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The efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock: a meta-analysis of randomized controlled studies



The efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock remains controversial. We conduct a meta-analysis to explore the influence of dopamine versus epinephrine on shock reversal for pediatric or neonatal septic shock.


We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of dopamine versus epinephrine for pediatric or neonatal septic shock.


Three RCTs are included in the meta-analysis. Overall for pediatric or neonatal septic shock, dopamine and epinephrine reveal comparable shock reversal within 1 h (risk ratios (RR) = 0.61; 95% CI = 0.16 to 2.31; P = 0.47), mortality (RR = 1.16; 95% CI = 0.87 to 1.55; P = 0.30), heart rate (standard mean differences (SMD) = 0.03; 95% CI = -0.28 to 0.34; P = 0.85), systolic blood pressure (SMD = -0.18; 95% CI = -0.69 to 0.33; P = 0.49), mean arterial pressure (SMD = -0.15; 95% CI = -1.64 to 1.34; P = 0.84) and adverse events (RR = 1.00; 95% CI = 0.94 to 1.07; P = 0.91).


Dopamine and epinephrine show the comparable efficacy for the treatment of pediatric or neonatal septic shock.


Septic shock becomes the leading cause of mortality and morbidity among neonates and children worldwide [1,2,3]. Some studies report 10–50% of mortality in developed countries and up to 80% of mortality in developing countries [4,5,6]. The Surviving Sepsis Campaign 2012 guidelines have recommended dopamine as the first-line vasoactive agent in fluid-refractory septic shock [7]. Dopamine has a dose-dependent agonist effects on dopaminergic and adrenergic (α and β) receptors. Dopamine is inotropic via β-adrenergic stimulation in the dose range of 5–10 μg/kg/min, while it has both predominant inotropic effect and mild vasopressor effect via α1-adrenergic stimulation in the dosing range of 10–15 μg/kg/min. In the dose of more than 15 μg/kg/min, dopamine is predominantly a vasopressor (via α1-adrenergic effect) with minimal inotropic action [8].

Dopamine infusion in septic shock can reduce the release of prolactin, increase oxidative stress, suppress pro-inflammatory cytokine production and increase anti-inflammatory cytokine production [9, 10]. In young children and infants with decompensated hypotensive septic shock, dopamine response may be unpredictable because of receptor insensitivity to dopamine or catecholamine depletion [11]. In adults with septic shock, dopamine results in the increase in mortality and occurrence of arrhythmias when compared with norepinephrine [8, 12]. Epinephrine has the ability to increase mean arterial pressure and cardiac output, but may increase serum lactate and impair gut perfusion in septic shock [13, 14].

Recently, several studies have investigated the efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock, but the results are conflicting [15,16,17]. This systematic review and meta-analysis of RCTs aims to assess the efficacy and safety of dopamine versus epinephrine for pediatric or neonatal septic shock.

Materials and methods

This systematic review and meta-analysis are performed based on the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and Cochrane Handbook for Systematic Reviews of Interventions [18, 19]. No ethical approval and patient consent are required because all analyses are based on previous published studies.

Literature search and selection criteria

We have systematically searched several databases including PubMed, EMbase, Web of science, EBSCO, and the Cochrane library from inception to July 2019 with the following keywords: dopamine, and epinephrine, and septic shock, and pediatric or neonates. The inclusion criteria are as follows: (1) study design is RCT, (2) patients are diagnosed as pediatric or neonatal septic shock, and (3) intervention treatments are dopamine versus epinephrine.

Data extraction and outcome measures

Some baseline information is extracted from the original studies, and they include first author, number of patients, age, the number of male, weight, mechanical ventilation requirement, and detail methods in two groups. Data are extracted independently by two investigators, and discrepancies are resolved by consensus. We have contacted the corresponding author to obtain the data when necessary.

The primary outcomes are shock reversal within 1 h and mortality. Secondary outcomes include heart rate, systolic blood pressure, mean arterial pressure and adverse events.

Quality assessment in individual studies

The methodological quality of each RCT is assessed by the Jadad Scale which consists of three evaluation elements: randomization (0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1 points) [20]. One point would be allocated to each element if they have been conducted and mentioned appropriately in the original article. The score of Jadad Scale varies from 0 to 5 points. An article with Jadad score ≤ 2 is considered to be of low quality. The study with Jadad score ≥ 3 is thought to be of high quality [21].

Statistical analysis

We assess standard mean differences (SMD) with 95% confidence intervals (CIs) for continuous outcomes (heart rate, systolic blood pressure, and mean arterial pressure), and risk ratios (RR) with 95% CIs for dichotomous outcomes (shock reversal within 1 h, mortality, and adverse events). Heterogeneity is evaluated using the I2 statistic, and I2 > 50% indicates significant heterogeneity [22]. The random-effects model is used for all meta-analysis. We search for potential sources of heterogeneity for significant heterogeneity. Sensitivity analysis is performed to detect the influence of a single study on the overall estimate via omitting one study in turn or performing the subgroup analysis. Owing to the limited number (< 10) of included studies, publication bias is not assessed. Results are considered as statistically significant for P < 0.05. All statistical analyses are performed using Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK).


Literature search, study characteristics and quality assessment

Figure 1 shows the detail flowchart of the search and selection results. 234 potentially relevant articles are identified initially and three RCTs are finally included in the meta-analysis [15,16,17].

Fig. 1

Flow diagram of study searching and selection process

The baseline characteristics of three included RCTs are shown in Table 1. These studies are published between 2015 and 2018, and the total sample size is 220. The methods of dopamine or epinephrine are various in each RCT. Two studies involve pediatric septic shock [16, 17], and the remaining study involves neonatal septic shock [15].

Table 1 Characteristics of included studies

Two studies report shock reversal within 1 h and mortality [15, 16], two studies report heart rate, systolic blood pressure and mean arterial pressure [15, 17] and two studies report adverse events [16, 17]. Jadad scores of the three included studies are four, and all three studies have high-quality based on the quality assessment.

Primary outcomes: shock reversal within 1 h and mortality

The random-effect model is used for the analysis of primary outcomes. The results find that dopamine and epinephrine intervention demonstrate comparable shock reversal within 1 h (RR = 0.61; 95% CI = 0.16 to 2.31; P = 0.47) with significant heterogeneity among the studies (I2 = 71%, heterogeneity P = 0.06, Fig. 2) and mortality (RR = 1.16; 95% CI = 0.87 to 1.55; P = 0.30) with no heterogeneity among the studies (I2 = 0%, heterogeneity P = 0.86, Fig. 3) for pediatric or neonatal septic shock.

Fig. 2

Forest plot for the meta-analysis of shock reversal within 1 h

Fig. 3

Forest plot for the meta-analysis of mortality

Sensitivity analysis

There is significant heterogeneity for shock reversal within 1 h, but no heterogeneity is observed for PFS for mortality. Because there are just two studies included for the analysis of shock reversal within 1 h, we do not perform the sensitivity analysis via omitting one study in turn.

Secondary outcomes

In comparison with epinephrine intervention for pediatric or neonatal septic shock, dopamine shows similar heart rate (SMD = 0.03; 95% CI = -0.28 to 0.34; P = 0.85; Fig. 4), systolic blood pressure (SMD = -0.18; 95% CI = -0.69 to 0.33; P = 0.49; Fig. 5), mean arterial pressure (SMD = -0.15; 95% CI = -1.64 to 1.34; P = 0.84; Fig. 6) and adverse events (RR = 1.00; 95% CI = 0.94 to 1.07; P = 0.91; Fig. 7).

Fig. 4

Forest plot for the meta-analysis of heart rate

Fig. 5

Forest plot for the meta-analysis of systolic blood pressure (mm Hg)

Fig. 6

Forest plot for the meta-analysis of mean arterial pressure (mm Hg)

Fig. 7

Forest plot for the meta-analysis of adverse events


Both dopamine and epinephrine can provide vasopressor and inotropic actions [23,24,25]. Vasopressors serve as the first-line vasoactive drugs in the management of neonatal septic shock because of decreased systemic vascular resistance [26, 27]. Dopamine is recommended to be the first-line vasoactive agent in fluid-refractory septic shock [7]. It is also the first-line vasoactive drug in neonatal septic shock mainly through the release of norepinephrine from presynaptic vesicles [28,29,30]. Dopamine may be ineffective in sick neonates due to the depletion of norepinephrine stores within few hours of sickness onset [31].

In contrast, epinephrine acts directly on adrenergic receptors [23], and has the ability to decrease myocardial oxygen extraction ratio and increase the coronary sinus oxygen content in animal models [32]. Epinephrine is found to show three times more likely to achieve the resolution of shock within first hour of resuscitation than dopamine in pediatric fluid-refractory hypotensive septic shock. Early resolution of shock with epinephrine benefits to improve organ functions [16]. Our meta-analysis suggests that dopamine and epinephrine obtains the comparable shock reversal for pediatric or neonatal septic shock.

In adults with septic shock, strong evidence is observed that dopamine increases the mortality and adverse events [8, 12]. In another study, the mortality in children receiving dopamine is significantly increased than those taking epinephrine in the short period of time in pediatric septic shock [17]. However, there is no statistical difference of mortality between dopamine and epinephrine in the management of pediatric or neonatal septic shock based on this meta-analysis. In addition, no significance of heart rate, systolic blood pressure, mean arterial pressure or adverse events is observed between these two groups. Regarding the sensitivity analysis, significant heterogeneity is observed for shock reversal within 1 h (I2 = 71%, heterogeneity P = 0.06, Fig. 2), systolic blood pressure (I2 = 53%, heterogeneity P = 0.14, Fig. 5) and mean arterial pressure (I2 = 94%, heterogeneity P < 0.0001, Fig. 6). Many factors such as different population with septic shock, doses, duration and methods of drug use may result in this heterogeneity.

Several limitations exist in this meta-analysis. Firstly, our analysis is based on only three RCTs, and more RCTs with large sample size should be conducted to explore this issue. Next, there is significant heterogeneity, which may be caused by different population with septic shock, doses, duration and methods of drug use etc. Finally, it is not feasible to perform the subgroup analysis based on pediatric or neonatal septic shock based on limited RCTs.


Dopamine and epinephrine shows the similar efficacy and safety for pediatric or neonatal septic shock, and more studies should be conducted to investigate this issue.

Availability of data and materials

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Randomized controlled trial


Risk ratios

Std. MD:

Standard mean difference


  1. 1.

    Chan KH, Sanatani S, Potts JE, Harris KC. The relative incidence of cardiogenic and septic shock in neonates. Paediatrics & Child Health; 2019.

    Google Scholar 

  2. 2.

    Schlapbach LJ, Straney L, Alexander J, MacLaren G, Festa M, Schibler A, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002–13: a multicentre retrospective cohort study. Lancet Infect Dis. 2015;15:46–54.

    Article  Google Scholar 

  3. 3.

    Miescier MJ, Lane RD, Sheng X, Larsen GY. Association between initial emergency department lactate and use of vasoactive medication in children with septic shock. Pediatr Emerg Care. 2019;35:455–60.

    Article  Google Scholar 

  4. 4.

    Weiss S, Fitzgerald J, Pappachan J, Wheeler D, Jaramillo-Bustamante J, Salloo A, et al. Sepsis prevalence, outcomes, and therapies (SPROUT) study investigators and pediatric acute lung injury and Sepsis investigators (PALISI) network: global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015;191:1147–57.

    Article  Google Scholar 

  5. 5.

    Inwald DP, Tasker RC, Peters MJ, Nadel S. Emergency management of children with severe sepsis in the United Kingdom: the results of the Paediatric Intensive Care Society sepsis audit. Arch Dis Child. 2009;94:348–53.

    CAS  Article  Google Scholar 

  6. 6.

    Wolfler A, Silvani P, Musicco M, Antonelli M, Salvo I. Group IPSS. Incidence of and mortality due to sepsis, severe sepsis and septic shock in Italian pediatric intensive care units: a prospective national survey. Intensive Care Med. 2008;34:1690–7.

    Article  Google Scholar 

  7. 7.

    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis campaign guidelines committee including the pediatric subgroup surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.

    Article  Google Scholar 

  8. 8.

    Sakr Y, Reinhart K, Vincent J-L, Sprung CL, Moreno R, Ranieri VM, et al. Does dopamine administration in shock influence outcome? Results of the Sepsis occurrence in acutely ill patients (SOAP) study. Crit Care Med. 2006;34:589–97.

    CAS  Article  Google Scholar 

  9. 9.

    Lauwers P. Dopamine suppresses pituitary function in infants and children. Crit Care Med. 1994;22:1747–53.

    Article  Google Scholar 

  10. 10.

    Dong J, Zhang L, Rao G, Zhao X. Complicating symmetric peripheral gangrene after dopamine therapy to patients with septic shock. J Forensic Sci. 2015;60:1644–6.

    Article  Google Scholar 

  11. 11.

    Eldadah MK, Schwartz PH, Harrison R, Newth C. Pharmacokinetics of dopamine in infants and children. Crit Care Med. 1991;19:1008–11.

    CAS  Article  Google Scholar 

  12. 12.

    De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362:779–89.

    Article  Google Scholar 

  13. 13.

    Wilson W, Lipman J, Scribante J, Kobilski S, Lee C, Krause P, et al. Septic shock: does adrenaline have a role as a first-line inotropic agent? Anaesth Intensive Care. 1992;20:470–4.

    CAS  Article  Google Scholar 

  14. 14.

    Day NP, Phu NH, Bethell DP, Mai NT, Chau TT, Hien TT, et al. The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection. Lancet. 1996;348:219–23.

    CAS  Article  Google Scholar 

  15. 15.

    Baske K, Saini SS, Dutta S, Sundaram V. Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial. Eur J Pediatr. 2018;177:1335–42.

    CAS  Article  Google Scholar 

  16. 16.

    Ramaswamy KN, Singhi S, Jayashree M, Bansal A, Nallasamy K. Double-blind randomized clinical trial comparing dopamine and epinephrine in pediatric fluid-refractory hypotensive septic shock. Pediatr Crit Care Med. 2016;17:e502–e12.

    Article  Google Scholar 

  17. 17.

    Ventura AM, Shieh HH, Bousso A, Góes PF, Iracema de Cássia F, de Souza DC, et al. Double-blind prospective randomized controlled trial of dopamine versus epinephrine as first-line vasoactive drugs in pediatric septic shock. Crit Care Med. 2015;43:2292–302.

    CAS  Article  Google Scholar 

  18. 18.

    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Bmj. 2009;339:b2535.

    Article  Google Scholar 

  19. 19.

    JPTG H. Cochrane handbook for systematic reviews of interventions version 5.1. 0 [updated March 2011]. The cochrane collaboration; 2011.

    Google Scholar 

  20. 20.

    Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.

    CAS  Article  Google Scholar 

  21. 21.

    Kjaergard LL, Villumsen J, Gluud C. Reported Methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med. 2001;135:982–9.

    CAS  Article  Google Scholar 

  22. 22.

    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  Google Scholar 

  23. 23.

    Noori S, Seri I. Neonatal blood pressure support: the use of inotropes, lusitropes, and other vasopressor agents. Clin Perinatol. 2012;39:221–38.

    Article  Google Scholar 

  24. 24.

    Slain KN, Shein SL, Rotta AT. The dose makes the poison: comparing epinephrine with dopamine in pediatric septic shock. Crit Care Med. 2016;44:e308.

    Article  Google Scholar 

  25. 25.

    Ibáñez-Redín G, Wilson D, Gonçalves D, Oliveira O Jr. Low-cost screen-printed electrodes based on electrochemically reduced graphene oxide-carbon black nanocomposites for dopamine, epinephrine and paracetamol detection. J Colloid Interface Sci. 2018;515:101–8.

    Article  Google Scholar 

  26. 26.

    De Waal K, Evans N. Hemodynamics in preterm infants with late-onset sepsis. J Pediatr. 2010;156:918–22 e1.

    Article  Google Scholar 

  27. 27.

    Saini SS, Kumar P, Kumar RM. Hemodynamic changes in preterm neonates with septic shock: a prospective observational study. Pediatr Crit Care Med. 2014;15:443–50.

    Article  Google Scholar 

  28. 28.

    Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC, et al. American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med. 2017;45:1061–93.

    Article  Google Scholar 

  29. 29.

    Li J, Zhang G, Holtby H, Humpl T, Caldarone CA, Van Arsdell GS, et al. Adverse effects of dopamine on systemic hemodynamic status and oxygen transport in neonates after the Norwood procedure. J Am Coll Cardiol. 2006;48:1859–64.

    CAS  Article  Google Scholar 

  30. 30.

    Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol. 2010;37:439–79.

    Article  Google Scholar 

  31. 31.

    Seri I. Cardiovascular, renal, and endocrine actions of dopamine in neonates and children. J Pediatr. 1995;126:333–44.

    CAS  Article  Google Scholar 

  32. 32.

    Barrington K, Chan W. The circulatory effects of epinephrine infusion in the anesthetized piglet. Pediatr Res. 1993;33:190.

    CAS  Article  Google Scholar 

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LW carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. LX participated in the design of the study, performed the statistical analysis and helped to revise the manuscript. All authors read and approved the final manuscript.

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Correspondence to Liangyin Xu.

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Wen, L., Xu, L. The efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock: a meta-analysis of randomized controlled studies. Ital J Pediatr 46, 6 (2020).

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  • Dopamine
  • Epinephrine
  • Pediatric septic shock
  • Shock reversal
  • Randomized controlled trials