What is the recommendation for push dose pressor epinephrine dosing for pediatric and neonatal patients for peri-code blood pressure control? Is there a max dose limit?

Comment by InpharmD Researcher

Current guidelines and literature do not appear to provide a specific recommendation to guide use of push-dose pressor epinephrine for peri-code blood pressure control in pediatric or neonatal patients. Additionally, there appears to be no defined maximum cumulative dose limit for this specific use. Related literature, as included below, generally supports use of low/standard dose epinephrine for pediatric cardiac arrest, as well as longer dosing intervals.

Background

Per the 2025 American Heart Association (AHA)/American Academy of Pediatrics (AAP) Pediatric Advanced Life Support (PALS) guidelines, there is no specific recommendation regarding the use of push-dose pressor epinephrine for peri-code blood pressure control in pediatric or neonatal patients, and no maximum dose limit is specified for such use. The guidelines focus on epinephrine for the management of cardiac arrest, where it is recommended to administer the initial dose as early as possible for nonshockable rhythms and may be reasonable after two defibrillation attempts for shockable rhythms, with subsequent doses every 3 to 5 minutes until return of spontaneous circulation (ROSC) is achieved. [1]

Several other reviews address use of epinephrine during neonatal and pediatric resuscitation, but not directly push-dose pressor epinephrine for peri-code blood pressure control in patients with a pulse. These discussions do not identify any specific pediatric or neonatal regimen for intermittent push-dose epinephrine, including no recommended concentration, bolus dose range, titration strategy, or maximum cumulative dose for transient hypotension or peri-code blood pressure support. The available data are centered on cardiac arrest, severe bradycardia, or asystole, rather than hypotension management before arrest. [2], [3], [4]

For neonatal resuscitation, the most consistently described dosing is epinephrine 0.01 to 0.03 mg/kg IV or IO, repeated every 3 to 5 minutes when needed, with endotracheal epinephrine 0.05 to 0.1 mg/kg considered when vascular access is unavailable. Higher bolus doses (0.1 to 0.2 mg/kg) raise safety concerns, as these have been associated with severe tachycardia, hypertension, reduced stroke volume/cardiac output, and worse post-resuscitation outcomes in neonatal or pediatric models and clinical pediatric arrest data. Repeated neonatal IV doses of 0.03 mg/kg may also produce substantial cumulative exposure, with animal pharmacokinetic data showing plasma epinephrine concentrations exceeding 1000 ng/mL after four doses, along with concern for tachyarrhythmias, suggesting caution against extrapolating repeated or high-dose boluses for blood pressure support outside established arrest algorithms. [2], [3], [4]

For pediatric cardiac arrest, earlier first-dose epinephrine appears to be associated with better outcomes in non-shockable in-hospital and out-of-hospital cardiac arrest, particularly when given within 3 minutes. However, the certainty of evidence is very low, and the optimal repeat-dose interval remains unclear. Evidence evaluating intervals shorter than 5 minutes is inconsistent, and more frequent dosing does not clearly establish benefit. Overall, this supports early standard-dose epinephrine in pediatric arrest but does not provide a basis for push-dose use in peri-code hypotension. [2], [3], [4]

References: [1] Lasa JJ, Dhillon GS, Duff JP, et al. Part 8: Pediatric Advanced Life Support: 2025 American Heart Association and American Academy of Pediatrics Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2025;152(16_suppl_2):S479-S537. doi:10.1161/CIR.0000000000001368
[2] Isayama T, Mildenhall L, Schmölzer GM, et al. The Route, Dose, and Interval of Epinephrine for Neonatal Resuscitation: A Systematic Review. Pediatrics. 2020;146(4):e20200586. doi:10.1542/peds.2020-0586
[3] Vali P, Sankaran D, Rawat M, Berkelhamer S, Lakshminrusimha S. Epinephrine in neonatal resuscitation. Children. 2019;6(4):51. doi:10.3390/children6040051
[4] Ohshimo S, Wang CH, Couto TB, et al. Pediatric timing of epinephrine doses: A systematic review. Resuscitation. 2021;160:106-117. doi:10.1016/j.resuscitation.2021.01.015
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What is the recommendation for push dose pressor epinephrine dosing for pediatric and neonatal patients for peri-code blood pressure control? Is there a max dose limit?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-5 for your response.

A Comparison of High-Dose and Standard-Dose Epinephrine in Children with Cardiac Arrest
Design

Prospective, randomized, double-blind trial

N= 68
Objective To compare high-dose epinephrine (0.1 mg/kg) with standard-dose epinephrine (0.01 mg/kg) as rescue therapy for in-hospital cardiac arrest in children after failure of an initial, standard dose of epinephrine
Study Groups

High-dose epinephrine (n= 34)

Standard-dose epinephrine (n= 34)
Inclusion Criteria Children who remained in cardiac arrest despite CPR and an initial, standard dose of epinephrine from October 31, 1999, to September 30, 2001
Exclusion Criteria Neonates, children with sustained trauma, those whose cardiac arrest commenced outside the hospital, and those with do-not-resuscitate orders
Methods Children were randomly assigned to receive either standard-dose epinephrine (0.01 mg/kg) or high-dose epinephrine (0.1 mg/kg) after failure of an initial standard dose. Randomization was performed by a pharmacist using a random-number generator. CPR was provided according to American Heart Association guidelines.
Duration October 31, 1999, to September 30, 2001
Outcome Measures

Primary: Survival 24 hours after the arrest

Secondary: Rate of return of spontaneous circulation, survival to hospital discharge
Baseline Characteristics   High-dose epinephrine (n= 34) Standard-dose epinephrine (n= 34)
Age — mo 74±62 62±64
Weight — kg 20±15 17±13
Male sex — no. 13 20
Race — no. - White 20 13
Race — no. - Other 14 21
Preexisting disease — no. (%) 32 (94) 31 (91)
Hepatic failure 11 (32) 7 (21)
Cancer 6 (18) 3 (9)
Neurologic disease 4 (12) 4 (12)
Pneumonia 1 (3) 4 (12)
Renal failure 2 (6) 2 (6)
Acquired immunodeficiency syndrome 1 (3) 2 (6)
Other 7 (21) 9 (26)
Initial electrocardiographic rhythm — no. (%) - Asystole 21 (62) 28 (82)
Initial electrocardiographic rhythm — no. (%) - Pulseless electrical activity 9 (26) 6 (18)
Initial electrocardiographic rhythm — no. (%) - Ventricular fibrillation or pulseless ventricular tachycardia 4 (12) 0
Results   High-dose epinephrine (n= 34) Standard-dose epinephrine (n= 34) Unadjusted Odds Ratio (95% CI) p-Value
Return of spontaneous circulation 20 (59) 21 (62) 1.1 (0.4–3.0) 0.80
For ≤20 min 4 (12) 6 (18) 1.6 (0.4–6.3) 0.49
For >20 min but <24 hr 15 (44) 8 (24) 0.4 (0.1–1.1) 0.07
Survival at 24 hr 1 (3) 7 (21) 8.6 (1.0–397.0) 0.05
Survival to hospital discharge 0 4 (12) -- 0.11
Adverse Events Not explicitly mentioned in the provided text
Study Author Conclusions We did not find any benefit of high-dose epinephrine rescue therapy for in-hospital cardiac arrest in children after failure of an initial standard dose of epinephrine. The data suggest that high-dose trapy may be worse than standard-dose therapy.
Critique

The study was well-designed as a prospective, randomized, double-blind trial, which strengthens the validity of the findings. However, the small sample size and occurrence of protocol violations may limit the generalizability of the results. Additionally, the study focused on short-term outcomes (24-hour survival) rather than long-term survival or neurological outcomes, which are more clinically relevant. The study's findings are significant for the specific population studied, but may not be applicable to all pediatric cardiac arrest scenarios, particularly those involving different underlying conditions or settings.

 

References:
[1] [1] Perondi MB, Reis AG, Paiva EF, Nadkarni VM, Berg RA. A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest. N Engl J Med. 2004;350(17):1722-1730. doi:10.1056/NEJMoa032440
Efficacy of Low-Dose Epinephrine Continuous Infusion in Neonatal Intensive Care Unit Patients
Design

Single-center, retrospective review

N= 115
Objective To evaluate the efficacy and safety of low-dose epinephrine continuous infusion at doses <0.05 mcg/kg/min in infants
Study Groups All patients (n= 115)
Inclusion Criteria Patients <44 weeks’ postmenstrual age upon initiation of low-dose epinephrine continuous infusion (<0.05 mcg/kg/min)
Exclusion Criteria Initiation of epinephrine prior to NICU admission, unknown starting dose, non-intravenous administration, bolus during resuscitation, infusion time <3 hours, incomplete BP documentation
Methods Retrospective review of hypotensive infants from 2011–2018. Data collected included initial and maximum epinephrine doses, additional vasoactive agents, short-term efficacy, and adverse effects. Primary outcome was percentage of patients whose dose did not require titration to ≥0.05 mcg/kg/min. Efficacy assessed by significant increase in urine output or BP measurements.
Duration January 1, 2011, to December 31, 2018
Outcome Measures

Primary: Percentage of patients whose dose did not require titration to ≥0.05 mcg/kg/min

Secondary: Significant increase in urine output or BP measurements
Baseline Characteristics   Result
Sex, n (%), male 66 (57)
Gestational age at birth, mean ± SD, wk 31.4 ± 6.0
Prematurity, n (%) 85 (74)
Birth weight, mean ± SD, g 1739 ± 107
Results   Baseline After Epinephrine p-Value
Systolic BP, median (IQR), mm Hg 44 (32-54) 52 (42-64) <0.001
Diastolic BP, median (IQR), mm Hg 26 (18-34) 32 (24-40) <0.001
Mean BP, median (IQR), mm Hg 34 (24-42) 40.5 (32-50) <0.001
UOP; mean ± SD, mL/kg/hr 1.8 ± 2.5 2.8 ± 3.3 <0.001
Adverse Events No significant differences in glucose, lactate, or base deficit levels before and after low-dose epinephrine initiation
Study Author Conclusions

Low-dose epinephrine infusion may be considered as an alternative treatment to standard starting doses in hypotensive NICU patients, as it was efficacious without increased adverse effects. 
Critique

The study's retrospective design limits the ability to control for confounding variables and ascertain causality. The long study period may have introduced practice changes over time. Despite these limitations, the study provides valuable insights into the efficacy of low-dose epinephrine in a specific patient population.

 

References:
[1] [1] Lee G, Kaiser JR, Moffett BS, Rodman E, Toy C, Rios DR. Efficacy of Low-Dose Epinephrine Continuous Infusion in Neonatal Intensive Care Unit Patients. J Pediatr Pharmacol Ther. 2021;26(1):51-55. doi:10.5863/1551-6776-26.1.51
Epinephrine dosing strategies during pediatric extracorporeal cardiopulmonary resuscitation reveal novel impacts on survival: A multicenter study utilizing time-stamped epinephrine dosing records
Design

Multicenter, retrospective study

N= 191
Objective To describe epinephrine dosing distribution using time-stamped data and assess the impact of dosing strategy on survival after ECPR in children
Study Groups

Frequent epinephrine group (n= 73)

Limited epinephrine group (n= 71)
Inclusion Criteria Children <18 years with an in-hospital ECPR event ending with successful cannulation onto ECMO
Exclusion Criteria Patients with ROSC >20 minutes prior to cannulation, events without adequate documentation of epinephrine dosing, events with zero or one dose of epinephrine documented, and cardiac arrests in the neonatal intensive care unit
Methods

Retrospective review of in-hospital ECPR events from January 2012 to December 2019. Mean number of epinephrine doses calculated for each 10-minute CPR interval and compared between survivors and non-survivors. Patients divided by dosing strategy into frequent epinephrine group (≤5 min/dose for first 30 minutes) and limited epinephrine group (≤5 min/dose for first 10 minutes, then >5 min/dose for 10-30 minutes).
Duration January 2012 to December 2019
Outcome Measures

Primary: Survival to hospital discharge

Secondary: Acute kidney injury (AKI), favorable neurologic outcomes
Baseline Characteristics   Survivors (n= 83) Non-survivors (n= 108)
Age, median (IQR), months 2.2 (0.4–12) 10.5 (1.3–80.5)
Gestational age, median (IQR), weeks 38.3 (37–39.2) 38 (36–39)
Weight, median (IQR), kg 4.5 (3.3–8.5) 8.5 (3.9–20.2)
Male gender, n (%) 48 (58) 48 (44)
Illness category - Medical cardiac 27 (32) 37 (34)
Illness category - Surgical cardiac 53 (64) 49 (45)
Illness category - Non-cardiac 3 (4) 22 (20)
Genetic syndrome, n (%) 17 (20) 41 (38)
Admission PCPC = 1, n (%) 68 (86) 68 (67)
Results   Frequent epinephrine (n= 73) Limited epinephrine (n= 71) p-value
Hospital survival, n (%) 28 (38) 33 (46) 0.324
Length of ECMO, median (IQR), hours 81 (46–166) 88 (43–159) 0.666
Vasodilator use, n (%) 35 (48) 20 (28) 0.014
Adverse Events No difference in AKI incidence or favorable neurologic outcome between frequent and limited epinephrine groups. No statistically significant difference in incidence of brain death or hypoxic ischemic encephalopathy
Study Author Conclusions

Survivors received fewer doses than non-survivors after the first 10 minutes of CPR. Although there was no statistical difference in survival based on dosing strategy, the findings question the conventional approach to ECPR analysis that assumes dosing is evenly distributed.
Critique

The study's strength lies in its multicenter design and use of time-stamped data, providing a detailed analysis of epinephrine dosing strategies. However, its retrospective nature and reliance on documentation during high-stress events may introduce inaccuracies. The lack of hemodynamic and oxygen delivery data limits the ability to correlate epinephrine dosing with clinical outcomes.

 

References:
[1] [1] Ortmann LA, Reeder RW, Raymond TT, et al. Epinephrine dosing strategies during pediatric extracorporeal cardiopulmonary resuscitation reveal novel impacts on survival: A multicenter study utilizing time-stamped epinephrine dosing records. Resuscitation. 2023;188:109855. doi:10.1016/j.resuscitation.2023.109855
Use and Efficacy of Endotracheal Versus Intravenous Epinephrine During Neonatal Cardiopulmonary Resuscitation in the Delivery Room
Design

Retrospective review

N= 47
Objective To determine the frequency of endotracheal epinephrine use in newborns in the delivery room and to assess the effectiveness of the previously recommended dose of 0.01 to 0.03 mg/kg of endotracheal epinephrine in establishing a return of spontaneous circulation
Study Groups

ETT epinephrine (n= 44)

Intravenous epinephrine (n= 3)
Inclusion Criteria Infants who received ≥1 dose of endotracheal epinephrine in the delivery room during resuscitation
Exclusion Criteria Lethal congenital anomalies, delivery outside the hospital, and missing medical charts
Methods

Retrospective review was conducted of neonates who received epinephrine in the delivery room between January 1999 and December 2004. Endotracheal epinephrine was delivered undiluted by direct injection into the hub of the endotracheal tube followed by 1 mL of normal saline flush before positive pressure breaths. Return of spontaneous circulation was defined as return of an audible heart rate ≥60 beats per minute.
Duration January 1999 to December 2004
Outcome Measures

Primary: Return of spontaneous circulation
Baseline Characteristics   ETT Epinephrine (n= 14) Intravenous Epinephrine (n= 23)
Birth weight, g 2771 ± 1223 2668 ± 1162
Gestational age, wk 36 ± 6 36 ± 6
Preterm (≤34 wk), n (%) 3 (21) 7 (30)
Male, n (%) 9 (64) 11 (48)
Breech, n (%) 2 (14) 2 (9)
Meconium stained fluid, n (%) 5 (36) 7 (30)
Cesarean section, n (%) 11 (79) 16 (70)
Emergent Cesarean section, n (%) 9 (64) 11 (48)
Results   ETT Epinephrine (n= 14) Intravenous Epinephrine (n= 23) p-Value
Return of spontaneous circulation 32% 77% <0.001
Time to ROSC (minute of life) 7.3 ± 6.0 11.7 ± 5.8 0.038
Median total number of EPI doses 1 3 <0.001
Adverse Events No specific adverse events reported in the study
Study Author Conclusions

Endotracheal epinephrine is frequently used in the delivery room but the previously recommended dose is often ineffective. Higher endotracheal doses may be needed to improve efficacy. Intravenous administration should be the preferred route until more information is available.
Critique

The study highlights the ineffectiveness of the current endotracheal epinephrine dosing regimen, suggesting the need for higher doses. However, the retrospective nature and single-center design may limit generalizability. The study also lacks long-term outcome data and direct comparison between ETT and intravenous administration due to the study design.

 

References:
[1] [1] Barber CA, Wyckoff MH. Use and efficacy of endotracheal versus intravenous epinephrine during neonatal cardiopulmonary resuscitation in the delivery room. Pediatrics. 2006;118(3):1028-1034. doi:10.1542/peds.2006-0416
Epinephrine Dosing Interval and Survival Outcomes During Pediatric In-Hospital Cardiac Arrest
Design

Retrospective cohort study

N= 1,630
Objective To investigate whether longer epinephrine dosing intervals were associated with improved survival to discharge during pediatric in-hospital cardiac arrest
Study Groups

1 to 5 minutes (n= 1133)

>5 to <8 minutes (n= 368)

8 to <10 minutes (n= 129)
Inclusion Criteria Patients 18 years and younger who experienced index arrest events; events on a ward, a ward with telemetry or ICU; had bolus epinephrine administered; and received >2 epinephrine doses
Exclusion Criteria Resuscitations in the delivery room, nursery or NICU; resuscitations with vasoactive boluses other than epinephrine; events with extracorporeal cardiopulmonary resuscitation (ECPR); and resuscitation events with missing data
Methods

Retrospective review of AHA Get With The Guidelines-Resuscitation registry. Average epinephrine dosing interval was defined by dividing duration of resuscitation after first dose of epinephrine by total doses. Multivariable logistic regression models controlled for age, gender, illness category, location of arrest, arrest duration, time of day, and time to first epinephrine dose.
Duration January 2000 to January 2014
Outcome Measures

Primary: Survival to hospital discharge
Baseline Characteristics   Entire study group (N= 1630)    
Average patient age, years 4.12 ± 5.64    
Male 59%    
ICU occurrence 84%    
Ward occurrence 12%    
Ward with telemetry occurrence 4%    
Results   1 to 5 minutes (n= 1133) >5 to <8 minutes (n= 368) 8 to <10 minutes (n= 129)
Adjusted OR for survival to hospital discharge 1 (reference) 1.81 (95% CI 1.26-2.59) 2.64 (95% CI 1.53-4.55)
Adverse Events Not specifically reported
Study Author Conclusions Longer average dosing intervals than currently recommended for epinephrine administration during pediatric IHCA were associated with improved survival to hospital discharge.
Critique The study's retrospective design limits the ability to determine exact timing of epinephrine dosing, and the assumption of regular intervals may not reflect actual practice. The stringent inclusion criteria and focus on ICU settings may limit generalizability. Despite these limitations, the study provides valuable insights into the potential benefits of longer dosing intervals in pediatric IHCA.
References:
[1] Hoyme DB, Patel SS, Samson RA, et al. Epinephrine dosing interval and survival outcomes during pediatric in-hospital cardiac arrest. Resuscitation. 2017;117:18-23. doi:10.1016/j.resuscitation.2017.05.023