Clinical signs and symptoms of clonidine overdose include CNS depression, bradycardia, and miosis. Other effects include early hypertension, followed by hypotension and respiratory depression, especially in children.

Although clonidine overdose in children is well described, frequency of clinical signs/symptoms in adults is not well characterized.

Recently, a retrospective study was performed in a hospital in Australia looking at clonidine overdose in adults.  

Among isolated clonidine overdose, patients experienced:

• GCS < 15: 55%
• GSS < 9: 5%
• Miosis: 25%
• Bradycardia (HR< 60): 68%
• Median HR: 48 (IQR: 40-62)
• Hypotension (SBP < 90 mmHg): 25%
• Median LOS: 21 hr (IQR: 11 – 27 hr)
• Intensive care: 23%
• No deaths

Bottom line:

1. The most common symtom of clonidicine overdose was bradycardia
2. Clonidine overdose results in non-life threatening but prolonged clinical effect in adult.

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Methadone overdose produces classic signs and symptoms of opioid intoxication - CNS and respiratory depression with pinpoint pupils. However, methadone overdose has also been associated with hypoglycemia – a relatively uncommon adverse effect.

Bottom line:

• Methadone-induced hypoglycemia can occur, although rare, in an acute overdose.

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A small retrospective study of an acute poisoning cohort attempted to identify risk factors for severe outcome in salicylate poisoning.

Severe outcomes were defined as

1. Acidemia pH < 7.3 or bicarbonate < 16 mEq/L
2. Hemodialysis
3. Death

A multivariate analysis of 48 patients showed that older age and increased respiratory rate were independent predictors of severe outcomes when adjusted for salicylate level.

Initial salicylate acid level was not predictive of severe outcome.  

Elevated lactic acid level was also a good predictor of severe outcome in univariate analysis but not in multivariate analysis.

Limitations

1. Small sample size with single center study
2. Retrospective study design
3. Validation study of these predictors is needed.

Bottom line

1. Older age and increases respiratory rate is associated with severe outcome (acidemia, hemodialysis or/and death) in this study.
2. Data must be interpreted with caution due to small sample and retrospective study design.

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Smoke inhalation victims (house fires) are at risk of carbon monoxide (CO) and cyanide poisoning (CN). CO exposure/poisoning can be readily evaluated by CO - Oximetry but CN level can be obtained in majority of the hospital.

Lactic acid level is often sent to evaluate for CN poisoning.

Bottom line:

1. Lactatic acid levels should be sent in all smoke inhalation victims.
2. Elevate lactate > 10 mmol/L is highly suggestive of CN poisoning
   .

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Recent study evaluated whether an acetaminophen (APAP) level obtained less than 4-hour post acute ingestion can predict which patient would not require n-acetylcysteine (NAC).  APAP cutoff level of 100 ug/mL was used for analysis. This was a secondary analysis of the Canadian Acetaminophen Overdose Study database (retrospective study). 

Bottom line:

1. If initial APAP level of 100 ug/mL was applied as a cutoff point, it missed 27 patients (N= 1821) who had toxic APAP level at > 4-hour post ingestion that require NAC.  
2. Only a very low (< 15 ug/mL) or undetectable initial APAP reliably identify (sensitivity 100%) patients who do not require NAC.
3. Absorption of APAP can be delayed by coingestion of opioids or antimuscarinics.

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Recently a review paper was published regarding the duration of observation in heroin overdose patients who received naloxone.

It made several conclusions regarding heroin overdose:

1. Treat (naloxone) and release in a prehospital setting may be safe.
2. Short observation period (minimum of 1 hour) for heroin OD patients who were treated in the ED may be safe.
3. Bystander and first responder naloxone administration is effective and safe.

It should be pointed out that this is a review paper of limited number of articles with variable quality. Additionally, the clinical history of “heroin use” may be unreliable as fentanyl and novel synthetic opioids are also sold as “heroin.” Providers should exercise appropriate clinical judgement when caring for these patients. 

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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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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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Antipsychotic as a class has diverse range of toxicity. The atypical (2^nd generation) antipsychotics are considered to possess less toxicologic manifestation compared to the typical (1^st 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.

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.

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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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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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:

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

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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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)

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

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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)

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.

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