Weight-Based Versus Flat Dosing of Epinephrine During Cardiac Arrest in the Pediatric Intensive Care Unit: A Multi-Center Survey

Abstract

Objectives:

Pediatric Advanced Life Support (PALS) guidelines include weight-based epinephrine dosing recommendations of 0.01 mg/kg with a maximum of 1mg, which corresponds to a weight of 100kg. Actual practice patterns are unknown.

Design:

Multi-center cross-sectional survey regarding institutional practices for the transition from weight-based to flat dosing of epinephrine during cardiopulmonary resuscitation in pediatric intensive care units (PICUs). Exploratory analyses compared epinephrine dosing practices with several institutional characteristics using Fisher’s exact test.

Setting:

Internet-based survey.

Subjects:

U.S. PICU representatives (one per institution) involved in resuscitation systems of care.

Interventions:

None.

Measurements and main results:

Of 137 institutions surveyed, 68 (50%) responded. Most responding institutions are freestanding children’s hospitals or dedicated children’s hospitals within combined adult/pediatric hospitals (67; 99%); 55 (81%) are academic and 41 (60%) have PICU fellowship programs. Among respondents, institutional roles include PICU medical director (13; 19%), resuscitation committee member (23; 34%) and attending physician with interest in resuscitation (21; 31%). When choosing between weight-based and flat dosing, 64 (94%) respondents report using patient weight, 23 (34%) patient age and 5 (7%) patient pubertal stage. Among those reporting using weight, 28 (44%) switch at 50 to <60kg, 17 (27%) at 60 to <80kg, 5 (8%) at 80 to <100kg and 8 (12%) at ≥100kg. Among those reporting using age, 4 (17%) switch at 14 to <16 years, 5 (22%) at 16 to <18 and 6 (26%) at ≥18. Twenty-nine (43%) respondents report using ideal body weight when dosing epinephrine in obese patients. Using patient age in choosing epinephrine dosing is more common in institutions that require ACLS certification for some/all code team responders compared to institutions that do not require ACLS certification (52% vs 22%, p = 0.02).

Conclusions:

The majority of PICUs surveyed report epinephrine dosing practices that are inconsistent with PALS guidelines.

Introduction

In-hospital cardiac arrest (IHCA) affects 15,000 children in the U.S. each year.¹ Pediatric Advanced Life Support (PALS) guidelines recommend high-quality chest compressions and ventilations with epinephrine administration every 3–5 minutes during cardiopulmonary resuscitation (CPR). Epinephrine is administered to augment coronary perfusion pressure and increase the likelihood of return of spontaneous circulation (ROSC). Current PALS guidelines, which apply until age 18, suggest a dose of 0.01mg/kg (weight-based dosing) to a maximum (adult) dose of 1mg (flat dosing).² Unlike other emergency medications which reach adult dosing at smaller doses, a child would have to weigh 100kg or more to receive flat dosing. Thus, clinicians may administer flat doses of epinephrine to pediatric patients under variable circumstances.

The objective of this study was to characterize institutional practices in the transition from weight-based to flat epinephrine dosing during CPR in US Pediatric Intensive Care Units (PICUs).

Materials and Methods

The Institutional Review Board (IRB) at the Children’s Hospital of Philadelphia deemed this non-human subjects research; thus, no IRB review was required. The survey and study data were collected and managed using Research Electronic Data Capture (REDCap; Vanderbilt University, Nashville, TN) tools hosted at the Children’s Hospital of Philadelphia. REDCap is a secure, web-based software platform designed to support data capture for research studies.³

American children’s hospitals were identified through the Children’s Hospital Association website (www.childrenshospitals.org) (225 hospitals). Those with pediatric critical care services were subsequently identified using individual institutional websites (197 hospitals). Pediatric critical care physicians with knowledge of hospital resuscitation systems (e.g., PICU medical director, resuscitation committee leader/member) were successfully identified through email, phone calls and social media at 137 of 197 (70%) hospitals and subsequently provided with individualized survey links via email. One individual was contacted per institution. The email provided the purpose of the survey, contact information for the study leads and explained the voluntary and anonymous nature of the survey.

The cross-sectional survey consisted of 20 mandatory questions and additional questions based on conditional branching logic. Survey questions were created, edited and then pilot tested among the author group, the members of which hold the same pediatric subspecialty board certification, completed similar training and serve in similar roles to the survey recipients. Thus, the author group was considered an appropriate population for pre-testing survey questions. Survey directions specifically requested information regarding the institutional (rather than personal) dosing strategies for epinephrine in the PICU. All emails were delivered and the survey remained open for five weeks (April 27, 2020 to June 1, 2020), during which time three reminder emails were sent to individuals who had not responded.

All survey responses remained de-identified throughout the survey distribution period and during all analyses. Descriptive statistics were calculated and reported as frequencies and percentages. In exploratory analyses, epinephrine dosing practices were compared to several institutional factors (hospital size [hospital bed number], hospital type [freestanding children’s hospital vs others], Advanced Cardiac Life Support (ACLS) certification [required for some or all code team respondents vs not required] and presence of a fellowship program). Comparative statistics were calculated using Fisher’s exact test and reported as proportions. A p-value < 0.05 was considered statistically significant.

Results

Of 137 institutions surveyed, 68 (50%) responded. All questions were completed. Only one survey was completed for each individualized link provided, indicating one response per institution. Supplementary Table 1 summarizes institution and respondent demographics. Thirty-eight hospitals (56%) are dedicated children’s hospitals within combined pediatric/adult hospitals; 29 (43%) are freestanding children’s hospitals and 1 (1%) institution has pediatric beds within an adult hospital. Most are academic (55; 81%) and 41 (60%) have a pediatric critical care fellowship program. Respondents include 13 (19%) PICU medical directors, 23 (34%) resuscitation committee members/leaders and 21 (31%) attending physicians with interest in resuscitation. The maximum patient age within responding PICUs is 18 years in 10 (15%), 21 in 17 (25%), a different age in 15 (22%) and no maximum age in 26 (38%). In 41 centers (60%), ACLS certification is not required for code team responders.

Table 1 summarizes epinephrine dosing practices during cardiac arrest in PICUs. In switching from weight-based to flat dosing, most providers report considering weight (64; 94%); 23 (34%) consider age and 5 (7%) consider pubertal stage (respondents were not limited to one patient characteristic). Among those reporting using weight, 28 (44%) switch to flat dosing at 50 to <60kg, 17 (27%) at 60 to <80kg, 5 (8%) at 80 to <100kg and 8 (13%) at ≥100kg. Six (9%) responded that it varies within the institution and/or is not standardized. Among those reporting using age, 4 (17%) switch at 14 to <16 years, 5 (22%) at 16 to <18 and 6 (26%) at ≥18. Eight (35%) responded that it varies within the institution and/or is not standardized. Twenty-nine (43%) institutions report using ideal body weight when dosing epinephrine in obese patients.

Table 1.

Institutional Practices for Epinephrine Dosing.

Question/Topic	n (%)
Consideration of patient age when switching from weight-based to adult (flat) dosing
Yes	23 (34)
No	45 (66)
If yes, age range for switching
12 to < 14 years	0 (0)
14 to < 16 years	4 (17)
16 to < 18 years	5 (22)
≥ 18 years	6 (26)
It varies within our institution and/or is not standardized	8 (35)
Consideration of patient weight when switching from weight-based to adult (flat) dosing
Yes	64 (94)
No	4 (6)
If yes, weight range for switching
50 to < 60kg	28 (44)
60 to < 80kg	17 (27)
80 to < 100kg	5 (8)
≥ 100kg	8 (12)
It varies within our institution and/or is not standardized	6 (9)
Consideration of patient pubertal stage when switching from weight-based to adult (flat) dosing)
Yes	5 (7)
No	63 (93)
If yes, pubertal stage for switching
Pre-pubertal	0 (0)
Pubertal	3 (60)
Post-pubertal	0 (0)
It varies within our institution and/or is not standardized	2 (40)
Use of ideal body weight for obese patients
Yes	29 (43)
No	39 (57)
Use of a cognitive aid for medication dosing
Yes	68 (100)
No	0 (0)

In an exploratory comparative analysis of institutional factors, using age when choosing epinephrine dosing is more common in institutions that require ACLS certification for some/all code team responders compared to institutions that do not require ACLS certification (52% vs 22%, p = 0.02). Other institutional factors explored are not associated with epinephrine dosing practices (Supplementary Tables 2–5).

Discussion

In this multi-center survey, nearly all survey respondents report considering patient weight when choosing an epinephrine dosing strategy during cardiac arrest in PICUs. The largest proportion of those respondents consider flat dosing for patients weighing 50 to <60kg. One-third of respondents report making epinephrine dosing decisions using patient age and there is variability in the age thresholds used. Approximately half of respondents report using ideal body weight when dosing epinephrine in obese patients. Taken together, survey results show heterogeneity in practice with most institutions reporting epinephrine dosing practices that are inconsistent with PALS recommendations.

Current PALS guidelines apply to patients <18 years of age with an implicit recommendation that patients <100kg should receive weight-based epinephrine dosing. However, only 6 (9%) respondents report switching to flat dosing at 18 and 8 (12%) report employing weight-based dosing up to 100kg. This discordance of institutional practices with guidelines may reflect the lack of supportive evidence for specific dosing strategies and/or the potentially counterintuitive nature of most adolescents receiving a lower dose of epinephrine than adults of the same weight. Further, such heterogeneity has clinical implications; a 50kg child receives twice the weight-based dose in a flat dose, potentially causing differing effects on coronary perfusion pressure, myocardial oxygen demand and cerebral blood flow and thereby outcomes.

The lack of ACLS certification requirements for code responders at 60% of institutions deserves mention. Because adults with childhood-onset chronic disease are commonly admitted to PICUs,^4,5 some resuscitation leaders may consider PICU patients older than 18 physiologically more similar to children than adults. Our exploratory analysis demonstrated that more institutions requiring ACLS certification use patient age when dosing epinephrine, a practice most consistent with PALS guidelines, providing evidence that certification requirements may lead to more guideline-compliant care. Otherwise, PALS-noncompliant epinephrine dosing is widespread and not related to the institutional factors explored.

This study has limitations. The 50% response rate may have been due to the COVID-19 pandemic. Therefore, responses may not reflect the full diversity of institutional policies throughout U.S. PICUs. Second, survey responses are prone to bias as respondents may choose responses perceived as more consistent with guidelines or optimal practice. As respondents were not asked to provide institutional protocols beyond completing the survey, the possibility of responses reflecting the respondent’s individual practice or inaccurate institutional policies cannot be excluded.

Further research into epinephrine dosing during cardiac arrest is needed as recommendations are largely based on expert opinion. That said, reported deviation from PALS dosing recommendations is prevalent, suggesting a need to re-evaluate guideline structure and recommendations.

Conclusions

Survey respondents reported considerable institutional practice variation in the transition from weight-based to flat epinephrine dosing during CPR in PICUs. The majority of PICUs surveyed report epinephrine dosing practices that are inconsistent with PALS guidelines.