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Avoiding Furosemide Ototoxicity Associated With Single-Ventricle Repair in Young Infants*

Robertson, Charlene M. T., MD1,2; Bork, Karin T., MSc, AuD3; Tawfik, Gerda, BSc (Pharm)4; Bond, Gwen Y., MN2,5; Hendson, Leonora, MD, MSc6; Dinu, Irina A., PhD (Biostatistics)7; Khodayari Moez, Elham, MSc (Epidemiology)7; Rebeyka, Ivan M., MD8; Garcia Guerra, Gonzalo, MD, MSc5; Joffe, Ari R., MD5

Pediatric Critical Care Medicine: April 2019 - Volume 20 - Issue 4 - p 350–356
doi: 10.1097/PCC.0000000000001807
Cardiac Intensive Care

Objective: To reduce bilateral delayed-onset progressive sensory permanent hearing loss using a systems-wide quality improvement project with adherence to best practice for the administration of furosemide.

Design: Prospective cohort study with regular audiologic follow-up assessment of survivors both before and after a 2007–2008 quality improvement practice change.

Setting: The referral center in Western Canada for complex cardiac surgery, with comprehensive multidisciplinary follow-up by the Complex Pediatric Therapies Follow-up Program.

Patients: All consecutive patients having single-ventricle palliative cardiac surgery at age 6 weeks old or younger.

Interventions: A 2007–2008 quality improvement practice change consisted of a Parenteral Drug Monograph revision indicating slow IV administration of furosemide, an educational program, and an evaluation.

Measurements and Main Results: The outcome measure was the prevalence of permanent hearing loss by 4 years old. Firth multiple logistic regression compared pre (1996–2008) to post (2008–2012) practice change occurrence of permanent hearing loss, adjusting for confounding variables, including all hospital days, extracorporeal membrane oxygenation, cardiopulmonary bypass time, age at first surgery, dialysis, and sepsis. From 1996 to 2012, 259 infants had single-ventricle palliative surgery at age 6 weeks old or younger, with 173 (64%) surviving to age 4 years. Of survivors, 106 (61%) were male, age at surgery was 11.6 days (9.0 d), and total hospitalization days by age 4 years were 64 (42); 18 (10%) had cardiopulmonary resuscitation and 38 (22%) had sepsis at any time. All 173 (100%) had 4-year follow-up. Pre- to postpractice change permanent hearing loss dropped from 17/100 (17%) to 0/73 (0%) of survivors. On Firth multiple logistic regression, the only variable statistically associated with permanent hearing loss was the pre- to postpractice change time period (odds ratio, 0.03; 95% CI, 0–0.35; p = 0.001).

Conclusions: A practice change to ensure slow IV administration of furosemide eliminated permanent hearing loss. Centers caring for critically ill infants, particularly those with single-ventricle anatomy or hypoxia, should review their drug administration guidelines and adhere to best practice for administration of IV furosemide.

1Department of Pediatrics, Division of Developmental Pediatrics, University of Alberta, Edmonton, AB, Canada.

2Department of Pediatrics, Division of Developmental Pediatrics, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada.

3Department of Audiology, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada.

4Department of Pharmacy, Stollery Children’s Hospital, Edmonton, AB, Canada.

5Department of Pediatrics, Division of Pediatric Critical Care, Stollery Children’s Hospital and University of Alberta, Edmonton, AB, Canada.

6Department of Pediatrics, Section of Neonatology, University of Calgary, Calgary, AB, Canada.

7School of Public Health, University of Alberta, Edmonton, AB, Canada.

8Department of Surgery, Stollery Children’s Hospital, Edmonton, AB, Canada.

*See also p. 384.

Drs. Robertson and Bork, Ms. Bond, and Drs. Hendson, Rebeyka, Garcia Guerra, and Joffe made substantial contributions to conception and design of the work. Dr. Robertson and Ms. Bond made substantial contributions to acquisition of the data. Drs. Robertson and Dinu, and Ms. Khodayari Moez made substantial contributions to analysis of the data. All authors made substantial contributions to interpretation of the data. Dr. Robertson drafted the first version of the article. All authors revised the article critically for important intellectual content. All authors had final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Drs. Robertson and Joffe take responsibility for the integrity of the work as a whole, from inception to published article. Drs. Robertson and Dinu had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by Alberta Health; Stollery Children’s Hospital; Women and Children’s Health Research Institute, University of Alberta; and Glenrose Rehabilitation Hospital Research Trust, Edmonton, AB, Canada. These funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Dr. Joffe’s institution received funding from Women and Children’s Health Research Institute, Glenrose Rehabilitation Hospital Research Trust, and Alberta Health. The remaining authors have disclosed that they do not have any potential conflicts of interest.

This work was performed at the University of Alberta.

The dataset used/analyzed during the current study is available from Dr. Joffe on reasonable request.

For information regarding this article, E-mail:

©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
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