Intentional drug overdose (IDO) can lead to significant morbidity and can increased patient's risk of death. A study was recently performed to identify the predictors of death in a cohort of patient who intentionally overdose on drug(s). 

National Self-Harm Registry and National Drug-Related Death Index were reviewed (between January 1^st, 2007 and December 31^st, 2014) to identify the study cohort.

Results

Risk of death

• 1.7 times higher in MALE compared to female
• 5 times higher in age > 45 years vs. 15-24 years
• 3 times higher in patient who ingested 2 – 5 distinct agents, 6x higher in > 6 agent vs. single agent
• 15 times higher after TCA ingestion
• 12 times higher after opioids ingestion
• 4 times higher after antidepressants or illicit substance ingestion/exposure

Conclusion

• Older age (> 45 years), male gender and ingestion of multiple agents (>2) were associated with higher risk of death from intention drug overdose.

Show References

Many patients are treated in the emergency room for non-fatal opioid overdose. However, it is unknown what proportion of these patient population experience subsequent fatality after their ED visit. 

A recent study investigated the 1-year mortality rate among Massachusetts ED patients who were treated and discharged from ED for non-fatal opioid overdose.

Results

• 11,557 patients were identified between July 1, 2011 and September 30, 2015.
• There were 635 fatalities (5.5%) within 1 year in this cohort.
  • Of these, 428 (67.4%) died due to opioid overdose

Of those who died, 

• 130 (20.5%) died within 1 month
• 29 (4.6%) died within 2 days.

Manner of death

• Natural causes: 121 (19.1%)
• Accidental: 460 (72.4%)
• Suicide: 13 (2.0%)
• Other/pending investigation: 41 (6.5%)

Place of death

• Hospital: 310 (48.8%)
• Residence: 146 (23.0%)
• Other/unknown/nursing home: 179 (28.2%)

Conclusion

• There is high rate of fatality within 1 month (20.5%) after non-fatal opioid overdose ED visits.
• Subsequent fatal opioid overdose was observed in 428 (67.4%) of the cohort.

Show References

Pharmacobezoars (clumps of medication/pills) formation has been demonstrated in few medications such as aspirin, and ferrous sulfate tablets. Their presence can alter management due to prolonged absorption and may cause GI obstruction.

Acetaminophen (APAP) is a commonly available over-the-counter medication that is often implicated in an acute overdose event. A recently published in-vitro study (using pig stomach) investigated whether APAP can form a pharmacobezoar.

APAP group/dosage

• 25 gm (50 tablets)
• 37.5 gm (75 tablets)
• 50 gm (100 tablets)

Positive control group

• ferrous sulfate (15 gm/50 tablets)

Negative control group

• chlorpheniramine (200 mg (50 tablets)

Results

• APAP formed clumps in 37.5 gm and 50 gm groups
• 83% (5 out of 6) of the 25 gm APAP group did not form clumps.

• Dissolution profile: APAP clumps released more slowly (over 60 min tested) compared to individual tablet without reaching a peak.

Conclusion

• APAP can form pharmacobezoar at doses greater than 37.5 gm (in-vitro model) and can result in prolonged or delayed toxicity due to pharmacobezoar formation.

Show References

Non-opioid medications such as gabapentin are frequently prescribed for the management of pain. 

A retrospective study of the National Poison Data System (data collected by the U.S. Poison Centers) from 2013 – 2017 showed increasing trend of gabapentin exposure.

Gabapentin exposure increased between 2013 and 2017 by:

• Total exposure: 72.3% 
• Isolated intentional suicide attempt: 80.5%
• Isolated exposure: 67.1%
• Isolated intentional abuse/misuse: 119.9%

5 most commonly co-ingested substances with gabapentin

• Sedative-hypnotic: 22.9%
• Antidepressant: 12.7%
• Antihypertensive: 9.9%
• Opioid: 9.0%
• Antipsychotics: 6.3%

16.7% of the isolated gabapentin exposure required hospitalization.

Conclusion:

• Gabapentin abuse/misuse and ingestion with self-harm intent is increasing in the U.S.

After many years of national shortage and FDA’s black box warning in 2001 (QT prolongation) droperidol is slowing becoming available.

In 2015, a prospective observational study was published involving ED patients who received droperidol for agitation (acute behavioral disturbance). 

Method

• Study period: August 2009 to April 2013 in 6 EDs in Australia
• Intervention: droperidol 10 – 20 mg IM or IV (if available)
• EKG performed within 2 hours of droperidol administration.
• QT was manually measured and plotted against the heart rate on the QT nomogram – if above “at-risk line” = abnormal

Results

• Droperidol was administered in 1,403 ED patients
• EKG available in 1,009 ED patients
• Median age: 34 years (IQR: 25-44)
• Men: 59.9%

Four leading reason for ED presentation

1. Alcohol intoxication: 421
2. Deliberate or threatened self-harm: 200
3. Psychostimulant use: 130
4. Mental illness/psychosis: 142

• Median droperidol dose: 10 mg (IQR: 10 to 17.5 mg) 
• Abnormal QT interval: 13 (1.3%, 95% CI: 0.3% to 2.3%)
  • 7 patient had other potential contributing factors: methadone, escitalopram, Amiodarone or preexisting condition. 
• Median time to sedation: 20 min (IQR: 10 to 30 min)

Adverse events

• Desaturation (<90%): 22 (1.6%)
• Airway obstruction: 8 (0.6%)
• Hypotension: 28 (2.0%)
• Extrapyramidal symptoms: 7 (0.5%)
• Arrhythmia: 1 (0.1%)
• Hypoventilation (RR < 12 breaths/min): 4 (0.2%)
• Seizure: 1 (0.1%)
• No adverse events: 1,333 (95.0%)

Conclusion

• Droperidol is a safe sedating agent with no evidence of increased risk for QT prolongation with the doses used. 

Show References

As of November 20, 2019:

2290 cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) from 49 states (except Alaska), District of Columbia and 2 U.S. territories.

• Largest number of cases (150-199) reported from CA, TX and IL
• 47 deaths

Analysis of 29 bronchoalveolar lavage (BAL) fluid samples from EVALI patients submitted to CDC from 10 states showed:

• Vitamin E acetate in all samples 
• THC: 82%
• Nicotine: 62%
• No other chemicals of concern were identified (e.g. plant oil, mineral oil, terpenes, etc.) 

*** Vitamin E acetate appears to be associated with EVALI but the investigation is continuing.*** 

• Oral ingestion of vitamin E acetate does not cause harm.
• High dose vitamin E supplementation (>2000 IU/day [2000 mg/day]) can cause GI symptoms: nausea, vomiting, diarrhea and abdominal pain.

Some research has suggested that oral vitamin E use has potential beneficial effects (i.e. anti-inflammatory/antioxidant) in the lung (e.g. asthma and allergic lung disease), cardiovascular disease and prostate cancer (Cook-Mills JM et al. 2013; Jiang Q et al. 2001)

Common uses of vitamin E

• Topical cosmetic skin products (skin cream) for antioxidant effect.
• Essential dietary vitamin (fat soluble) found in many food items and as dietary supplement.
• In vaping products: vitamin E is used as an additive/thickening agent in THC containing e-cigarette, or vaping products.

There is limited to no data on pulmonary effect of vitamin E from inhalation in the scientific literature.

Stay tuned for additional updates from CDC.

Show References

Metformin is one of the most commonly prescribed oral hypoglycemic agents. Metformin associated lactic acidosis (MALA) is uncommon but potentially life-threatening complication of metformin overdose. 

Lactic acidosis occurs due to inhibition of mitochondrial glycerophosphate dehydrogenase, resulting in decreased conversion of lactic acid to pyruvate.

A small retrospective study (using Illinois Poison Center data) attempted to characterize the development of MALA after an acute overdose.

MALA was defined as 

• Lactate: > 5 mmol/L
• Acidemia: (HCO₃< 20 mmol/L or pH < 7.35)

Results

40 cases of MALA identified between Jan. 2001 to Dec. 2014

• Meadian age: 41 year
• Female: 55%
• Acute on chronic ingestion: 62.5%
• Hypoglycemia: 3 (7.5%)

Time to development of MALA (n=30)

• <=6 hours: 18 (60%)
• 6-12 hours: 9 (30%)
• >12 hours: 3 (10%)
• Unknown: 10

Death: 1 (2.5%)

Conclusion

1. The majority of MALA developed within 6 hours. However, delayed onset of MALA can occur, up to 12 hours post ingestion.
2. Minimum of 12 hour of observation is recommended after an acute metformin overdose.

Show References

Droperidol has recently become available again in select U.S. institutions. It has been used as an antiemetic and to treat agitation prior to the FDA’s black box warning (for QT prolongation) and national shortage. 

Recently, a retrospective study was conducted (Melbourne, Australia) in the use of droperidol in the management of cannabinoid hyperemesis syndrome (CHS).

Results

689 medical records were identified from January 2006 to December 2016.

76 cases met diagnostic criteria of CHS (below)

• Long-term cannabis use
• Symptoms of recurrent vomiting
• Absence of illness that could otherwise explain symptoms.

Droperidol group (DG) = 37; no droperidol group (NDG)= 39 

Median length of stay: 

• DG: 6.7 hr vs. NDG: 13.9 hours (p=0.014)

Median time to discharge after final drug administration: 

• DG: 137 min (IQR: 65, 203) vs. NDG: 185 min (IQR: 149, 403)

Frequency of droperidol (dose) used: 

1. 0.625 mg (n=25)
2. 1.25 mg (n=20)
3. 2.5 mg (n=17)

Metoclopramide and Ondansetron use in non-droperidol group was twice that of droperidol group

Conclusion

• Droperidol use to treat CHS associated nausea/vomiting resulted in decreased length of stay and lower use of antiemetics.  

Patients with drug-induced cardiogenic shock [DIC] (e.g. overdose of CCB/BB, membrane stabilizing agents, etc.) are often managed with medical interventions such as vasopressors, bicarbonate infusion, high-dose insulin, lipid emulsion therapy. A fraction of these patients may be refractory to the standard medical therapy. VA-ECMO (venoarterial extracorporeal membrane oxygenation) has been utilized in such situation; yet clinical experience of using VA-ECMO in DIC is limited.

A recent retrospective study of the Extracorporeal Life Support Organization’s ECMO registry showed

• Increasing VA-ECMO utilization for drug-induced cardiogenic shock (n=104) over the past 15 years (2003 to 2018) but it represents a fraction (0.067%) of VA-ECMO use.
• VA-ECMO improved hemodynamic and metabolic status at 24 hrs-post cannulation.
• Persistent acidosis (HCO3 level) and acidemia (pH) at 24 hrs-post cannulation was associated with mortality.
• 52.9% of the cases survived to discharge. 

Conclusion

• VA-ECMO may be clinically beneficial (improvement of hemodynamic and metaboic status) in patients with refractory drug-induce cardiogenic shock

Show References

The rate of suicide attempt has been increasing over the past decade. A recently published article investigated the temporal trend of suicide attempts in adolescent/young adult population (10 – 25 years old) from 2000 to 2018.

 Methods

• All intentional – suspected suicide cases were identified from the National Poison Data System from Jan 1, 2000 to December 31, 2018. 
• Following age groups were compared: 10-12, 13-15, 16-18, 19-21 and 22-25 years old.

Results

• A total of 1,677,435 cases were identified with 0.1% fatality (n=1579).
• Female: 70.6% (n=1,184,691) 
• Single substance (64.1%; n=1,074,423)
• Highest suicide attempt rate: 16-18 years (30.1%; n=504,682)
• Lowest suicide attempt rate: 10-12 years (2.3%; n=38,428)

• The suicide attempt rate increased significantly starting 2011 in 10-12, 13-15 and 16-19 years age groups with seasonal trend
  •  Higher during school months (Sept to May) vs. non-school months (June-August)

Top 5 substance involved in suicide attempt

1. OTC analgesics
2. Antidepressants
3. Sedative hypnotics
4. Antihistamines
5. Antipsychotics

Agents associated with serious medical outcome (after 2011)

1. Antidepressants
2. OTC analgesics
3. Antihistamines 
4. ADHD medications

• ADHD medicaitons: common in 10-15 years population
• Sedative hypnotics (e.g. benzodiazepines): common in older age group (16-25 years)

Conclusion

• Rate of suicide attempt in adolescent and young adults has increase, especially since 2011.
• The substance used in suicide attempt usually involves medications available to the specific age group.
• OTC medications (analgesics and antihistamines) were involved in a third of the suicide attemps.

Show References

E-cigarette (vaping) use has become increasingly popular over the past 10 years, especially among adolescents. Intentional exposure (i.e. ingestion in self harm) of nicotine (e-cigarette liquid) can be life threatening where it can produce mixture of stimulatory (early), cholinergic toxicity and muscle paralysis/respiratory failure by blocking the neuromuscular junction. However, the severity of clinical toxicity in unintentional exposure can vary widely depending on the dose/route/circumstance of their exposure.

A recently published study investigated the characteristics of e-cigarette liquid exposure between Jan 1, 2010 to Dec 31, 2018 using the National Poison Data System

Result

• Total reported exposure: 17,358.
• e-cigarette exposure report increased starting 2013 (n=1435), peaking in 2014 (3742). 2018 (n=2901).

Top 4 clinical/demographic characteristics are listed below.

Age group:

• < 5 years: 64.8%
• 25+ years: 15.4%
• 18-24 years: 8.3%
• 12-17 year: 3.4%

Route of exposure

• Ingestion: 77.5%
• Dermal: 13.0%
• Inhalation/nasal: 10.4%
• Ocular: 7.1% 

Level of care:

• Not referred to health care facility (HCF): 60.9%
• Treated and released from HCF: 27.4%
• Admitted: non-critical care: 0.8%, critical care: 0.6%

Clinical effects - overall

• Vomiting: 25.4%
• Nausea: 11.8%
• Ocular irritation: 11.3%
• Dizziness/vertigo: 5.1%

In <5 years group

• Vomiting: 47.1%
• Cough/choking: 10.2%
• Drowsiness/lethargy: 5.7%
• Nausea: 5.5%

Conclusion

• e-cigarette exposure predominantly occurs in young children (< 5 y/o)
• Clinical toxicity are usually self-limited and often not referred to HCF.
• Severe toxicity is possible, although infrequent, from unintentional exposure.

Show References

Cannabinoid hyperemesis syndrome [CHS] (i.e. cyclic/recurrent nausea, vomiting and abdominal pain) is associated with long-term and frequent use of marijuana. Patients with CHS often report temporary relief of symptoms with hot water/shower exposure. Emergency room providers may encounter a growing number of patients with CHS with increasing legalization of marijuana-containing products.

Topical capsaicin has been gaining interest as a potential adjunct to the conventional management of patients with CHS (e.g. antiemetics, opioids, benzodiazepines and antipsychotics).

A small retrospective study was performed involving 43 patients who had multiple visits, and were treated with and without capsaicin. The primary outcome was the ED length of stay (LOS).

Results

• Most frequently administered medications in both groups were:

1. Anti-emetics
2. Haloperidol
3. Diphenhydramine 

• Median ED LOS: no significant difference
  • Capsaicin vs. non-capsaicin: 179 min (IQR: 147, 270) vs. 201 min (IQR: 168, 310) (p=0.33)

• Capsaicin group showed
  • Decreased opioid used: 69 mg vs. 166.5 mg oral morphine equivalents
  • Fewer additional medication administration: 3 vs. 4 doses (p=0.015)
  • Shorter median time to discharge after last medication administration: 60 min (IQR: 35, 115) vs. 92 min (IQR: 47, 155) (p=NS) 

• 67% of the visit where capsaicin was used required no additional medication.

Conclusion

• Capsaicin use did not decrease ED LOS.
• However, there was a decrease in total medications administered and opioid requirement.

Show References

Breath analyzers are commonly used by law enforcment officers to test for alcohol intoxication. Breath analyzer uses ethanol partition ratio between blood:breath of 1:2100 = 1 gm of ethanol in 2100 mL of breath/air.

Mouth wash products are frequently used for oral hygiene, and at times, to "mask" odor of substances. These products are readily available in any grocery stores or pharmacy and contain upto 26.9% ethanol (e.g. Listerine) (18.9% - Scope; 14.0% - Cepacol).  

Recently, a small study using healthy volunteers (n=11) was published to investigate the impact of limited ethanol exposure (mouth wash and ethanol vapor) on the breath-alcohol concentration (BrAC).

Method

1. Ethanol vapor exposure (856 mg/m3) for 15 minute. 
2. Oral rinse (for 30 sec) using mouth wash containing 22% ethanol, 1 hour after the ethanol vapor exposure
3. Blood and breath samples were collected before, between and after exposure.

Results

Blood: No or very low levels of ethanol (0.002 mg/g) were detected in blood at all collection time for both exposures.

BrAC - first collection -- seconds after exposure

• Ethanol vapor: 0.14 mg/L (0.014 mg/dL)
• Mouth wash: 4.4 mg/L (0.44 mg/dL)

Mean time to negative BrAC level (Swedish statutory limit of 0.1 mg/L = 0.01 mg/dL in air) (FYI: US limit = 80 mg/dL)

• Ethanol vapor: 0.5 min (0.06 - 0.7 min)
• Mouth wash: 11 min (6 - 15 min) 

Conclusion

• Ethanol vapor did not affect the BrAC
• Mouth wash use can transiently increase BrAC; however, their use does not sufficiently increase the BrAC to result in "false positive" based upon US limit.

Show References

Numerous different household products can potentially be misused/abused. One such product is whipped cream charger/propellant that contains nitrous oxide.

Acute toxicity produce dose dependent response

• Euphoria 
• Anxiolysis
• Sedation
• Unconsciousness
• Asphyxiation

Chronic toxicity causes myeloneuropathy (demyelination of the dorsal and lateral columns of the spinal cord) due to vitamin B12 deficiency

• Extremity paresthesias
• Ataxia
• Peripheral sensory neuropathy (loss of vibration sense and proprioception)
• Weakness 
• Hematologic effects: leukopenia, thrombocytopenia, megaloblastic anemia

Management

• Cessation of nitrous oxide use
• Vitamin B12 (cyanocobalamin) repletion (IM)

Show References

Center for Disease Control and Prevention (CDC) recently issued alerts regarding cases of pulmonary illnesses that may be linked to "vaping" (in 15 states with 149 possible cases). These cases are still under investigation but all cases reported vaping weeks/months prior to hospitalization.

Most cases involve young adults who have been using THC-containing products

Common complaints included

• Gradual onset of shortness of breath, cough, and chest pain
• GI symptoms: nausea, vomiting and diarrhea
• Fever, fatigue

Imaging studies:

• Chest x-ray can show bilateral opacity
• CT lung demonstrates ground-glass opacities with sub-pleural sparing.

Clinical course

• Some cases required mechanical intubation
• Corticosteroid treatment appears to improve clinical course
• Infectious evaluation was negative in almost all cases.
• No clear causative etiology has been identified
• No death has been reported 

What to do:

• Inquire about vaping history when treating patients with suspected cases.
• Providers should contact their local health department, poison center or CDC (VapingAssocIllness@cdc.gov) to report possible case of vaping associated pulmonary injury 

Show References

Direct hepatotoxicity from a drug is predictable and dose-dependent.

Most commonly implicated agents include:

• Acetaminophen
• Niacin
• Aspirin
• Cocaine
• IV Amiodarone
• IV methotrexate
• Cancer chemotherapy

On the contrary, idiosyncratic prescription drug-induce liver injury is rare, unpredictable and not related to dose.

Most commonly implicated agents are:

1. Amoxicillin-clavulanate
2. Isoniazid
3. Nitrofurantoin
4. TMP-SMZ
5. Miocycline
6. Cefazolin
7. Azithromycin

Bottom line:

• Drug-induced liver injury is uncommon and can be a diagnostic challenge.
• Recognition of commonly implicated agents can help recognize/identify drug-induced liver injury. 

Hematologic toxicity (coagulopathy/bleeding) can occur with pit viper envenomation. Copperhead is the most commonly implicated pit viper envenomation in the U.S. However, the prevalence of hematologic toxicity from copperhead envenomation is variable, possibly due to regional variation in venom potency and species misidentification. 

An observation study was performing using multi-center (Virginia Commonweath university, University of Virginia Medical Center and Eastern Virginia Medical medical center) electronic hospital/medical records (Jan 1, 2006 to Dec 31, 2016) of suspected copperhead bites. Authors state that copperhead snakes are "nearly exclusively endemic" to the VCU and UVA medical center region.

Results:

388 patients were identified but 244 met inclusion/exclusion criteria.

• Mean age: 34 years
• Male: 59%
• Antivenom administration: 76%
• No bleeding was reported.

Hematologic toxicity: 14%

• Elevated PT: 10.0%
• Elevated PTT: 3.9%
• Thrombocytopenia: 1.2%
• Hypofibrinogenemia: 0.7%

Conclusion

In a small sample of copperhead envenomation in Virginia, “subtle” hematologic abnormalities were observed but clinically significant hematologic toxicity was not observed (i.e. bleeding)

Show References

Pulmonary complications - aspiration, pulmonary edema, etc. are frequently reported in both heroin intoxication and in reversal of opioid overdose with naloxone. 

Suspected opioid overdose victims (N=1831) who received naloxone from EMS providers were studied retrospectively. Pulmonary complications were defined as pulmonary edema, aspiration pneumonia and aspiration pneumonitis.

Results

• Out of hospital naloxone dose > 4.4 mg – 62% more likely of experiencing pulmonary complication (OR 2.14, 95% CI: 1.44 to 3.18) 
• Increased risk of pulmonary complication if initial naloxone dose is > 0.4 mg (OR 2.57, 95% CI 1.45 to 4.54)

Conclusion

Higher out of hospital naloxone administration is associated with increased odds of developing pulmonary complications

Show References

“Push dose pressors” – administration of small doses of vasopressors in the emergency room has become a common practice. A recently published study investigated the incidence of human error and adverse hemodynamic events.

Push dose pressors were defined as:

• Phenylephrine (any dose)
• Epinephrine (<= 100 mcg) 

Adverse hemodynamic event was defined as:

• Extreme tachycardia (HR > 140 bmp)
• New bradycardia (HR < 60 bmp)
• Hypertension (SBP > 180 mmHg)
• Ventricular tachycardia

249 out of 1522 patients were identified and analyzed from Jan 2010 to November 2017

• median initial epinephrine dose (20 mcg; IQR: 10-100; range 1-100)
  • recieved more than one dose: 78 (57%)
• median initial phenylephrine dose (100 mcg; IQR: 100-100; range 25 to 10,000)
  • received more than one dose: 62 (56%)

Adverse event

• Phenylephrine group (n=110): 30 (27%; 95% CI: 19-36%)
• Epinephrine group (n=139): 68 (50%; 95% CI: 41-58%)

Errors

• Human error: 47 (19%) - similar proportion of human error between two agents.
• Dosing error: 7 (3%; 2.5 to 100-fold)
• Documentation error: 43 (17%)
• Only one dosing error occurred when a pharmacist was present

Conclusion

• Human errors and adverse hemodynamic event were common when “push dose pressors” were administered.
• Consultation with a pharmacist can/may reduce dosing error.

Show References

Cyanide poisoning, while uncommon, is frequently fatal. Current antidotes include methemoglobinemia inducers (nitrites), sulfur donators (thiosulfate), and hydroxocobalamin. Each has risks and benefits that must be considered. Three new potential antidotes, including sodium tetrathionate, have recently been evaluated in swine models.

 
Intramuscular sodium tetrathionate¹

• Sodium tetrathionate can bind and eliminate two cyanide molecules compared to one cyanide molecule by thiosulfate.
• Studied in a large (50 kg) female swine model of cyanide poisoning.
• All pigs were given cyanide via IV until 6 minutes post-onset of apnea, then given an approximately 1.5 mL IM injection of sodium tetrathionate (18 mg/kg).
• Survival at 90 minutes was 100% (6/6) in the treated group and 16% in the control arm (1/6). 

Advantages:

• Small volume injection (~1.5-2 mL in humans)
• No interference with routine laboratory tests.
• Ease of administration in pre-hospital or potential mass casulty setting.

Bottom line:

• New cyanide antidotes are being developed.
• The FDA does NOT require human trials of efficacy for cyanide antidotes.
• It is unclear where these drugs are in the approval process at this time, but look for them in the future.

Show References