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Clonidine for sedation in infants during therapeutic hypothermia with neonatal encephalopathy: pilot study

Journal of Perinatology volume 42, pages 319–327 (2022)Cite this article

A Correction to this article was published on 22 November 2021

This article has been updated

Abstract

Objective

To determine a safe dose of clonidine (CLON) to be used in infants with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).

Study design

A pilot prospective study was performed to determine the effect of CLON on autonomic parameters, the pharmacokinetics (PK) of CLON, and the amount of morphine (MOR) given “as needed” for shivering and agitation in a cohort of infants (n = 12) with HIE undergoing TH compared to a historical control group (n = 28).

Results

The CLON group received less “as needed” MOR than the MOR-only group for agitation/shivering (p < 0.001), and the CLON vs. MOR-only group spent 92% vs. 79% of cooling time at the target core body temperature (CBT; p = 0.03, CLON vs. MOR).

Conclusions

Intravenous CLON (1 mcg/kg Q8h) is well tolerated in infants treated with TH for HIE. CLON stabilizes CBT in the ideal range during cooling, which may be optimal for neuroprotection.

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Fig. 1: Consort diagram.
Fig. 2: Effect of clonidine on heart rate and blood pressure.
Fig. 3: The effect of clonidine on core body temperature (CBT) during the cooling phase of TH.

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Acknowledgements

The authors would like to acknowledge and thank Ms Tarrah Ezell who was the research coordinator for this study. She was exceptional in this role. She was dedicated to ensuring protocol adherence and careful collection of data in real time. We thank Dr Jennifer K. Lee, Professor of Anesthesiology at Johns Hopkins, for her helpful discussions regarding design of the study protocol and review of the manuscript. The nurses in the Johns Hopkins NICU are clinically superb and create a supportive research culture in the NICU that is paramount to the success of the work presented here and other interventional trials that we have participated in over the years. Similarly, we thank our professional colleagues in the investigational pharmacy at Johns Hopkins who were also supportive and helpful throughout the trial. The authors thank Mr Joseph McMahon for editing several versions of this manuscript, and Ms Sonia Dos Santos and Dr Ahuva Brown for proofreading the final versions. Last, this interventional trial was accomplished because parents of the sickest infants at one of their most vulnerable times were willing to enroll their infant into the trial and for this we are immensely grateful.

Funding

The work was supported by grants to EBG from the Thomas Wilson Foundation Baltimore, Maryland, and the National Institute for Drugs of Abuse IR25DA021630. RC-V is supported by National Institute of Neurological Disorders and Stroke (KO8NS096115), the Johns Hopkins University School of Medicine Clinician Scientist Award, and the Sutland-Pakula Endowment for Neonatal Research. MAR: Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH Grants P30CA006973 and UL1TR001079, and the Shared Instrument Grant [S10OD020091]), UL1TR001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research.

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Author notes

  1. These authors contributed equally: Estelle B. Gauda, Raul Chavez-Valdez.

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Estelle B. Gauda

  2. Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Estelle B. Gauda, Raul Chavez-Valdez & Frances J. Northington

  3. Neurosciences Intensive Care Nursery, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Raul Chavez-Valdez & Frances J. Northington

  4. Division of Clinical Pharmacology, Department of Pharmacy, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Carlton K. K. Lee

  5. Department of Oncology, Cancer Chemical and Structural Biology Program; Department of Medicine, Division of Clinical Pharmacology; Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Michelle A. Rudek

  6. Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, MD, USA

    Beatriz Guglieri-Lopez & Vijay Ivaturi

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Correspondence to Estelle B. Gauda.

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Gauda, E.B., Chavez-Valdez, R., Northington, F.J. et al. Clonidine for sedation in infants during therapeutic hypothermia with neonatal encephalopathy: pilot study. J Perinatol 42, 319–327 (2022). https://doi.org/10.1038/s41372-021-01151-1

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