Asthma Management from the ED

We treat a lot of patients with asthma in the ER, and a lot of times our patients have trouble following up with their PCP, establishing care with a new PCP, or even getting insurance. Usually, we discharge patients with just a short-acting beta-agonist (SABA) inhaler like albuterol and possibly a separate inhaled corticosteroid (ICS), but maybe we should consider prescribing combined ICS and long-acting beta-agonist (LABA) inhaler.

Guidelines and Evidence

• Global Initiative for Asthma (GINA) recommends symptom-driven treatment or daily ICS-containing inhalers to reduce severe exacerbation risks

• Formoterol is a LABA with a rapid onset, suitable for both maintenance and rescue therapy

• Multiple studies were done with low dose ICS and combination therapies
  

  • Low-dose ICS in mild asthma reduces severe exacerbations by ~50%, improves symptom control, and enhances quality of life (Reddel 2019 or SYGMA-2)

  • Fixed-dose LABA/ICS used as needed is as effective as regular ICS, reducing hospital visits and daily ICS exposure without increasing adverse events (Crossingham 2021)

  • Budesonide/formoterol improves oxygen saturation, peak expiratory flow rate, and reduces respiratory rates post-treatment (Chew 2012)

Caveat: Noninferiority Study Design

• SYGMA-2 was initially designed as a superiority trial but was later reclassified as a noninferiority trial without clear justification or protocol amendments

• The trial set a noninferiority margin of 20% (rate ratio of 1.2), meaning the as-needed ICS-formoterol regimen could be up to 20% less effective than the standard therapy and still be considered noninferior. The 95% confidence interval for the primary outcome was 0.97 to 1.16, approaching the noninferiority threshold, suggesting a potential risk of inferiority in broader clinical practice.

• Noninferiority does not mean similarity, the trial's design and outcomes need to be carefully interpreted especially when informing global guidelines

Conflict of Interest Concerns

• While investigators collected the SYGMA-2 trial data, the analysis was conducted by employees of the sponsoring pharmaceutical company

• All but two authors disclosed receiving support from the sponsor. Notably, one author served on the Board and Science Committee of GINA. Although these conflicts were declared, the article does not specify how they were addressed or mitigated

• Close ties between study authors and the sponsor raise questions about the impartiality of the evidence informing the GINA guidelines

• The study outcomes and guideline recommendations that favor the sponsor's product is now called into question

Benefits of Discharging with ICS-LABA (e.g., Symbicort)

• Formoterol’s rapid onset makes it suitable as a rescue medication even though it is a LABA

• Improves adherence by simplifying to one inhaler for both rescue and maintenance

• Suggested Prescription: Budesonide/formoterol 80/4.5 μg per puff. Maintenance: 1-2 puffs once or twice daily OR Rescue: 1-2 puffs every 2-4 hours as needed for symptoms

  • Of note, Symbicort is NOT FDA approved as a rescue inhaler

Cost of Symbicort Without Insurance

• The out-of-pocket cost for Symbicort can be substantial:

  • Brand-name Symbicort (80/4.5 mcg): Approximately $344.41 for a 30-day supply.

  • Generic versions: Around $232.12 for the same dosage.

  • Authorized generic (Breyna): Approximately $206.71.

• Some pharmacies offer Symbicort for as low as $97.09 with a GoodRx coupon

• As of June 1, 2024, AstraZeneca has capped the out-of-pocket cost of Symbicort at $35 per month for both insured and uninsured patients (with possible limitations)

Prior Authorizations and Alternative

• Obtaining prior authorization (PA) for medications like Symbicort from the ED is not feasible due to the complex process:

  • Verify the patient's insurance coverage and determine if Symbicort requires prior authorization

  • Access and fill out the required PA forms found on the insurance provider's website

  • Send the completed forms to the insurance company via their preferred method (fax, online portal, etc.)

  • Follow the status of the PA request and provide any additional information if requested

• The other way is to refer your patients and their family members to this site:

  • https://www.azpatientsupport.com/

  • They can obtain a card that caps the cost of Symbicort at 35$ with a valid prescription

Takeaways

• There's evidence supporting the use of ICS-formoterol as both maintenance and rescue therapy, however due to COI and dubious study design the recommendations are called into question

• For patients discharged from the ED with mild to moderate asthma exacerbations, consider prescribing combined ICS/LABA instead of separate albuterol and ICS after shared decision making with patient and family

• Educate your patients on the capped cost of Symbicort and possibly send them with a prescription and a savings card

References:

https://rebelem.com/clinical-conundrum-should-acute-asthma-exacerbations-be-discharged-from-the-ed-with-combination-beta-agonist-corticosteroid-inhalers/

A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks Chew KS, Kamarudin H, Hashim CW. A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks. Int J Emerg Med. 2012;5:16. Published 2012 Apr 13. doi:10.1186/1865-1380-5-16 PMID: 22503137

Budesonide/formoterol versus salmeterol/fluticasone for asthma in children: an effectiveness and safety analysis. Jiang P, Zhao L, Yao Z. Budesonide/formoterol versus salmeterol/fluticasone for asthma in children: an effectiveness and safety analysis. J Comp Eff Res. 2021;10(17):1283-1289. doi:10.2217/cer-2021-0142 PMID: 34668718

Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. Crossingham I, Turner S, Ramakrishnan S, et al. Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. BMJ Evid Based Med. 2022;27(3):178-184. doi:10.1136/bmjebm-2021-111764 PMID: 34282031

GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents Reddel HK, FitzGerald JM, Bateman ED, et al. Eur Respir J. 2019;53(6):1901046. doi: 10.1183/13993003.01046-2019. PMID: 31249014

Contrast: PO or no to PO, that is the question.

In the past, we have always used PO and IV contrast for CT abdomen/pelvis scans in studies to "rule out" SBOs, but recently we have been told by the Chief of Surgery Dr. Nicastro that PO contrast is not necessary to rule out SBOs however some surgical residents and attendings may still ask for PO contrast. Here are some learning points so that you can advocate for your patient and discuss with the surgical team about why we may not need PO contrast in your next SBO patient!

Historical Use of PO Contrast in SBO Evaluation

• Early CT protocols included PO and IV contrast for abdominal imaging to better outline the bowel lumen and identify transition points. 

• PO contrast was initially thought to improve diagnostic accuracy by helping to distinguish dilated bowel from collapsed bowel and aiding in localizing the obstruction. (Balthazar 1997)

Advancements in CT Technology

• Multidetector CT scanners introduced in the 2000s drastically improved resolution, allowing clear visualization of bowel loops, wall enhancement, and obstruction points without the need for PO contrast.

• IV contrast became the primary agent for assessing bowel wall integrity, ischemia, and complications, which are critical components in SBO management. (Jaffe 2006; Taylor 2013)

• Evidence showed high diagnostic accuracy (90–95%) with IV contrast alone, questioning the need for PO agents in most cases. (Gore 2000; American College of Radiology 2020)

Other Contraindications for PO Contrast Use

• PO contrast often delays imaging as patients may need 1–2 hours to ingest the contrast and allow it to move through their digestive tract, delaying care. 

• Patients with high-grade SBO may be unable to tolerate oral intake, increasing the risk of vomiting and aspiration. (Maglinte 2013)

• Excessive intraluminal contrast can also obscure bowel wall features, including mural enhancement or signs of ischemia. (Paulson 2005)

However, even though PO contrast may not be useful in suspected high-grade SBOs, it still has its uses if other diagnoses are suspected:

Indications for PO Contrast in CT abdomen/pelvis

• PO contrast can help delineate the transition point in indeterminate, low-grade, or partial obstructions.

• Water-soluble oral contrast (e.g., Gastrografin) may help identify extraluminal leak sites after bowel surgery. 

• PO contrast can help visualize and evaluate known or suspected enteric fistulas between bowel segments or between bowel and other structures (e.g., bladder, skin). 

• Oral contrast can help assess strictures, skip lesions, or fistulas—especially in combination with enterography techniques to evaluate inflammatory bowel disease (IBD). 

• CT Enterography or CT Enteroclysis requires neutral or low-density PO contrast to assess small bowel mucosa and pathology (e.g., Crohn’s disease, obscure GI bleeding). 

• PO contrast may help clarify mass relationships to bowel loops or identify lumen involvement in preoperative planning for known mass lesions. 

Takeaways

• IV contrast-enhanced CT is now the standard for initial SBO evaluation, with PO contrast reserved for select, stable cases of suspected partial obstruction.

• There may still be an indication for PO contrast based on the patient’s clinical stability, level of obstruction, and specific diagnostic question.

References:

Balthazar EJ, et al. “CT of SBO: value in establishing diagnosis and determining degree and cause.” AJR Am J Roentgenol. 1994, 1997.

Gore RM, et al. “Bowel obstruction.” Radiol Clin North Am. 2000.

Jaffe TA, et al. “CT of small-bowel obstruction: how reliable is diagnosis and extent?” AJR Am J Roentgenol. 2006.

Maglinte DDT, et al. “Radiologic diagnosis of small-bowel obstruction: current role and future trends.” Radiol Clin North Am. 2013.

Paulson EK, et al. “Small-bowel obstruction: the role of CT evaluation and contrast agents.” Radiology. 2005.

Taylor GA, et al. “ACR Appropriateness Criteria® on suspected small-bowel obstruction.” J Am Coll Radiol. 2013.

American College of Radiology. “ACR Appropriateness Criteria® Suspected Small-Bowel Obstruction.” 2020.

Hyperkalemia

40 y/o male with PMHx of metastatic colon cancer s/p chemo, resection with ostomy, cirrhosis due to liver mets, recent admission for hyponatremia and recurrent ascites who presents to the ED North side resus as a transfer from Bay Ridge for hypotension, requiring critical care. Patient did not have labs drawn at Bay ridge but EKG was done:

Low voltage, slight sinus tachycardia at a rate of 101.

Upon arrival on North side the patient had labs drawn:

After the ED team got the lab results, the nurse came over and stated the patient's cardiac monitor looks like QRS was widened, so they got the patient's EKG:

sinus tachycardia at 100bpm, widened QRS

And ordered the patient 2g Calcium Gluconate and Insulin Lispro 5u, which in our order set looks like this:

The nurse drew up the medications and brought it bedside, but before administering the medications, the patient's family looked concerned as the patient just became unresponsive.

Nurse checked for a pulse, the patient did not have a pulse, CPR started.

ROSC was achieved within 10 minutes, patient was intubated, placed on pressors for hypotension.

Patient's repeat labs revealed only slight hyperkalemia, but profoundly acidotic, did not have a repeat arrest while in the Emergency Department, but expired during his course.

Hyperkalemia is something that we see very often in the Emergency Department. We have an order set to help manage it, but there isn't an official hyperkalemia management algorithm.

Our order set is based off literature from the last 20+ years, but here is a review of hyperkalemia management and ongoing controversies

Hyperkalemia Treatment

• Membrane Stabilization (Rafique 2021, Weisberg 2008)

  • For ECG changes or K⁺ > 6.5–7.0 mEq/L

  • IV calcium

    • Calcium gluconate (preferred) 

    • Calcium chloride (more potent but vesicant)

  • 10 mL of 10% solution IV over 2–5 minutes

  • Repeat every 5–10 minutes if ECG changes persist

  • Onset: <5 minutes; Duration: 30–60 minutes

  • Safe even in digoxin toxicity per updated literature (contraindication is outdated)

• Intracellular Redistribution (Moussavi 2019, Keeney 2019, Ibarra 2024)

  • Insulin + Glucose - Shifts potassium into cells via Na⁺/K⁺ ATPase activation

    • 5 units or 0.1u/kg of regular insulin + prolonged D10 infusion (250 mL over 2 hours) reduces rebound hypoglycemia

    • Onset: ~15-30 minutes; lowers K⁺ by 0.6-1.2 mEq/L

  • Beta-2 Agonist (Albuterol)

    • Nebulized 10–20 mg

    • Onset: ~30 minutes; lowers K⁺ by ~0.5 mEq/L

    • Additive to insulin; useful when IV access is delayed

    • Less effective in patients on beta-blockers

• Elimination of Potassium

  • Hemodialysis - most rapid and definitive method indicated in:

    • Refractory hyperkalemia

    • Anuric or oliguric renal failure

    • Cardiac arrest due to hyperkalemia

  • Loop Diuretics

    • Furosemide if volume status and renal function permit

  • GI Binders:

    • Sodium polystyrene sulfonate (SPS / Kayexalate

      • Onset 2-6 hrs; low efficacy; risk of colonic necrosis, especially when combined with sorbitol

    • Patiromer & Sodium Zirconium Cyclosilicate (ZS-9)

      • Safer alternatives with better GI tolerability but not for emergent use due to slow onset

Controversies in Hyperkalemia Management

• Reliability of ECG (Meyers 2017, Weisberg 2008)

  • ECG findings are neither sensitive nor specific

  • Many patients with severe hyperkalemia have normal ECGs

  • Others progress directly to VF/asystole with minimal ECG changes

  • Normal ECGs cannot rule out severe hyperkalemia 

• Sodium Polystyrene Sulfonate (SPS) Use (Sterns 2010, Parks 2019, Gupta 2021)

  • Poor efficacy in acute setting

  • Associated with intestinal necrosis, especially with sorbitol

  • Should be avoided in ED settings; consider alternatives 

• Insulin Dosing and Dextrose (Moussavi 2019, Keeney 2019, Ibarra 2024)

  • Previously thought that 10u regular insulin is required

    • 5u or weight-based (0.1u/kg) is equally effective

    • Reduces risk of hypoglycemia, especially in ESRD, low body weight, or nondiabetics 

  • D50 bolus alone may not match insulin duration

    • D10 infusion lowers risk of delayed hypoglycemia and is now preferred 

• Pseudo- and Spurious Hyperkalemia

  • Hemolysis, high WBC/platelet count, poor draw technique can falsely elevate K⁺

  • If patient has normal GFR and ECG, may not require treatment even if K⁺ > 5.5–6.0

• Bicarbonate Use (Weisberg 2008, Rafique 2021, Long 2018, Gupta 2021)

  • Controversial benefit unless pH <7.2

  • It helps correct acidemia and facilitates K shifts into cells via H⁺/K⁺ exchange 

  • May augment the effect of insulin and beta-agonists when used in acidemic patients, although it is rarely sufficient as monotherapy
    
    
    
    
    
    

  • Bicarbonate is specifically indicated in cases of TCA overdose requiring alkalinization, which may coincide with hyperkalemia
    
    
    
    
    
    

  • Minimal or no effect on serum potassium in patients with normal acid-base status

  • Bicarbonate infusion is slow-acting, taking hours to shift potassium compared to minutes with insulin or albuterol

  • Large-volume sodium bicarbonate infusions may lead to hypernatremia, volume overload, or metabolic alkalosis, particularly in patients with renal or heart failure

  • Alkalosis induced by bicarbonate can lower ionized calcium, potentially worsening arrhythmogenic risk in some settings

  • Sodium bicarbonate alone is not shown to reverse ECG changes caused by hyperkalemia and is not a substitute for calcium in membrane stabilization

Takeaways:

• Give Calcium gluconate every 5-10 minutes until ECG changes resolve

• Even if Potassium is not >6.0, patient may still have severe hyperkalemia

• If there are ECG changes and suspected hyperkalemia, treat aggressively but a "normal" ECG alone cannot "rule out" hyperkalemia

• Sodium Bicarbonate may only be effective in patients with acidosis to help augment other agents in reducing potassium levels, but otherwise not recommended