The Tox Cave

The Tox Cave will dissect interesting ED cases from the perspective of a toxicologist, focusing on applying up-to-date management of the poisoned patient. The name Tox Cave was coined by a former toxicology fellow to describe our small office space, likening it to the Bat Cave. The Tox Cave is where Drexel toxicology fellows and attendings have gathered to discuss the nuances of toxicology over the years.

Tuesday, January 2, 2018

Part 2 in a Four-part Series​

A 57-year-old man presented with acute onset altered mental status. His family said he had been behaving normally. Prior to dinner, however, he became difficult to arouse, and was speaking gibberish. He was somnolent but arousable to physical stimuli on arrival in the ED.

He answered questions inappropriately and would then go back to sleep. His past medical history was consistent with hypertension, hypercholesterolemia, and spinal fusion a month ago. His medications included lisinopril, atorvastatin, and hydrocodone. His vital signs were a blood pressure of 110/65 mm Hg, heart rate of 90 bpm, temperature of 98.5°F, respiratory rate of 6 bpm, and pulse oxygen of 95% on room air. He had no focal neurologic deficits and pupils at 3-2 mm bilaterally.

How Naloxone Works and the Correct Dosage

Naloxone works as a competitive mu opioid-receptor antagonist. The dosage is empirical and depends on the amount of opioid taken, the type of opioid, and how dependent the patient is on opioids.

All three factors should be considered before administering naloxone. The initial dose should be small (0.04 mg), followed by escalating doses (0.5 mg, 1 mg, 2 mg, 4 mg, 10 mg, 15 mg) every two to three minutes until there is a response. (N Engl J Med 2012;367[2]:146.) More potent opioids, such as synthetic fentanyl analogs and buprenorphine, may require higher levels of naloxone. Patients who are opioid-dependent like the patient in this case will have precipitated withdrawal even at levels as low as 0.4 mg. Use of the minimum effective dose followed by quick escalation to achieve reversal is the most prudent treatment strategy. A continuous infusion is indicated for recurrent symptoms.

Selecting Patients for Naloxone

The indication for administering naloxone is the presence of respiratory depression. These patients generally do not have a problem of oxygenation but rather of ventilation; they should not be automatically treated with supplemental oxygen. In fact, supplemental oxygen may be a detriment to these patients because it can cause a falsely elevated oxygen saturation on the pulse oximeter and subsequently a delay in the recognition of hypoventilation.

Optimal monitoring should be done with a continuous end-tidal CO2; otherwise a pulse oximeter that can measure the respiratory rate is useful. If patients develop respiratory depression as measured by their respiratory rate, end-tidal CO2, or CO2 measured on a VBG, they should be administered naloxone and observed.

Disposition of Opioid-Intoxicated Patients after Receiving Naloxone

Disposition depends on the opioid that the patient used. For patients who say they used heroin, a short-acting opiate, a single dose of naloxone should suffice. These patients can be monitored for three to four hours.

The vitals and observations that may predict safe discharge in these patients:

  • They can mobilize as usual.
  • Oxygen saturation of >92% on room air
  • Respiratory rate of >10 bpm and <20 bpm
  • Temperature >35°C and <37.5°C
  • Heart rate >50 bpm and <100 bpm Glasgow Coma Scale of 15

The patient should meet all of these criteria without verbal or physical stimuli.

Some clinicians recommend a prescription of naloxone for these patients to help in case of future overdoses. Patients taking longer-acting opioids (i.e., oxycodone, hydrocodone, methadone, and buprenorphine) or who require additional administration of naloxone during an observation period should be admitted to the hospital to a monitored bed. Pediatric patients with an accidental ingestion of one of these longer-acting opioids should be admitted for a 24-hour observation. Fentanyl derivatives generally require such large doses of naloxone for reversal that these patients should be admitted directly to an ICU or a step-down unit.

Timing of Naloxone Prescription

Due to the severity of the opioid epidemic, recent legislation has focused on increasing the availability of naloxone not only to emergency responders but also to the public. President Barack Obama signed the Comprehensive Addiction and Recovery Act in 2016 to increase the availability of naloxone to first responders and the public. There are several formulations from which providers can choose to prescribe to patients, but some are cost-prohibitive. The provider should educate the patient and his friends and family members about the use and limitations of naloxone.

Naloxone Product              Manufacturer           Previous cost    Cost (2016)

Injectable or intranasal,              Amphastar              $20.34 (2009)        $39.60

1 mg/mL vial (2 mL)

(mucosal atomizer separate)



0.4 mg/mL vial (10 mL)               Hospira                  $62.29 (2012)        $142.49

0.4 mg/mL vial (1 mL)                Mylan                     $23.72 (2014)        $23.72

0.4 mg/mL vial (1 mL)                West-Ward             $20.40 (2015)        $20.40


Auto-injector, two-pack               Kaleo                     $690 (2014)           $4,500

of single-use prefilled

auto-injectors (Evzio)


Nasal spray, two-pack                 Adapt Pharma         $150 (2015)           $150

of single-use intranasal

devices (Narcan)​

Chart adapted N Engl J Med 2016;375[23]:2213.

tox cave narcan.jpg

Nasal Narcan produced by Adapt Pharma.​

The patient was a chronic opiate user, so was administered 0.04 mg IV naloxone. His respirations increased to 12 bpm, and he remained somnolent but was easily arousable to voice. When awake, he was alert and oriented. After one hour, he required another 0.04 mg IV naloxone. The patient was admitted to a step-down unit for observation because he was known to be prescribed oxycodone, and he was placed on a naloxone infusion at two-third of the effective naloxone dose.

Wednesday, November 1, 2017

Part 1 in a Four-part Series

A 32-year-old man was taken to the ED by EMS after being found unresponsive in a subway station. His pupils were pinpoint, and he was breathing at fourth breaths per minute. He had a blood pressure of 94/63 mm Hg, pulse oximetry of 91% on room air, and a heart rate of 51 beats per minute. He was given 2 mg of intranasal Narcan by EMS and became more responsive, breathing at 14 breaths per minute with a blood pressure of 125/82 mm Hg, heart rate of 74 bpm, and 98% on room air. He admitted in the ED to using three bags of heroin.​

The opioid epidemic is a national public health crisis in the United States with more than 90 deaths a day due to drug overdose. ( That is more than the number of deaths per day from motor vehicle crashes. Nearly half of those overdose deaths are due to opioids. More than 64,000 people died in 2016 from overdose, a nearly 20 percent rise from 2015 and nearly quadruple the number of overdose deaths in 2000. (New York Times. June 5, 2017;


There are three main opioid receptors: the mu (mu1 and mu2), kappa, and delta. (National Institute on Drug Abuse. June 30, 2017; Respiratory depression is mu2-mediated. Euphoria is mediated by the mu-delta receptor agonism and subsequent dopamine release in the mesolimbic system. Kappa agonism can also produce analgesia, but it can also cause dysphoria.​


The opioid toxidrome consists of miosis, bradycardia, hypotension, hypoventilation, decreased bowel sounds, and constipation. These do not all have to be present or can be present at varying degrees. They may also be only partially present, especially if there are other medications or drugs (legal or illicit) on board.

There are many types of opioids, with three main categories. Naturally occurring opioids include morphine and codeine; synthetic includes meperidine, fentanyl (acetyl-fentanyl, carfentanil, butyrfentanyl, and U47700), and methadone, semi-synthetic ones include hydrocodone, oxycodone, heroin, hydromorphone, Oxymorphone, and buprenorphine.

Another consideration is the potency of the drugs:





Time to Effect



Routine Dosage Equivalent
Morphine sulfateIV5-10 min3-6 hours10 mg IV
IM15-30 min3-6 hours10 mg IM
PO30-60 min3-6 hours30-60 mg PO
OxycodonePO10-15 min4-6 hours10-20 mg PO
HydrocodonePO30-60 min4-6 hours15-30 mg PO
FentanylIVImmediate1-2 hours50 mcg IV
HydromorphonePO15-30 min4-6 hours7.5 mg
IV15 min4-6 hours1.5 mg
IM15 min4-6 hours1.5 mg
CodeinePO30-60 min4-6 hours200 mg
NalbuphineIM15 min3-6 hours10 mg

Routine dosage is equivalent to morphine 10 mg IM or IV. Table is adapted from​

Fentanyl and its analogues have been largely responsible for overdose deaths. They are significantly more potent than morphine.


​Number of Times More Potent Than Morphine

Acetyl fentanyl15

The patient was monitored in the ED for four hours. He was awake, alert, and oriented with normal vital signs. He ambulated around the ED, and persistently asked to leave. He did not require any additional Narcan while in the ED​.

Monday, October 2, 2017

An 18-year-old woman presented for altered mental status. EMS reported that she was at a beach party when she became unresponsive. Friends said she may have been drinking alcohol, but denied other illicit drug use. Initial vital signs included a blood pressure of 117/69 mm Hg, heart rate of 110 bpm, respiratory rate of 11 bpm, SPO2 99% on room air, and a temperature of 98.9°F.

The patient was somnolent and reacted intermittently to physical stimuli on exam. She intermittently moved all four extremities. Her gag reflex was intact. Pupils were 4 mm bilaterally reactive without nystagmus. She had tachycardia, her lungs were clear, and her abdomen was soft and nontender. Pertinent labs findings included glucose of 98, serum ethanol of 200 mg/dL, and liver function tests within normal limits. Several hours later, her parents arrived in the ED. The patient was more awake and alert, and she reported that she had only drunk one glass of white wine.

The estimated serum level of alcohol in a 70-kg adult after drinking a four-ounce (120 mL) glass of wine containing 12 percent alcohol is 43 mg/dL; one shot (30 mL) of 40 percent alcohol (80 proof) is 27 mg/dL; and a10-ounce (300 mL) bottle of beer containing five percent alcohol is 43 mg/dL.

Calculating the Serum Ethanol Concentration

The estimated dose of alcohol should be calculated to determine the serum level. The concentration of alcohol may be found expressed in several terms: "% alcohol" by volume and historically as "proof." A hundred percent proof contains 50 percent alcohol by volume in the United States. A hundred percent proof in the United Kingdom contains 57 percent alcohol by volume.

Dose of alcohol (g) = volume ingested (mL) x concentration of drink (mL alcohol/100 mL) x specific gravity (0.8 g/mL)


Serum ethanol level (mg/dL)        =       dose (mg)             

                                                     0.6 L/kg x weight (kg) x 10

Acute Ethanol Effects on a Non-Tolerant Adult

with Different Serum Concentrations

0.01-0.05No loss of coordination, slight euphoria, loss of shyness
0.04-0.06Well-being feeling, relaxation, lower inhibitions, minor impairment of reasoning and memory, euphoria
0.07-0.09Slight impairment of balance, speech, vision, reaction time, and hearing. Euphoria. Reduced judgment and self-control. Impaired caution, reasoning, and memory.
0.10-0.125Significant impairment of motor coordination and loss of good judgment. Speech may be slurred; balance, vision, reaction time, and hearing will be impaired. Euphoria.
0.13-0.15Gross motor impairment and lack of physical control. Blurred vision and major loss of balance. Euphoria is reduced, and dysphoria is beginning to appear.
0.16-0.20Dysphoria (anxiety, restlessness) predominates; nausea may appear. The drinker has the appearance of a "sloppy drunk."
0.25Needs assistance in walking. Total mental confusion. Dysphoria with nausea and some vomiting.
0.30Loss of consciousness
0.40 and upOnset of coma, possible death due to respiratory depression/arrest.

Effects are dependent on individual use, chronicity, and tolerance, and other factors. Adapted from Medscape table. (

Blood Ethanol Level and Serum Ethanol Level

Serum levels are typically used in hospital settings, while whole blood levels are used in forensic settings. Serum ethanol levels will be slightly higher than whole blood levels because of its higher water content. The estimated ratio of serum-to-whole blood ethanol concentrations is between 0.88 to 1.59.

Clearance Rate of Ethanol in an Adult?

The majority of ethanol consumed is eliminated by the liver. A small percentage is eliminated by the kidneys, sweat, and lungs. The rate is 10 to 15 mg/dL/hour in non-tolerant drinkers, and 20 to 40 mg/dL/hour in tolerant drinkers. The difference is explained by the additional pathway of metabolism with CYP2E1 in tolerant/chronic drinkers.

Factors that Modify Absorption, Metabolism, and Elimination of Ethanol


-Increases with factors that stimulate gastric emptying such as erythromycin, ranitidine, and gastric bypass surgery.

-Decreases with factors that slow gastric emptying, including food, aspirin, and narcotics.


-Increases for chronic drinkers due to the activation of CYP450 enzymes.

-Decreases for patients with liver cirrhosis (decreased amounts of alcohol dehydrogenase).


-Decreases for individuals with aldehyde dehydrogenase deficiency.​

The patient was observed in the emergency department. Intravenous fluids were administered. She became more responsive, and returned to her neurologic baseline in five hours. The patient later admitted that she likely drank more than one glass of wine.

tox cave-alcohol1.jpg


Rick/Creative Commons​

Friday, September 1, 2017

A 27-year-old man with an unknown past medical history presented with altered mental status. Bystanders found him on the sidewalk acting strangely, according to EMS. The patient was drowsy with incomprehensible speech on arrival. He was diaphoretic, tachycardic, and combative. No signs of trauma were noted. His heart rate was 130 bpm, blood pressure 169/90 mm Hg, respiratory rate 30 bpm, SPO2 98% on room air, and temperature 105.3°F. His blood glucose was 150. The patient continued to be minimally responsive.

Etiologies of Hyperthermia

  • Neuroleptic malignant syndrome
  • Serotonin syndrome
  • Anticholinergic syndrome
  • Sympathomimetic
  • Heat stroke
  • Baclofen withdrawal
  • Thyroid storm
  • Seizures
  • Other drugs: salicylates, 2,4-dinitrophenol
  • Malignant hyperthermia
  • Infection

Complications Associated with Hyperthermia

Hyperthermia is generally considered to be body temperatures greater than 104.0°F. Prolonged hyperthermia is associated with high morbidity and mortality. Complications include altered mental status, rhabdomyolysis, multisystem organ failure, DIC, and death. (Curr Opin Pediatr 2004;16[2]:211.)

Cooling Drug-Induced Hyperthermic Patients

You must stop the psychomotor agitation for patients with hyperthermia. (Am J Health Syst Pharm 2013;70[1]:34.) Treatment may include benzodiazepines and paralytics if agitation is still severe. Some causes of hyperthermia may have specific antidotes such as physostigmine for anticholinergic syndrome and dantrolene for malignant hyperthermia. (Am J Health Syst Pharm 2013;70[1]:34.)

Patients should be aggressively cooled while agitation is being controlled. The optimal cooling method, however, remains controversial. (Clin Toxicol [Phila] 2015;53[3]:181.) Ice-water submersion results in faster cooling in some studies, but is resource-intensive for preparation, monitoring, and attention to patient and staff safety compared with other techniques. This method requires a water-impermeable bed or tub, access to a large volume of ice, experienced staff, and control of patient agitation.

Other cooling methods include applying ice packs to the axilla and groin, evaporative cooling with water sprays or mists with fans, specialized cooling devices, cold intravenous fluids, gastric lavage with ice water, and bladder irrigation with fluids.

The goal should be to decrease the patient's temperature below 104°F within 30 minutes because studies have demonstrated that mortality approaches zero when hyperthermia is reversed in this time frame. Core temperature should be continuously monitored and aggressive cooling stopped at 101°F so hypothermia is not overshot. Be aware that patients can also develop rebound hyperthermia.

Medications Contraindicated in Drug-Induced Hyperthermia

Generally, antipsychotics should be avoided. Most of these patients are at high risk of developing seizures, and antipsychotics may lower the seizure threshold, worsening psychomotor agitation. (Am J Health Syst Pharm 2013;70[1]:34.) Certain causes of hyperthermia such as serotonin syndrome, neuroleptic malignant syndrome, and anticholinergic toxidromes also may be exacerbated by antipsychotics. (Eur J Clin Pharmacol 2007;63[6]:627.)​

A sympathomimetic toxidrome was suspected for our patient. He was rapidly intubated for his severely altered mental status and psychomotor agitation. He was submerged in ice water, and his core temperatures were recorded. Intravenous fluids and lorazepam were also administered. He was removed when his temperature decreased to 101°F. His core temperature continued to be monitored, and the patient was admitted to the ICU. He remained intubated for 24 hours, and was discharged from the hospital four days later with minimal sequelae.

tox cave-hyperthermia.jpg


Lippincott Williams & Wilkins, 2007​

Tuesday, August 1, 2017

A 14-year-old boy with no past medical history was brought to the ED in some distress by his parents. One hour earlier while looking for his baseball glove in the garage he had felt a small pinprick just above his right ankle. The patient, however, became increasingly uncomfortable and began complaining of diffuse abdominal pain.

His initial vital signs were a temperature of 97°F, heart rate of 112 bpm, blood pressure of 151/91 mm Hg, and 98% pulse oximetry on room air. He appeared uncomfortable, was diaphoretic, and had a rigid abdomen. A small puncture wound with some mild erythema to the lateral right ankle was noted.

Poisonous Spiders in the United States

-The black widow (Latrodectus spider) is the most commonly reported spider envenomation in the United States, and is involved in more than 2,500 calls to poison control centers annually. (Perm J 2011;15[3]:76.) The 8-10 mm females are identified as being shiny and black with a ventral red hourglass on their belly. Males may be smaller with a white and gray marking and a less prominent hourglass. There are five Latrodectus spiders in the country, with Latrodectus mactans and variolus (predominantly in the southern and eastern states) being the two main ones.

-The brown recluse spider or the Fiddleback spider contains a violin-shaped marking on its cephalothorax. Bites are uncommon and likely overdiagnosed. When bites occur, a dermonecrotic lesion can develop over hours and progress over weeks. They are mainly found in the central Midwestern states in the United States.

tox cave-spiders.jpg

Black Widow Spiders' Toxicity

Latrodectus venom is one of the most potent poisons by volume. It contains five neurotoxins, the primary one affecting humans being alpha-latrotoxin. The venom acts at the neuromuscular junction by binding to glycoproteins and causing a large release of acetylcholine and norepinephrine at the presynaptic terminal, while simultaneously inhibiting the reuptake of choline.

The primary feature of envenomation is pain, particularly in the abdomen or back. (Ann Emerg Med 1992;21[7]:782.) Severe muscle cramping and pain are commonly seen in a waxing/waning-type picture. Neuromuscular symptoms include cramping, rigidity, priapism, ptosis, fasciculations, and tremors. Cardiopulmonary symptoms include hypertension and tachycardia. Other systemic symptoms include nausea, vomiting, and diaphoresis, which may be localized to the extremities that are bitten but also frequently on the forehead. Latrodectus facies may also occur, which presents with periorbital swelling, facial muscle spasms, lacrimation, and photophobia.

Diagnosis is aided with visual identification of the spider. The site of the spider bite may be unremarkable with a tiny punctum and slightly erythematous and indurated surrounding skin. No routine diagnostic lab testing is necessary, but workup of alternative diagnosis should be considered. Wound care includes tetanus prophylaxis. The primary component of management is pain control. Pain may be managed with cold packs, NSAIDs, opioids, and benzodiazepines. (Ann Emerg Med 2014;64[6]:620.) Use of IV calcium gluconate has been described, but studies show little benefit.

A Latrodectus antivenin exists in the United States, and is equine-derived. Adverse events include anaphylactoid reaction and serum sickness. One report in the literature describes a fatality due to an anaphylactoid reaction from the antivenin, and antivenin should only be administered in the most severe cases. (Dosing below.) The antivenin is a category C drug, and has safely been given in pregnancy. Patients should be monitored for at least six to eight hours, and follow-up seven to 12 days after the antivenin is given is important as serum sickness can occur within this time frame. Hospitalization may be considered for patients with moderate to severe symptoms and hypertension. Pain symptoms may last for days.


-Dilute one to two vials in 50-100 ml 5% dextrose and infuse over one hour.

-Patients may be pretreated with diphenhydramine and steroids to blunt any hypersensitivity reaction.

-Multiple allergies, asthma, or previous reactions to equine-based products should be considered a contraindication.

The patient in our case was treated symptomatically with Toradol and diazepam IV. He was monitored closely for six hours. His symptoms improved, and he did not require antivenin. A repeat examination of his abdomen was noted to be soft and nontender.​