Background:
The 2010 Infectious Diseases Society of America (IDSA) cystitis and pyelonephritis guidelines recommend fluoroquinolones (FQs) as first line agents for pyelonephritis treatment and also support trimethoprim-sulfamethoxazole (TMP-SMX) usage if the urinary pathogen is known to be susceptible. However, alternative regimens need to be evaluated as FQs are increasingly associated with serious adverse events, and E coli resistance rates to both FQs and TMP-SMX are rising nationally. The Cephalosporins for Outpatient Pyelonephritis in the Emergency Department (COPY-ED) study aimed to evaluate the effectiveness of oral cephalosporins in acute pyelonephritis treatment when compared to IDSA guideline-endorsed first line treatments.
Study design:
This multicenter, retrospective observational cohort study screened patients with a primary diagnosis of uncomplicated or complicated pyelonephritis using ICD-10 codes. They included all patients >18 years of age who reported symptoms of a UTI and were discharged home on oral antimicrobial therapy. Exclusion criteria included pregnancy, acute or chronic prostatitis, orchitis, epididymitis, or urinary tract surgery within 7 days prior to ED visit or surgery planned during the study period.
The primary outcome was rate of outpatient treatment failure within 14 days of discharge from the emergency department with cephalosporins compared to FQs and TMP-SMX.
Patient Population:
Results:
Rates of treatment failure at 14 days were not statistically significant between groups, with a rate of 17.2% in the cephalosporin group and a rate of 22.5% in the FQ + TMP/SMX group. After adjusting for gender, complicated infections, previous use of intravenous or oral antibiotics, and urinary tract abnormality, the odds of treatment failure at 14 days were still not significantly different in patients who received fluoroquinolone or TMP/SMX (adjusted OR 1.275 [95% CI 0.86 to 1.9]) compared to cephalosporins.
Secondary outcomes included rates of treatment failure with first generation cephalosporins (cephalexin, cefadroxil, cefuroxime) and third generation cephalosporins (cefpodoxime, cefuroxime), rates of appropriate therapy selected based on urine culture susceptibilities, and rates of treatment failure compared to duration of treatment prescribed. None of these outcomes found statistically significant differences between groups.
Study Limitations:
Key Takeaways:
Albuterol, a common bronchodilator used in the treatment of asthma and chronic obstructive pulmonary disease (COPD), can cause a surprising increase of lactate levels. The increase in lactate is usually mild to moderate (typically < 4 mmol/L) and transient. It does not necessarily indicate underlying sepsis, tissue hypoxia, or severe metabolic acidosis.
Mechanism:
Albuterol can cause a transient increase in lactate levels due to its beta-2 agonist effects, which promote glycogenolysis and increase anaerobic metabolism. This can result in elevated lactic acid production, even in the absence of tissue hypoxia or shock.
Timing:
This effect is typically seen within 30 minutes of albuterol administration and can persist for 1-2 hours after discontinuing treatment.
Monitoring:
If lactate levels are elevated in a patient receiving albuterol, consider the possibility of a pharmacologic cause rather than immediately assuming a more serious etiology like shock or severe metabolic disturbance.
Differentiating Causes of Elevated Lactate:
In a critically ill patient, elevated lactate can indicate hypoperfusion (e.g., septic shock, cardiogenic shock, or hypovolemic shock). However, when elevated lactate is associated with albuterol administration, the rise in lactate is often lower and resolves without intervention.
Management:
If albuterol-induced lactate elevation is suspected, continue with supportive care and monitor lactate trends. No specific treatment is necessary for the elevated lactate unless there are other concerning clinical findings that suggest a different underlying cause.
Conclusion:
In emergency settings, it's important to recognize that albuterol can cause a transient increase in lactate levels. Understanding this phenomenon can help avoid misdiagnosis and prevent unnecessary interventions in patients receiving albuterol therapy. Always correlate lactate levels with the broader clinical picture to guide management decisions.
On March 3, 2025, the FDA approved tenecteplase to treat acute ischemic stroke. Historically, only alteplase was FDA-approved, but the stroke guidelines suggest tenecteplase as a reasonable alternative and many centers have made the change to use tenecteplase.
The EXTEND-IA TNK trial showed benefit of tenecteplase over alteplase in patients who were candidates for mechanical thrombectomy. The newer AcT trial found that tenecteplase was non-inferior to alteplase for patients eligible for thrombolysis, regardless of thrombectomy candidacy. There was no difference in safety outcomes, specifically ICH or angioedema in either trial.
Tenecteplase will soon be available in a new 25 mg vial with stroke-specific packaging (potentially as early as June 2025). Currently, there is only a 50 mg vial that is used for STEMI and PE which has higher maximum dosing compared to stroke.
The dosing is now recommended in weight-based groupings based on the supplemental appendix from the AcT trial. This is likely a change in practice for most centers that previously implemented tenecteplase for stroke before the FDA approval. Consult with your stroke and pharmacy team to discuss potential protocol changes at your institution.
Background:
Approximately 10% of patients presenting to the emergency department (ED) report penicillin allergies, which may lead to use of second- or third-line agents. Alternative therapies (such as aztreonam, clindamycin and fluroquinolones) carry an increased risk of mortality and complications such as Clostridioides difficile infection. Considering that less than 10% of penicillin allergies may be confirmed by formal testing results, the PEN-FAST clinical decision tool was created to identify patients with low risk of true penicillin allergy who do not require formal skin testing for rechallenging with a beta-lactam:
Though PEN-FAST has only been validated in the clinic and inpatient settings, a study from Tran et al. published this January sought to determine the safety and efficacy of utilizing this tool to assess penicillin allergies and re-challenge patients in the ED.
Study design:
This was a single-center, prospective, observational cohort study. Emergency medicine (EM) pharmacists screened patients in the ED with:
Screened patients were excluded from the study if orders were placed by a non-EM physician, if they previously tolerated a penicillin/cephalosporin within the healthcare system of the study site, if they were unable to participate in bedside interview, if the antibiotics selected were appropriate despite the penicillin allergy or if there were time constraints that would delay care if the PEN-FAST assessment needed to be completed.
Study Intervention:
EM pharmacists completed the PEN-FAST assessment for all included patients. They recommended rechallenging with an appropriate beta-lactam for patients with a score of 0-2, recommended to consider rechallenging for patients scoring 3, and did not recommend rechallenging for scores of 4-5 or if it was confirmed patients previously experienced anaphylaxis, angioedema or severe cutaneous reactions with a beta-lactam. Orders for any change in therapy were only placed with discussion and agreement from EM physicians. Rechallenged patients were assessed at bedside for any immune-mediated reactions 45 to 75 minutes after initiation of antibiotics. The primary outcome was the percent of patients with a PEN-FAST score of 0-2 who tolerated a beta-lactam after being rechallenged.
Patient Characteristics:
After screening, one hundred patients were included in this study.
Results:
Primary Outcome:
Secondary Outcomes:
Key Takeaways:
This meta analysis of studies looking at thrombolytics and prostaglandins in treating significant frost bite offers some insight into the possibilities these therapeutics offer. Unfortunately, the studies available are not high quality and most are case reports.
“Our results suggest that thrombolysis or intravenous iloprost is effective when administered promptly to treat severe frostbite. For grade 3–4 frostbite the Wilderness Medical Society frostbite guidelines recommend the use of intravenous iloprost within 48 h of injury, and thrombolysis within 24 h of injury. The Helsinki protocol recommends the use of tPA for patients with grade 3–4 frostbite presenting within 48 h of injury with angiographic evidence of thrombosis."
“Iloprost is a synthetic prostaglandin I2 that has been used to treat frostbite . Like other prostacyclins, it inhibits platelet aggregation and promotes vasodilation. Iloprost may stimulate the release of endogenous tissue plasminogen activator or counteract its inhibitory effects [35]. Iloprost reduces vasoconstriction induced by thromboxane A2 , and may reduce oxidative stress from free radicals, moderating reperfusion injury [37, 38]. The effect on platelet aggregation may be reversed within two hours), but prostacyclin effects may disrupt the vicious cycle of activated platelets and leukocytes that damages endothelium .”
More research in this area is needed. Transfer to a center with these capabilities seems worth a discussion in the case of severe frostbite.
Background
Treatment of acute agitation often involves combining antipsychotics and benzodiazepines. Injectable olanzapine, a second-generation antipsychotic, uniquely carries a warning against concomitant use with parenteral benzodiazepines. The olanzapine prescribing information states that “concomitant administration of intramuscular (IM) olanzapine and parenteral benzodiazepines is not recommended due to the potential for excessive sedation and cardiorespiratory compromise”. The European Medicines Agency (similar to the United States FDA) cautions against use of the two within 60 minutes of each other using similar language.
The above warnings were based on a 2010 publication of 160 adverse event reports from a post-marketing database maintained by the drug manufacturer, and have resulted in many institutions prohibiting co-administration of IM olanzapine and parenteral benzodiazepines. The publication cited 29 fatal adverse events involving injectable olanzapine, concluding that caution should be exercised when using IM olanzapine and parenteral benzodiazepines simultaneously. However, 25 of the 29 patients received other sedating medications in addition to olanzapine and benzodiazepines, and the majority of fatalities were >12 hours after the last dose of olanzapine. Following this publication, a 2013 randomized controlled trial by Chan et al. found no difference in adverse event rates between patients receiving IV midazolam alone and patients receiving IV midazolam plus IV olanzapine for acute agitation.
This December 2024 study by Cole et al. aimed to re-evaluate the risks of cardiorespiratory compromise with concomitant injectable olanzapine and injectable benzodiazepine administration.
Study design
This was a single-center retrospective cohort study of 693 patients who received 2 parenteral doses of eligible sedating medications within 60 minutes of each other. A total of 549 patients received 2 doses of olanzapine, and 144 received olanzapine and a benzodiazepine (midazolam, lorazepam, or diazepam). To avoid cohorts with a higher baseline risk of sedation, patients who received other sedating medications and patients who received more than 2 doses of olanzapine or 1 dose of a benzodiazepine were excluded.
Patient Population
Results
*One death during hospitalization was due to missed occlusion myocardial infarction
Study Critique:
Key Takeaways
A recent review article highlighted the adverse effects that emergency physicians should know of with the novel antineoplastic agents. The adverse effects and the associated agents are briefly summarized from the article in the table below. A link to the full article is below.
Link to article: Antibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know - Annals of Emergency Medicine
Background:
Epinephrine administration is a critical component of treating severe allergic reactions, and delayed administration is associated with increased morbidity and mortality. Epinephrine auto-injectors are the current standard of care and allow for rapid administration in all care settings, but compliance issues can limit their use. The most common reason patient’s site for failure to administer or delayed administration of auto-injectors is needle phobia (particularly with pediatric patients). This has led to interest in developing needle-free epinephrine delivery devices that are easy to administer.
New Drug Approval:
This August, the FDA approved an epinephrine nasal spray (brand name: Neffy) for use as emergency treatment for Type 1 allergic reactions, including life-threatening anaphylaxis. The approval was based on four studies, including 175 total patients, comparing epinephrine 2 mg nasal spray with an epinephrine 0.3 mg intramuscular injection in healthy adults and children. These studies showed similar blood concentrations of epinephrine between treatment arms through 60 minutes after administration. In addition, both treatment arms showed similar elevations in heart rate and systolic blood pressure.
Bottom Line:
Epinephrine nasal spray is a newly approved option for the treatment of severe allergic reactions and anaphylaxis. While this approval was based on studies in healthy adults and children who did not currently have anaphylaxis, this medication may be worth considering for patients who have issues or concerns about using an injectable device to administer epinephrine.
The benefits of calcium treatment for hyperkalemia have historically been attributed to “membrane stabilization,” as it has been hypothesized to restore cardiac resting membrane potential. However, the true mechanism by which calcium improves cardiac function in this setting remains unclear. This has led to inconsistencies in the clinical threshold for treating hyperkalemia with calcium.
Piktel et al. recently conducted an experimental study investigating the adverse electrophysiologic effects of hyperkalemia and therapeutic effects of calcium treatment in isolated canine myocytes using ex vivo tissue and in vivo cellular techniques.
Key study findings:
Effects of hyperkalemia:
Effects of calcium treatment in the setting of hyperkalemia:
Limitation:
Bottom line: Findings of this study suggest that calcium's beneficial effects in hyperkalemia are not attributed to “membrane stabilization,” but rather to restoration of conduction velocity through L-type calcium channels and subsequent narrowing of the QRS complex. This supports calcium treatment in hyperkalemia when the ECG shows conduction slowing and QRS widening.
At our institution we have developed a guideline for the use of hypertonic saline in hyponatremia.
Administration of 3% sodium chloride for acute or symptomatic hyponatremia
Acute hyponatremia with severe symptoms
Acute hyponatremia with moderate symptoms
Hyponatremia Fluid Rate Calculations (**Be Careful with Online Calculators**)
FYI: 3% Sodium Chloride (1.95 mL/mEq; 513 mEq/1 L); 0.9% Sodium Chloride (6.5 mL/mEq; 154 mEq/1 L)
Equations for Calculations
***See Visual Diagnosis for an Example with Calculations***
Two recommendations from the recent GRACE 4 publication in Academic Emergency Medicine to consider:
1. Use phenobarbital along with benzodiazepines in patients with moderate to severe alcohol withdrawal. The evidence isn’t robust but is positive when compared to benzos alone.
2. Adults with alcohol use disorder can benefit from anti-craving medications such as naloxone and gabapentin at time of discharge.
A panel comprised of 21 participants selected by four clinical toxicology societies (America’s Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) sought to develop consensus guidelines for management of acetaminophen poisoning in the US and Canada. Highlights from this framework include:
Acetylcysteine Stopping Criteria
A common misconception is that acetylcysteine is administered for 21 hours then discontinued. The consensus statement codifies the practice of reassessing the patient at the end of the acetylcysteine infusion and only stopping acetylcysteine if all of the following criteria are met:
Ingestion of Extended-Release Acetaminophen Products
Extended release acetaminophen products are available on the US market. Management is largely the same as for instant release acetaminophen except for several exceptions:
Management of Repeated Supratherapeutic Acetaminophen Ingestion
When a patient presents following repeated acetaminophen ingestions over a period of greater than 24 hours the Matthew-Romack nomogram is no longer applicable for guiding decisions regarding treatment with acetylcysteine. The consensus statement recommends initiating treatment in this scenario if the patient’s acetaminophen concentration is > 20 mcg/mL or if patient’s AST/ALT are abnormal.
Final Thoughts:
These guidelines will function as a useful reference and officially codify a general framework with evidence-based recommendations for the management of acetaminophen poisoning. As always, a poison center or clinical toxicologist should be consulted for any complicated or serious acetaminophen poisoning.
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that affects an estimated 14 to 20 patients per 100,000 in the United States. Most patients with MG have autoantibodies against acetylcholine receptors (AChRs), which disrupt neuromuscular transmission through downregulation, destruction, blocking of AChRs or disrupting receptors in the postsynaptic membrane.
Several medications may worsen MG or precipitate myasthenic crisis, however, incidence is difficult to describe as literature is largely limited to case reports and there is often presence of other confounding factors. There are two proposed mechanisms for medications to cause or exacerbate MG:
Several medications commonly used in the emergency department are known to impair neuromuscular transmission and may induce or worsen MG. The following medications should be avoided, or used with extreme caution in patients with MG*:
*This list contains several common medications utilized in the emergency department, but is not an all-inclusive list of medications that may exacerbate MG. Please refer to the reference section for additional information.
Naloxone is given frequently in the emergency department to improve the respiratory rate in patients with suspected or known opioid ingestion. In order to minimize the risk of severe opioid withdrawal (nausea, vomiting, diarrhea, anxiety, piloerection, sweating, agitation, etc.), consider diluting naloxone and administering small aliquots of 0.04-0.08mg at a time. This requires IV access and a patient with a present, but low respiratory rate.
Dilution instructions:
Supplies:
Instructions:
Administer 1 -2 mL (0.04 – 0.08 mg) naloxone every 2 minutes and assess response.
Don't forget to prescribe/give naloxone upon discharge from the emergency department.
MYTH: Bactrim cannot be used as monotherapy for nonpurulent skin and soft tissue infections.
Not True!
Organisms of concern: Streptococcus spp.
Here’s why:
TRUTH: Bactrim CAN be used as monotherapy for nonpurulent skin and soft tissue infections.
Prepared by Rianna Fedora, PharmD on 2/26/24
Empiric antimicrobial treatment for necrotizing soft tissue infections (NSTIs) should include coverage of a wide range of pathogens including Staphylococcus spp, Streptococcus spp, anaerobic bacteria and gram negative bacteria. Treatment should also include an agent that suppresses toxin production by group A Streptococcus (GAS), with the Infectious Diseases Society of America (IDSA) guidelines recommending clindamycin plus penicillin for treatment of GAS causing necrotizing fasciitis and toxic shock syndrome. A typical empiric NSTI regimen would be vancomycin plus clindamycin plus piperacillin-tazobactam.
Linezolid is an appealing alternative to clindamycin and vancomycin, as it has anti-toxin effects via inhibition of exotoxin expression, potent in vitro activity against Streptococcus spp, activity against methicillin-resistant Staphylococcus aureus (MRSA), and potential for less adverse effects than clindamycin plus vancomycin. Several recent studies have looked at using linezolid in lieu of clindamycin plus vancomycin when treating NSTIs.
Published Studies:
Dorazio and colleagues published a retrospective single center study compared 62 matched pairs of patients who received linezolid vs. clindamycin plus vancomycin as part of their NSTI treatment.
Heil and colleagues published a retrospective single center cohort study examined patients who received either linezolid (n = 29) or clindamycin (n = 26) for treatment invasive soft tissue infection or necrotizing fasciitis with GAS isolated from blood and/or tissue.
Lehman and colleagues published a retrospective single center study compared patients who received linezolid (n = 21) versus clindamycin plus vancomycin (n = 28) in addition to gram-negative and anaerobic coverage for empiric treatment of NSTIs.
Bottom Line:
When added to an agent with good gram negative and anaerobic coverage (i.e. piperacillin-tazobactam), linezolid may be a more viable option for coverage of MRSA and GAS toxin production during empiric NSTI treatment when compared to clindamycin plus vancomycin. This is largely due to a more favorable side effect profile.
Nirmatrelvir-ritonavir (Paxlovid™) is a combination of two protease inhibitors used for the treatment of mild-moderate symptomatic COVID-19. Nirmatrelvir inhibits the SARS-CoV2 main protease, and ritonavir inhibits metabolism of nirmatrelvir, acting as a “booster” to increase nirmatrelvir concentrations.
The EPIC-HR trial, which included non-hospitalized adults with mild-moderate COVID-19 who were unvaccinated and at risk of progressing to severe disease, showed an 89% reduction in COVID-19-related hospitalization or 28-day all-cause mortality in patients treated with nirmatrelvir-ritonavir compared to placebo. The efficacy rates in this trial were similar to remdesivir (87% relative risk reduction), and greater than molnupiravir (31% relative risk reduction), two alternative agents used for treatment of mild-moderate COVID-19. However, these three agents have never been directly compared. Nirmatrelvir-ritonavir was initially approved by the FDA under Emergency Use Authorization (EUA), but is now fully FDA-approved as of May 2023.
Which patients benefit?
Drug-Drug Interactions:
Dosing:
Common side effects:
Bottom Line: Paxlovid is appropriate for patients with symptomatic mild-moderate COVID-19 with risk factors for progression to severe disease. Ask your pharmacist for assistance evaluating drug-drug interactions!
For the agitated geriatric patient, if verbal deescalation, distraction, and providing a safe quiet area do not work and you require chemical sedation use oral antipsychotics first. Follow this with IV or IM antipsychotics. Avoid benzodiazepines due to often worsening delirium or respiratory depression. For dosing, start low and go slow.
Bottom Line: Droperidol is an effective alternative to haloperidol in the treatment of gastroparesis although most patients will also receive prokinetic agents as well such as metoclopramide. It may also have some analgesic benefit.
Prior studies have demonstrated the efficacy and safety of haloperidol in the management of gastroparesis. A recent retrospective study was conducted to assess the impact of droperidol as it is an effective antiemetic similar to haloperidol.
This study enrolled 233 patients. Visits were matched with their most recent ED visit > 7 prior where droperidol was not administered.
Most patients were female, 51% African American, and the median age was 40. Doses ranged from 0.625 mg – 2.5 mg with the most common dose being 1.25 mg.
Results:
Background: It is estimated that nearly 6% of U.S. adults and children report having a food allergy.1,2 Epinephrine autoinjectors are used to provide life-saving pre-hospital treatment for patients experiencing anaphylaxis in the community, but can have serious consequences if administered incorrectly. Accidental finger-stick injuries with epinephrine auto-injector can result in significant pain and ischemia due to vasoconstriction and decreased blood flow to the digit. Treatments for digital epinephrine injection include supportive care, topical vasodilators, and injectable vasodilators.3
Supportive care3,4:
