UMEM Educational Pearls - By Hong Kim

Category: Toxicology

Title: Buprenorphine/naloxone (Suboxone) exposure in pediatric population

Keywords: buprenorphine exposure, pediatrics, retrospective study (PubMed Search)

Posted: 10/26/2016 by Hong Kim, MD, MPH (Emailed: 10/27/2016)
Click here to contact Hong Kim, MD, MPH

Takeaways

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.

 

Bottom line

  • 83% and 80% of the patients experienced respiratory and CNS depression, respectively.
  • Majority of the patients became symptomatic within 8 hours of exposure (range not available).
  • Naloxone reversed respiratory depression. Median dose for single naloxone dose: 0.09 mg/kg; median dose for multiple naloxone doses: 0.19 mg/kg.
  • The reported “ceiling effect” on respiratory depression in adult does not exist in pediatric population.
  • The optimal time of observation is unclear but it is prudent to observe pediatric buprenorphine exposure for up to 24 hours.

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Takeaways

US, Canadian and European critical care and toxicology societies recently published a consensus recommendation is the management of CCB poisoning.

Bottom line:

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.

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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)

 

Findings:

  • 12 medical resources (48%) recommend using 0.05 mg or less IV as an initial dose.
  • 9 medical resources (36%) recommend using 0.4 – 0.5 mg or higher as an initial dose.
  • Maximum dose also ranged widely from 2 to 20 mg.

 

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.

 

Bottom line:

In opioid-induced respiratory depression/apneic patients:

  1. Ventilate with bag-valve mask for apnea/hypoxia
  2. Administer naloxone: 0.04 mg IV every 2 – 3 min until reversal of respiratory depression/hypoxia is achieved.

To make 0.04 mg naloxone solution:

  • Dilute 1 mL of 0.4 mg naloxone with 9 mL normal saline in 10 mL syringe. 

 

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Category: Toxicology

Title: Atypical antipsychotics: are they truly safer than typical antipsychotics?

Keywords: atypical antipsychotic toxicity (PubMed Search)

Posted: 9/8/2016 by Hong Kim, MD, MPH (Updated: 10/18/2021)
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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)

  • Clozapine
  • Olanzapine
  • Quetiapine
  • Risperidone
  • Ziprasidone

 

Antimuscarinic effect (anticholinergic toxicity)

  • Clozapine
  • Olanzapine
  • Quetiapine

 

Delayed rectifier K channel blockade (QT prolongation)

  • Ertindole
  • Ziprasidone

 

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.

 

 


Category: Toxicology

Title: Lethal in small dose or single pill in pediatric population (age < 5 years old)

Keywords: One pill killers, pediatric (PubMed Search)

Posted: 8/17/2016 by Hong Kim, MD, MPH (Emailed: 8/18/2016) (Updated: 8/18/2016)
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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.

  • Benzocaine
  • B-adrenergic antagonist (sustained release)
  • Calcium Channel blockers (sustained release) 
  • Camphor
  • Clonidine
  • TCAs
  • Diphenoxylate/atropine (Lomotil)
  • Toxic alcohol (methanol or ethylene glycol)
  • Methylsalicylate
  • MAO-Is
  • Opioids
  • Phenothiazines
  • Quinine or chloroquine
  • Sulfonylureas
  • Theophylline

 

Suspected ingestion of above medications/xenobiotics may warrent observation up to 24 hours in asymptomatic pediatric population.

 

 


Category: Toxicology

Title: Are synthetic opioids next novel designer drugs of abuse in the U.S?

Keywords: novel synthetic opioid, U-47700 (PubMed Search)

Posted: 8/1/2016 by Hong Kim, MD, MPH (Emailed: 8/3/2016) (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

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.

  • Dallas, TX: A couple in their 20’s purchased U-47700 on the internet believing it to be “synthetic cocaine.” They both suffered CNS and respiratory depression after insufflation. Naloxone was not administered in both cases. The man was intubated while the woman was awake at time of presentation to the ED. U-47700 exposure was confirmed by liquid chromatography/tandem mass spectrometry.

 

  • San Diego, CA: a 22 year old man with history of heroin abuse was found unresponsive and apneic (4 breaths per minute and pulse oximetry of 60%). He received naloxone 2 mg IV which completely reversed his CNS and respiratory depression. He admitted to purchasing U-47700 on the internet and its use prior to being found unresponsive. U-47700 exposure was confirmed using liquid chromatography/mass spectrometry.

 

  • Central CA: 41 year old woman presented with CNS depression and pinpoint pupils after ingesting 3 tablets of “Norco” purchased from the street.  Her intoxication was completely reversed with naloxone 0.4 mg IV and discharged after 4 hour observation. Fentanyl and U-47700 was detected in serum blood test.

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.  

 

Bottom line:

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. 

  1. Airway management: bag-valve assisted ventilation if needed
  2. Naloxone administration (initial dose: 0.04 to 0.4 mg IV) with titration as needed. 
  • naloxone's clinical duration of effect ranges from 30 to 90 minutes.

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Category: Toxicology

Title: Laundry detergent pods exposure - the hidden danger.

Keywords: Pediatric exposure, laundry detergent pods (PubMed Search)

Posted: 6/23/2016 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

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):

  • GI: nausea & vomiting: 29.1%
  • Cough/choking: 8.3%
  • Ocular irritation/pain: 5.6%
  • Red eye/conjunctivitis: 3.4%
  • Drowsiness/lethargy: 2.8%

Laundry detergent pod vs. nonpods:

  • Higher referral to health care facility: 17.4% vs. 4.7%
  • Higher odds of experiencing > 1 clinical effects (OR: 3.9; 95% CI: 3.7 4.1)
  • Higher odds of hospital admission (OR: 4.8; 95% CI: 4.0 5.8)
  • Higher odd of intubation (OR: 6.9; 95% CI: 3.5 13.6)

Laundry detergent pods (only) also resulted in following:

  • Coma: 17 cases
  • Respiratory arrest: 6 cases
  • Pulmonary edema: 4 cases
  • Cardiac arrest: 2 cases

Cases of caustic exposure-like injuries have also been reported (corneal abrasion and esophageal injury)

Bottom line:

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.

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Category: Toxicology

Title: Loperamide high more than a fix for diarrhea.

Keywords: loperamide, opioid alternative, cardiac toxicity (PubMed Search)

Posted: 6/15/2016 by Hong Kim, MD, MPH (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

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.

 

Bottom line:

  • Clinicians should be aware of potentially lethal cardiac toxicity of loperamide abuse (Na and K channel blockade).

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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:

 

Phase

Time

Signs and symptoms

Therapy

I

0 – 24 hr

·  Nausea, vomiting, diarrhea

·  Salt and water depletion

·  Leukocytosis

·  Antiemetic

·  GI decontamination

·  IV fluids

·  Observation for leukopenia

II

1 – 7 days

·  Sudden cardiac death (24 – 48 hr)

·  Pancytopenia

·  Acute kidney injury

·  Sepsis

·  Acute respiratory distress syndrome

·  Electrolyte imbalance

·  Rhabdomyolysis

·  Resuscitation

·  G-CSF

·  Hemodialysis

·  Antibiotics

·  Mechanical ventilation

   ·  Electrolyte repletion

III

>7 days

·  Alopecia (2-3 weeks later)

· Myopathy, neuropathy, myoneuropathy.

 

 

Management

  • Primarily supportive care as no antidote is available.
  • ICU admission due to risk of sudden cardiac death in symptomatic patients.
  • Patients who does not manifest GI symptoms within 8 -12 hr are unlikely to be significantly poisoned.

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:

  1. Ingestion (common in children): soil, water, lead-based paint chips, toys, certain folk remedies.
    • Absorption: adult: 3 – 10% vs. children: 40 – 50%
  2. Inhalation (mostly occupational exposure): lead dust
    • Absorption: 30 – 40%
  3. Dermal (minor): cosmetic products
    • Absorption: < 1%

 

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

Clinical severity

Typical blood lead level (microgm/dL)

Severe

  • CNS: encephalopathy (coma, seizure, altered sensorium, ataxia, apathy, incoordination, loss of developmental skills, cranial nerve palsy, signs of increased ICP
  • GI: persistent vomiting
  • Heme: anemia

> 70 – 100

Mild to moderate

  • CNS: hyperirritable behavior, intermittent lethargy, decrease interest in play, “difficult” child
  • GI: intermittent vomiting, abdominal pain, anorexia

50 – 70

Asymptomatic

  • CNS: impaired cognition, behavior, balance, fine-motor coordination
  • Misc: impaired hearing or growth

> 10

 

Evaluation for lead poisoning

  1. Blood lead level (BLL)
  2. CBC: hypochromic microcytic anemia, basophilic stippling
  3. Imaging: abdominal XR – check for foreign bodies in GI tract; long-bone XR – lead lines

 

Management of children with EBLL

  1. Removal from exposure
  2. Environmental investigation/intervention (BLL: 15 - 44 ug/dL)
  3. Chelation
    • Asymptomatic (BLL: 45 – 69 ug/dL): Succimer (PO)
    • Symptomatic (BLL: > 70 ug/dL): Dimercaprol (IM) and CaNa2EDTA (IV)

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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)

 

GI

Respiratory

Cardiovascular

Neurologic

Early (1 hr)

Nausea

Vomiting

Salivation

Abdominal pain

Bronchorrhea

Hyperpnea

Hypertension

Tachycardia

Pallor

Agitation

Anxiety

Dizziness

Blurred vision

Headache

Hyperactivity

Tremors

Fasciculation

Seizures

Late

(0.5-4 hr)

Diarrhea

Hypoventilation

Apnea

Bradycardia

Hypotension

Dysrhythmias

Shock

Lethargy

Weakness

Paralysis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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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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.

Conclusion

  • 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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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.

 

Niacin

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

 

Trichloroethylene

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

 

Scrombroids

  • 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.

 

Hydroxocobalamin

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

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: 10/18/2021)
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)

 

Characteristics

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%

 

Conclusion

  • 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.

Show References


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: 10/18/2021)
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: 10/18/2021)
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. 

Show References


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: 10/18/2021)
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

HU-210

Hebrew University laboratory

Oleamide

Fatty acid

UR-144

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. 

Show References


Category: Toxicology

Title: why is your patient blue? xenobiotic-induced methemoglobinemia

Keywords: methemoglobinemia, methylene blue (PubMed Search)

Posted: 5/20/2015 by Hong Kim, MD, MPH (Emailed: 5/21/2015) (Updated: 5/21/2015)
Click here to contact Hong Kim, MD, MPH

Methemoglobin (MetHb) is produce when Fe+2 in heme is oxidized to Fe+3 under oxidative stress (caused by mediation and chemicals). MetHb does not bind to oxygen and thus decrease RBC’s O2 carrying capacity.

Among medication, overdose of local anesthesia - benzocaine, dapsone, and phenazopyridine are often implicated. (Table 1)

Think about methemoglobinemia in presence of low pulse oximetry (~85%) with lack of response to supplemental oxygen, cyanosis, dyspnea, etc. (see Table 2 – signs and symptoms of MetHb) in patients who are taking or overdosed on medication listed in Table 1.

Diagnosis: CO-oximetry detects toxin-induced hemoglobinopathies, including COHb and MetHb.

Treatment: Methylene blue (1 mg/kg over 5 min) in symptomatic patients or MetHb level > 25%. Resolution of methemoglobinemia should be noted in 30 – 60 min.

G6PD deficiency: Prevalence in the U.S. is 4-7% with highest prevalence in African American population (11%). Methylene blue causes hemolytic anemia in patients with G6PD deficiency within 24 hours of administration. However, G6PD status is often unknown in ED patients.  When caring for patients with known G6PD deficiency and methemoglobinemia, providers must carefully consider the risk and benefit of treating MetHb (including severity of poisoning/MetHb) with methylene blue.

Table 1. Causes of MetHb

Medication

 

Chemicals

Benzocaine, Lidocaine, Prilocaine

Aniline dye

Dapsone

Chlorobenzene

Phenazopyridine

Organic nitrites (e.g. isobutyl nitrite)

Nitroglycerin

Naphthalene

Nitroprusside

Nitrates (well water contamination)

Quinones (Primaquine & Chloroquine)

Nitrites (food preservatives)

Sulfonamides

Silver nitrate

Nitric oxide

Trinitrotoluene

Amyl nitrite

 

 

Table 2. Signs and symptoms

MetHb level (%)

Signs and symptoms

1-3% (normal)

 

·  None

3-15%

·  Low pulse oximetry (<90%)

·  Gray cutaneous coloration

15-20%

·  Chocolate brown blood

·  Cyanosis

20-50%

·  Dizziness, syncope

·  Dyspnea

·  Weakness

·  Headache

50-70%

·  CNS depression, coma, seizure

·  Dysrhythmias

·  Tachypnea

·  Metabolic acidosis

>70%

·  Death

·  Hypoxic injury

 


Category: Toxicology

Title: When should NAC be stopped after an acute acetaminophen poisoning?

Keywords: acetaminophen toxicity, NAC, hepatic toxicity (PubMed Search)

Posted: 3/19/2015 by Hong Kim, MD, MPH (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

Elevation of AST or ALT >1000 after acute ingestion of acetaminophen indicate hepatic toxicity. N-acetylcysteine (NAC) is an effective treatment for acute acetaminophen poisoning. However, in a setting a significant transaminitis, (> 1000s) NAC infusion is continued beyond the routine 21-hour protocol.

 

Currently, there is no specific guideline or “level” of AST or ALT where discontinuing NAC is deemed safe and appropriate.

 

A recent retrospective study (n = 37 patients with 343 pairs of AST/ALT) evaluated AST/ALT ratio as a possible indicator for discontinuing NAC infusion after an acute acetaminophen induced hepatic toxicity.

 

This study found that post peak AST/ALT ratio of < 0.4 had sensitivity of 99% for identifying patients with resolving hepatic injury.

 

This finding requires validation prior to clinical application but this may be the first step to identifying a safe indicator to help guide clinician when NAC can be discontinued safely.

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Category: Toxicology

Title: Can Hydroxocobalamin be administered via intraosseous access for acute cyanide toxicity?

Keywords: intraosseous, hydroxocobalamin, cyanide poisoning (PubMed Search)

Posted: 1/15/2015 by Hong Kim, MD, MPH (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

Hydroxocobalamin is an effective cyanide antidote when administered intravenously. Although intraosseous (IO) access is often used in critically ill patients with difficult or delayed IV access, the efficacy of IO administration has not been investigated until recently.

In a recent randomized animal study, acute cyanide toxicity was induced in two groups of swine where 150 mg/kg Hydroxocobalamin was administered via IV vs. IO. The survival rate, reversal of hypotension, and laboratory results were similar between the IV and IO group.

The finding of this study suggest that IO administration of Hydroxocobalamin is as efficacious as IV administration and its administration in acute cyanide toxicity should not be delayed due to lack of IV access when IO access is available.

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