Category: Toxicology
Keywords: acetaminophen, Rumack-Matthew nomogram (PubMed Search)
Posted: 12/7/2013 by Bryan Hayes, PharmD
(Emailed: 12/12/2013)
(Updated: 12/12/2013)
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Can acetaminophen concentrations < 100 mcg/mL obtained between 1-4 hours after acute ingestion accurately predict a nontoxic 4-hour concentration? NO!
Despite a high negative predictive value, a new study found there are still cases with toxic concentrations after 4 hours despite earlier levels < 100 mcg/mL.
The Rumack-Matthew nomogram is to be utilized starting at 4 hours after an acute acetaminophen ingestion. Unless the concentration is zero, a second level must be drawn at 4 hours if an earlier one is positive.
Froberg BA, et al. Negative predictive value of Acetaminophen concentrations within four hours of ingestion. Acad Emerg Med 2013;20(10):1072-5. [PMID 24127715]
Rhyee SH. Early serum acetaminophen levels: how soon is too soon? Acad Emerg Med 2013;20(10):1070-1. [PMID 24127714]
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Category: Pharmacology & Therapeutics
Keywords: healthcare-associated pneumonia, HCAP, atypical, macrolide, fluoroquinolone (PubMed Search)
Posted: 12/2/2013 by Bryan Hayes, PharmD
(Emailed: 12/7/2013)
(Updated: 12/7/2013)
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In a potentially ground breaking study of healthcare-associated pneumonia (HCAP) patients, atypical pathogens were identified in 10% of cases!
Application to clinical practice: Add atypical coverage with a macrolide or respiratory fluoroquinolone for HCAP patients who have been in the community for any length of time.
The study also identified HCAP patients who may not require 3 'big gun' broad-spectrum antibiotics. This is a practice changing article for ED providers. For more analysis of the study, please note the bonus reading links below.
Bonus reading:
Dr. Emily Heil (@emilylheil) analyzes the full study in more depth at Academic Life in Emergency Medicine: http://academiclifeinem.com/new-treatment-strategy-not-so-sick-health-care-associated-pneumonia/
Dr. Ryan Radecki (@emlitofnote) critiques the study at Emergency Medicine Literature of Note: http://www.emlitofnote.com/2013/10/down-titrating-antibiotics-for-hcap.html
Maruyama T, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective mulitcenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis 2013;57(10):1373-83. [PMID 23999080]
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Category: Toxicology
Keywords: benzodiazepine, lorazepam, liver (PubMed Search)
Posted: 11/11/2013 by Bryan Hayes, PharmD
(Emailed: 11/14/2013)
(Updated: 11/14/2013)
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All benzodiazepines are metabolized by the liver. Some are just metabolized by pathways that are less dependent on global liver function.
The ‘LOT’ drugs are metabolized by conjugation, have no active metabolites, and have minimially affected half-lives even in the setting of liver disease.
L – Lorazepam
O – Oxazepam
T – Temazepam
The rest of the benzodiazepines are primarily metabolized via hepatic CYP-mediated oxidation and may have prolonged duration of effect in patients with marked liver impairment.
For a bit more detail and commentary by Dr. David Juurlink, please read my recent post on the Academic Life in Emergency Medicine blog: http://academiclifeinem.com/all-benzodiazepines-are-metabolized-by-the-liver/
Mihic SJ, Harris RA. Chapter 17. Hypnotics and Sedatives. In: Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=16663643. Accessed November 7, 2013.
Lee DC, Ferguson KL. Chapter 74. Sedative-Hypnotics. In: Lee DC, Ferguson KL, eds.Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6520459. Accessed November 7, 2013.
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Category: Pharmacology & Therapeutics
Keywords: contrast-induced nephropathy, n-acetylcysteine, NAC (PubMed Search)
Posted: 10/31/2013 by Bryan Hayes, PharmD
(Emailed: 11/2/2013)
(Updated: 11/2/2013)
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A recent meta-analysis has called into question whether contrast-induced AKI even occurs after an IV dye load for radiologic imaging. [1] This conclusion is most certainly up for debate.
Irrespective of that conclusion, prevention of contrast-induced nephropathy is still important. Is there any benefit to using N-acetylcysteine over normal saline in the ED? Probably not according to a new study. [2]
Conclusions
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Category: Toxicology
Keywords: nms, neuroleptic malignant syndrome, anti-NMDAR encephalitis (PubMed Search)
Posted: 10/4/2013 by Bryan Hayes, PharmD
(Emailed: 10/10/2013)
(Updated: 10/10/2013)
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Toxicologists should be aware of non-toxicological mimics of delirium, including anti-NMDA receptor encephalitis. It is an under-recognized progressive neurological disorder caused by antibodies against NMDA receptors.
Cases often present with altered mental status, autonomic instability, increased muscle tone, and movement disorders. It can easily be mistaken for neuroleptic malignant syndrome (NMS). A new case series describes two such patients for which toxicologists were consulted.
Must read links:
Dr. Leon Gussow provides a great review of the case series on his Poison Review blog.
Dr. Chris Nickson reviews the basics of the disease on the Life in the Fast Lane blog.
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth considering in the differential diagnosis of delirium. Clin Toxicol 2013;51(8):794-7. [PMID 23962100]
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Category: Pharmacology & Therapeutics
Keywords: cryptococcal, meningitis, amphotericin, flucytosine (PubMed Search)
Posted: 9/25/2013 by Bryan Hayes, PharmD
(Emailed: 10/5/2013)
(Updated: 10/5/2013)
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Treatment of patients with HIV/AIDS can frequently mean consideration for, and need to treat cryptoccocal meningitis.
Since 1997, studies have demonstrated that high-dose Amphotericin B combined with flucytosine has improved outcomes compared to low dose treatment or monotherapy.
A recent 2013 study reiterated this approach, showing significant decrease in deaths at 70 days post-treatment and increased rates of yeast clearance with combination therapy of Amphotericin B plus flucytosine.
Recommendation:
Antifungal treatment of cryptococcal meningitis should start with Amphotericin B at 0.7-1 mg/kg IV daily plus concurrent flucytosine 25 mg/kg orally q6 hours. Fluconazole can be substituted in place of flucytosine if it is not available or not tolerated.
Category: Toxicology
Keywords: hypoglycemia, overdose, diabetes, antidiabetic (PubMed Search)
Posted: 9/10/2013 by Bryan Hayes, PharmD
(Emailed: 9/12/2013)
(Updated: 9/12/2013)
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With several new diabetes medications available, it is important to know which ones are likely to cause hypoglycemia after overdose. Based on mechanism of action and reported cases, the likelihood of hypoglycemia after overdose is listed below by drug class.
Keep in mind that other drugs can interact with antidiabetics resulting in hypoglycemia. This table applies only to single agent ingestion/administration.
Drug Class | Examples | Hypoglycemic Potential |
---|---|---|
Insulins | Glargine, Aspart, Detemir | High |
Sulfonylureas | Glyburide, Glipizide | High |
Meglitinides | Nateglinide, Repaglinide | High |
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists | Exenatide | Low-Moderate |
Alpha-glucosidase inhibitors | Acarbose, Miglitol | Low |
Thiazolidinediones | Rosiglitazone, Piaglitazone | Low |
Biguanides | Metformin | Low |
Dipeptidyl Peptidase 4 (DPP-4) Inhibitors | Sitagliptin, Saxagliptin | Low |
Bosse GM. Chapter 48. Antidiabetics and Hypoglycemics. In: Bosse GM, ed. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6514172. Accessed September 10, 2013.
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Category: Pharmacology & Therapeutics
Keywords: antibiotic, obese, obesity, critically ill, antimicrobial (PubMed Search)
Posted: 8/31/2013 by Bryan Hayes, PharmD
(Emailed: 9/7/2013)
(Updated: 9/7/2013)
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Although there is a paucity of data to guide dosing of antimicrobials in the critically ill obese patient, we can draw some conclusions from existing kinetic studies. Assuming normal renal and hepatic function, here's what to do:
Penicillins: Use the high end of dosing range. For example, if the plan is to use piperacillin/tazobactam 3.375 gm IV every 6 hours for a complicated intra-abdominal infection, use 4.5 gm instead.
Cephalosporins: Use the high end of the dosing range.
Carbapenems: Use the high end of the dosing range.
Quinolones: Use the high end of the dosing range.
Aminoglycosides: Dose using adjusted body weight. ABW (kg) = IBW + 0.4 X (actual body weight - IBW)
Vancomycin: 15-20 mg/kg actual body weight every 8 to 12 hours. Adjust based on trough level.
When dosing most antibiotics in critically ill obese patients, use the high end of the dosing range (if not more).
Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med 2004;30(1):18-32. [PMID 14625670]
Medico CJ, Walsh P. Pharmacotherapy in the critical ill obese patient. Crit Care Clin 2010;26(4):679-88. [PMID 20970057]
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Category: Toxicology
Keywords: sulfonamide, antibiotic, cross-reactivity (PubMed Search)
Posted: 8/15/2013 by Bryan Hayes, PharmD
(Updated: 1/29/2014)
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There is minimal evidence of cross-reactivity between sulfonamide antibiotics and non-antibiotics [1-4]. Despite this, the U.S. FDA-approved product information for many non-antibiotic sulfonamide drugs contains warnings concerning possible cross-reactions.
Key Findings from a New Review Article [5]:
Bottom line: You can feel safe prescribing furosemide, glyburide, and hydrochlorothiazide to your patient with an allergy to sulfamethoxazole/trimethoprim.
Other blog reference on this topic: http://lifeinthefastlane.com/2011/04/sulfa-drug-discombobulation/
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Category: Toxicology
Keywords: naloxone, nebulized, opioid (PubMed Search)
Posted: 7/30/2013 by Bryan Hayes, PharmD
(Emailed: 8/8/2013)
(Updated: 8/8/2013)
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Naloxone can be administered via pretty much any route. One that has gained popularity in the past several years is nebulized naloxone. Although anecdotal reports tout the benefits of nebulized naloxone, what does the literature say?
Bottom Line: Many of the studied patients may not have needed naloxone in the first place (initial respiratory rate 13-14), with a few developing withdrawal symptoms. Nebulized naloxone may have a role in the not-too-sick opioid overdose in whom you want to prove your diagnosis and wake the patient up enough to obtain a history. It is not a therapy for the apneic opioid overdose.
1. Mycyk MB, et al. Nebulized naloxone gently and effectively reverses methadone intoxication. J Emerg Med 2003;24(2):185-7. [PMID 12609650]
2. Weber JM, et al. Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose? Prehosp Emerg Care 2013;16(2):289-92. [PMID 22191727]
3. Baumann BM, et al. Use and efficacy of nebulized naloxone in patients with suspectd opioid intoxication. Am J Emerg Med 2013;31(3):585-8. [PMID 23347721]
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Category: Pharmacology & Therapeutics
Keywords: fluid, saline, chloride (PubMed Search)
Posted: 7/22/2013 by Bryan Hayes, PharmD
(Emailed: 8/3/2013)
(Updated: 8/2/2013)
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A recent review identified 5 key points to consider when prescribing fluids.
Raghunathan K, et al. Fluids are drugs: type, dose and toxicity. Curr Opin Crit Care 2013;19(4):290-8. [PMID 23817025]
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Category: Toxicology
Keywords: salicylate, aspirin, toxicity, sodium bicarbonate (PubMed Search)
Posted: 7/10/2013 by Bryan Hayes, PharmD
(Emailed: 7/11/2013)
(Updated: 7/11/2013)
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In June 2013 the American College of Medical Toxicology (ACMT) released a Guidance Document on the Management Priorities in Salicylate Toxicity. Here are some key highlights:
The full document can be accessed here.
The Poison Review blog by Dr. Leon Gussow discusses the guidance document here.
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Category: Pharmacology & Therapeutics
Keywords: pain, hydromorphone (PubMed Search)
Posted: 7/3/2013 by Bryan Hayes, PharmD
(Emailed: 7/6/2013)
(Updated: 7/6/2013)
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A recent, randomized study evaluated two approaches for treating acute pain in an inner-city ED.
Application to clinical practice: For most patients with acute, severe pain in the ED, start with hydromorphone 1 mg. It may be all the patient needs and can potentially avoid giving them extra opioid they don't need.
Chang AK, et al. Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the "1 + 1" hydromorphone titration protocol in treatment of acute, severe pain in the first hour of emergency department presentation. Ann Emerg Med. 2013 May 16. [Epub ahead of print]. PMID 23694801
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Category: Toxicology
Keywords: acetylcysteine, NAC, INR, PT, prothrombin time (PubMed Search)
Posted: 6/12/2013 by Bryan Hayes, PharmD
(Emailed: 6/13/2013)
(Updated: 6/13/2013)
Click here to contact Bryan Hayes, PharmD
In the treatment of acetaminophen poisoning with N-acetylcysteine (NAC), the PT/INR can be slightly elevated even in the absence of hepatotoxicity. Considering Prothombin Time (PT) is one of the criteria used to assess severity of liver damage in this setting, it is important to know how much the PT/INR can be affected by NAC and if it has an actual effect on coagulation factor levels.
Clinical Practice Pearls
1. Pizon AF, et al. The in vitro effect of n-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med 2011;18:351-4. [PMID 21496136]
2. Jang DH, et al. In vitro study of n-acetylcysteine on coagulation factors in plasma samples from healthy subjects. J Med Tox 2013;9:49-53. [PMID 22733602]
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Category: Pharmacology & Therapeutics
Keywords: cellulitis, cephalexin, sulfamethoxazole/trimethoprim, Bactrim, streptococcus (PubMed Search)
Posted: 5/20/2013 by Bryan Hayes, PharmD
(Emailed: 6/1/2013)
(Updated: 5/31/2013)
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Background
In the current era of community-acquired MRSA (CA-MRSA), most of our outpatient treatment options for cellulitis aim to cover MRSA. Choices include sulfamethoxazole/trimethoprim (SMZ-TMP), doxycycline, linezolid, and clindamycin (depending on local susceptibility patterns).
A New Study
Take Home Clinical Points
Pallin DJ, et al. Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial. Clinical Infectious Diseases 2013;56(12):1754-62. [PMID 23457080]
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Category: Toxicology
Keywords: strychnine, seizure, tetanus (PubMed Search)
Posted: 5/7/2013 by Bryan Hayes, PharmD
(Emailed: 5/9/2013)
(Updated: 5/9/2013)
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Strychnine poisoning is still occasionally found in rat poisons and in adulterated street drugs and herbal products. The typical symptoms are involuntary, generalized muscular contractions resulting in neck, back, and limb pain. The contractions are easily triggered by trivial stimuli (such as turning on a light) and each episode usually lasts for 30 seconds to 2 minutes, for 12 to 24 hours. Classic signs include opisthotonus, facial trismus, and risus sardonicus.
Differential diagnosis includes:
Chan Y. Chapter 112. Strychnine. In: Chan Y, ed. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6528306. Accessed May 7, 2013.
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Category: Pharmacology & Therapeutics
Keywords: phosphate, fosphenytoin, phenytoin, hyperphosphatemia (PubMed Search)
Posted: 4/29/2013 by Bryan Hayes, PharmD
(Emailed: 5/4/2013)
(Updated: 5/2/2013)
Click here to contact Bryan Hayes, PharmD
Introduction
Fosphenytoin is a prodrug and is metabolized quickly to phenytoin after administration. The conversion of fosphenytoin to phenytoin involves the release of phosphate. In fact, each mmol of fosphenytoin releases 1 mmol of phosphate.
Clinical Question
Are patients at risk for hyperphosphatemia after fosphenytoin loading?
Data
There are only two cases of reported hyperphosphatemia.
Bottom Line
Despite the phosphate load from fosphenytoin administration, hyperphosphatemia is very rare and probably associated with renal insufficiency and dosing errors.
McBryde KD, et al. Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient. Pediatr Nephrol. 2005;20(8):1182-5. [PMID 15965770]
Rose R, et al. Fosphenytoin-induced bradyasystole arrest in an infant treated with charcoal hemofiltration [abstract]. J Toxicol Clin Toxicol. 1998;36:473.
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Category: Pharmacology & Therapeutics
Keywords: alteplase, tPA, dabigatran, anticoagulant, apixaban, rivaroxaban (PubMed Search)
Posted: 4/3/2013 by Bryan Hayes, PharmD
(Emailed: 4/6/2013)
(Updated: 4/5/2013)
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A new recommendation in the 2013 Ischemic Stroke Guidelines provides guidance on what to do in patients taking new oral anticoagulants who are deemed eligible for IV fibrinolysis. Here is what the guidelines say:
Until further data are available, a history consistent with recent use of new oral anticoagulants generally precludes use of IV tPA.
Jauch EC, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44(3):870-947. PMID 23370205
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Category: Toxicology
Keywords: gastric lavage, GI decontamination (PubMed Search)
Posted: 3/9/2013 by Bryan Hayes, PharmD
(Emailed: 3/14/2013)
(Updated: 3/14/2013)
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In 2013, the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists published a second update to their position statement on gastric lavage for GI decontamination (original 1997, 1st update 2004).
Bottom line: Gastric lavage generally causes more harm than good. It should not be thought of as a viable GI decontamination method.
Bonus: Dr. Leon Gussow (@poisonreview) reviews the position paper on his blog, The Poison Review, here: http://www.thepoisonreview.com/2013/02/23/gastric-lavage-fuggedaboutit/
Benson BE, et al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol 2013 Feb 18. [Epub ahead of print]
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Category: Pharmacology & Therapeutics
Keywords: ischemic stroke, hypertension, blood pressure (PubMed Search)
Posted: 2/25/2013 by Bryan Hayes, PharmD
(Emailed: 3/2/2013)
(Updated: 3/2/2013)
Click here to contact Bryan Hayes, PharmD
The newest iteration of 'Guidelines for the Early Management of Patients with Acute Ischemic Stroke' was recently published. Here are the key revisions specific to blood pressure management:
If administering rtPA, blood pressure needs to be <185/110 mm Hg. That recommendation didn't change.
Jauch EC, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013 Jan 31 [Epub ahead of print]. PMID 23370205.
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