Tag Archives: #FOAMtox

TOXCARD: TOXIC ALCOHOL POISONING

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)

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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.

Question:

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

Pearl:

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.

 

References:
  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.

EKG TCA PED

Question

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

Pearl

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.

References
  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)
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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.
Question:
What are the most common signs/symptoms of carbon monoxide (CO) poisoning, and what are the general management plans?
Pearl:

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.
References:
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)

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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.

Question:

What treatments should a salicylate poisoned patient receive?

Pearl/Pitfall: 

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.

 

References:

  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

Limitations of CIWA score

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)

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Case Presentation:

You are working a busy ED shift and are also managing a handful of boarded patients admitted to your ICU. Nursing resources are especially strained today. One of your intubated patients that you admitted for alcohol withdrawal starts having a seizure. His vitals are T 101F, HR 135, BP 175/100, RR 16, O2 sat 89% on 40% O2.

Question:

What are some of the limitations of using the CIWA score?

Pearl:

Although the CIWA score is a widely cited example of symptom-triggered therapy it has several important limitations and can be difficult to properly execute in the emergency department setting.

  • Symptom-triggered treatment for alcohol withdrawal using the CIWA score has many benefits including reduced progression to mechanical ventilation requirement, 4-fold decrease in benzodiazepine requirements, shorter duration of treatment, and shorter hospitalization stays by 2 days when compared to fixed-dosing scheduling.(1)
  • However, an important clinical limitation of CIWA as a tool to assess alcohol withdrawal is that it does not incorporate vital sign assessment, which can be an important and sometimes the only clue available in recognizing inappropriately treated DT patients.(2)
  • The CIWA score also does not address choice of benzodiazepines, frequency of administration, use of adjuvant medications and underlying medical conditions (renal failure, liver failure, respiratory failure, cardiac disease, age, etc.) in treating withdrawal.(2)
  • The CIWA score requires patients to be able to respond to questions and follow commands. This can be difficult in patients with language barriers, altered mental status or who are intubated.(2)
    • For example “Do you feel sick to your stomach, have you vomited?”; “Do you have any itching, pins-and-needles sensations, burnings, or numbness…?” and “Are you seeing anything that is disturbing you?” are some questions asked.
  • Many of the studies that have evaluated CIWA have excluded patients with seizures, which is an important sign of severe withdrawal and should be taken into consideration.(3)
  • Moreover, the CIWA score can be especially difficult to execute properly without adequate nursing staff. Many busy EDs are often understaffed and have limited nursing resources. Thorough staff training is required to appropriate use CIWA.(2) Studies have shown that the CIWA score tends to be administered irregularly by nursing staff, often used for patients who are not appropriate for symptom-guided treatment and can have a higher proportion of protocol errors.(4)
  • Scoring systems are important for symptom-triggered therapy and provide the ability for comparison analysis in clinical trials. However, many other scoring systems exist. An example is the Richmond Agitation Sedation Scale (RASS), which is observer based.(5) Many hospitals have their own scoring systems as well.
Main point:

Symptom triggered therapy has been shown to have better outcomes than fixed benzodiazepine scheduling in managing alcohol withdrawal. The CIWA score is a widely cited method of using symptom triggered therapy. However, physicians should not rely on just the CIWA score and other hospital and research protocols exist. The CIWA score has several important limitations including the exclusion of vital signs as an assessment, reliance of the patient’s ability to answer questions and follow commands, and can be time consuming in a busy ED environment.

References:
  1. Daeppen J, Gache P, Landry U, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepines for alcohol withdrawal. JAMA. 2002;162(10):1117-1121.
  2. Sankoff J, Taub J, Mintzer D. American College of Medical Quality: Accomplishing much in a short time: use of a rapid improvement event to redesign the assessment and treatment of patients with alcohol withdrawal. Am J Med Qual. 2013; 28(2):95-102.
  3. Saitz R, Mayo-Smith MF, Roberts MS, Redmond HA, Bernard DR, Calkins DR. Individualized treatment for alcohol withdrawal: a randomized double-blind controlled trial. JAMA. 1994;272:519-523.
  4. Hecksel KA, Bostwick JM, Jaeger TM, Cha SS. Inappropriate use of symptom-triggered therapy for alcohol withdrawal in the general hospital. Mayo Clin Proc. 2008;83:274-279. 10.
  5. Sessler CN. The Richmond Agitation-Sedation Scale” validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002; 166:1338-1344.

TOX CARDS: CIWA-AR

Author: Brian P. Murray, DO (@bpatmurray Senior EM Resident Physician, Resident Brooke Army 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)
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Case Presentation:

A 53-year-old man presents to the Emergency Department with a history of 12 alcoholics drinks daily. His last drink was 24 hours ago, and he is feeling anxious and jittery. Vital signs: HR 90, BP 135/90, RR 18, T 98.9oF, SpO2 97% room air.  

Question:

How can you determine the severity of withdrawal and the need for inpatient versus outpatient management?

Pearl:

The use of the 10 item CIWA-AR score is a rapid and effective tool that can help objectively rate the level of alcohol withdrawal. [1]

  • Alcohol withdrawal syndrome is a spectrum of disorders ranging from mild symptoms to life threatening seizures and delirium tremens. [2]
  • The CIWA-AR score cannot differentiate the different types of alcohol withdrawal syndromes nor between delirium tremens and medical causes of delirium. [3]
  • The score ranges from 0 (no withdrawal) to 67 (severe withdrawal) and can be easily repeated for evaluation of worsening or improving withdrawal.
  • The score incorporates the scores from the categories “Nausea and Vomiting” (0-7), “Tremors” (0-7), “Paroxysmal Sweats” (0-7), “Anxiety” (0-7), “Agitation” (0-7), “Tactile Disturbance” (0-7), “Auditory Disturbance” (0-7), “Visual Disturbance” (0-7), “Headache of Fullness” (0-7), and “Clouding of Sensorium” (0-4).
  • A score of 0-9 is considered mild withdrawal and can be managed as an outpatient with supportive can with or without medical management, at the discretion of the physician.
  • A score of 10-19 is considered moderate withdrawal and should be considered for admission for acute medical detoxification.
  • A score of >20 is considered severe withdrawal and the patient should be admitted to a high acuity unit, such as an ICU, for close monitoring and medical detoxification.
  • If the CIWA-AR score remains high even after adequate medical management, the patient likely has a comorbid medical delirium. [4]
  • A similar 20 item CIWA-B score is also available for use with acute benzodiazepine withdrawal. [5]
Main Point:

The CIWA-AR score is an effective tool that can be employed in less than 5 minutes to objectively score the level of withdrawal. It can also be repeated to assess efficacy of treatment of progression of withdrawal. The tool can be useful in determining the ultimate disposition of the patient; whether they can be discharged to outpatient care (score 0-9), require floor admission (10-19), or ICU admission (score >20).

 
References:

1.      Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA‐Ar). British journal of addiction. 1989 Nov 1;84(11):1353-7.

2.      Kattimani S, Bharadwaj B. Clinical management of alcohol withdrawal: A systematic review. Industrial psychiatry journal. 2013 Jul;22(2):100.

3.      Chabria SB. Inpatient management of alcohol withdrawal: A practical approach. Signa Vitae. 2008;3:24–9.

4.      Bharadwaj B, Bernard M, Kattimani S, Rajkumar RP. Determinants of success of loading dose diazepam for alcohol withdrawal: A chart review. Journal of Pharmacology and Pharmacotherapeutics. 2012 Jul 1;3(3):270.

5.      Busto UE, Sykora K, Sellers EM. A clinical scale to assess benzodiazepine withdrawal. Journal of clinical psychopharmacology. 1989 Dec 1;9(6):412-6.

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)

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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).

Question:

What dose Narcan should you give?

Pearl:

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]

 

References

  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.

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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.

Introduction

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

Pathophysiology/Toxicity

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

Evaluation

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

Treatment

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.

Pearls

  • 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.