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Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units

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Abstract

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010–2017), we identified infants < 32-week gestational age with CPCDs, defined by “significant exposure” to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6–7.5% and 0–100%, respectively) and late CPCDs (2.5–15% and 14–83%, respectively), all p < 0.01. Units’ late-CPCD incidence and mortality demonstrated an inverse relationship (slope =  −2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01).

Conclusions: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work.

What is Known:

• Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide.

• Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality.

What is New:

• This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state.

• Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

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Abbreviations

BPD:

Bronchopulmonary dysplasia

BW:

Birth weight

CPCD:

cardio-pulmonary critical decompensation

CNN:

Canadian Neonatal Network

GA:

Gestational age

HRF:

Hypoxic respiratory failure

iNO:

Inhaled nitric oxide

IVH:

Intraventricular hemorrhage

MLR:

Multiple logistic regression model

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care unit

PMA:

Post-menstrual age

PPROM:

Preterm premature rupture of the membranes

QI:

Quality improvement

ROP:

Retinopathy of prematurity

SGA:

Small for gestational age

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Acknowledgements

The authors thank all site investigators and data abstractors of the Canadian Neonatal Network (CNN). A list of CNN site investigators and their affiliations is presented as follows: Prakesh S Shah, MD, MSc (Director, Canadian Neonatal Network and Site Investigator), Mount Sinai Hospital, Toronto, Ontario; Marc Beltempo, MD, (Associate Director, Canadian Neonatal Network and Site Investigator), Montreal Children’s Hospital at McGill University Health Centre, Montreal, Quebec; Jaideep Kanungo, MD, Victoria General Hospital, Victoria, British Columbia; Jonathan Wong, MD, British Columbia Women’s Hospital, Vancouver, British Columbia; Dr. Miroslav Stavel, MD, Royal Columbian Hospital, New Westminster, British Columbia; Rebecca Sherlock, MD, Surrey Memorial Hospital, Surrey, British Columbia; Ayman Abou Mehrem, MD, Foothills Medical Centre, Calgary, Alberta; Jennifer Toye, MD, and Joseph Ting, MD, Royal Alexandra Hospital, Edmonton, Alberta; Carlos Fajardo, MD, Alberta Children’s Hospital, Calgary, Alberta; Jaya Bodani, MD, Regina General Hospital, Regina, Saskatchewan; Lannae Strueby, MD, Jim Pattison Children’s Hospital, Saskatoon, Saskatchewan; Mary Seshia, MBChB, and Deepak Louis, MD, Winnipeg Health Sciences Centre, Winnipeg, Manitoba; Ruben Alvaro, MD, and Ann Yi, MD, St. Boniface General Hospital, Winnipeg, Manitoba; Amit Mukerji, MD, Hamilton Health Sciences Centre, Hamilton, Ontario; Orlando Da Silva, MD, MSc, London Health Sciences Centre, London, Ontario; Sajit Augustine, MD, Windsor Regional Hospital, Windsor, Ontario; Kyong-Soon Lee, MD, MSc, Hospital for Sick Children, Toronto, Ontario; Eugene Ng, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Brigitte Lemyre, MD, The Ottawa Hospital, Ottawa, Ontario; Thierry Daboval, MD, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; Faiza Khurshid, MD, Kingston General Hospital, Kingston, Ontario; Victoria Bizgu, MD, Jewish General Hospital, Montreal, Quebec; Keith Barrington, MBChB, Anie Lapointe, MD, and Guillaume Ethier, NNP, Hôpital Sainte-Justine, Montreal, Quebec; Christine Drolet, MD, and Bruno Piedboeuf, MD, Centre Hospitalier Universitaire de Québec, Sainte Foy, Quebec; Martine Claveau, MSc, LLM, NNP, Montreal Children’s Hospital at McGill University Health Centre, Montreal, Quebec; Marie St-Hilaire, MD, Hôpital Maisonneuve-Rosemont, Montreal, Quebec; Valerie Bertelle, MD, and Edith Masse, MD, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec; Dr. Hamid Mehdizadeh-Hakak, MD, Moncton Hospital, Moncton, New Brunswick; Hala Makary, MD, Dr. Everett Chalmers Hospital, Fredericton, New Brunswick; Cecil Ojah, MBBS, Saint John Regional Hospital, Saint John, New Brunswick; Dr. Jo-Anna Hudson, MD, Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland; Jehier Afifi, MB BCh, MSc, IWK Health Centre, Halifax, Nova Scotia; Ameer Aslam, MD, Cape Breton Regional Hospital, Sydney, Nova Scotia; Shoo K Lee, MBBS, PhD (Chairman, Canadian Neonatal Network), Mount Sinai Hospital, Toronto, Ontario. We thank the staff at the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada, for organizational support of CNN.

Author information

Authors and Affiliations

  1. Department of Paediatrics, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada

    Ashraf Kharrat, Edmond Kelly, Prakesh S. Shah & Amish Jain

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

    Ashraf Kharrat, Dany E. Weisz, Edmond Kelly, Prakesh S. Shah & Amish Jain

  3. Department of Pediatrics, University of Iowa, Iowa City, USA

    Patrick J. McNamara

  4. Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Dany E. Weisz

  5. Department of Pediatrics, University of Sherbrooke, Sherbrooke, Canada

    Edith Masse

  6. Department of Pediatrics, McMaster University, Hamilton, Canada

    Amit Mukerji

  7. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada

    Deepak Louis

  8. Department of Pediatrics, Dalhousie University, Halifax, Canada

    Jehier Afifi

  9. Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, ON, Canada

    Xiang Y. Ye & Prakesh S. Shah

  10. Lunenfeld-Tanenbaum Research Institute, Toronto, Canada

    Prakesh S. Shah & Amish Jain

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  1. Ashraf Kharrat
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on behalf of the Canadian Neonatal Network

Contributions

AK and AJ conceived, designed, and planned the study; contributed to planning data extraction and analysis, and interpretation of results; wrote first and final draft of the publication; and approved the final publication. XY contributed to planning of the study and performed the statistical analysis, and contributed to and approved the final publication. DW and PS contributed to study design and data analysis and interpretation of results, and contributed to and approved the final publication. PM, EK, EM, AM, DL, and JA contributed to data analysis, critically reviewed the manuscript, and approved the final publication.

Corresponding author

Correspondence to Ashraf Kharrat.

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Ethics approval

Research ethics approval for the study was obtained from Mount Sinai Hospital (17–0287-C).

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Conflict of interest

The authors declare no competing interests.

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Communicated by Daniele De Luca

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Kharrat, A., McNamara, P.J., Weisz, D.E. et al. Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units. Eur J Pediatr 181, 3319–3330 (2022). https://doi.org/10.1007/s00431-022-04508-6

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  • DOI: https://doi.org/10.1007/s00431-022-04508-6

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