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Dopamine or norepinephrine for sepsis-related hypotension in preterm infants: a retrospective cohort study

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Abstract

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)].

Conclusion: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents.

What is Known:

•Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants.

•For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock.

What is New:

•This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants.

•Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis.

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Data Availability

Individual de-identified participant data that underlie the results reported in this manuscript will be available, pending approval by the institutional research ethics board, immediately following publication, for investigators who provide a methodologically sound proposal approved by an independent review committee, to achieve aims cited in the approved proposal. Data request and proposals should be directed to the corresponding author. Requestors will need to sign a data sharing agreement.

Abbreviations

BP:

Blood pressure

DA:

Dopamine

EOS:

Early-onset sepsis

FiO2:

Fraction of inspired oxygen

HR:

Heart rate

MAP:

Mean airway pressure

MgSO4:

Magnesium sulfate

NE:

Norepinephrine

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care unit

PMA:

Post-menstrual age

PROM:

Premature rupture of the membranes

PS:

Propensity score

SNAP II:

Score for neonatal acute physiology

SNI:

Significant neurological injury

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Author information

Authors and Affiliations

  1. Department of Paediatrics, Mount Sinai Hospital, ON, Toronto, Canada

    Sagee Nissimov, Ashraf Kharrat, Faith Zhu, Poorva Deshpande & Amish Jain

  2. Department of Respiratory Therapy, Mount Sinai Hospital, Toronto, ON, Canada

    Michelle Baczynski

  3. Lunnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Xiang Y. Ye & Amish Jain

  4. Department of Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Julie Choudhury

  5. Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Dany E. Weisz

  6. Division of Neonatology, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada

    Bonny Jasani

  7. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Ashraf Kharrat, Faith Zhu, Bonny Jasani, Poorva Deshpande, Dany E. Weisz & Amish Jain

  8. Clinic of Neonatology, Lausanne University Hospital, Lausanne, Switzerland

    Sébastien Joye

  9. Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Gabriella Ripstein

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  1. Sagee Nissimov
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Contributions

All the authors made a substantial contribution to the study conception and design. Dr. Sagee Nissimov conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Drs. Faith Zhu, Sebastien Joye, and Bonny Jasani and Ms. Gabriella Ripstein, Julie Choudhury, and Michelle Baczynski were responsible for data collection and critically reviewed the manuscript. Drs. Ashraf Kharrat, Poorva Deshpande, and Dany Weisz coordinated and supervised the data collection and critically reviewed the manuscript for important intellectual content. Mr. Xiang Ye performed the statistical analyses and assisted in reviewing and revising the manuscript. Prof Amish Jain conceptualized and designed the study, coordinated and supervised the data collection, and critically reviewed the manuscript for important intellectual content. All the authors approved the final version of the manuscript as submitted and agreed to be accountable for all aspects of the work.

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Correspondence to Amish Jain.

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Communicated by Daniele De Luca

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Nissimov, S., Joye, S., Kharrat, A. et al. Dopamine or norepinephrine for sepsis-related hypotension in preterm infants: a retrospective cohort study. Eur J Pediatr 182, 1029–1038 (2023). https://doi.org/10.1007/s00431-022-04758-4

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