פרמקולוגיה - האיגוד הישראלי לרפואה דחופה

Reference: Jessen et al. Pharmacological interventions for the acute treatment of hyperkalaemia: A systematic review and meta-analysis. Resuscitation 2025

Date: August 6, 2025

Guest Skeptic: William Toon is a paramedic who, this past May achieved over 50 years of continuous EMS certification. His professional path has taken him from front-line paramedic to national presenter, expert witness, flight medic, EMS program director, and senior training executive with a doctorate in Higher Education.

Case: A 65-year-old patient presents to the emergency department (ED) with general weakness, mild abdominal cramping, and nausea over the past 12 hours. The patient has poorly controlled type 2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease stage 4 on hemodialysis. The patient missed their last dialysis appointment two days ago. The patient takes several medications for kidney disease and blood pressure, including a potassium-sparing diuretic. His ECG shows peaked T-waves. Stat chemistry reveals a serum potassium of 6.5 mmol/L. He is not yet oliguric and is hemodynamically stable. The team must initiate pharmacologic treatment immediately while preparing for possible escalation to dialysis.

Background: Hyperkalemia is a potentially life-threatening electrolyte abnormality frequently encountered in the ED. It’s common in patients with chronic kidney disease, diabetes, or those on renin-angiotensin-aldosterone system (RAAS) inhibitors. While treatments like insulin, beta-agonists, and calcium gluconate are well-known, the comparative efficacy and safety of pharmacologic agents used to rapidly reduce serum potassium remain uncertain.

Clinicians must balance rapid action with safety when choosing treatment for hyperkalemia. Understanding which pharmacologic interventions work best and how quickly they act is vital to optimizing care. Unfortunately, much of the existing data on hyperkalemia treatment is derived from small or methodologically limited trials.

Reference: Jessen et al. Pharmacological interventions for the acute treatment of hyperkalaemia: A systematic review and meta-analysis. Resuscitation 2025

Authors’ Conclusions: “Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous salbutamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.”

Quality Checklist for Therapeutic Systematic Reviews:

Results: Studies included adult patients with hyperkalemia from EDs, inpatient wards, and dialysis units. Ages ranged widely, with a predominance of patients with chronic kidney disease (CKD) and cardiovascular comorbidities.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions but would emphasize the limited certainty and highlight the need for better patient-oriented outcome data before changing practice broadly. 

Case Resolution: You administer 10 units of IV insulin with an amp of D50 and initiate inhaled albuterol. You consult nephrology and start sodium zirconium cyclosilicate, which is available in your ED. Repeat potassium at four hours drops to 5.4 mmol/L. No dialysis is needed.

William Toon

Clinical Application: This SRMA reaffirms insulin-glucose as the first-line treatment for hyperkalemia in the ED. It also supports adding beta-agonists when needed, de-emphasizing bicarbonate and sodium polystyrene sulfonate in acute settings, and suggests newer agents like SZC for future integration into your ED’s hyperkalemia protocol.

However, it does not mean we should not use calcium gluconate or chloride in patients with hyperkalemia. These agents are not meant to lower potassium levels, and it would be inappropriate to have expected them to do so. The SRMA did not demonstrate a patient-oriented outcome (POO) of benefits. We should interpret the findings cautiously. The absence of evidence of benefit is not the same as evidence of no benefit. Therefore, calcium should not be abandoned for the acute treatment of hyperkalemia solely based on this SRMA.

What Do I Tell the Patient? We’re treating your high potassium levels quickly to protect your heart. We’ve given insulin and another medicine to bring the levels down safely. We’ll keep monitoring you closely over the next few hours.

Keener Kontest: Last week’s winner was David Michaelson. He knew that TENS units are thought to reduce pain through the gate control mechanism and the release of endorphins.

Listen to the SGEM podcast for this week’s question. If you know, then send an email to [email protected] with “keener” in the subject line. The first correct answer will receive a shoutout on the next episode.

The post PODCAST: The Warrior – Pharmacological Interventions for the Acute Treatment of Hyperkalemia first appeared on האיגוד הישראלי לרפואה דחופה.

Written by Amanda Mathews

Update your pharmacopia 

How does this change my practice?

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The post EM Pharmacotherapy Literature of 2024 first appeared on האיגוד הישראלי לרפואה דחופה.

Reference: Muldowney et al. A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting. Ann Emerg Med. 2025

Date: April 24, 2025

Guest Skeptic: Dr. Howie Mell received his Medical Doctorate (MD) from the University of Illinois at Chicago, College of Medicine at Rockford. Prior to that, he received a Master of Public Health (MPH) degree emphasizing Environmental and Occupational Health from the University of Illinois at Chicago, School of Public Health, while serving as a firefighter/paramedic in the Chicago suburbs. He completed his residency in emergency medicine at the Mayo Graduate School of Medicine, Rochester, Minnesota. Dr. Mell is board-certified by the American Board of Emergency Medicine in both Emergency Medicine (EM) and Emergency Medical Services (EMS) Medicine. He is a Fellow of the American College of Emergency Physicians (FACEP). Dr. Mell serves as an Ambassador Emergency Physician for Vituity (formerly CEP-America), and he is currently assigned to Schneck Medical Center in Seymour, Indiana (John Cougar Mellencamp’s “Small Town”).

Case: You’re an experienced paramedic working a busy night shift in an urban EMS system. Dispatch sends you to a call for a 35-year-old male found acting erratically in a public park. Upon arrival, you find him disoriented, agitated, and combative. Bystanders report that he has been using methamphetamine and alcohol.

The patient is uncooperative, making verbal de-escalation ineffective. Physical restraint is needed for transport. Your EMS protocol allows for pharmacologic sedation with either midazolam (1 to 5 mg IV/IM, repeat every 2 to 5 minutes as needed) or ketamine (5 mg/kg IM, max 500 mg).

The patient is tachycardic (HR 122 bpm), hypertensive (BP 156/96 mmHg), and has a Glasgow Coma Scale (GCS) score of 12. You need to act quickly for scene safety and the patient’s well-being.

Background: Acutely agitated patients in the pre-hospital setting present a unique challenge for emergency medical services (EMS). Agitation can stem from various underlying conditions, including psychiatric disorders, substance intoxication, metabolic disturbances, traumatic brain injury, or postictal states​. If not managed appropriately, severe agitation can escalate, leading to self-harm, harm to others, or interference with necessary medical care.

Initial management emphasizes verbal de-escalation techniques, which should always be attempted first. However, when these strategies fail, pharmacologic sedation may be necessary to ensure the safety of both the patient and pre-hospital providers. The choice of sedative agent is a critical decision. The paramedic must balance the need for rapid sedation with the risk of adverse effects, including respiratory depression and cardiovascular instability​.

Benzodiazepines, such as midazolam, have historically been used for pre-hospital sedation due to their anxiolytic and muscle-relaxant properties. However, their use is associated with risks such as respiratory depression and paradoxical agitation. In recent years, ketamine has gained popularity due to its rapid onset, potent dissociative properties, and preservation of airway reflexes​. Despite its advantages, ketamine is not without concerns, including the potential for emergence reactions, increased blood pressure, and the need for airway management in some cases.

Current guidelines lack consensus on the optimal pharmacologic approach, leading to significant variation in practice across EMS systems. The ongoing debate surrounding the best sedation strategy highlights the need for robust clinical research to guide evidence-based practice. A newly published study aims to address this knowledge gap by comparing ketamine and midazolam in the out-of-hospital setting, shedding light on their relative efficacy and safety.

Reference: Muldowney et al. A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting. Ann Emerg Med. 2025

Authors’ Conclusions: “In this cohort study of patients with acute behavioral disturbance, emergent airway support and other outcomes did not differ following out-of-hospital treatment with midazolam or ketamine.”​

Quality Checklist for Observational Study:

Results: 376 patients with acute behavioural disturbances were included in the study. The median age was 35 years, 78% were male, and the most common cause of agitation was substance use (51%).

1) Retrospective Design: A major limitation of the retrospective study design is its reliance on existing records, which can introduce selection bias, information bias, and confounding. Unlike prospective studies, where variables can be controlled and standardized in real time, retrospective studies depend on previously collected data, which may be incomplete, inconsistent, or inaccurately documented. A prospective or randomized design would be stronger.

2) Selection Bias: This type of bias occurs when the study population is not representative of the broader patient population due to systematic differences in how participants are included or excluded. In this retrospective EMS study, selection bias could arise if certain patients with acute agitation were not documented or excluded due to incomplete records, leading to an overrepresentation of cases where sedation outcomes were more favourable or easier to track.

3) Information Bias. This occurs when inaccuracies in data collection, which can lead to systematic errors in measuring exposures or outcomes. In this retrospective EMS study, information bias could arise from inconsistent documentation of key variables, such as the exact dose and route of sedative administration, the severity of agitation, or the criteria used for initiating airway management. Suppose some EMS providers were more meticulous in documenting adverse events, while others underreported complications like transient hypoxia or delayed sedation onset. In that case, the study might underestimate or overestimate the true risks associated with ketamine or midazolam.

4) Confounders: This is a limitation of observational studies. Confounding variables are factors that are associated with both the intervention (midazolam vs ketamine) and the outcome (need for airway management), potentially distorting the true relationship between them. In this EMS study, patient characteristics such as underlying medical conditions (e.g., COPD, obesity, or intoxication level), severity of agitation, or additional sedative medications administered could have influenced airway management independently of whether ketamine or midazolam was used. If, for example, ketamine was more frequently given to severely agitated patients who were already at higher risk for airway compromise, this could make ketamine appear riskier than it is. Conversely, if midazolam was preferentially used in patients with known respiratory conditions, providers might have been more cautious, leading to fewer airway interventions. Without randomization or robust statistical adjustments, these confounders could obscure true differences between the medications and limit the study’s validity​.

5) Generalizability: The external validity of this study depends on how well its findings apply to other EMS systems, patient populations, and clinical settings. Since the study was conducted in an urban EMS system, its results may not translate directly to rural or suburban settings, where transport times, provider training, and access to advanced airway management differ.

Additionally, variability in EMS protocols, such as differences in sedation dosing, monitoring practices, or local guidelines, could limit the applicability of these findings to regions with different pre-hospital care standards. The patient population also plays a role—if the study included a higher proportion of substance-related agitation, the results may not fully reflect outcomes in psychiatric agitation or postictal states.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions.

Case Resolution: You administer intramuscular ketamine, and the patient becomes much calmer. His vital signs are stable, maintains spontaneous respirations with no signs of airway compromise and is safely transported to the ED.

Clinical Application: Given the comparable safety profiles, your decision should weigh speed of onset, route of administration, and context (i.e. it all depends).

What Do I Tell the Patient? When we found you, you were very agitated and possibly at risk of hurting yourself or others. For your safety and ours, we had to give you medication to calm you down. We used a sedative that works quickly and is commonly used in emergencies like yours. Thankfully, you didn’t need a breathing tube, and everything went smoothly.

Keener Kontest: Last week’s winner was Dr. Steven Steltz from New Zealand. He knew the first computer that stored a program in its memory was the Manchester Baby, also known as the Small-Scale Experimental Machine (SSEM). It was developed at the University of Manchester in England and ran its first program on June 21, 1948.

Listen to the SGEM podcast for this week’s question. If you know, then send an email to [email protected] with “keener” in the subject line. The first correct answer will receive a shoutout on the next episode.

Other FOAMed on Agitation:

The post PODCAST: Did You Ever Have To Make Up Your Mind – Midazolam or Ketamine for Acute Agitation in the Pre-Hospital Setting first appeared on האיגוד הישראלי לרפואה דחופה.