UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: A Simpler IV Acetylcysteine Regimen for Acetaminophen Overdose?

Keywords: acetaminophen, acetylcysteine (PubMed Search)

Posted: 1/7/2016 by Bryan Hayes, PharmD (Emailed: 1/14/2016) (Updated: 1/14/2016)
Click here to contact Bryan Hayes, PharmD

The three-bag IV acetylcysteine regimen for acetaminophen overdose is complicated and can result in medication/administration errors. [1] Two recent studies have attempted simplifying the regimen using a two-bag approach and evaluated its effect on adverse effects. [2, 3]

Study 1 [2]

Prospective comparison of cases using a 20 h, two-bag regimen (200 mg/kg over 4 h followed by 100 mg/kg over 16 h) to an historical cohort treated with the 21 h three-bag IV regimen (150 mg/kg over 1 h, 50 mg/kg over 4 h and 100 mg/kg over 16 h).

The two-bag 20 h acetylcysteine regimen was well tolerated and resulted in significantly fewer and milder non-allergic anaphylactic reactions than the standard three-bag regimen.

Study 2 [3]

Prospective observational study of a modified 2-phase acetylcysteine protocol. The first infusion was 200 mg/kg over 4-9 h. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with ALT > 1000 U/L or abnormal ALT.

The 2-phase acetylcysteine infusion protocol resulted in fewer reactions in patients with toxic paracetamol concentrations.

Final word: Two-bag regimens seem to offer advantages compared to the traditional three-bag regimen with regard to reduced adverse drug reactions. Look for more data, particularly on effectiveness, and a potential transition to a two-bag approach in the future.

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Category: Toxicology

Title: Caffeine: The socially acceptable psychoactive drug

Keywords: Caffeine, Energy drinks (PubMed Search)

Posted: 1/7/2016 by Kathy Prybys, DO (Emailed: 1/8/2016) (Updated: 1/8/2016)
Click here to contact Kathy Prybys, DO

Caffeine is the most commonly used psychoactive substance in the world. It is widely available in coffee, tea, chocolate,soft drinks, OTC medicines, and energy drinks. The vast majority of people consuming caffeine appear to suffer no harm while enjoying it's stimulating effects. This has led to the widely held perspective that caffeine is a completely benign substance with no adverse health effects exists.

Although, children and adolescents are at particular risk, many caffeine containing products are specifically marketed at them. Alarmingly, statistics demonstrate that caffeine intake among children and adolescents has increased by 70% in the last 30 years. Energy drinks are of special concern as they represent the fastest growing component of the beverage industry, contain significant quantities of caffeine as well as high levels of sugar, and can place children at high risk for caffeine intoxication.

There are many negative health consequences documented with caffeine use which occur in a dose dependent manner with individuals differing in their susceptibility to caffeine-related adverse effects:

Acute Toxicity:
  • Arrhythmias
  • Anxiety
  • Agitation
  • Seizure
  • Nausea,vomiting, diarrhea
  • Diuresis
  • Metabolic disturbances
  • Hypotension
  • Rare fatalities

Chronic Effects:

  • Insomia
  • Palpitations
  • Headaches
  • Diuresis
  • Gastric acid secretion
  • Urinary incontinence in women
  • Adverse effect on wound healing process, the aging process of the human skin
  • Low birth weight babies
  • Withdrawal state
  • Increased risk of cardiovascular events (heart attack,strokes, peripheral artery disease and kidney failure) in young adults with mild hypertension.

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Category: Toxicology

Title: Lipid Emulsion's Effect on Labs

Keywords: laboratory, lipid, toxicology (PubMed Search)

Posted: 12/10/2015 by Bryan Hayes, PharmD
Click here to contact Bryan Hayes, PharmD

The American Academy of Clinical Toxicology's Lipid Emulsion workgroup has published its first of 4 systematic reviews on the use of lipid emulsion in toxicology, this one on lipid's effect on laboratory analyses. [1] As expected, administering a fat bolus can significantly alter labs drawn subsequently.

The key point: If you are considering lipid for overdose, draw labs prior to giving it.

Which labs are affected? Most. Here's a helpful mnemonic courtesy of Dr. Kyle DeWitt.

  • B - Blood Gas
  • L - Liver transaminases
  • E - Electrolytes
  • A - Analgesics (acetaminophen, salicylates)
  • C - Coags
  • H - H/H, platelets

Also remember to give lipid in its own line. It isn't compatable with most resuscitation drugs. [2]

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Carbon monoxide (CO) is a colorless, odorless, tasteless toxic gas produced by incomplete combustion in fuel-burning devices and is a leading cause of poisoning morbidity and mortality.

Symptoms can be easily misinterpreted (e.g., headache, nausea, dizziness, or confusion) thus victims may not realize they are being poisoned.

CO detectors use an audible alarm and are effective in alerting potential victims of presence of CO. Some versions offer a digital readout of the CO concentration. Detectors are not a simple alarm level (as in smoke detectors) but are a concentration-time function.

In the UL 2034 Standard, Underwriters Laboratories specifies response times for CO alarms:

  • 70 ppm sounds alarm within 60-240 minutes
  • 150 ppm sounds alarm within 10-50 minutes.
  • 400 ppm: sounds alarm within 4-15 minutes.

Current Occupational Safety and Health Administration permissible exposure limit for CO is 50 parts per million as an 8-hour time-weighted average concentration.

CO detectors have a limited lifespan of up to 7 years.

Forty percent of residential detectors studied failed to alarm in hazardous concentrations, despite outward indications that they were operating as intended.

CO detectors 10 years and older had the highest failure rates.

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Category: Toxicology

Title: Nicotine poisoning from liquid nicotine ingestion

Keywords: e-cigarettes, liquid nicotine, nicotine toxicity (PubMed Search)

Posted: 11/19/2015 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

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:

  • Brain
  • Spinal cord
  • Autonomic ganglia
  • Adrenal medulla
  • Neuromuscular junction
  • Chemoreceptors of carotid/aortic bodies


Clinical manifestation of toxicity (similar to cholinergic toxidrome) is biphasic with early central stimulation followed by depression. (see table below)






Early (1 hr)




Abdominal pain









Blurred vision







(0.5-4 hr)




























Management: There is no specific antidote or reversal agent. The management of nicotine toxicity focuses on organ-specific dysfunction. 

e.g. bronchorrhea = atropine; apnea = intubation; seizure = benzodiazepine.

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Category: Toxicology

Title: Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity

Keywords: Andexanet, apixaban, rivaroxaban, factor Xa (PubMed Search)

Posted: 11/12/2015 by Bryan Hayes, PharmD
Click here to contact Bryan Hayes, PharmD

Not to be outdone by the recent FDA approval of Idarucizumab to reverse dabigatran, a new factor Xa reversal agent is under investigation. "Andexanet binds and sequesters factor Xa inhibitors within the vascular space, thereby restoring the activity of endogenous factor Xa and reducing levels of anticoagulant activity, as assessed by measurement of thrombin generation and anti factor Xa activity, the latter of which is a direct measure of the anticoagulant activity."


Two parallel randomized, placebo-controlled trials (ANNEXA-A [apixaban] and ANNEXA-R [rivaroxaban]) were conducted in healthy vounteers to evaluate the ability of andexanet to reverse anticoagulation, as measured by the percent change in anti factor Xa activity after administration.

What they Found

Compared to placebo, andexanet significantly reduced anti-factor Xa activity, increased thrombin generation, and decreased unbound drug concentration in both the apixaban and rivaroxaban groups.

Application to Clinical Practice

  1. This drug is not yet FDA approved.
  2. These trials were funded by the maker of andexanet (Portola Pharmaceuticals) and supported by the makers of apixaban and rivaroxaban.
  3. Studies are needed in patients requiring urgent reversal.
  4. The trials looked only at laboratory markers of anticoagulation. We don't know how fast (or the extent of) the reversal activity is in the clinical setting.

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Category: Toxicology

Title: Designer drugs & Synthetic Marijuana: Hijacking of chemical research for no good!

Keywords: THC, Spice, JWH (PubMed Search)

Posted: 11/5/2015 by Kathy Prybys, DO (Emailed: 11/6/2015) (Updated: 11/6/2015)
Click here to contact Kathy Prybys, DO

Designer drugs are structural or functional analogs of controlled substances produced to mimic pharmacological effects of the original compound while circumventing legal restrictions and detection on drug screens. Considered "legal highs" by the public, these highly potent drugs are produced in clandestine laboratories with no regulations for quality control or clinical testing for phamacological effects and thus present major threat to public health. Examples include synthetic hallucinogens (DOM: STP), opiates ( methylfentanyl:china white), stimulants (methamphetamine:crank, MDMA: ecstasy, cathinones:bath salts) and synthetic cannabinoids (spice).

The synthetic cannabinoids are the newest designer drugs and numerous cases of intoxication are being reported including some fatalties.Cannabinoids fall into 3 classes: endocannabinoids, phytocannabinoids, synthetic. Marijuana, the best known cannabinoid is plant derived and its psychoactive effects are mainly due to delta-9-tetrahydrocannabinol (THC) which binds with the endocannabinoid receptors CB1 and CB2 found throughout the central and peripheral nervous system and peripheral organs. The CB receptors interact with opiate receptors which is likely responsible for the analgesic effect.

Since 1984, the John Huffman research group at Clemenson University synthesized over 450 cannabinoid compounds for biomedical reseach known as "JWH compounds". These compounds hold great promise in the investigation of multiple diseases and development of new novel therapies. Over the last several years, these cannabinoid compounds began cropping up sprayed onto herbs marketed in colorful packets and sold on the internet, convienence stores, and head shops. Although clearly labeled as "not for human consumption" considered on the street as a legal alternative to marijuana.

Key Points:

  • Common names: Spice, K2, Smoke, Skunk, Purple Haze, Scooby snax, Crazy Monkey.
  • JWH 018 (4-5 fold greater affinity for CB receptor than THC), JWH 081,122, 210
  • Exact composition of products unknown and ever changing to avoid legal restrictions.
  • Cannabinoid dose can vary greatly between products and even within same package "hot spots" are found where the drug is more concentrated.
  • Often shown to be contaminated with impurities like beta agonists clenbulterol
  • No clinical human studies on effects or any routine detection assays available.
  • Clinical effects can vary from commonly described anxiety agitation, tachycardia to sedation and somulence.

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Category: Toxicology

Title: Lipid Emulsion Therapy - Propranolol OD

Keywords: propranolol, lipid emulsion (PubMed Search)

Posted: 10/22/2015 by Fermin Barrueto, MD
Click here to contact Fermin Barrueto, MD

There have been a variety of case reports that have been describing the effects of lipid emulsion therapy on severe hemodynamic overdoses. As time has gone on, we have realized that this therapy is not for all severe overdoses. The type of medication and its pharmacokinetic properties factor into the decision. There is minimal evidence and no ideal randomized control trials that will tell us what the right answer is but take beta-blockers for instance:

Atenolol - in overdose, consider hemodialysis, very effectively removed by HD [1]

Propranolol - very lipophilic and one of the few beta-blockers that can cause widened QRS, seizures as well as the prototypical hypotension and bradycardia.

Because of its lipophilicity, ability to cross the blood brain barrier and ability to cause lethal dysrrthmias, lipid emulsion therapy has been effective in reversing the clinically severe effects of a propranolol overdose. [2]

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Toxicity due to body packing and body stuffing can be a significant concern due to unknown quantity and/or substance that was ingested.

  • Body stuffers usually ingest small quantities of poorly wrapped illicit substance (intended for sale) to evade law enforcement.
  • Body packer ingests large quantities of well-packaged illicit substance for trafficking purpose. Rupture of these packets can potentially result in fatal toxicity.

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%)

  • Negative: 17  

CT w/o PO contrast:

  • Positive: 9 (sensitivity 36.5%)

  • Negative: 15

All 24 patients passed ingested packets

B. Body packers (n= 11)

CT w/ PO contrast

  • Positive: 6 (sensitivity 60%)
  • Negative: 5

CT w/p PO contrast

  • Positive: 7 (sensitivity 70%)
  • Negative: 3

10 patients expulsed packets; one patient did not have any packets.


  • CT without PO contrast was better at identifying the ingested packets in both body stuffers and packers.

Bottom line:

  • CT abdomen/pelvis has limited clinical utility in identifying the packets (presence) among body stuffers. If symptomatic, appropriate supportive care should be initiated
  • Among packers who may experience life-threatening toxicity from the leakage/rupture of the packets, CT may be helpful to confirm the presence of packets and to follow the progress of expulsion of packets.
  • Caution should be exercised as CT did not identify packets (body stuffer or packers) in all patients in this case series.

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Category: Toxicology

Title: Dabigatran and Hemodialysis: Watch for the Rebound

Keywords: hemodialysis, dabigatran, rebound (PubMed Search)

Posted: 10/7/2015 by Bryan Hayes, PharmD (Emailed: 10/8/2015) (Updated: 10/8/2015)
Click here to contact Bryan Hayes, PharmD

In patients receiving renal replacement therapy as a treatment modality for dabigatran-related bleeding, watch for a rebound concentration increase after hemodialysis is stopped.

More than 50% of patients demonstrate a rebound effect with a median increase in dabigatran concentration of 33%.

OOIt is unclear whether this rebound effect is clinically
important, and whether this translates to prolonged clini-

It is unclear whether this rebound effect is clinically important, and whether it translates to prolonged clinically relevant bleeding. Extended hemodialysis sessions or consideration of CVVHD should offset this potential problem.


Bonus Pearl:

The North American Congress of Clinical Toxicology starts today and runs through October 12. Look for toxicology pearls and updates on Twitter under the official conference hashtag #NACCT15.

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The majority of prescriptions used for the treatment of nausea and vomiting in pregnancy (NVP) in the United States have been with medications not labeled for and not classified as safe in use during pregnancy by the Food and Drug Administration. Over the last decade, the extremely potent 5HT3 receptor antagonist, Ondansetron (Zofran) has been increasingly used for NVP. However, the FDA has cautioned against its use in pregnancy based on recent studies regarding the association between Zofran use in early pregnancy and congenital cardiac malformations and oral clefts (cleft lip and palate). In addition, Zofran poses maternal risk of arrhythmias from possible QT interval prolongation which can result in the potentially fatal arrhythmia (Torsades de pointes) and Serotonin syndrome. The American College of Obstetricians and Gynecologists (ACOG) has issued new guidelines for the diagnosis and management of NVP. A safe and effective category A drug is available in the U.S., Diclegis (doxylamine succinate and Vitamin B6, pyridoxine hydrochloride) which has been studied in hundreds of thousands of pregnant women. Unisom SleepTabs (Sanofi Aventis; oral vitamin B6 and doxylamine), which are available OTC in the U.S., have been studied in more than 6000 patients and control participants, with no evidence of teratogenicity. In randomized trials, this combination has been associated with a 70% reduction in nausea and vomiting. ACOG therefore recommends this combination as first-line therapy for NVP. Following treatment failure with dietary modifications and alternative therapy remedies such as ginger capsules (250 mg qid) and acupuncture, pharmacologic therapies should include: 1. Vitamin B6 (pyridoxine), 10 to 25 mg every 8 hours, and doxylamine, 25 mg at bedtime and 12.5 mg each in the morning and afternoon. 2. If parental antiemetics are required, phenothiazides such as prochlorperazine or promethazine or Ondansetron in refractory cases. 3. Prokinetic agent Metoclopramide (Reglan; tablets, Alaven; injection, Baxter) is a dopamine antagonist. The FDA has issued a black-box warning concerning the use of Reglan in general. Because the risk for exrapyramidal complications, tardive dyskinesia increases with the duration of treatment and the total cumulative dose, treatment duration should not exceed 12 weeks. 4. Intravenous fluid replacement with multivitamins, especially thiamine is indicated with use of dextrose containing solutions (to prevent Wernicke's encephalopathy) until ketosis resolves.

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Monosodium glutamate

  • Rapid onset 30 min and lasts about 1 hour
  • May accompanied with headache & chest pain.
  • No associated GI sx.
  • History of eating Chinese fodd. AKA "Chinese restaurant syndrome"


Metabisulfites (Na sulfite, Na/K bisfulfite, Na/K metabisulfite, etc.)

  • Food preservatives found in dried fruit, wine, molasses, sauerkraut, etc.
  • Bronchospasm – asthma like, headache, mild hypotension can occur
  • Most significant reaction in people with asthma/allergies
  • History of trying to eat "healthy"


Tyramine reaction

  • Mostly among patients taking MAO inhibitors
  • Source of tyramine (food): fermented, pickled product, avocado, chocolate, etc.



  • Burning warm sensation to body
  • Often used for sexual enhancement, elevated cholesterol and beating drug urine screens



  • Occupational exposure – AKA “Degreaser’s flush”
  • Facial flushing, head pressure, lacrimation & blurred vision may occur
  • Require several weeks of exposure prior to symptoms



  • Occurs after a “fish meal” (e.g. dark meat fish - tuna)
  • Associated with GI symptoms (nausea, vomiting, diarrhea)
  • Histamine related reaction due to poor refrigeration after catching fish.



  • Antidote for CN poisoning
  • Skin become red after administration due to its color (red)

Category: Toxicology

Title: Eye Drops and Effect on Pupil Size

Keywords: eye drops, pupil size, ophthalmic (PubMed Search)

Posted: 9/8/2015 by Bryan Hayes, PharmD (Emailed: 9/10/2015) (Updated: 9/11/2015)
Click here to contact Bryan Hayes, PharmD

In the evaluation of ED patients, it may be important to understand the effect on pupil size from the ophthalmic medications they use. Here is a summary chart of common eye drops and their effect on pupil size.

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Category: Toxicology

Title: Body stuffers how long should they be observed in the ED?

Keywords: body stuffers, observation period (PubMed Search)

Posted: 8/20/2015 by Hong Kim, MD, MPH (Updated: 1/30/2023)
Click here to contact Hong Kim, MD, MPH

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

  • < 2 hr: 58%
  • 2-6 hr: 10%
  • > 6 hr: 7%


Clinical findings

76% of the patients experience clinical signs of toxidrome at time of presentation.

Most common findings:

  • Hypertension: 30%
  • Tachycardia: 20%
  • Agitation: 16%

Patients who ingested heroin were more symptomatic vs. cocaine (87% vs. 70%)


Patients were discharged:

  • Within 6 hr: 72%
  • Between 6 – 12 hr: 10%
  • Between 12-24 hr: 10%
  • > 24 hr: 8%



  • Patients developed new or worsening drug toxicity within 6 hr of presentation
  • Majority of patients were discharged within 6 hr.
  • Asymptomatic patients at ED presentation should be observed for 6 hr.

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Category: Toxicology

Title: Is Flumazenil Making a Comeback? (Hint: no)

Keywords: flumazenil, benzodiazepine, overdose (PubMed Search)

Posted: 8/7/2015 by Bryan Hayes, PharmD (Emailed: 8/13/2015) (Updated: 8/13/2015)
Click here to contact Bryan Hayes, PharmD

Flumazenil is generally avoided in most adult patients with suspected benzodiazepine overdose due to resedation, seizures/withdrawal, inconsistent reversal of respiratory depression, and the potential for proconvulsant coingestants.

Three relatively recent poison center studies have attempted to demonstrate the safety of flumazenil in this setting. [1-3] In the first study there were 904 adult patients with 13 reported seizures and 1 death. [1] A second study specific to pediatric patients reported 83 patients with no seizures and no deaths. [2] A third study found 80 patients with 1 seizure and 0 deaths. [3]

On the surface, it may appear that flumazenil is safe to give. But, retrospective poison center studies from voluntary reporting cannot be used to prove a drug's safety. The true denominator is unknown. In the pediatric study, we wouldn't expect children to experience withdrawal since they aren't on chronic benzodiazepine therapy. [2] So, it's no surprise there weren't any seizures or deaths.

A recent systematic review and meta-analysis of randomized trials summed it up perfectly: "Flumazenil should not be used routinely, and the harms and benefits should be considered carefully in every patient." [4] Cases in which to consider flumazenil are pediatric patients and reversal of procedural sedation if needed.

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Poison ivy, oak, and sumac (Toxicodendron sp) causes a highly puritic, allergic contact dermatitits (ACD) that affects between 10 and 50 million in the US every year. It is a significant occupational hazard as well a scourge for outdoor enthusiasts.

Toxicodendron species contain oleoresins, known as Urushiol compound, secreted by all parts of the plant. Contact with the oil usually occurs by brushing against or direct handling of the plant or contaminated items. This toxin triggers a type IV delayed hypersensitivity reaction in approximately 75% of the population. Within 12-24 hours an erythematous, often linear, vesicular rash develops but new lesions can occur up to 2 weeks later.

There is no ideal treatment for ACD induced by Toxicodendron species. Avoidance and barrier protection are the best strategies. Recommended medications include antihistamines, topical preparations, and systemic steroids. However, steroids require a 2-3 week course to prevent recrudescence of the rash and are not without undesirable side affects.

Zanfel, an OTC granular polyethlene paste, removes urushiol by binding with it to create an aggregate cluster that can be washed away with water. It is highly effective, providing rapid relief even as a sole agent but requires multiple initial applications and is expensive. Mean Green hand scrub has similar ingredients and is claimed to bond urushiol also. Excessive scrathing and abrasive scrubs can cause secondary cellulitis requiring antibiotics.

Category: Toxicology

Title: Sugar for sulfonylurea-induced hypoglycemia? Try octreotide.

Keywords: sulfonylurea, hypoglycemia, octreotide (PubMed Search)

Posted: 7/28/2015 by Hong Kim, MD, MPH (Emailed: 7/31/2015) (Updated: 1/30/2023)
Click here to contact Hong Kim, MD, MPH

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:

  1. Dextrose (D50 50mL via IV) administration if symptomatic: e.g. altered mental status
  2. Feeding: food items that are more substantial than juice: e.g. food tray or sandwich
  3. Serial finger stick glucose check


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.

Category: Toxicology

Title: How did physostigmine get a bad rap?

Keywords: physostigmine, anticholinergic toxicity, TCA overdose, asystole (PubMed Search)

Posted: 7/16/2015 by Hong Kim, MD, MPH (Updated: 1/30/2023)
Click here to contact Hong Kim, MD, MPH

Physostigmine is a cholinergic agent (acetylcholine esterase inhibitor) that can be used to reverse anticholinergic toxicity. Its use has been declining since the publication of several case reports of physostigmine induced cardiac arrest in tricyclic antidepressant (TCA) overdose.


The first case report (and often cited) was by Pental P. et al. (Ann Emerg Med 1980), who presented 2 cases (32 and 25 year old) of asystole after administration of physostigmine (2 mg) in severe TCA overdose. These two cases both had widened QRS interval (120, 240 msec) due to TCA poisoning. Bradycardia preceded the asystole.


The second case report (Shannon M Pediatr Emerg Care 1998) reported a 15 year-old girl with QRS widening (120 msec) received 2 mg of physostigmine and developed severe bradycardia and then asystole.


Another case series (Knudson K et al. BMJ 1984) of 41 patients with overdose of maprotiline showed that physostigmine administration was associated with higher incidence of seizures. No asystole was noted.


Today physostigmine is contraindicated in TCA poisoning. But if we think about it, physostigmine administration probably wasn’t a good idea in the first place. Correcting anticholinergic toxicity of TCA has limited benefit; mortality from TCA overdose is usually associated with cardiac toxicity (Na-channel blockade) and should be treated with NaHCO3 administration


Physostigmine still has a role in treating isolated anticholinergic toxicity  (e.g. diphenhydramine, benztropine, dimenhydrinate, scopolamine, jimson weed overdose). Prior to physostigmine administration:


  1. Get a screening EKG to demonstrate there is no evidence of Na-channel blockade. Even diphenhydramine can cause Na-channel blockade and seizures in severe OD.
  2. Have atropine at bedside. Physostigmine is a cholinergic agent. When given too much, your patient will develop cholinergic toxicity.
  3. Administer 0.5 mg IV over 3-5 min. repeat as needed (every 3-5 min) to max dose of 2.0 mg for clinical effect (improvement of mental status).


Bottom line: If you suspect isolated anticholinergic toxicity, think about physostigmine. Like any medication, risk and benefit of administration should be considered prior to administration. 

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Category: Toxicology

Title: Reversing Dabigatran with Idarucizumab

Keywords: dabigatran, bleeding, idarucizumab, reversal (PubMed Search)

Posted: 7/6/2015 by Bryan Hayes, PharmD (Emailed: 7/9/2015) (Updated: 7/9/2015)
Click here to contact Bryan Hayes, PharmD

The New England Journal of Medicine and Lancet both published studies evaluating idarucizumab for reversal of dabigatran. It is a monoclonal antibody fragment that binds dabigatran with high affinity. Dr. Ryan Radecki summarizes the two articles on his EM Lit of Note blog.

Here are a few take home points from these early studies:

  1. Both studies were funded by Boehringer Ingelheim, who not suprisingly also markets dabigatran. Skepticism is always welcome when the same company makes the drug and the antidote.
  2. The Lancet study was conducted in healthy volunteers, while the NEJM study was conducted in patients needing reversal but lacked a control group.
  3. Idarucizumab seems to reverse laboratory markers of anticoagulation from dabigatran rapidly and completely, including dilute thrombin time and ecarin clotting time. Not all institutions have these assays available.
  4. The dose that seems to 'work' the best is 5 gm given IV (two-2.5 gm infusions given no more than 15 minutes apart).
  5. Median investigator-reported time to cessation of bleeding was 11.4 hours in the NEJM study.
  6. 21 of the 90 patients in the NEJM study had 'serious adverse effects' including thrombotic events.
  7. The acquisition cost of this medication will most assuredly be high if and when it is FDA-approved in the U.S.

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Category: Toxicology

Title: K2 strikes back: A surge in synthetic cannabinoid use.

Keywords: Synthetic cannabinoid, K2 (PubMed Search)

Posted: 6/18/2015 by Hong Kim, MD, MPH (Updated: 1/30/2023)
Click here to contact Hong Kim, MD, MPH

Recently, there has been a surge in synthetic cannabinoid in the U.S., including the Baltimore area. According to U.S. poison control center data, there has been 229% increase in calls related to SC between January to May of 2015 compared to similar time period in 2014.


The most commonly reported adverse/clinical effects included:

  • Agitation: 35.3%
  • Tachycardia: 29%
  • Drowsiness/lethargy: 26.3%
  • Vomiting: 16.4%
  • Confusion: 16.4%


End-organ injuries have been also reported in case reports, including AKI, seizure, MI, and CVA.


Synthetic cannabinoid includes a list of chemical compounds that are structurally different compared to THC – the active compound in marijuana. However, they possess full CB1 (cannabinoid) receptor agonism effect, unlike the THC, which is a partial CB1 receptor agonist. 


These chemicals (particularly JWH series) were originally synthesized to study the effect of cannabinoid receptors. Overall, it is difficult to identify the compound and the dose within each packets of SC.


Commonly marketed names include: Spice, K2, K9, herbal highs, Scooby snax, WTF.

Table. Identified synthetic cannabinoids

Chemical name

Chemical origin

JWH-018; JWH-073; JWH-250

Laboratory of J.W. Huffman

CP47,497; CP47,497-C8; CP59,540; cannabicyclohexanol

Pfizer laboratory


Hebrew University laboratory


Fatty acid


CB2 receptor agonist

XLR-11, AKB-48, AM-2201, AM-694



Management: Majority of the patients with acute SC intoxication mostly requires supportive care, including benzodiazepine for acute agitation. However, ED providers should be mindful of potential end-organ injury. 

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