Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline

BackgroundThe effect of the timing of initiation of hydrocortisone in neonatal shock has not been evaluated. The objective of this systematic review was to compare the effect of earlier vs. later initiation of hydrocortisone in neonatal shock.MethodsMedline, Embase, and CENTRAL were searched from in...

Full description

Saved in:
Bibliographic Details
Main Authors: Viraraghavan Vadakkencherry Ramaswamy, Gunjana Kumar, Abdul Kareem Pullattayil S, Abhishek S. Aradhya, Pradeep Suryawanshi, Mohit Sahni, Supreet Khurana, Shiv Sajan Saini, Ravishankar K, Shashi Kant Dhir, Deepak Chawla, Praveen Kumar, Kiran More
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fped.2025.1491976/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850069104882352128
author Viraraghavan Vadakkencherry Ramaswamy
Gunjana Kumar
Abdul Kareem Pullattayil S
Abhishek S. Aradhya
Pradeep Suryawanshi
Mohit Sahni
Supreet Khurana
Shiv Sajan Saini
Ravishankar K
Shashi Kant Dhir
Deepak Chawla
Praveen Kumar
Kiran More
author_facet Viraraghavan Vadakkencherry Ramaswamy
Gunjana Kumar
Abdul Kareem Pullattayil S
Abhishek S. Aradhya
Pradeep Suryawanshi
Mohit Sahni
Supreet Khurana
Shiv Sajan Saini
Ravishankar K
Shashi Kant Dhir
Deepak Chawla
Praveen Kumar
Kiran More
author_sort Viraraghavan Vadakkencherry Ramaswamy
collection DOAJ
description BackgroundThe effect of the timing of initiation of hydrocortisone in neonatal shock has not been evaluated. The objective of this systematic review was to compare the effect of earlier vs. later initiation of hydrocortisone in neonatal shock.MethodsMedline, Embase, and CENTRAL were searched from inception until 15 May 2024. Randomized controlled trials (RCTs) and non-RCTs were eligible for inclusion. A random effects meta-analysis was used to synthesize the data. The evidence certainty was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A clinical practice guideline was formulated as recommended by the GRADE group.ResultsOf the 3,757 titles and abstracts screened, 20 studies were included: 7 RCTs and 13 non-RCTs. While clinical benefit or harm could not be ruled out for the outcome of mortality from the meta-analysis of the RCTs [early initiation risk ratio (RR): 0.46, 95% confidence interval (CI): 0.03–7.92; late initiation RR: 0.43, 95% CI: 0.12–1.47], the non-RCTs included in the narrative review suggested that late hydrocortisone initiation might be associated with increased risk of mortality. The meta-analysis indicated that early and late hydrocortisone administration may be associated with an increased response to treatment therapy (early initiation RR: 1.85, 95% CI: 1.26–2.71; late initiation RR: 2.50, 95% CI: 1.16–5.39). Late hydrocortisone initiation may increase the risk of necrotizing enterocolitis (NEC) ≥ stage 2 (RR: 2.46, 95% CI: 1.19–5.08). The evidence certainty was very low for most of the outcomes evaluated.ConclusionThe early use of hydrocortisone in neonates with shock requiring vasopressors is associated with better outcomes and no major adverse effects. Later institution of hydrocortisone therapy in neonatal shock may improve the response to therapy but may be associated with adverse outcomes including mortality and NEC. The results are to be interpreted with caution as the evidence certainty was predominantly very low.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023432169, identifier: CRD42023432169.
format Article
id doaj-art-2bdfd7b7f34c4b579c2c796d894b6675
institution DOAJ
issn 2296-2360
language English
publishDate 2025-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pediatrics
spelling doaj-art-2bdfd7b7f34c4b579c2c796d894b66752025-08-20T02:47:52ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-03-011310.3389/fped.2025.14919761491976Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guidelineViraraghavan Vadakkencherry Ramaswamy0Gunjana Kumar1Abdul Kareem Pullattayil S2Abhishek S. Aradhya3Pradeep Suryawanshi4Mohit Sahni5Supreet Khurana6Shiv Sajan Saini7Ravishankar K8Shashi Kant Dhir9Deepak Chawla10Praveen Kumar11Kiran More12Department of Neonatology, Ankura Hospital for Women and Children, Hyderabad, IndiaDepartment of Neonatology, National Institute of Medical Sciences, Jaipur, IndiaQueen's University Library, Queen's University, Kingston, ON, CanadaDepartment of Neonatology, Ovum Women and Child Specialty Hospital, Bengaluru, IndiaDepartment of Neonatology, Bharati Vidyapeeth Medical College Hospital, Pune, IndiaDepartment of Neonatology, Nirmal Hospital, Surat, IndiaDepartment of Neonatology, Government Medical College and Hospital, Chandigarh, IndiaDepartment of Neonatology and Head, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Neonatology, Sowmya Children’s Hospital, Hyderabad, India0Department of Pediatrics, Guru Gobind Medical College, Faridkot, IndiaDepartment of Neonatology, Government Medical College and Hospital, Chandigarh, IndiaDepartment of Neonatology and Head, Postgraduate Institute of Medical Education and Research, Chandigarh, India1Division of Neonatology, MRR Children’s Hospital, Mumbai, IndiaBackgroundThe effect of the timing of initiation of hydrocortisone in neonatal shock has not been evaluated. The objective of this systematic review was to compare the effect of earlier vs. later initiation of hydrocortisone in neonatal shock.MethodsMedline, Embase, and CENTRAL were searched from inception until 15 May 2024. Randomized controlled trials (RCTs) and non-RCTs were eligible for inclusion. A random effects meta-analysis was used to synthesize the data. The evidence certainty was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A clinical practice guideline was formulated as recommended by the GRADE group.ResultsOf the 3,757 titles and abstracts screened, 20 studies were included: 7 RCTs and 13 non-RCTs. While clinical benefit or harm could not be ruled out for the outcome of mortality from the meta-analysis of the RCTs [early initiation risk ratio (RR): 0.46, 95% confidence interval (CI): 0.03–7.92; late initiation RR: 0.43, 95% CI: 0.12–1.47], the non-RCTs included in the narrative review suggested that late hydrocortisone initiation might be associated with increased risk of mortality. The meta-analysis indicated that early and late hydrocortisone administration may be associated with an increased response to treatment therapy (early initiation RR: 1.85, 95% CI: 1.26–2.71; late initiation RR: 2.50, 95% CI: 1.16–5.39). Late hydrocortisone initiation may increase the risk of necrotizing enterocolitis (NEC) ≥ stage 2 (RR: 2.46, 95% CI: 1.19–5.08). The evidence certainty was very low for most of the outcomes evaluated.ConclusionThe early use of hydrocortisone in neonates with shock requiring vasopressors is associated with better outcomes and no major adverse effects. Later institution of hydrocortisone therapy in neonatal shock may improve the response to therapy but may be associated with adverse outcomes including mortality and NEC. The results are to be interpreted with caution as the evidence certainty was predominantly very low.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023432169, identifier: CRD42023432169.https://www.frontiersin.org/articles/10.3389/fped.2025.1491976/fullneonateshydrocortisoneshockclinical practical guidelinesmeta-analysissystematic review
spellingShingle Viraraghavan Vadakkencherry Ramaswamy
Gunjana Kumar
Abdul Kareem Pullattayil S
Abhishek S. Aradhya
Pradeep Suryawanshi
Mohit Sahni
Supreet Khurana
Shiv Sajan Saini
Ravishankar K
Shashi Kant Dhir
Deepak Chawla
Praveen Kumar
Kiran More
Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline
Frontiers in Pediatrics
neonates
hydrocortisone
shock
clinical practical guidelines
meta-analysis
systematic review
title Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline
title_full Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline
title_fullStr Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline
title_full_unstemmed Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline
title_short Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline
title_sort timing of hydrocortisone therapy in neonates with shock a systematic review meta analysis and clinical practice guideline
topic neonates
hydrocortisone
shock
clinical practical guidelines
meta-analysis
systematic review
url https://www.frontiersin.org/articles/10.3389/fped.2025.1491976/full
work_keys_str_mv AT viraraghavanvadakkencherryramaswamy timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT gunjanakumar timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT abdulkareempullattayils timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT abhisheksaradhya timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT pradeepsuryawanshi timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT mohitsahni timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT supreetkhurana timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT shivsajansaini timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT ravishankark timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT shashikantdhir timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT deepakchawla timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT praveenkumar timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline
AT kiranmore timingofhydrocortisonetherapyinneonateswithshockasystematicreviewmetaanalysisandclinicalpracticeguideline