Bradycardia with haemodynamic compromise in children: PLS 4030.30 TF ScR

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: none

The following authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chair: Amanda O’Halloran and Alexis Topjian were co-authors of one included study.¹ They were excluded from data extraction from this study.

Task Force Synthesis Citation

Topjian A, Scholefield B, Gray J, Ashworth J, (Pediatric Life Support (PLS) Taskforce), Kienzle M, Ross C, O’halloran A, Gray S (Content experts), Morrison LJ (SAC) on behalf of the Pediatric Life Support Task Force. Bradycardia with haemodynamic compromise – a scoping review: Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium, International Liaison Committee on Resuscitation (ILCOR) Pediatric Life Support Task Force, 2025, Available from http://ilcor.org

Methodological Preamble and Link to Published Scoping Review

The continuous evidence evaluation process started with a review of prior PICOSTs related to the treatment of bradycardia with hemodynamic instability. Three evidence updates were identified of which two had existing PICOSTS

• In infants and children with bradycardia that is unresponsive to oxygenation and/or ventilation(P), does the use of atropine(I), as compared with epinephrine(C), improve patient outcome (return to age-appropriate heart rate, subsequent pulseless arrest, survival)(O)?
• In infants and children with cardiac arrest (out-of-hospital and in-hospital) or symptomatic bradycardia (P), does the use of atropine (I) compared with no atropine use (C), improve outcome (O) (eg. ROSC, survival)?

There was additional evidence updated without a PICOST that addressed the use of transcutaneous pacing for symptomatic bradycardia.

For 2024, to focus on the management of infant and children with bradycardia with hemodynamic instability, we formulated a new 2024 PICOST.

Scoping Review

Webmaster to insert the Scoping Review citation and link to Pubmed using this format when/if it is available.

Topjian A, Scholefield B, Gray J, Ashworth J, Kienzle M, Ross C, O’halloran A, Gray S, Morrison LJ on behalf of the Pediatric Life Support Task Force. Bradycardia with haemodynamic compromise in children: a scoping review (in preparation)

PICOST

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: In children with bradycardia (heart rate of < 60 or heart rate low for age) with hemodynamic compromise in hospital or out of hospital setting

Intervention: Any specific management strategies including but not limited to 1) oxygenation or ventilation 2) anticholinergic drugs (e.g. Atropine), 3) inotropes or chronotropes (e.g. epinephrine, isoproterenol) or 4) electrophysiologic pacing (e.g. transcutaneous pacing, temporary cardiac pacing) or 5) CPR.

Comparators: Another specific management strategy including another drug, therapy, placebo or no drug.

Outcomes: Any outcome as defined in the Pediatric Core Outcome Set for Cardiac Arrest²

Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies), case series > 10 studies are eligible for inclusion. Grey literature and social media and non-peer reviewed studies, case reports, unpublished studies, conference abstracts and trial protocols are excluded in this review.

Timeframe: Default is all years.

Literature search updated to October 6, 2024

Search Strategies

Articles for review are obtained by searching PubMed, EMBASE, and Cochrane

Key search terms included “bradycardia”, “cardiac output, low”, “bradycardia with poor perfusion”, “atropine”, “epinephrine”, “isoproterenol”, “glycopyrrolate”, “cholinergic antagonists”, “Cardiac pacing”, “adolescent”, “child”

Inclusion and Exclusion criteria

Citations obtained from each database (Cochrane, Embase, and Medline) were listed and merged, and duplicates were removed with electronic filtering. The final set of citations with title and abstracts were retrieved and imported into Covidence. Two reviewers independently screened titles and abstracts. In the event of discordant selection, consensus was achieved with discussion and review with at least a third reviewer.

Inclusion criteria were children < 18 years of age who had bradycardia with hemodynamic compromise. Bradycardia with hemodynamic compromise was defined as 1) heart rate less than normal for age or 2) HR < 60 independent of age. Hemodynamic compromise was defined as age-based hypotension, altered mental status (GCS <15, non-responsive, or comatose) or other signs of shock (low urine output, elevated lactate), including cardiac arrest. We included studies about therapies: oxygenation or ventilation, anticholinergics, inotropes, chronotropes, electrical pacing, and CPR.

Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies), case series including more than 10 subjects were eligible for inclusion.

We excluded studies that included newborns or occurred in the delivery room. We excluded animal studies. Studies where atropine or epinephrine were used as pre-medications were excluded because they were not given in response to bradycardia with hemodynamic compromise. Studies about intracardiac and transesophageal pacing were excluded because they cannot be used emergently in response to an acute episode of bradycardia. Grey literature, social media, non-peer reviewed studies, case reports, unpublished studies, conference abstracts and trial protocols are excluded in this review.

Table 1: Studies reporting treatment and outcomes for bradycardia with hemodynamic compromise

Task Force Insights

1. Why this topic was reviewed.

Bradycardia in children has classically been defined as a heart rate less than normal for age or less than 60 beats per minute, independent of age⁶. Bradycardia can be caused by intrinsic dysfunction, injury, or irregularities of the heart and its conduction system. Infants may be born with congenital heart defects, or antibody induced congenital heart-block resulting in bradycardia. A multitude of external factors can affect the heart muscle, the parasympathetic and sympathetic nerve supply and the conduction system. These factors include hypoxemia, metabolic acidosis or metabolic disorders (e.g., hypothyroidism or inborn errors of metabolism), medication or exposure to medication (e.g., dexmedetomidine), vagal stimulation of the airway or diaphragm (e.g., during laryngoscopy or abdominal insufflation surgery) and following cardiac surgery with injury to the sinus or atrio-ventricular node or conduction pathways⁶.

Children and infants with bradycardia may be asymptomatic with normal perfusion, and bradycardia can be temporary and reverse spontaneously. However, bradycardia can be associated with hemodynamic compromise with resultant cardiopulmonary failure and shock. In this scenario, end-organ dysfunction and injury (including neurological injury) can occur due to cellular hypoxia and poor perfusion. Without emergency medical intervention, bradycardia with hemodynamic compromise can lead to true cardiac arrest and resultant significant morbidity.

Bradycardia with poor perfusion as the initial rhythm occurs in approximately 50% of pediatric in-hospital cardiac arrests, occurring in 8000 children in the per year in the US ⁷. Approximately one third of patients who receive CPR for bradycardia with poor perfusion progress to pulseless arrest. Survival from cardiac arrest due to bradycardia with poor perfusion has increased over time ⁸. Rates of survival to hospital discharge for patients who receive CPR for bradycardia with poor perfusion are 70%, compared to 30% for those with bradycardia with poor perfusion that progress to pulselessness and 37.5% of those with initial pulseless cardiac arrest ⁹.

Possible treatment for bradycardia with hemodynamic compromise includes: reversing hypoxemia, if present, through supplemental oxygen or bag-mask ventilation, using anticholinergics if increased vagal tone is the cause, administering epinephrine or chronotropic medication, external or internal electrical cardiac pacing, and providing CPR prior to the progression to pulseless arrest¹⁰.

Current resuscitation guidelines recommend epinephrine for persistent bradycardia with poor perfusion during CPR to increase the likelihood of ROSC and thus increase rates of survival to hospital discharge¹⁰. However, data are limited both about the natural progression of bradycardia during CPR and the efficacy of epinephrine. A recent study suggested that in children receiving CPR for bradycardia with poor perfusion, receipt of epinephrine was associated with worse outcomes ⁵.

This topic was chosen for review by the PLS Task Force because it has never been systematically reviewed by ILCOR.

2. Narrative summary of evidence identified

Of the initial 4851 abstracts, 4657 were excluded. 194 abstracts were included for full text review. (Figure 1) Of these, 23 were included for text extraction, of which 19 described the epidemiology of prevalence and outcomes in children who had a cardiac arrest with an initial documented rhythm of bradycardia with poor perfusion and these were used to inform the Task Force discussions. A total of 4 papers reported on interventions of interest. Two papers commented on the impact of atropine for bradycardia with hemodynamic compromise, one in patients receiving CPR and one in patients who never received CPR. Three of these papers studied the administration of epinephrine during CPR for a first documented rhythm of bradycardia with poor perfusion. (Table 1) No studies were identified that assessed the administration of oxygen, ventilation or transcutaneous pacing. There were insufficient studies identified to support a more specific systematic review.

3. Narrative Reporting of the task force discussions

Nineteen studies published between 2002 and 2023 described cohorts of patients who received CPR for cardiac arrest where bradycardia with poor perfusion was the first documented rhythm^{8, 11-27}. Only one study included OHCA patients ¹². In almost all studies, on univariate analysis, survival to hospital discharge rates were higher when cardiac arrest was due to a first documented rhythm of bradycardia with poor perfusion (43-77%) compared to PEA or asystole.

One study evaluated trends in survival over time in the United States of patients who received CPR for an initial non-pulseless rhythm (i.e., bradycardia with poor perfusion) and found that survival rates improved from 2000-2005 to 2016-2018 from 57% to 66% (p<0.001)⁸. Two studies evaluated outcomes of patients who had an initial non-pulseless rhythm (i.e., bradycardia with poor perfusion) that either progressed to pulselessness or continued to be non-pulseless during CPR and found that patients that went on to lose a pulse during CPR had lower rates of ROSC and SHD ^{9, 28}

The task force identified numerous gaps in the literature. These included the absence of studies evaluating bradycardia with poor perfusion in patients not receiving CPR and the lack of comparison groups for interventions (e.g., CPR vs no CPR) for bradycardia with hemodynamic compromise.

All studies evaluating CPR for bradycardia with poor perfusion were in patients who were already receiving CPR for presumed cardiac arrest. There was discussion around the timing of initiation of CPR for bradycardia for poor perfusion in studies, specifically as many of these studies are retrospective, and thus the true reason for CPR initiation (i.e., what was the heart rate and what was poor perfusion) is unknown.

For patients who received CPR there was discussion of indirect evidence support to CPR for bradycardia with poor perfusion, specifically from studies that show 1) patients who receive CPR for bradycardia with poor perfusion have better survival rates than those who receive CPR for asystole or PEA, and 2) patients who receive CPR for bradycardia with poor perfusion and maintained that rhythm had higher survival rates than those who progressed to pulselessness. There was concern that there is harm associated with delaying the initiation of CPR for patients with bradycardia and hemodynamic compromise who are not responsive to oxygenation and ventilation as progression to pulselessness is associated with worse outcomes.

The task force discussed the three papers related to the administration of epinephrine for bradycardia with poor perfusion all of which assessed patients who were already receiving CPR. One study showed no benefit of early epinephrine, one demonstrated worse outcomes in patients who received epinephrine compared to no epinephrine and one did not report epinephrine-based outcomes. The task force discussed that once the patient moves to CPR for pulseless cardiac arrest the use of epinephrine is reviewed for a different indication.

The task force agreed that there was no data to support a good practice statement for atropine, epinephrine or transcutaneous pacing.

Good practice statement:

For patients with bradycardia and poor perfusion not responsive to oxygenation and ventilation, consider initiating CPR (Good practice Statement)

Withdrawn Prior Treatment Recommendations:

The following three previous treatment recommendations are all unsupported based on a rigorous ILCOR Task Force led Scoping Review. The lack of any available direct or indirect evidence, considered appropriate by the TF for inference, suggests these treatment recommendations should all be withdrawn.

• Epinephrine may be administered to infants and children with bradycardia and poor perfusion that is unresponsive to ventilation and oxygenation (2010, unchanged 2020 EvUp, withdrawn 2025)
• It is reasonable to administer atropine for bradycardia caused by increased vagal tone or anti-cholinergic drug toxicity. There is insufficient evidence to support or refute the routine use of atropine for pediatric cardiac arrest. (2010, unchanged 2020 EvUp, withdrawn 2025)
• In selected cases of bradycardia caused by complete heart block or abnormal function of the sinus node, emergency transthoracic pacing may be lifesaving. Pacing is not helpful in children with bradycardia secondary to a post-arrest hypoxic/ischemic myocardial insult or respiratory failure. Pacing was not shown to be effective in the treatment of asystole in children. (2000, unchanged 2020 EvUp, withdrawn 2025)

Knowledge Gaps

Specific gaps include:

• The effect of atropine or epinephrine administration for bradycardia with hemodynamic instability in patients not receiving CPR

• The effect of transcutaneous pacing for bradycardia with hemodynamic instability in patients not receiving CPR

• The effect of epinephrine on outcomes if administered for bradycardia with poor perfusion during CPR

• What the heart rate threshold should be used to determine the initiation of CPR

References

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