation is the management of CCB poisoning.
1. First line therapy remains unchanged: IV calcium, atropin, high-dose insulin (HIE) therapy, vasopressor support (norepinephrine and/or epinephrine).
2. Refractory to first line therapy: increase HIE, lipid-emulsion, transvenous pacemaker
3. Refractory shock, periarrest or cardiac arrest: Above (#1 & #2) plus ECMO if available.
Overall, there has not been a signficant changes to the current management of CCB poisoning. However, there is a nice flow chart of the algorithm/recommendation in the article. The authors note that the "level of evidenc was very low" for all intervention.
A. asymptomatic patients
B. First line therapy
C. Refractory to first line therapy
D. Refratory shock or periarrest
E. Cardiac arrest
St-Onge, M et al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Crit Care Med 2016 (http://journals.lww.com/ccmjournal/Abstract/publishahead/Experts_Consensus_Recommendations_for_the.96757.aspx)
Keywords: naloxone, opioid intoxication (PubMed Search)
Naloxone has been used to reverse opioid-induced respiratory depression for decades. The “standard” dose of opioid intoxication has been 0.4 mg. However, over the past decade, initial naloxone dose for opioid intoxication has evolved to recommend a lower initial dose (0.04 – 0.05 mg).
A recent article by Connors et al. reviewed 25 medical resources (internet, medical texts and study guides) of different medical specialties (internal medicine, medical toxicology, emergency medicine, pediatrics, anesthesiology, pain medicine and general medicine)
Recent editions of emergency medicine text (Rosen’s and Tinitinalli) recommend using 0.04 – 0.05 mg IV in ED patients with history of opioid dependence. Higher doses of naloxone are recommended for non-opioid dependent/apneic patients.
However, history of opioid dependence is difficult to obtain in patients with opioid induced CNS/respiratory depression.
Administering 0.4 mg or higher dose may/can acute agitation or opioid withdrawal symptoms that can utilize more ED resources to calm agitated patient/management of withdrawal. Thus it may be prudent to use low-dose strategy (0.04 mg IV with titration) to minimize the risk of precipitating naloxone-induced opioid withdrawal/agitation.
In opioid-induced respiratory depression/apneic patients:
To make 0.04 mg naloxone solution:
Connors NJ, Nelson LS. The evolution of recommneded naloxone dosing for opioid overdose by medical specialty. J Med Toxicol 2016;12:276-281.
Keywords: atypical antipsychotic toxicity (PubMed Search)
Antipsychotic as a class has diverse range of toxicity. The atypical (2nd generation) antipsychotics are considered to possess less toxicologic manifestation compared to the typical (1st generation) antipsychotics - lower K channel blockade and minimum Na channel blockade properties. However, select atypical antipsychotics overdose can results in significant morbidity in addition to sedation.
Alpha-1 blockade (hypotension)
Antimuscarinic effect (anticholinergic toxicity)
Delayed rectifier K channel blockade (QT prolongation)
Bottom line: Although lethal overdose from atypical antipsychotics are rare, they can result in significant clinical toxicity when ingested alone or in combintation with other classes of medications.
Keywords: One pill killers, pediatric (PubMed Search)
In pediatric population, small dose or single pill ingestion can potential result in severe or lethal toxicity.
Clinicians should be mindful of potential toxicity following xenobiotic exposure (below) in pediatric population, especially under the age of 5 years old, even if the patient may initially appear asymptomatic.
Suspected ingestion of above medications/xenobiotics may warrent observation up to 24 hours in asymptomatic pediatric population.
Keywords: novel synthetic opioid, U-47700 (PubMed Search)
Recently, there have been several news reports regarding the emergence of synthetic opioids in the U.S. and Canada. There are multiple synthetic opioids that have been identified as potential agents of abuse including W-18, U-47700, fentanyl derivatives, AH-7921 and MT-45. These compounds share a similar story with synthetic cannabinoid where they were synthesized for research purpose or by pharmaceutical companies but were not marketed. They are often sold as “research chemicals” over the internet.
In July 2016, three case reports have been published regarding several cases of U-47700 intoxication in San Diego, CA and Dallas, TX.
It is unknown if currently available heroin is cut with above mentioned synthetic opioids. Like other opioid receptor agonists, administration of naloxone will likely reverse the opioid toxidrome. But clinical experience in reversing synthetic opioids intoxication with naloxone is limited.
Irrespective of whether an ED patient is exposed to synthetic opioids or "traditional" opioids of abuse (prescription opioid pain medication or heroin), the management of opioid intoxication management remains unchanged for respiratory depression.
Keywords: Pediatric exposure, laundry detergent pods (PubMed Search)
Laundry detergent pods were introduced in 2012 to make washing clothes more "convenient." Since then, pediatric exposures to laundry detergent pods have increased as the use of these detergent pods have become more common in homes. Like other household chemical exposure, small, colorful candy like appearances of laundry detergent pods can attract the attention of < 3 years old children resulting in unintentional exposure due to curiosity or taste.
Most frequent clinical effects (2013 - 2014 national poison center data) from exposure to detergents in general (laundry detergent pods and nonpods & dishwasher detergent):
Laundry detergent pod vs. nonpods:
Laundry detergent pods (only) also resulted in following:
Cases of caustic exposure-like injuries have also been reported (corneal abrasion and esophageal injury)
Pediatric laundry detergent (nonpods) exposures usually have self-limited symptoms. However, laundry detergent pod exposure can cause more serious clinical effects that may require hospitalization.
Keywords: loperamide, opioid alternative, cardiac toxicity (PubMed Search)
Loperamide is a peripheral mu-opioid receptor agonist that is found in over the counter anti-diarrheal medication. Following the trend of opioid abuse epidemic, loperamide has been promoted on online drug-use forum as a treatment for opioid withdrawal and as a possible alternative to methadone. At the same time, recreational use of loperamide has been increasing as an opioid alternative. Unlike therapeutic use of loparamide (2 – 4 mg), loraparmide abusers take supratherapeutic doses (e.g. 50 – 100 mg) to penetrate the CNS to produce opioid effects.
In published case reports, loperamide caused cardiac Na channel blockade (similar to TCA and bupropion) and K channel blockade, resulting in EKG changes including QRS interval > 100 msec with terminal R wave in aVR and QTc prolongation, respectively. Loperamide associated death has also been reported (autopsy finding), although the exact cause of death was not determined.
It is unclear if administration of NaHCO3 can reverse the cardiac Na channel blockade as in TCA and bupropion as the clinical experiences have been limited.
Keywords: colchicine toxicity (PubMed Search)
Colchicine is an alkaloid compound found in Colchicum autumnale that is often mistaken by foragers as wild garlic (Allium ursinum). Unintentional ingestion wild garlic or therapeutic misadventures among elderly population with history of gout often result in unintentional toxicity.
It is a potent inhibitor of microtubule formation and function involved in cell division and intracellular transport mechanism. Thus toxicity is related to diffuse cellular dysfunction of all major organs and results in significant morbidity and mortality.
Colchicine toxicity occurs in three phases:
Signs and symptoms
0 – 24 hr
· Nausea, vomiting, diarrhea
· Salt and water depletion
· GI decontamination
· IV fluids
· Observation for leukopenia
1 – 7 days
· Sudden cardiac death (24 – 48 hr)
· Acute kidney injury
· Acute respiratory distress syndrome
· Electrolyte imbalance
· Mechanical ventilation
· Electrolyte repletion
· Alopecia (2-3 weeks later)
· Myopathy, neuropathy, myoneuropathy.
Keywords: lead poisoning, children (PubMed Search)
Lead is a ubiquitous metal in the environment partly due to decades of using leaded gasoline (organic lead) and lead-based paint (inorganic lead). Outside of occupational exposure, children are disproportionately affected from environmental lead exposure.
Common route of exposure are:
Majority of the absorbed lead are stored in bone (years) > soft tissue (months) > blood (30-40 days) (half-life). Thus blood lead level does not accurately reflect the true body lead burden.
Incidence of elevated blood lead level (EBLL > 5 microgram/dL) in children increased from 2.9 to 4.9% in Flint, MI before and after water source change. In the area with the highest water lead level, the incidence increased by 6.6%.
Clinical manifestation in children
Typical blood lead level (microgm/dL)
> 70 – 100
Mild to moderate
50 – 70
Evaluation for lead poisoning
Management of children with EBLL
Keywords: e-cigarettes, liquid nicotine, nicotine toxicity (PubMed Search)
Electronic cigarettes have been gaining popularity in the U.S. as a smokeless delivery system for nicotine. These devices require liquid nicotine (e-liquid) that are vaporized and inhaled (vaping).
E-liquid can have nicotine concentration as high as 100 mg/mL, which are diluted prior to use. When ingested in high concentration and in sufficient volume (1 vial = 15 mL) patients can develop significant nicotinic toxicity. Recently a case of cardiac arrest has been reported after ingesting two 15 ml vial (100 mg/mL).
Nicotine mimics the effects of acetylcholine (Ach) release by binding to nicotinic receptors located in:
Clinical manifestation of toxicity (similar to cholinergic toxidrome) is biphasic with early central stimulation followed by depression. (see table below)
Early (1 hr)
Management: There is no specific antidote or reversal agent. The management of nicotine toxicity focuses on organ-specific dysfunction.
Keywords: body stuffer, body packer, CAT Scan (PubMed Search)
Toxicity due to body packing and body stuffing can be a significant concern due to unknown quantity and/or substance that was ingested.
A recent prospective observational case series compared the utility of CT abdomen/pelvis with and without PO contrast in identifying the ingested packets.
The gold standard comparison: surgical removal or expulsion of packets.
All patients received CT abd/pelvis with and without PO contrast.
A. Body stuffers (n = 24)
CT w/ PO contrast:
Positive: 7 (sensitivity 29.2%)
CT w/o PO contrast:
Positive: 9 (sensitivity 36.5%)
All 24 patients passed ingested packets
B. Body packers (n= 11)
CT w/ PO contrast
CT w/p PO contrast
10 patients expulsed packets; one patient did not have any packets.
Shahnazi M et al. Comparison of abdominal computed tomography with and without oral contrast in diagnosis of body packers and body stuffers. Clin Toxicol 2015;53:596-603.
Keywords: flushed skin (PubMed Search)
Metabisulfites (Na sulfite, Na/K bisfulfite, Na/K metabisulfite, etc.)
Keywords: body stuffers, observation period (PubMed Search)
People who hide illicit drugs can be classified in to three different types.
1. Body stuffers – people who ingest drugs that are poorly wrapped to “eliminate” evidence from police – e.g. street dealers.
2. Body packers – people who ingest large amounts of “well” packed drug packets to transport drugs (usually internationally) – aka “mule.”
3. Body pushers – people hiding drugs in rectum or vagina.
Body stuffers are more frequently encountered in local ED compared to body packers. Stuffers can become symptomatic as the ingested drugs (cocaine, heroin, amphetamines) are often poorly wrapped (e.g. in plastic bag/wrap, cellophane paper, aluminium oil, etc.).
Recent retrospective article looked at the utility of 6-hour observation period in the ED as a management strategy for body stuffers. (n=126)
1. Ingested drugs (self-reported): heroin (48%), cocaine (46%), other drugs [cannabis, MDMA, diazepam, methamphetamine] (16%), unknown (8%)
2. Time of ingestion to ED presentation
76% of the patients experience clinical signs of toxidrome at time of presentation.
Most common findings:
Patients who ingested heroin were more symptomatic vs. cocaine (87% vs. 70%)
Patients were discharged:
Yamamoto T et al. Management of body stuffers presenting to the emergency department. Europ J Emerg Med. May 8 [Epub ahead of print] PDIM: 25969343
Keywords: sulfonylurea, hypoglycemia, octreotide (PubMed Search)
Oral hypoglycemic agents (e.g. sulfonylureas) can cause symptomatic hypoglycemia. Unlike metformin, sulfonylureas stimulate the release of insulin from beta-cells (in pancreas) in response to serum glucose level.
ED management of hypoglycemia involves:
However, for recurrent hypoglycemia (> 3 episodes of hypoglycemia), think about octreotide, rather than starting a dextrose (D5) infusion.
For example, D5 infusion at 150 mL/hour has only 7.5 gm of dextrose (calculation: D5% = 5gm/100 mL). One gram of dextrose contains about 4 calories (equivalent to one piece of Skittles) So, with a D5 infusion at 150 mL/hour, you are giving your patients 8 pieces of Skittles per hour. A bottle of Snapple lemon ice tea (non-diet) has more calories (150 calories in 16 oz. or 473 mL)!
Octreotide 50 mcg SQ (q6 hour) injection will decrease the insulin release from the beta-cell by blocking the voltage-gated Ca channel on the beta-cell.
All patient who received octreotide in the ED requires admission to the hospital for observation. Patients can be safely discharge from the hospital when finger stick glucose level remains normal for 24 hours after the last dose of octreotide.
Bottom line: In sulfonylrea-induced recurrent hypoglycemia, administer octreotide, rather than continuous infusion of dextrose (D5) solution.