Special Circumstances

Pharmacologic Interventions for Severe Hyperkalemia With Cardiac Arrest

Last Full Review: ILCOR 2025

Hyperkalemia is defined as a serum or plasma potassium level above the upper limits of normal, usually greater than 5.0 milliequivalents (mEq) per liter (L). Causes of hyperkalemia in children and infants include chronic kidney disease or acute kidney injury with impaired ability to excrete potassium, medications such as nonsteroidal anti-inflammatory drugs and certain antihypertensives, and cellular release of potassium such as with burns, hemolysis and acidosis. While mild hyperkalemia is usually asymptomatic, high levels (e.g., 6.5 mEq/L to 7 mEq/L or more), particularly with an acute change, may lead to life-threatening cardiac arrhythmias. Treatment of symptomatic or acute hyperkalemia with life-threatening arrhythmias traditionally involves use of intravenous calcium, albuterol, insulin (with glucose) and sodium bicarbonate. Once cardiac arrest occurs, however, the benefit of these treatments is unknown. A new International Liaison Committee on Resuscitation (ILCOR) systematic review evaluates this question.

 

Evidence Summary

A 2025 ILCOR systematic review (Jessen et al. 2025, 110489) and Consensus on Science with Treatment Recommendations (CoSTR) (Djakow et al. 2024; Drennan et al. 2025, S72) sought evidence with clinical, laboratory and electrocardiogram (ECG) outcomes in adults and children (less than 18 years old) with hyperkalemia in any setting and with and without cardiac arrest who received any acute pharmacological intervention with the aim of mitigating the harmful effect of hyperkalemia or with the aim of lowering potassium levels, compared with no intervention or a different intervention. The review identified few studies reporting patient-centered outcomes such as mortality. Changes in potassium levels and ECG changes were reported by intervention. A parallel CoSTR (Granfeldt et al. 2024; Drennan et al. 2025, S72) completed by the ILCOR Advanced Life Support Task Force evaluated evidence in adults with acute hyperkalemia as well as hyperkalemia associated with cardiac arrest, while the pediatric review focused on cardiac arrest associated with or caused by hyperkalemia.

Four studies (Kemper et al. 1996, 495; McClure et al. 1994, 126; Murdoch et al. 1991, 527; Noyan et al. 1995, 355) in 53 acutely hyperkalemic neonates and children reported changes in potassium levels with the use of intravenous beta-2 agonists, 4 to 5 micrograms (mg) per kilogram (kg) compared with no treatment. A mean decrease in potassium of 1.0 milliosmole (mOsm) (95% CI, 1.5 lower to 0.6 lower; follow-up range 60 minutes) was shown with meta-analysis. A single study (Arias-Reyes et al. 1989, 603) showed a reduction in the mean potassium level with the use of intravenous beta-agonists and insulin plus glucose from 6.8 mOsm (SD, 0.6 mOsm) to 5.0 (SD, 1.2) after 45 minutes. Meta-analysis of three studies (Singh et al. 2002, 16; Saw et al. 2019, 55; Mu et al. 1997, 9) in 51 total acutely hyperkalemic neonates showed inhaled beta-2 agonists (400 micrograms salbutamol) compared to no treatment lowered potassium levels by a mean of 0.9 mOsm (95% CI, 1.2 lower to 0.5 lower) at a follow-up range of 120 minutes (Djakow et al. 2024; Drennan et al. 2025, S72).

No studies in the pediatric population evaluated potassium levels following the use of sodium bicarbonate for hyperkalemia, while the parallel CoSTR in adults showed no change in potassium levels.

There were few studies reporting outcomes during cardiac arrest. One study in adults (Wang et al. 2016, 105) found a lower unadjusted rate of return of spontaneous circulation (ROSC) following the administration of calcium, sodium bicarbonate, or both. A single study in the pediatric population (Cashen et al. 2023, 109673) reported worse outcomes with use of calcium during cardiac arrest.

The ILCOR CoSTR (Djakow et al. 2024; Drennan et al. 2025, S72) concludes that there is insufficient evidence to recommend for or against the use of calcium and for or against the use of sodium bicarbonate in pediatric patients in cardiac arrest associated with hyperkalemia. A good practice statement suggests using intravenous salbutamol or insulin with glucose or a combination of both to lower the potassium levels in pediatric patients with cardiac arrest associated with hyperkalemia with the aim to lower the potassium levels during the concurrently ongoing high-quality resuscitation efforts.

Insights and Implications

The limited number of studies in the pediatric population and the lack of studies comparing one treatment with another treatment make it difficult to provide evidence-based recommendations for prioritizing interventions for acute hyperkalemia during cardiac arrest, as well as dosing and timing considerations. In the United States, the intravenous formulation of albuterol (salbutamol) is not currently available, further limiting the choice of treatments to inhaled albuterol and intravenous insulin plus glucose. In Canada, an intravenous 1 milligram per milliliter (ml) (5 ml) solution is available. Inhaled albuterol during cardiac arrest may be impractical, although it is feasible for intubated patients. Adverse effects of treatment must also be considered in children, particularly the risk of hypoglycemia and hyperglycemia and tachycardia with beta-agonist administration.

For the use of sodium bicarbonate and calcium during cardiac arrest associated with hyperkalemia, the evidence is very limited and the benefits are uncertain. Sodium bicarbonate administration is considered appropriate along with standard resuscitation for life-threatening dysrhythmias due to poisoning from cocaine and other sodium channel blockers, while calcium, in addition to high-dose insulin therapy and vasopressors, is recommended for calcium channel blocker toxicity (Lavonas et al. 2023, e149). In these special circumstances, the administration of sodium bicarbonate or calcium may be considered; early consultation with a toxicologist is suggested to guide management. The one study of calcium administration for hyperkalemia in cardiac arrest showed an association with worse outcomes (Cashen et al. 2023, 109673) while another study (Wang et al. 2016, 105) in adults found a lower rate of ROSC with calcium, sodium bicarbonate, or both. No evidence was identified in pediatric patients that evaluated the use of sodium bicarbonate for lowering potassium, and evidence in adults does not show lowering of potassium levels or improved outcomes after cardiac arrest.

Management of Reversible Causes of Cardiac Arrest: Pulmonary Embolus

Last Full Review: ILCOR 2025

Cardiac arrest secondary to pulmonary embolism (PE) in pediatric patients is an uncommon but critical event with high morbidity and mortality. Standard cardiopulmonary resuscitation (CPR) alone may be insufficient in cases of massive PE, prompting consideration of adjunctive or alternative interventions. Emerging therapies, such as systemic fibrinolysis, surgical or catheter-directed embolectomy, and extracorporeal cardiopulmonary resuscitation (ECPR) have been explored primarily in adult populations, with limited evidence in children. A new systematic review examines the current evidence surrounding CPR and these alternative interventions in the pediatric population, aiming to inform clinical decision-making and identify gaps for future research.

 

Evidence Summary

A 2025 systematic review and Consensus on Science with Treatment Recommendations (CoSTR) by the International Liaison Committee on Resuscitation (ILCOR) (Tiwari et al. 2024; Scholefield et al. 2025, S116) examined clinical outcomes in infants and children experiencing cardiac arrest due to confirmed or suspected PE across in-hospital and out-of-hospital settings. The review assessed the impact of modifying standard CPR protocols by incorporating interventions such as fibrinolytic therapy, surgical embolectomy, mechanical thrombectomy and the use of ECPR. The aim was to determine whether these specific treatment alterations offered advantages over conventional CPR in pediatric cases involving PE. No studies were identified in the pediatric population that directly answered the question.

The evidence identified included two case series (Morgan et al. 2018, e229; Pelland-Marcotte et al. 2019, e144) with 10 infants and children who received adjunctive therapies in addition to standard care for cardiac arrest due to confirmed or suspected PE. In the first case series (Morgan et al. 2018, e229), PE was identified as the cause of in-hospital cardiac arrest in 5 out of 79 children who underwent at least 5 minutes of CPR. These patients received intravenous tissue plasminogen activator (tPA) in addition to standard resuscitation efforts. Four of the five patients survived to hospital discharge, with three achieving favorable neurological outcomes. Another retrospective cohort study (Pelland-Marcotte et al. 2019, e144) from two pediatric hospitals reported on 170 children with massive or submassive PE, five of whom experienced cardiac arrest. These patients were treated with various combinations of embolectomy, thrombolysis, catheter-directed thrombolysis, and extracorporeal membrane oxygenation (ECMO) alongside standard CPR protocols. All five achieved return of spontaneous circulation (ROSC), and four survived to hospital discharge. The limited number of cases and variability in data prevent definitive conclusions about the efficacy of these interventions compared to standard CPR for pediatric cardiac arrest due to suspected of confirmed PE (Tiwari et al. 2024; Scholefield et al. 2025, S116).

Insights and Implications

While these findings suggest potential benefits of incorporating advanced interventions in pediatric PE-related cardiac arrest, the small sample sizes and lack of comparative studies underscore the need for further research.

 

Management of Bradycardia with Hemodynamic Compromise

Last Full Review: ILCOR 2025

The normal heart rate for children and infants varies with age. Bradycardia in this population is defined as below the normal range for age and can be caused by intrinsic heart dysfunction of the conduction system or by extrinsic factors such as poisonings (beta-blockers, calcium channel blockers, cardiac glycosides, clonidine and other central alpha-2 agonists, organophosphates). The most common cause of severe bradycardia in children is hypoxia, typically secondary to respiratory failure. If not promptly addressed, severe bradycardia can lead to hemodynamic compromise with progression to pulseless electrical activity (PEA) and cardiac arrest. Past International Liaison Committee on Resuscitation (ILCOR) reviews of bradycardia in infants and children have focused on bradycardia unresponsive to oxygenation and/or ventilation treated with atropine versus epinephrine, or the reviews have focused on cardiac arrest or symptomatic bradycardia treated with atropine compared with no atropine. Transcutaneous pacing for symptomatic bradycardia was included in an evidence update. The various management strategies for bradycardia with hemodynamic compromise in children was the topic of a 2025 ILCOR scoping review.

 

Evidence Summary

An ILCOR scoping review (Topjia et al. 2025; Scholefield et al. 2025, S116) sought evidence for specific management strategies for bradycardia (defined as a heart rate of less than 60 beats per minute or a heart rate low for age) with hemodynamic compromise in the in-hospital or out-of-hospital setting. Management strategies included oxygenation or ventilation, anticholinergic drugs (e.g., atropine), inotropes or chronotropes (e.g., epinephrine, isoproterenol), pacing (e.g., transcutaneous or temporary cardiac pacing), or cardiopulmonary resuscitation (CPR). The comparator was another specific management strategy, including another drug, therapy, placebo or no drug. Studies with newborns or animals were excluded. Of the studies identified with the literature search, none assessed the administration of oxygen, ventilation or transcutaneous pacing. Two articles addressed the use of atropine for bradycardia with hemodynamic compromise (Atabek et al. 2002, 13; Khera et al. 2019, 370) and three described the use of epinephrine during CPR for a documented rhythm of bradycardia with poor perfusion (Holmberg et al. 2020, 180; Khera et al. 2019, 370; O’Halloran et al. 2024, 242).

Atabek et al. (Atabek et al. 2002, 13) described a case series of fourteen 2- to 5-year-olds given atropine (6 to 10 doses) for Amitraz (pesticide) poisoning. Eight patients had bradycardia with poor perfusion, and all had resolution of bradycardia and survived to hospital discharge. Khera et al. (Khera et al. 2019, 370), in a multicenter retrospective cohort of 5,592 infants less than 30 days of age and children less than 18 years of age, assessed the prevalence and predictors of survival with progression from bradycardia with a pulse as an initial rhythm to pulseless in-hospital cardiac arrest despite CPR. Half of this cohort (50.1%, 2,799) received CPR for bradycardia with poor perfusion, with a further 869 (31% of the cohort) becoming pulseless after a median 3 minutes of CPR. The highest survival to discharge rate (70%, 1,351/1,930) was for children with bradycardia with a pulse, while children who became pulseless despite CPR had a 19% lower likelihood of surviving to hospital discharge than those who were initially pulseless. Of children who received both CPR and atropine, none survived to hospital discharge, and of children who received CPR and epinephrine, none survived to hospital discharge.

Two other studies (Holmberg et al. 2020, 180; O’Halloran et al. 2024, 242) described the administration of epinephrine in children with bradycardia with poor perfusion and who were receiving CPR. In a retrospective cohort study of 7,056 patients with bradycardia with poor perfusion (Holmberg et al. 2020, 180), children who received epinephrine given within 10 minutes of CPR were compared with those who received CPR without epinephrine. Survival to hospital discharge, survival to 24 hours, return of spontaneous circulation (ROSC) and favorable neurological outcome at discharge were all lower in the CPR plus epinephrine group. A second retrospective cohort study (O’Halloran et al. 2024, 242) of 452 patients less than 19 years old compared early “bolus” epinephrine within the first 2 minutes of CPR versus no bolus of epinephrine or epinephrine more than 2 minutes after CPR. A benefit was not shown with early epinephrine administration for the outcome of favorable neurologic outcome at hospital discharge.

The ILCOR review (Topjia et al. 2025; Scholefield et al. 2025, S116) notes that once bradycardia progresses to pulseless cardiac arrest, the administration of epinephrine follows the pediatric cardiac arrest recommendations. The ILCOR Pediatric Life Support Task Force agreed that there was no data to support a good practice statement for the use of atropine, epinephrine or transcutaneous pacing. They have consequently withdrawn previous treatment recommendations from 2010 (unchanged after a 2020 Evidence Update) for epinephrine administration to infants and children with bradycardia and poor perfusion unresponsive to ventilation and oxygenation. In addition, the previous 2010 recommendation for the administration of atropine for bradycardia caused by increased vagal tone or anticholinergic drug toxicity has been withdrawn, as well as the recommendation for transthoracic pacing in selected cases of bradycardia caused by complete heart block or abnormal function of the sinus node. In their place, a new good practice statement states: “For patients with bradycardia and poor perfusion not responsive to oxygenation and ventilation, consider initiating CPR” (Topjia et al. 2025; Scholefield et al.2025, S116).

Insights and Implications

The ILCOR scoping review (Topjia et al. 2025; Scholefield et al.2025, S116) found insufficient evidence to support the prior treatment recommendations from 2010. Since the 2010 ILCOR review on this topic, ILCOR review processes have changed and now follow more stringent GRADE methodology for evidence evaluation. More research is needed to conclusively determine the effect of atropine or epinephrine administration or transcutaneous pacing for bradycardia with hemodynamic instability in children not receiving CPR.

The Red Cross guidelines are informed by the ILCOR review and treatment recommendations and have been revised to reflect the lack of evidence. While there is no direct evidence for the use of atropine in pediatric bradycardia with poor perfusion, its use has been proposed for bradycardia induced by certain poisonings (e.g., digoxin, diltiazem, clonidine, grayanotoxin ingestion, organophosphates, carbamates) (Demir et al. 2011, 526426; Duke 1972, 754; Lavonas et al. 2023,e149; Wills et al. 2010, 328) or increased vagal tone (e.g., Bezold-Jarisch reflex, swallow syncope). Temporary transcutaneous pacing has been suggested for atrioventricular nodal blocks or failing permanent pacemaker and is reasonable for the treatment of life-threatening bradydysrhythmias induced by poisoning from β-blockers, calcium channel blockers, cardiac glycosides or local anesthetic systemic toxicity (Lavonas et al. 2023,e149). Evidence for the use of atropine or pacing in these very specific situations is primarily from case reports and thus subject to bias and of very low certainty.

 

Resuscitation of Adult and Pediatric Patients with Durable Mechanical Circulatory Support and Acutely Altered Perfusion or Cardiac Arrest

Last Full Review: ILCOR 2025

Mechanical circulatory support devices, including left ventricular assist devices (LVADs) and biventricular assist devices (BiVADs), have become indispensable in managing advanced heart failure. These devices serve various roles as:

• Bridges to transplantation.
• Therapy for patients ineligible for transplant.
• Temporary support during recovery or decision-making processes.

 

By mechanically augmenting or replacing the heart’s pumping function, mechanical circulatory support devices restore systemic circulation, thereby improving end-organ perfusion (Sen et al. 2016, 153). Despite their benefits, mechanical circulatory support devices introduce unique clinical challenges. Patients with continuous-flow LVADs often exhibit diminished or absent pulses, complicating traditional assessments of perfusion and blood pressure. Complications such as infections, particularly at the driveline site, occur in over 25% of patients within the first 2 years (Ali et al. 2020, 835). Other risks include right ventricular failure, arrhythmias and pump thrombosis. Notably, cardiac arrest in LVAD patients carries a high in-hospital mortality rate, exceeding 60% (Barssoum et al. 2022, 246). The topic of resuscitation of patients with durable mechanical circulatory support who have acutely altered perfusion or cardiac arrest was first reviewed by the International Liaison Committee on Resuscitation (ILCOR) in 2025.

 

Evidence Summary

A 2025 scoping review by ILCOR (Moskowitz et al. 2025; Drennan et al. 2025, S72) sought to identify and thematically map relevant studies of patients of any age who were receiving durable mechanical support of any kind and who develop acute impaired perfusion resulting in the need for acute resuscitation in the in-hospital or out-of-hospital setting. The search included all study types from two databases as well as the gray literature. After full text review, 32 studies were included in the review. Of the 32 included studies, 30 were case reports, eight were case series with three to ten patients, and two were cohort studies. The durable mechanical support for all studies was via a left ventricular or biventricular assist device. Thematic grouping of identified studies included:

1. Studies highlighting challenges of identifying patients with durable mechanical circulatory support devices with acutely altered perfusion and cardiac arrest. Because patients with continuous-flow LVADs do not have native heartbeats, pulselessness as well as difficulty measuring blood pressure with noninvasive electronic devices present challenges in determining if perfusion is adequate. This can lead to delays in the initiation of chest compressions and contribute to poor outcomes. In some cases, paramedics were unsure of whether chest compressions can be provided to patients using mechanical circulatory support devices. Some studies and reviews presented proposed algorithms for the resuscitation of patients with durable mechanical circulatory support.
2. Patient outcomes in mechanical circulatory support device-supported patients with cardiac arrest after performance of chest compressions versus no chest compressions. A cohort study (Barssoum et al. 2022, 246) of 578 patients with LVADs who had cardiac arrest reported higher in-hospital mortality in patients who received chest compressions than those who did not receive chest compressions (74.3% versus 55%).
3. Outcomes in mechanical circulatory support device-supported patients who have cardiac arrest and receive compressions. Across these studies, a favorable outcome was reported in 71 out of 226 (31.4%) mechanical circulatory support device-supported patients with cardiac arrest. Causes of cardiac arrest reported included device thrombus, cardiac tamponade, accidental disconnection and driveline failure.
4. Complications of chest compressions. Device dislodgement or other complications related to the function of a mechanical circulatory support device after chest compressions were not reported in any studies. It was considered and evaluated by pump function assessment, imaging, and/or autopsy in several studies. The authors of the review highlighted that the absence of reported cases of device dislodgement following cardiopulmonary resuscitation strongly suggests that the risk of such dislodgement due to chest compressions is low.

 

The evidence identified with this scoping review was considered insufficient to support a systematic review or meta-analysis. However, several good practice statements were made by ILCOR (Moskowitz et al. 2025; Drennan et al. 2025, S72):

• In patients receiving durable mechanical circulatory support who develop acutely impaired perfusion because of cardiac arrest and who are not in the immediate peri-device implantation period, we suggest performing rather than withholding chest compressions.
• When caring for patients with durable mechanical circulatory support devices who suffer acutely impaired perfusion as a result of cardiac arrest, we suggest minimizing delays in initiating chest compressions while simultaneously assessing for device-related reversible causes of acutely impaired perfusion.
• We suggest rescuers follow an algorithmic approach to concurrently assess and respond to acutely impaired perfusion in patients receiving durable mechanical circulatory support.

 

The scoping review authors describe an additional review of a scientific statement from the American Heart Association and guidance from the British Societies LVAD Emergency Algorithm Working Group (Akhtar et al. 2024, 493; Peberdy et al. 2017, e1115). The latter group recommends delaying chest compressions in LVAD patients for up to 2 minutes while efforts to restart the device are made and efforts to restart the LVAD device could occur in parallel with chest compressions as long as multiple rescuers are available.

Insights and Implications

As this ILCOR review was a scoping review, no treatment recommendations can be generated. The good practice statements made, however, are reasonable and have informed new Red Cross guidelines and algorithmic treatment. Perhaps most importantly, there was no evidence of device dislodgement with chest compressions in the studies identified, which reinforces the recommendation to provide chest compressions without hesitation when indicated. In addition, evidence suggests that patients with durable mechanical circulatory support devices in cardiac arrest who receive compressions earlier may have better outcomes. By combining assessment of device-related reversible causes of acutely impaired perfusion with initiating chest compressions, delays are minimized.