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Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study

Abstract

The study objective was to analyze the association between low plasma vasopressin and progression of sepsis to septic shock in neonates < 34 weeks gestation. Septic neonates of < 34 weeks gestation were consecutively enrolled; moribund neonates and those with major malformations were excluded. Subjects were monitored for progression of sepsis to septic shock over the first 7 days from enrolment. Plasma vasopressin levels and inducible nitric oxide synthase levels were measured at the onset of sepsis (T0), severe sepsis (T1), and septic shock (T2). Primary outcome was plasma vasopressin levels at the point of sepsis in those who progressed to septic shock in comparison with matched nested controls in the non-progression group. Forty-nine (47%) enrolled subjects developed severe sepsis or septic shock. Plasma vasopressin levels (pg/ml) at the onset of sepsis were significantly low in those who progressed to septic shock (median (IQR), 31 (2.5–80) versus 100 (12–156); p = 0.02). After adjusting for confounders, vasopressin levels were independently associated with progression to septic shock (adjusted OR (95% CI), 0.97 (0.96, 0.99); p = 0.01).

Conclusion: Preterm septic neonates who progressed to septic shock had suppressed vasopressin levels before the onset of shock. Low vasopressin levels were independently associated with progression to septic shock.

What is known:
• In animal sepsis models and adult septic patients, exuberant production of nitric oxide metabolites and low vasopressin levels have been reportedly associated with progression to septic shock.
• Vasopressin levels have been variably reported as low as well as elevated in children with septic shock.
What is New:
• Preterm neonates who progressed from sepsis to septic shock had significantly lower levels of vasopressin before the onset of shock in comparison with those who did not progress.
• Low vasopressin levels independently predicted the progression from sepsis to septic shock in this population.

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Abbreviations

CSF:

Cerebrospinal fluid

iNOS:

Inducible nitric oxide synthase

IQR:

Inter-quartile range

MD:

Mean difference

OD:

Organ dysfunction

OR:

Odds ratio

ROC:

Receiver operating characteristic curve

RR:

Risk ratio

SIRS:

Systemic inflammatory response syndrome

SNAP:

Score for neonatal acute physiology

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Financial information

The study was supported by an institute special research grant (Postgraduate Institute of Medical Education and Research, Chandigarh – PGIMER/Spl research grant/2016) and dissertation grant (Indian council of medical research – 3/2/March-2016/PG-Thesis-HRD(19)).

Author information

Abhishek Somasekhara Aradhya collected the data, analyzed the data, drafted the initial manuscript and reviewed the manuscript.

Venkataseshan Sundaram conceptualized and designed the study, designed the data collection tool, supervised the conduct of the study, analyzed the data, and critically edited the manuscript.

Naresh Sachdeva contributed to the study design and conducted an analysis of metabolic and molecular parameters and critically edited the manuscript.

Sourabh Dutta, Shiv Sajan Saini, and Praveen Kumar contributed to designing the study and the data collection tool and critically reviewed the data analysis.

All authors read and approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Correspondence to Venkataseshan Sundaram.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the current study involving human participants were in accordance with the ethical standards of the institutional research committee (Institute Ethics Committee, PGIMER) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Communicated by Daniele De Luca

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Aradhya, A.S., Sundaram, V., Sachdeva, N. et al. Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study. Eur J Pediatr (2020). https://doi.org/10.1007/s00431-020-03610-x

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Keywords

  • Vasopressin
  • Neonate
  • Sepsis
  • Septic shock
  • Inducible nitric oxide synthase