Tag Archives: toxicology


Author: Kristin E. Fontes, MD (Emergency Physician, Santa Barbara Cottage Hospital and Goleta Valley Cottage Hospital) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital), and Brit Long, MD (@long_brit, EM Attending Physician, San Antonio Military Medical Center)

Case presentation:

A 28-year-old female is brought to the emergency department by ambulance from home after her roommate found her disoriented and poorly responsive. The roommate reports finding a small container of antifreeze in the patient’s bedroom. Vital signs are as follows: T 37.0C, HR 65, BP 126/76, RR 32, and SpO2 98% on room air.  Venous blood gas shows pH 6.97, pCO2 21, pO2 38, HCO3 4.8, and lactate 6.75.


What are the laboratory abnormalities that can occur with toxic alcohol poisoning and how can it be treated?


Common features of toxic alcohol poisoning are elevated anion gap metabolic acidosis and elevated osmolar gap (the latter being a distinguishing feature from ethanol poisoning); osmolar gap usually elevated early after ingestion.(1,2)

Recall the toxic alcohol metabolites and their effects:

toxic alcohol metabolism

  • EG toxicity can cause significant renal failure due to oxalate crystal deposition in the kidneys and glycolic acid, which is directly nephrotoxic; hypocalcemia and tetany can also result due to oxalate binding to calcium.(1)
  • MeOH toxicity classically causes visual disturbances (“snowfield” vision) due to formic acid-induced optic neuropathy.(1)
  • Isopropanol toxicity causes ketosis without acidosis (no lactic acid formed!).  Usually benign clinical course but can occasionally cause hemorrhagic gastritis. Fomepizole and HD not usually indicated.(1)
  • Propylene glycol toxicity often due to intravenous medication preparations containing this alcohol (e.g., diazepam, lorazepam, esmolol, nitroglycerin, phenobarbital, phenytoin) can result in severe lactic acidosis.(1)
Treatment Approach:
  • Fomepizole competitively inhibits alcohol dehydrogenase, which is involved in the metabolism of all alcohols, including ethanol. It is given to prevent the buildup of toxic metabolites from ethylene glycol (glycolic acid, glyoxylic acid, and oxalic acid) and methanol (formic acid) whose deposition in tissues can cause irreparable damage.(1)
  • Fomepizole is indicated for MeOH or EG ingestion resulting in a metabolic acidosis with an elevated osmolar gap (not accounted for by ethanol) and a serum MeOH or EG level of at least 20 mg/dL.(1)
  • Fomepizole dosing: 1) Load: 15 mg/kg (max 1.5 g) IV, diluted in 100 mL of normal saline or 5% dextrose, infused over 30 minutes; 2) Maintenance: 10 mg/kg IV every 12 hours for 4 doses, then increase to 15 mg/kg until serum toxic alcohol level is less than 20 mg/dL.(1,3)
  • Hemodialysis is indicated for toxic alcohol poisoning with an elevated osmolar gap and/or severe metabolic acidosis refractory to standard therapy, refractory hypotension, or end organ damage (i.e. acute renal failure).(1,3)
  • Vitamin Supplementation: Give folic or folinic acid to patients with MeOH toxicity to divert metabolism away from formic acid to carbon dioxide and water. Give folic acid, pyridoxine, and thiamine to patients with EG toxicity to divert metabolism to nontoxic metabolites.(1,3)
Main points:

Consider toxic alcohol poisoning in a patient with an unexplained elevated anion gap metabolic acidosis and elevated osmolar gap. Consider fomepizole and/or HD in patients with severe toxic alcohol poisoning, especially if refractory to standard therapy.


  1. Olson KR & California Poison Control System. (2012). Poisoning & drug overdose. New York: Lange Medical Books/McGraw-Hill.
  2. Emmett M and Palmer BF. Serum osmolal gap. In: UpToDate, Forman JP (Ed), UpToDate, Waltham, MA, 2016.
  3. LeBlanc C, Murphy N. Should I stay or should I go?: toxic alcohol case in the emergency department. Can Fam Physician 2009 Jan;55(1):46-9.

ToxCard: TCA Poisoning

Author: Tharwat El Zahran, MD (Medical Toxicology Fellow, Emory University School of Medicine) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital), and Brit Long, MD (@long_brit, EM Attending Physician, San Antonio Military Medical Center) screen-shot-2017-01-08-at-11-30-27-pm
Case Presentation:

2 yo male child presented to the ED with status epilepticus. His parents found an empty bottle of amitriptyline at home. He was intubated, given benzodiazepines and antiepileptic drugs. VS: BP 70/30, T 106 F, RR 24, HR 98, sat 98% RA, glucose 100 mg/dl. EKG is shown below.



What EKG findings occur in tricyclic antidepressant (TCA) poisoning? And how are they treated?


TCAs alter the conformation of the sodium channel and slow the rate of rise of the action potential, which produces both negative dromotropic and inotropic effects. Sodium bicarb is the primary treatment for TCA poisoning.

  • All TCA are competitive antagonists of the muscarinic acetylcholine receptors and antagonize peripheral α1 adrenergic receptors.
  • Most prominent effects of TCA overdose result from binding to cardiac Na channels.
  • Acute ingestion 10-20 mg/kg of most TCAs cause cardiovascular and CNS toxicity. In children,  >5mg/kg results in toxicity.(1)
  • Signs of acute cardiovascular toxicity are refractory hypotension, acidosis, and arrhythmias. EKG indicators include intraventricular conduction delay (R shift of QRS axis and prolonged QRS), R in avR≥ 3mm, R/S>0.7 and arrhythmias. A QRS≥100 msec indicates increased incidence of serious toxicity, including coma, intubation, hypotension, seizures, and dysrhythmias. Sinus tachycardia is the most common EKG abnormality. (2)(3)
  • Acute neurological toxicity include AMS, delirium, agitation , seizures, and/or psychotic behavior with hallucinations, lethargy, coma.
Treatment approach
  • If the decision is made to intubate, avoid apnea, consider awake intubation, pretreat w benzos to raise seizure threshold and hyperventilate to promote alkalosis.(4)
  • If the EKG indicates signs of TCA poisoning as mentioned above,  give 1-2 meq/kg of sodium bicarb IV boluses at 3-5 min intervals.(4)
  • Continue bicarb drip until QRS duration <100, vitals stable, Na ~150, pH ~7.55. Watch for hypokalemia and hypocalcemia with bicarb drip.  Consider hypertonic saline (3%) if refractory or if serum pH>7.55.(4)
  • Hypotension unresponsive to sodium bicarb, or fluid boluses should be treated with vasopressors (norepi recommended).(4)
  • Treat dysrhythmias with lidocaine bolus of 1mg/kg IV followed by infusion of 20-50 mcg/kg/min.
  • Benzodiazepines, barbiturates, or propofol are recommended for seizures. Consider continuous EEG monitoring with neuromuscular blockade in refractory cases. Avoid phenytoin.(4)
  • For refractory cardiovascular poisoning consider intralipid or ECMO if available.(4)
Main point

TCAs are sodium channel blockers and primary treatment of TCA poisoning is sodium bicarb. The EKG abnormalities like QRS≥100,  R wave in avR ≥3mm, and R/S> 0.7 can predict significant toxicity.  Sodium bicarb displaces the TCA from the Na binding site by raising the Na+ gradient and increasing the pH.  Prolonged resuscitation might be necessary.

  1. Caksen et al. Acute amitriptyline intoxication: an analysis of 44 children. Human & Experimental Toxicology (2006) 25: 107-110
  2. Olgun et al. Clinical, Electrocardiographic, and Laboratory Findings in Children With Amitriptyline Intoxication. Pediatr Emer Care 2009;25: 170-173
  3. Paksu et al. Amitriptyline overdose in emergency department of university hospital: Evaluation of 250 patients. Human and Experimental Toxicology 2014;33:980–990
  4. Goldfrank’s Toxicologic Emergencies, 10th E, Chapter 71: Cyclic Antidepressants, p 972- 982.



Tox Cards: CO Poisoning

Author: Patrick C. Ng (Chief Resident, San Antonio Military Medical Center) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital), and Brit Long, MD (@long_brit, EM Attending Physician, San Antonio Military Medical Center)
Case Presentation:
It is a cold day in the middle of December. A 56 yo female and her 29 yo daughter who is 8 months pregnant present to your ED with a chief complaint of generalized weakness and headache for 2 days. They mention that they think they both caught the flu due to the cold temperatures despite turning their heater on high and using oil lamps for extra heat in their apartment. Their vital signs are normal.
What are the most common signs/symptoms of carbon monoxide (CO) poisoning, and what are the general management plans?

CO poisoning presents with nonspecific symptoms that can be mistaken for other diagnosis such as the flu. Initial treatment includes high-flow supplemental O2. Hyperbaric oxygen therapy (HBOT) may or may not be the “standard of care” (controversial).

  • CO poisoning can be an elusive diagnosis, as non-specific symptoms such as headache, dizziness, nausea, fatigue, and chest pain are non-specific and can be consistent with many other disease processes.(1,2)
  • Key historical clues include people from the same household presenting with symptoms of headache and flu-like symptoms that improve throughout the course of the day (i.e. when patients leave their dwellings for work, school, etc.) and history of exposure to CO sources such as heaters and enclosed garages.(1,2)
  • A co-oximetry is a spectrophotometer that uses many different wavelengths to measure oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), as well as carboxyhemoglobin (COHb) and methemoglobin (MetHb) concentrations.(3)
  • The use of greater number of wavelengths in a co-oximeter as compared to a standard pulse oximeter allows the co-oximeter to distinguish between other types of hemoglobin,  whereas a standard pulse oximetry can only distinguish between oxyHb and deoxyHb.(3)
  • Blood COHg levels commonly reaches a level of 10 % in smokers and may even exceed 15 %, as compared with 1 to 3 % in nonsmokers.(2)
  • Standard treatment includes  high-flow O2  via NRB mask (or intubation in severe cases) until symptoms resolve and CO levels return to baseline; pregnant patients should continue for at least 24 hours with fetal wellbeing assessment. Patients also require follow up at 1-2 months for neuropsychiatric assessment.(1,2)
  • Normal half life of Hb-CO is 4-6 hrs with room air oxygen, 40- min with high-flow O2, and 15-30 min with HBOT.(2)
  • Although the indications for HBO are controversial, some recommend HBO for any CO-poisoned patient with mental status change or history of syncope, signs of cardiac ischemia or arrhythmia, history of ischemic heart disease and CO level > 20%, symptoms that do not resolve with normobaric O2 therapy after 4-6 hours, or any pregnant patient with CO > 15%. Coma is generally an undisputed indication for hyperbaric-oxygen therapy.(2)
  • The use of HBO has been reported to reduce the risk of neurological/cognitive sequelae thought to be associated with carbon monoxide poisoning.(4,5)
Main Point:
Carbon monoxide poisoning can be a deadly diagnosis associated with significant morbidity and long-term permanent neurological damage. It can present with very non-specific symptoms. Specific historical clues as well as co-oximetry can help the emergency physician quickly make the diagnosis. High-flow O2 therapy is the initial standard therapy with some advocating HBOT for select severe or at risk cases.
1. Piantadosi CA. Diagnosis and treatment of carbon monoxide poisoning. Respir Care Clin N Am. 1999;5:183-202.
2. Ernst A, Zibrak JD. Carbon Monoxide Poisoning. N Engl J Med 1998;339:1603-1608.
3. Hampson NB. Noninvasive pulse CO-oximetry expedites evaluation and management of patients with carbon monoxide poisoning. Am J Emerg Med. 2012 Nov;30(9):2021-4.

4. Tibbles PM, Perrotta PL. Treatment of carbon monoxide poisoning: a critical review of human outcome studies comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med. 1994;24:269-276.
5. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002;347:1057–1067

Treatment for Salicylate Poisoning

Author: Sean Kolowich (Emory University School of Medicine) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


Case presentation:

A 53 year-old previously healthy female is brought into the ED by family members 4 hours after ingesting 100 tablets of aspirin (325mg, unknown formulation). She has no complaints and denies any co-ingestions. VS: Temp 98.1 (oral), HR 93, BP 136/87, RR 20, pulse ox 98% on room air. CMP and ECG are unremarkable, ASA 47.1 mg/dL, ABG pH 7.48, pCO2 20, pO2 122.


What treatments should a salicylate poisoned patient receive?


Patients with salicylate poisoning should receive IV bicarb to alkalinize the urine. Indications for hemodialysis include cerebral edema, pulmonary edema, renal failure, intractable acidosis, clinical deterioration, or ASA level > 100 mg/dL or > 70 mg/dL if chronic.

  • Support ABCs, prevent further organ toxicity by encouraging salicylate elimination
    • Alkalinize the serum/urine
      • 1-2 mEq/kg sodium bicarb. IV bolus followed by sodium bicarb. infusion (3 amps into 1L D5W) @ 1.5-2 X maintenance rate
        • goal serum pH ~7.5
        • goal urine pH >7.5
  • Salicylate overdose + IV sodium bicarbonate therapy = potential hypokalemia
    • Avoid hypokalemia because it prevents alkalization of the urine ® prolonged elimination of salicylate
      • goal K+ 4.0 to 4.5 mEq/L
    • Monitor calcium levels (ionized/total); IV NaHCO3 can cause hypocalcemia
  • Consider glucose supplementation if altered mental status
    • Serum glucose may be normal but CNS levels may be low 2/2 effects of salicylates
  • Indications for extracorporeal treatment (intermittent hemodialysis is ECTR of choice):
    • Salicylate level > 100 mg/dL (> 90 mg/dL if impaired kidney function) or > 70 md/dL if chronic.
    • Cerebral edema (altered mental status, seizures)
    • Renal failure
    • Pulmonary edema or new hypoxemia requiring supplemental O2
    • IF standard therapy fails AND:
      • Salicylate level > 90 mg/dL (> 80 mg/dL if impaired kidney function)
      • Systemic pH < 7.20
  • Continue IV sodium bicarb therapy b/w ECTR sessions
Main Point:

Patients presenting with acute salicylate toxicity should receive supportive care and alkalinization with IV sodium bicarbonate. Hemodialysis should be considered early in treatment and is indicated if there is evidence of end organ damage (AMS, ARDS), failure of standard therapy, or severely elevated salicylate levels.



  1. Lugassy DM. Salicylates. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. Eds. Goldfrank’s Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; 2015.
  2. Levitan R, Lovecchio F. Salicylates. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill; 2016.
  3. Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup. Ann Emerg Med 2015; 66:165

Tox Cards: Narcan (naloxone)

Author: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


Case presentation:

25-year-old M brought in by EMS after being found not breathing, pupils are pinpoint. HR 61, BP 109/40, RR 6, T98, O2 Sat 70% RA. You ask for Narcan (Naloxone).


What dose Narcan should you give?


Start with small doses, i.e. 0.04 mg, and not the standard dose of 0.4 mg IV/IM.

  • The use of copious amounts of naloxone can precipitate opioid withdrawal.
  • Precipitated opioid withdrawal to an opioid-dependent person does not only cause patient distress and complicate care, but it can be life threatening.
  • Patients with precipitated opioid withdrawal (unlike regular opioid withdrawal) are at risk of seizures and arrhythmias.
  • The often referenced ‘standard dose’ and the dose usually given by EMS is 0.4 mg via the IV or IM route.
  • Although this ‘standard dose’ will reverse opioid-induced respiratory depressant effects in non-opioid-dependent patients, it can precipitate withdrawal in opioid-dependent persons.
  • Life-threatening complications like tonic-clonic seizure, and significant hypotension have occurred with IV/IM doses of 0.2 mg – 1.2 mg.[1, 2, 3]
  • Although severe life-threatening reactions after naloxone administration are relatively rare, it usually occurs when the ‘standard’ naloxone dose of 0.4mg IV/IM is given.

 Main Point:

Naloxone can be lifesaving. However, given the high prevalence of opioid addiction and the rare but potentially dangerous complication of precipitated opioid withdrawal, the use of initial small escalating doses of naloxone can avoid the development of precipitated opioid withdrawal. An appropriate strategy is to start with 0.04 mg and titrate up every 2-3 minutes as needed for ventilation to 0.5 mg, 2 mg, 5 mg, up to a maximum of 10-15 mg.[4, 5]



  1. Buajordet I., Næss A., Jacobsen D., Brørs O. Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg Med. 2004;11: 19–23.
  2. Osterwalder J. Naloxone – for intoxications with intravenous heroin and heroin mixtures – harmless of hazardous? A prospective clinical study. Clin Toxicol. 1996;34: 409–416.
  3. Yealy DM, Paris PM, Kaplan RM, Heller MB, Marini SE. The safety of prehospital naloxone administration by paramedics. Ann Emerg Med. 1990; 19(8): 902-5.
  4. Boyer EW: Management of opioid analgesic overdose. N Engl J Med. 2012; 367:146-155).
  5. Kim HK, Nelson LS. Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 mg): a Case Series. J Med Toxicol. 2016; 12(1):107-10.



Hydrofluoric Acid: The Burn that keeps on Burning

Authors: Brian Murray, DO (@bpatmurray, EM Senior Resident, SAUSHEC, USAF) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

screen-shot-2016-12-04-at-5-29-47-pmA 40-year-old man presented to the Emergency Department with the complaint of pain to his right hand. Three-hours prior he had been using rust remover to clean the air-conditioning unit in his house. Now the patient has exquisite pain to his distal thumb, index finger, and middle fingers.


Figure 1 A & B: Two images of the affected fingers showing A) the bluish hue of the blanched right index finger with incisions used to relieve the pressure of local infusion of 10% calcium gluconate into the tips of the fingers and B) the arterial catheter placed for arterial infusion of 10% calcium gluconate.


Hydrofluoric acid (HF) is one of the most dangerous corrosive inorganic acids due to its ability to destroy body tissue.1 It is well known for its ability to dissolve silica and glass and is used in numerous industrial processes (e.g. glass etching, brick cleaning, microchip etching, electroplating, and leather tanning) and even as an active ingredient in several household chemicals such as rust remover, aluminum brighteners, and heavy-duty cleaners.2 Industrial HF can be as concentrated as 100%, termed anhydrous, while the household variants are usually no more concentrated than 10-40% HF. However, due to the local, and potentially systemic effects of HF, even dilute HF has the potential to cause significant morbidity and mortality.3 From 2011 – 2014 the American Association of Poison Control Centers reported over 2000 HF exposures and 4 deaths.4,5,6,7 Deaths have been reported with exposures of 100% HF covering as little as 2.5% total body surface area.8 One of these deaths was due to the ingestion of 1 oz of dilute 1.92% HF which caused severe fluorosis, hypocalcemia, and ultimately death due to ventricular fibrillation.4


HF burns are more damaging and serious than other acidic burns because it causes tissue damage through two distinct mechanisms. The first, common to all acids, is by the rapid release of hydrogen ions and subsequent tissue dehydration and coagulation necrosis.9 HF is a weak acid with a pKa of 3.20. By comparison, the pKa of citric acid if 3.13 and the pKa of sulfuric acid is <-2 (considered a strong acid),10 and HF is approximately 1000 times less disassociated than equimolar strong acids such as hydrochloric acid.11 This acidic burn generated by free hydrogen ions is relatively insignificant compared to its second mechanism: the release of the highly reactive free fluoride ion, F, after the uncharged HF molecule penetrates deeply into the underlying tissue.9 The F causes liquefaction necrosis and creates strong bonds with calcium and magnesium forming the insoluble salts CaF2 and MgF2. Potassium ions are released from the peripheral nerve endings in response to Ca2+ depletion, which produces the severe pain classically associated with HF exposure.2

The severity of the burn is a product of the concentration, the surface area involved, and the time of exposure. Because HF is a weak acid, there may be a delay of up to several hours with dilute concentrations.9 Concentrations exceeding 50% almost always result in immediate pain due to the corrosive action of hydrogen ion disassociation.12 This delay can lead to deep penetration of HF before exposure is identified, increasing exposure time and tissue damage due to the F ion. This also allows for greater potential for systemic toxicity. Systemic symptoms occur from hypocalcemia and hypomagnesemia in response to systemic fluorosis after the absorption of a significant amount of HF. However, a significant amount is a relative term as massive exposure and death can result from as little as a 1% total body surface area from a >50% hydrofluoric acid solution, or exposure of >5% total body surface area of hydrofluoric acid of any concentration.13 When death does occur, it is typically due to dysrhythmia secondary to profound hypocalcemia and hypomagnesemia,14 as well as hyperkalemia caused by an efflux of potassium ions from cells due to hypocalcemia.15

Aside from dermal toxicity, patients can be poisoned though inhalation/pulmonary, ingestion/gastrointestinal, and ocular routes as well. Patients exposed to very low-concentration HF fumes may experience minor respiratory tract irritation,16 while inhalation of more concentrated fumes can lead to throat burning and shortness of breath leading to hypoxia and systemic hypocalcemia.17 Given the high propensity for evaporation, especially in concentrations greater than 60% which have boiling points around or below room temperature, inhalation injury should be assessed in all patients with cutaneous burns, especially those with exposures that involve the head and neck.18  Clothing soaked in HF can also produce deadly concentrations of inspired HF.19 Frequently, pulmonary exposures are also associated with ocular exposures, and as such patients should be evaluated for occult HF ocular injuries.11

Ingestion of any concentration of HF causes significant gastritis, and patients will promptly develop pain and vomiting. Systemic symptoms and death nearly always follow due to the high surface area involved, the extended time of contact, and the high degree of absorption, although actual absorption occurs rapidly along with the development of systemic symptoms and fatal dysrhythmias.2 Patients may present with altered mental status, airway compromise, and dysrhythmia.11 There is one case report of a person who ingested 8% HF, suffered multiple episodes of ventricular fibrillation, and was successfully resuscitated.20 This is the exception and not the norm, as ingestion of HF is almost universally fatal.2,11

Ocular exposures to HF typically cause more extensive damage to ocular tissue than other acids.21 HF, either by liquid splashes or exposure to HF gas, causes corneal and conjunctival epithelial denuding, leading to stromal corneal edema, conjunctival ischemia, sloughing, and chemosis. Fluoride ions penetrate deeply within the anterior chamber leading to corneal opacification and necrosis of the anterior chamber structure.2 Usually the effects are noted within one day, however case reports have noted situations where corneal damage was not apparent until 4-days post exposure.22 Long-term complications include corneal ulcers.11


All exposures should be discussed with a toxicologist.  Initial evaluation consists of a thorough history and physical, particularly to the chemical used (to help in identification of the HF concentration), the time of exposure, and the area of exposure.2 Laboratory evaluation of patients poisoned with HF consists of monitoring serum electrolytes, particularly ionized calcium, magnesium, and potassium.23 Additionally, as toxicity progresses, a venous blood gas may be useful, as metabolic acidosis may develop.  An ECG should be obtained and trended over time to assess for clinically significant hypocalcemia (prolonged QT interval) and hyperkalemia (peaked T-waves). Serum fluoride levels can be obtained, but will often lag behind clinically significant levels.11


The first treatment that should be performed, as with any chemical exposure, is removing soaked clothing and copious irrigation with water.1,9 This would ideally be performed immediately upon contact with HF, helping to reduce the risk of acidic burn and deeper penetration, but it will have some benefit even if performed later.

Cutaneous Exposures

There are three levels of treatment specific for HF burns. The first is to topically apply a 2.5% calcium gluconate slurry, which is made by mixing 3.5 gm of calcium gluconate in 5 oz of a water based lubricant such as Surgilube® or K-Y Jelly®. This treatment has excellent efficacy at preventing further tissue damage and decreasing pain, especially if used soon after the exposure. Putting a glove over the exposed hand when using the calcium slurry can help keep the gel in place and prevent loss of the calcium. It has limited ability to penetrate to deeper tissues and only helps to neutralize superficial HF.1,2,9

If topical calcium is not effective at treating the patient’s pain after 30 minutes and the area of tissue damage continues to increase, local infiltration with 5-10% calcium gluconate, not exceeding 0.5 ml per cm2 of affected body surface area, is used (the only currently available dosing recommendation in the literature).2,9,11,13 This method is more effective at treating deeper exposures. Calcium gluconate is used instead of calcium chloride, as calcium chloride is irritating and toxic to local tissue. If infiltration is going to be performed in the pads of the fingers, a prophylactic fasciotomy is recommended to prevent compartment syndrome from the injection of a large amount of fluid into a small compartment.1,2,9

If the pain is still not controlled, intra-arterial infusion of 10 ml of 10% calcium gluconate or calcium chloride (in 40-50 ml 5% dextrose) over 4 hours will allow large amounts of calcium to be delivered directly to the damaged tissue, and this infusion can be repeated until the patient is pain free.2,9,24

Systemic calcium and magnesium depletion should be treated by replacing the depleted electrolytes.9

Ocular Exposures

The most important step in the treatment of ocular HF exposure is early irrigation with 1L normal saline, lactated ringer solution, or sterile water. The use of 1% calcium gluconate eye drops is controversial, with some reports showing benefit.25,26,27,28,29  However, it can also be irritating to the eye and toxic to subconjunctiva, and sufficient evidence to support its recommended use over saline irrigation alone is lacking.2,11 Prompt ophthalmologic evaluation is essential after irrigation.

Ingestion Exposures

Ingestion of HF is almost universally fatal11 and are frequently associated with dermal exposure and inhalation exposures. If the ingestion occurred <2 hours prior to evaluation, it is recommended to pass a nasogastric tube for decontamination.13 The addition of 10% calcium gluconate to the lavage fluid may help neutralize the remaining fluoride ions that have not yet absorbed.13,30 Aggressive systemic therapy is indicated, and gastroenterology evaluation is necessary to address local tissue damage.11

Inhalation Exposures

The primary treatment for inhalation exposures is 4ml of nebulized 2.5-5% calcium gluconate.31,32 This is a benign therapy and is recommended to be given to all patients with symptomatic inhalational exposures.33 Attention should be paid to the patient’s airway and ability to maintain adequate oxygen saturation, as tracheobronchopulmonitis and local edema may impair both.34 Corticosteroids and antibiotics are not routinely recommended for all patients and should only be administered in coordination with a Medical Toxicologist.35 The systemic absorption of fluoride from inhalation exposures is extremely rapid and carries a high risk of systemic toxicity, even from relatively dilute concentrations.36

Case Outcome

The chemical was compound the patient was using was Condenser Coil Brightener and Cleaner (compound 90-920) that he had purchased online.  90-920 contains 10% HF solution, and therefore the patient did not begin to feel pain until 3 hours post exposure. Topical calcium and local infusion of calcium were not sufficient to control his pain and an intra-arterial catheter was placed and an infusion of 10% calcium gluconate was started. The patient was admitted to the burn ICU, where he eventually required excision of the tips of his fingers due to tissue necrosis. He otherwise experienced an uneventful recovery.


  • The F ion causes significant tissue damage and pain through formation of insoluble salts and calcium depletion.
  • Even small burns with concentrated HF can lead to significant systemic toxicity and death.
  • Electrolytes, VBG, and ECG are necessary in the evaluation.
  • The Toxicology service must be consulted.
  • Treatment with 2.5% topical calcium gluconate, 0.5 ml/cm2 of 10% calcium gluconate, and 10ml of 10% calcium gluconate or chloride in 40-50 ml 5% dextrose over 4 hours may be needed to neutralize the F


References/Further Reading

  1. Anderson WJ, Anderson JR. Hydrofluoric acid burns of the hand: mechanism of injury and treatment. The Journal of hand surgery. 1988;13(1):52–7.
  2. Kirkpatrick JJ, Enion DS, Burd DA. Hydrofluoric acid burns: a review. Burns. 1995 Nov;21(7):483–93.
  3. Department of Health and Human Services. NIOSH Skin Notation Profiles: Hydrofluoric Acid. CDC. 2011. Accessed online: https://www.cdc.gov/niosh/docs/2011-137/ on 18 Nov 2016
  4. Bronstein AC, Spyker DA, Cantilena LR Jr, Rumack BH, Dart RC. 2011 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 29th Annual Report. Clinical Toxicology. 2012 Dec 7;50(10):911–1164.
  5. Mowry JB, Spyker DA, Cantilena LR Jr, Bailey JE, Ford M. 2012 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 30th Annual Report. Clinical Toxicology. 2013 Dec 8;51(10):949–1229.
  6. Mowry JB, Spyker DA, Cantilena LR Jr, McMillan N, Ford M. 2013 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 31st Annual Report. Clinical Toxicology. 2014 Oct 6;52(10):1032–283.
  7. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015;53(10):962–1147.
  8. Tepperman PB. Fatality due to acute systemic fluoride poisoning following a hydrofluoric acid skin burn. J Occup Med. 1980;22:691-2.
  9. Bertolini JC. Hydrofluoric acid: a review of toxicity. J Emerg Med. 1992;10(2):163–8.
  10. “Appendix C: Dissociation Constants and pKa Values for Acids at 25°C”, appendix 3 from the book Principles of General Chemistry (v. 1.0) Accessed at: http://2012books.lardbucket.org/books/principles-of-general-chemistry-v1.0/s31-appendix-c-dissociation-consta.html on 10 November 2016
  11. Su M. Hydrofluoric Acid. In: Goldfrank’s Toxicologic Emergencies, 10e. 2016.
  12. Sheridan RL, Ryan CM, Quinby WC, Blair J, Tompkins RG, Burke JF. Emergency management of major hydrofluoric acid exposures. Burns. 1995 Feb;21(1):62–4.
  13. Hatzifotis M, Williams A, Muller M, Pegg S. Hydrofluoric acid burns. Burns. 2004 Mar;30(2):156–9.
  14. Yamaura K, Kao B, Iimori E, Urakami H, Takahashi S. Recurrent ventricular tachyarrhythmias associated with QT prolongation following hydrofluoric acid burns. Journal of Toxicology: Clinical Toxicology. 1997 Jan 1;35(3):311-3.
  15. Mclvor ME, Cummings CE, Mower MM, Wenk RE, Lustgarten JA, Baltazar RF, Salomon J. Sudden cardiac death from acute fluoride intoxication: the role of potassium. Annals of emergency medicine. 1987 Jul 31;16(7):777-81.
  16. Lee DC, Wiley JF II, Synder JW II. Treatment of inhalational exposure to hydrofluoric acid with nebulized calcium gluconate. J Occup Med. 1993;35:470.
  17. Wing JS, Brender JD, Sanderson LM et al. Acute health effects in a community after a release of hydrofluoric acid. Arch Environ Health. 1991;46:155–160.
  18. MacKinnon MA. Hydrofluoric acid burns. Dermatologic clinics. 1988 Jan;6(1):67-74.
  19. Mayer L, Guelich J. Hydrogen fluoride (HF) inhalation and burns. Archives of Environmental Health: An International Journal. 1963 Oct 1;7(4):445-7.
  20. Stremski ES, Grande GA, Ling LJ. Survival following hydrofluoric acid ingestion. Ann Emerg Med. 1992;21:1396–1399.
  21. McCulley JP, Whiting DW, Petitt MG, Lauber SE. Hydrofluoric acid burns of the eye. J Occup Med. 1983;25:447–450.
  22. Hatai JK, Weber JN, Doizaki K. Hydrofluoric acid burns of the eye: report of possible delayed toxicity. Journal of Toxicology: Cutaneous and Ocular Toxicology. 1986 Jan 1;5(3):179-84.
  23. Greco RJ, Hartford CE, Haith Jr LI, Patton ML. Hydrofluoric acid-induced hypocalcemia. Journal of Trauma and Acute Care Surgery. 1988 Nov 1;28(11):1593-6.
  24. Vance MV, Curry SC, Kunkel DB, Ryan PJ, Ruggeri SB. Digital hydrofluoric acid burns: treatment with intraarterial calcium infusion. YMEM. 1986 Aug;15(8):890–6.
  25. Bentur Y, Tannenbaum S, Yaffe Y, Halpert M. The role of calcium gluconate in the treatment of hydrofluoric acid eye burn. Ann Emerg Med. 1993;22:1488–1490.
  26. Dunser MW, Ohlbauer M, Rieder J et al. Critical care management of major hydrofluoric acid burns: a case report, review of the literature, and recommendations for therapy. Burns. 2004;30:391–398.
  27. Hatzifotis M, Williams A, Muller M, Pegg S. Hydrofluoric acid burns. Burns. 2004;30:156–159.
  28. Trevino MA, Herrmann GH, Sprout WL. Treatment of severe hydrofluoric acid exposures. Journal of Occupational and Environmental Medicine. 1983 Dec 1;25(12):861-3.
  29. Bentur Y, Tannenbaum S, Yaffe Y, Halpert M. The role of calcium gluconate in the treatment of hydrofluoric acid eye burn. Annals of emergency medicine. 1993 Sep 30;22(9):1488-90.
  30. Caravati EM. Acute hydrofluoric acid exposure. The American journal of emergency medicine. 1988 Mar 1;6(2):143-50.
  31. Kono K, Watanabe T, Dote T et al. Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure. Int Arch Occup Environ Health. 2000;73(suppl):S93–S97.
  32. Lee DC, Wiley JF II, Synder JW II. Treatment of inhalational exposure to hydrofluoric acid with nebulized calcium gluconate. J Occup Med. 1993;35:470.
  33. Dunser MW, Ohlbauer M, Rieder J et al. Critical care management of major hydrofluoric acid burns: a case report, review of the literature, and recommendations for therapy. Burns. 2004;30:391–398.
  34. Upfal M, Doyle C. Medical management of hydrofluoric acid exposure. Journal of Occupational and Environmental Medicine. 1990 Aug 1;32(8):726-31.
  35. Flood S. Hydrofluoric acid burns. American family physician. 1988;37(3):175-82.
  36. Watson AA, Oliver JS, Thorpe JW. Accidental death due to inhalation of hydrofluoric acid. Medicine, Science and the Law. 1973 Oct 1;13(4):277-9.

FOAMed Resource Series Part IV: Toxicology

Author: Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

Today we cover Part IV of the FOAMed series: Toxicology. Prior posts have evaluated ECG (http://www.emdocs.net/foamed-resource-series-part-ecg/), ultrasound (http://www.emdocs.net/foamed-resource-series-part-ii-ultrasound/), and pediatrics (http://www.emdocs.net/foamed-resource-series-part-iii-pediatrics/). Toxicology is an ever-expanding subject, as new substances with potential for abuse and overdose are consistently being discovered. EM providers not only need to understand classic toxicology such as salicylate and acetaminophen overdose, but also new agents such as the synthetic opioid U-47700. FOAMed provides a means to accomplish this.

The following list is comprised of blogs/podcasts with great education pearls, valid contact, and major impact on EM, with clear reference citation. This list is not all-encompassing, and if you have found other great resources, please mention them in the comments below!


  1. http://www.thepoisonreview.com


The Poison Review from Dr. Leon Gussow is a site that provides “critical update and evaluation of recent scientific literature, news stories, and cultural events related to the field of medical toxicology.” The site is updated almost weekly, and literature is graded based on “skulls.” This is a must-read resource for those interested in toxicology and if you want to stay updated with the most recent literature.

  1. http://lifeinthefastlane.com/tox-library/


The toxicology library at LIFTL is a great resource, especially while on shift. The website contains several great features. “Tox Tutes” are 10-30 minute podcasts covering toxicology basics and literature updates, “Basic Science” provides a framework for understanding of toxicology, Cases with “Tox Conundrums,” and finally “Toxicology Basics” provides the basics of management.  Several lists (antidotes, toxins, venoms, and more) are provided for quick reference. LIFTL again hits it out of the park with this resource.

  1. http://toxnow.org


ToxTalk is a podcast from Matt Zuckerman. The podcast provides entertaining education in the form of cases and literature updates of common ingestions facing EM providers. Unfortunately, show notes are not provided for the podcast, but we can’t help but love the content of the podcasts.

  1. http://www.ohsu.edu/emergency/education/podcast/


The Oregon Poison Center provides weekly conferences that are broadcast in podcast form, providing pearls on evaluation and management of a multitude of ingestions/overdoses. The goal audience includes medical students, nurses, residents, attendings, and fellows. Podcasts also cover literature updates, with article listings provided.

  1. http://www.acmt.net/ACMTPodcasts.html


This site from the American College of Medical Toxicology is extremely useful through the provision of guidelines, antidote card, and a podcast. The site contains several vital resources for EM providers everywhere, and the antidote card is particularly useful – http://www.acmt.net/_Library/Membership_Documents/ACMT_Antidote_Card_May_2015.pdf

  1. https://emin5.com/archives/


Yes, EMin5 from Dr. Anna Pickens makes our FOAMed list again. The succinct 5 minute videos on toxicology topics provide a foundation for learners of all stages. The site currently contains content on acetaminophen, salicylates, calcium channel blockers, cyanide, digoxin, laundry detergent pod, and tricyclic antidepressants.

  1. http://curriculum.toxicology.wikispaces.net


This is a great resource with a large number of different components. Separate pages cover core information on the toxicology history and examination, as well as complete information on separate toxins. Pages are broken into toxidromes, natural toxins, drug and alcohol issues, and chemicals. The quality of information is similar to an online encyclopedia right at your fingertips.

Thanks for reading! If you’ve found other resources, please let us know. Stay tuned for the next installment: critical care.

Drug Withdrawal: Pearls and Pitfalls

Authors: Drew A. Long, BS (@drewlong2232, Vanderbilt University School of Medicine, US Army) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Courtney Cassella, MD (@Corablacas, EM Resident Physician, Icahn SoM at Mount Sinai) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Case 1: A 45-year-old male presents to the ED with one day of myalgias, sweating, and anxiety. He is tachycardic and appears uncomfortable.  On examination, you notice lacrimation, excessive yawning, and a significant tremor.  He denies any illicit drug use, but he does have a history of chronic back pain for which he uses oxycodone. However, he ran out of oxycodone three days ago.

 Case 2: A 33-year-old female presents to the ED feeling depressed.  She has also been sleeping 16 hours per day and experiencing extreme hunger. She is trying to stop meth, for which her boyfriend was recently incarcerated.  Her examination and vital signs are normal, but she wants to know if she needs to be concerned about her symptoms, and more importantly, what she can do to feel better.


This is the second of a two-part series covering withdrawal states. Our first post evaluated the diagnosis and management of alcohol withdrawal. This second discussion will not be all encompassing, but it will cover the more commonly abused agents.



The incidence of opioid abuse has risen drastically in the United States.  Worldwide, between 26.4 million and 36 million people abuse opioids.1 In 2012, an estimated 2.1 million people in the United States had prescription opioid substance use disorders.2 The number of prescription opioids has escalated from an estimated 76 million people in 1991 to 207 million in 2013.3 Specifically, the number of heroin users has increased from 373,000 in 2007 to 681,000 in 2013.4 Along with this increase in opioid prescriptions and opioid abuse, the number of people dependent on opioids and number of opioid overdoses have also increased.

screen-shot-2016-09-10-at-12-11-58-amOpioids are most commonly used for pain management.  Opioids act on transmembrane neurotransmitter receptors (mu, kappa, delta) coupled to G proteins.  These receptors are located in both the central and peripheral nervous systems.  When these receptors are stimulated by opioids, the signal transduction pathway leads to the effects of analgesia in addition to triggering the reward center.5

Opioid withdrawal occurs when a person who is physiologically dependent on opioids either reduces or abruptly stops using opioids.  The diagnosis of opioid withdrawal is made by the history and physical exam.  The signs and symptoms of opioid withdrawal are often vague and nonspecific.  While opioid withdrawal may be uncomfortable, it is rarely life-threatening.  Broad categories of manifestations include gastrointestinal distress, flu-like symptoms, and sympathetic nervous system arousal, which are categorized in Table 1.6


Other common symptoms of opioid withdrawal include yawning, sneezing, dizziness, myalgias, arthralgias, and leg cramps.  While not always present, yawning and lacrimation are helpful due to high specificity for opioid withdrawal.7

The course of opioid withdrawal greatly depends upon which opioid the patient was using.  An opioid must be consumed daily for 3 weeks or more for the patient to become physiologically dependent.  The withdrawal period typically lasts two to three times the half-life of the opioid.6 Characteristics of commonly abused opioids are shown in Table 2. screen-shot-2016-09-10-at-12-15-48-am

A thorough history and physical is vital when assessing a patient suspected of undergoing opioid withdrawal.  Concomitant substance use disorders, mental disorders, and other disorders are common in patients with opioid use disorder.  Nicotine use has been associated with up to 85% of patients undergoing opioid withdrawal.  Mental disorders may be found in up to 70% of patients undergoing opioid withdrawal.  These include major depression, panic disorder, general anxiety disorder, and post traumatic stress disorder.9-11 A systemic review found a prevalence of co-occurring depressive disorders to be 27% and co-occurring anxiety disorders to be 29%.12 It is important to consider that opioid withdrawal may exacerbate co-occurring mental disorders.  Other disorders to consider include comorbid alcohol and benzodiazepine withdrawal, comorbid cocaine and methamphetamine withdrawal, or personality disorders.

Mimics of opioid withdrawal include other intoxication or withdrawal syndromes.  As opioid users usually have insight into their addiction, the history is often enough to establish a diagnosis.  Several other withdrawal syndromes, specifically ethanol and sedative-hypnotic withdrawal, may appear similar to opioid withdrawal.  However, these are much more likely to cause significant tachycardia and hypertension compared to opioid withdrawal.  Additionally, these syndromes may produce seizures and/or hyperthermia.  Another syndrome that may mimic opioid withdrawal is sympathomimetic intoxication.  However, similar to ethanol and sedative-hypnotic withdrawal, this syndrome produces much more severe findings (mydriasis, agitation, tachycardia, hypertension) than opioid withdrawal.7

Opioid withdrawal is not life-threatening, and the mainstay of treatment is management of symptoms.  Patients suffering from opioid withdrawal can undergo medically supervised opioid withdrawal (detoxification).  Symptoms from withdrawal can be managed with multiple agents, including opioids and non-opioids.  Popular agents utilized for managing opioids withdrawal include methadone and buprenorphine.  Methadone is a long-acting opioid, while buprenorphine is a partial opioid agonist.7  Methadone, which may be used in a psychiatric setting, is not an option for ED providers due to inability for patient follow up in the ED setting and risk of overdose.  Buprenorphine is a partial opioid receptor agonist with high affinity. These properties provide a lower risk of respiratory depression which, along with its long duration of action, make it an effective and safe therapy for opioid withdrawal. However, its use is also controversial. This medication is a synthetic agent with less abuse potential and dependence, acting as a partial agonist. If a patient is opioid dependent and given this medication, withdrawal will occur, as buprenorphine has higher receptor affinity and less activity than other opioids.  It is approved in the U.S. for outpatient treatment of opioid dependence, given once daily. Providers are required to have a special waiver from the DEA to prescribe this medication.



Benzodiazepines (BZDs) are sedative-hypnotic agents used for sedation and treatment of anxiety, seizures, withdrawal states, and insomnia.  BZDs act via modulation of the gamma-aminobutyric acid A (GABA-A) receptor, which is the main inhibitory neurotransmitter of the central nervous system.13


BZD withdrawal occurs when any chronic user abruptly decreases or ceases BZD consumption.  Rapid recognition and management of BZD withdrawal is vital as it can be life-threatening.  The signs and symptoms of BZD withdrawal are similar to those associated with withdrawal from other sedative-hypnotics (barbiturates, alcohol, etc.).  Milder symptoms of BZD withdrawal can include headache, nausea, vomiting, tremors, insomnia, agitation, and anxiety.  More severe symptoms may include hallucinations, psychotic behavior, altered mental status, and seizures.  Seizures, while uncommon, are a feared complication of benzodiazepine withdrawal.13,14

Like opioids, the timing of symptoms varies according to the half-life of the BZD involved.  Table 3 depicts the half-life of commonly abused BZDs.  In patients abusing BZDs with shorter half-lives (such as Xanax, Ativan, and Versed) withdrawal symptoms may occur in 1-2 days, while withdrawal symptoms from BZDs with longer half-lives may occur up to two weeks after cessation.15,16


Management of BZD withdrawal depends first on accurate diagnosis by history and characteristic signs and symptoms described above. After identifying withdrawal, treatment should be initiated with a BZD that has a prolonged clinical effect, such as diazepam.18-20 This BZD should be administered intravenously with a goal of eliminating symptoms of withdrawal without causing excessive sedation.  Patients undergoing withdrawal experiencing milder symptoms may be treated with a long-acting oral BZD.  While other agents have been used to treat BZD withdrawal (such as beta blockers, antipsychotics, SSRIs, and antihistamines), they have all been shown to be inferior with standard treatment.18,20 Valproic acid and carbamazepine have not shown any additional benefit and have not been extensively studied to be included in the standard management of BZD withdrawal.21,22

There are several scales for monitoring BZD withdrawal.  The Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) and Clinical Institute Withdrawal Assessment Scale-Benzodiazepines (CIWA-B) are two of the more commonly utilized scales.  The BWSQ is a 20-item self-report, validated questionnaire, while the CIWA-B uses 22-items to assess and monitor the severity of symptoms from withdrawal.  While these scales are helpful, they should not be solely relied upon to monitor complicated withdrawal.  Monitoring of withdrawal should always include careful observation and evaluation of the patient in addition to the Emergency Physician’s clinical judgment.23



Cocaine is a stimulant associated with many life-threatening complications, including seizure, stroke, and myocardial infarction.  Cocaine exerts its effect by enhancing monoamine neurotransmitters in the brain (dopamine, norepinephrine, and serotonin) via blockade of presynaptic reuptake of these neurotransmitters, both in the central and peripheral nervous systems.24


Withdrawal from cocaine, while uncomfortable, is not life-threatening.  The cocaine withdrawal syndrome is highlighted by prominent psychological features.  These include depression, anxiety, fatigue, difficulty concentrating, anhedonia, increased appetite, increased sleep, increased dreaming, and increased craving for cocaine.25,26  Intense symptoms at the beginning of the withdrawal period (the crash) may occur, which may include psychomotor retardation and severe depression with suicidal ideation.  Signs of cocaine withdrawal are typically minor and include musculoskeletal pain, tremors, chills, and involuntary motor movement.27Another potential complication of withdrawal includes myocardial ischemia, which is most commonly seen in the first week of withdrawal.28

Treatment for cocaine withdrawal is mainly supportive, including encouraging the patient to sleep and eat as necessary (especially if the patient is experiencing hypersomnia and increased appetite).29 No drugs have been shown to be beneficial in treating cocaine withdrawal.  For patients with severe agitation or insomnia, a short acting benzodiazepine may be helpful.  Patients with depression lasting several weeks or suicidal ideation may require admission to a psychiatric unit and treatment with antidepressants.29,30 As the relapse risk is high during the early withdrawal period, patients should be referred to an addiction treatment program for further support in abstaining from cocaine use.  Discharge from the ED is appropriate if the patient is stable with no other psychiatric concerns (severe depression, suicidal thoughts, etc.).



Similar to cocaine, methamphetamine is a stimulant that causes the release of monoamine neurotransmitters, while also blocking reuptake.  Amphetamine-type stimulants are the fastest rising drug of abuse worldwide and the second most widely used class of illicit drugs worldwide.31-33 Individuals with chronic amphetamine use have a high incidence of comorbid psychiatric disorders, including primary psychotic disorder, mood disorder, anxiety disorders, and ADHD.34 Depressive symptoms also commonly occur with methamphetamine use.35


Opposed to the euphoric effect of methamphetamine intoxication, withdrawal is marked by a dysphoric state, which is highlighted by depressive symptoms.  These include anhedonia, depression, anxiety, and social inhibition.26 Watson et al. reported that depression peaked at 2-3 days and persisted for 4 days following amphetamine cessation.36 Based on the initial dysphoric state, methamphetamine withdrawal can mimic major depressive disorder.  Other symptoms include irritability, poor concentration, hyperphagia, insomnia or hypersomnia, and psychomotor agitation or retardation.  These symptoms typically last 5 days to two weeks.37

Similar to the management of cocaine withdrawal, the mainstay of amphetamine withdrawal is supportive therapy.  No available treatment has shown to be effective in treatment of amphetamine withdrawal.  Similar to cocaine withdrawal, the patient must be evaluated for severity of depressive symptoms and suicidal ideation and receive in-patient psychiatric treatment if necessary.  If the patient is not actively suicidal nor is suffering from major depressive symptoms, they can be discharged home with warning to return if depressive symptoms worsen.  Importantly, they should be referred to an addiction support and treatment program to help in cessation of amphetamine abuse.38



Caffeinated beverages are the most consumed stimulants in the world.  About 90% of adults in the world consume caffeine on a daily basis.39 Consumption of up to 400 mg of caffeine on a daily basis is safe for most adults.40 Table 3 lists the caffeine content of various beverages.  The most common caffeinated beverages include coffee, tea, and soft drinks.  Caffeine is an antagonist of central and peripheral nervous system adenosine receptors, stimulating the release of excitatory neurotransmitters.41


Caffeine withdrawal, while uncomfortable, is not associated with any adverse medical consequences.  Withdrawal symptoms include headache, fatigue, decreased energy, decreased attentiveness, sleepiness, decreased sense of wellbeing, depressed mood, difficulty concentrating, and irritability.  Of these, headache is the most common symptom experienced.  It is estimated that only about 50 percent of chronic caffeine users experience withdrawal symptoms.  Symptoms typically begin to occur 12-24 hours after ceasing caffeine intake, peak at one to two days, and resolve within one week.43

Management of caffeine withdrawal is supportive.  Patients should be reassured that caffeine withdrawal is not associated with any adverse events or complications.  If the patient’s headache is severe, an anti-inflammatory agent such as ibuprofen can be utilized.  The patient can also be offered caffeine (any caffeinated beverage or soft drink), as re-administration of caffeine reverses the withdrawal symptoms.

Case Resolution

Case 1:  This 45-year-old male was diagnosed with opioid withdrawal from the history and physical.  On further evaluation, he denied any other substance abuse and had no psychiatric history or comorbidities.  As the patient requested detoxification, he was provided information for detoxification centers.

Case 2:  This 33-year-old female was concerned about cessation of methamphetamine.  On further evaluation, she stated she had been feeling down lately but denied any anhedonia or suicidal ideation.  On further evaluation, she admitted to intermittent alcohol use but denied any other substance abuse.  You reassure her that though these symptoms may last for up to two weeks, they are not life-threatening and will improve.  She expresses interest in cessation of methamphetamine abuse, and you refer her to an amphetamine addiction support group and counseling center.


  • The signs and symptoms of opioid withdrawal are often vague and nonspecific, and include gastrointestinal distress, flu-like symptoms, and sympathetic nervous system arousal. Yawning and lacrimation are specific for opioid withdrawal.
  • Alcohol withdrawal and stimulant intoxication can mimic opioid withdrawal. However, these are much more likely to cause significant tachycardia and hypertension compared to opioid withdrawal.
  • Quick recognition of benzodiazepine withdrawal is essential, as this syndrome can be life-threatening.
  • The onset and duration of symptoms of BZD withdrawal depends on the half-life of the BZD.
  • The mainstay of therapy for BZD withdrawal is a BZD with a prolonged clinical effect, with the goal of alleviating symptoms.
  • Both cocaine and amphetamine withdrawal can manifest with depressive symptoms. Patients should be evaluated for suicidal ideation and hospitalized if necessary.
  • Treatment for both cocaine and amphetamine withdrawal is supportive, in addition to consideration and care for any psychological symptoms.
  • Caffeine withdrawal is not associated with any adverse complications. If patients are requesting treatment for withdrawal symptoms, ibuprofen or a caffeinated beverage can provide timely relief.


References/Further Readin

  1. “World Drug Report 2012.”   United Nations Office on Drugs and Crime. http://www.unodc.org/unodc/en/data-and-analysis/WDR-2012.html
  2. “Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings.” NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.
  3. “America’s Addiction to Opioids: Heroin and Prescription Drug Abuse.” National Institute on Drug Abuse. https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/americas-addiction-to-opioids-heroin-prescription-drug-abuse#_ftn5
  4. Jones CM, Logan J, Gladden RM, Bohm MK. Vital Signs: Demographic and Substance Use Trends Among Heroin Users-United States, 2002-2013. MMWR Morb Mortal Wkly Rep. 2015 Jul;64(26):719-25.
  5. Strain E. Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis. UpToDate. May 2016.
  6. Sevarino K. Opioid withdrawal: Clinical manifestations, course, assessment, and diagnosis. UpToDate. May 2016.
  7. Stolbach A, Hoffman RS. Opioid withdrawal in the emergency setting. UpToDate. May 2016.
  8. Choo C. Medications Used in Opioid Maintenance Treatment. US Pharm. 2009;34(11):40-53.
  9. Teoh BGJ, Yee A, Habil MH. Psychiatric comorbidity among patients on methadone maintenance therapy and its influence on quality of life. Am J Addict. 2016 Jan;25(1): 49-55. Epub 2015 Dec 21.
  10. Fareed A, Eilender P, Haber M, Bremner J, Whitfield N, Drexler K. Comorbid posttraumatic stress disorder and opiate addiction: a literature review. J Addict Dis. 2013;32(2):168-79.
  11. Rosen D, Smith ML, Reynolds CF. The prevalence of mental and physical health disorders among older methadone patients. Am J Geriatr Psychiatry. 2008 Jun;16(6):488-97.
  12. Goldner EM, Lusted A, Roerecke M, Rehm J, Fischer B. Prevalence of Axis-1 psychiatric (with focus on depression and anxiety) disorder and symptomatology among non-medical prescription opioid users in substance use treatment: systematic review and meta-analysis. Addict Behav. 2014 Mar;39(3):520-31. Epub 2013 Dec 2.
  13. Greller H, Gupta A. Benzodiazepine poisoning and withdrawal. UpToDate. May 2016.
  14. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004;176(1):1.
  15. Hood HM, Metten P, Crabbe JC, Buck KJ. Fine mapping of a sedative-hypnotic drug withdrawal locus on mouse chromosome 11. Genes Brain Behav. 2006;5(1):1.
  16. Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, et al. Benzodiazepine dependence: focus on withdrawal syndrome. Ann Pharm Fr. 2009 Nov;67(6):408-13. Epub 2009 Sep 18.
  17. Gussow L, Carlson A. Rosen’s Emergency Medicine, 8th Ed., Chapter 165, 2076-2083.e1. Philadelphia PA: Saunders, 2014.
  18. Lader M, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. CNS Drugs. 2009;23(1):19.
  19. Voshaar RC, Couvee JE, van Balkom AJ, Mulder PG, Zitman FG. Strategies for discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry. 2006 Sep;189:213-20.
  20. Parr JM, Kavanagh DJ, Cahill L, Mitchell G, McD Young R. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction. 2009 Jan;104(1):13-24. Epub 2008 Oct 31.
  21. Lum E, Gorman SK, Slavik RS. Valproic acid management of acute alcohol withdrawal. Ann Pharmacother. 2006;40(3):441.
  22. Schweizer E, Rickels K, Case WG, Greenblatt DJ. Carbamazepine treatment in patients discontinuing long-term benzodiazepine therapy. Effects on withdrawal severity and outcome. Arch Gen Psychiatry. 1991;48(5):448.
  23. Alvanzo A. Management of Substance Withdrawal in Acutely Ill Medical Patients: Opioids, Alcohol, and Benzodiazepines. Society of General Internal Medicine 36th Annual Meeting. 27 April 2013.
  24. Gorelick DA. Cocaine use disorder in adults: Epidemiology, pharmacology, clinical manifestations, medical consequences, and diagnosis. UpToDate. May 2016.
  25. Coffey SF, Dansky BS, Carrigan MH, Brady KT. Acute and protracted cocaine abstinence in an outpatient population: a prospective study of mood, sleep and withdrawal symptoms. Drug Alcohol Depend. 2000;59(3):277.
  26. Lago JA, Kosten TR. Stimulant withdrawal. Addiction. 1994;89(11):1477.
  27. Khantzian EJ, McKenna GJ. Acute toxic and withdrawal reactions associated with drug use and abuse. Ann Intern Med. 1979;90(3):361.
  28. Nademanee K, Gorelick DA, Josephson MA, Ryan MA, Wilkins JN, Robertson HA, et al. Myocardial ischemia during cocaine withdrawal. Ann Intern Med. 1989;111(11):876.
  29. Schuckit MA. Drug and Alcohol Abuse. A Clinical Guide to Diagnosis and Treatment, 6th ed, Springer, New York 2007.
  30. Weiss RD, Greenfield SF, Mirin SM. Intoxication and withdrawal syndromes. In: Manual of Psychiatric Emergencies, Hyman, SE, (Ed), Little, Brown & Co, Boston, MA 1994. p. 279-93.
  31. Degenhardt L, Mathers B, Guarinieri M, Panda S, Phillips B, Strathdee SA, et al. Meth/amphetamine use and associated HIV: Implications for global policy and public health. Int J Drug Policy. 2010 Sep;21(5):347-58. Epub 2010 Feb 1.
  32. World Drug Report 2010, United Nations Publication, Vienna 2010.
  33. UNODC. World Drug Report 2012, Contract No: E.12.XI.1, United Nations Publication, New York 2012.
  34. Salo R, Flower K, Kielstein A, Leamon MH, Nordahl TE, Galloway GP. Psychiatric comorbidity in methamphetamine dependence. Psychiatry Res. 2011 Apr;186(2-3):356-61. Epub 2010 Nov 4.
  35. Zorick T, Sugar CA, Hellemann G, Shoptaw S, London ED. Poor response to sertraline in methamphetamine dependence is associated with sustained craving for methamphetamine. Drug Alcohol Depend. 2011 Nov;118(2-3):500-3. Epub 2011 May 17.
  36. Watson R, Hartmann E, Schildkraut JJ. Amphetamine withdrawal: affective state, sleep patterns, and MHPG excretion. Am J Psychiatry. 1972 Sep;129(3):263-9.
  37. McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM. The nature, time course and severity of methamphetamine withdrawal. Addiction. 2005 Sep;100(9):1320-9.
  38. Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P. Treatment for amphetamine withdrawal. Cochrane Library. 23 October 2001.
  39. Medicines in my Home: Caffeine and Your Body. Food and Drug Administration. http://www.fda.gov/downloads/UCM200805.pdf
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