Spectrum of Off-Label Nitric Oxide Utilization After Pediatric Cardiac Surgery Among Centers of Varying Surgical Volume

Abstract

Objective:

Nitric oxide is utilized after pediatric cardiac surgery as an off-label medication without much evidence, is expensive, and varies among centers of varying surgical volume. The objective of our study was to describe the spectrum of nitric oxide utilization and to evaluate the effect of nitric oxide utilization on outcomes among patients cared for in centers of varying surgical volume using Pediatric Health Information system.

Methods:

Patients aged ≤18 years undergoing heart surgery were included (2004-2015). Multivariable mixed-effects logistic regression models were fitted to evaluate association of center volume with odds of nitric oxide utilization among patients undergoing heart operations. Centers were classified into 3 volume categories based on tertiles of number of cardiopulmonary bypass cases performed (low volume: 34 792 patients, 21 centers; medium volume: 38 362 patients, 13 centers; high volume: 30 560 patients, 7 centers).

Results:

A total of 103 714 patients from 41 hospitals were included. Of these, 15 708 (15.1%) patients received nitric oxide after cardiac surgery. Of the patients receiving nitric oxide, only 3936 (25.1%) patients were associated with a diagnosis of pulmonary hypertension. In adjusted models, low- and medium-volume centers were associated with higher nitric oxide utilization after heart operations as compared to high-volume centers (low vs high, odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.38-1.60; medium vs high, OR: 1.33, 95% CI: 1.26-1.41). Despite higher nitric oxide utilization, the mortality was worse among patients treated in low- and medium-volume centers, as compared to high-volume centers (low vs high, OR: 1.42, 95% CI: 1.26-1.60; medium vs high, OR: 1.14, 95% CI: 1.04-1.25).

Conclusions:

This study demonstrates variation in nitric oxide utilization after heart operations among centers of varying surgical volume. Further, it raises questions on the benefit of nitric oxide administration after pediatric cardiac surgery.

Keywords

pediatric cardiac surgery nitric oxide center volume variation utilization.

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References

Wessel

Adatia

Giglia

Thompson

Kulik

. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation. 1993;88(5 pt 1):2128–2138.

Miller

Celermajer

Deanfield

Macrae

. Very-low-dose inhaled nitric oxide: a selective pulmonary vasodilator after operations for congenital heart disease. J Thorac Cardiovasc Surg. 1994;108(3):487–494.

Curran

Mavroudis

Backer

Sautel

Zales

Wessel

. Inhaled nitric oxide for children with congenital heart disease and pulmonary hypertension. Ann Thorac Surg. 1995;60(6):1765–1771.

Carey

Ellsworth

Harris

. Inhaled nitric oxide use in the neonatal intensive care unit: rising costs and the need for a new research paradigm. JAMA Pediatr. 2016;170(7):639–640.

Barr

Macrae

. Inhaled nitric oxide and related therapies. Pediatr Crit Care Med. 2010;11(2 suppl):S30–S36.

Gupta

Richardson

Hall

, et al. Effect of inhaled nitric oxide on outcomes in children with acute lung injury: propensity matched analysis from a linked database. Crit Care Med. 2016;44(10):1901–1909.

Food and Drug Administration. Highlights of Prescribing Information. Reference ID: 3831195. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020845s016s017lbl.pdf. Accessed February 21, 2017.

Campbell

Herbst

Briden

Neff

Ruscher

Hagadorn

. Inhaled nitric oxide use in neonates with congenital diaphragmatic hernia. Pediatrics. 2014;134(2):e420–e426.

Putnam

Tsao

Morini

; Congenital Diaphragmatic Hernia Study Group. Evaluation of variability in inhaled nitric oxide use and pulmonary hypertension in patients with congenital diaphragmatic hernia. JAMA Pediatr. 2016;170(12):1188–1194.

10.

Owner Hospitals. Child Health Corporation of America. http://www.chca.com/index_flash.html. Accessed February 21, 2017.

11.

Centers for Disease Control and Prevention, National Center for Health Statistics. International Classification of Diseases, Ninth Revision, Clinical Modification. http://www.cdc.gov/nchs/icd/icd9cm.htm. Accessed February 21, 2017.

12.

Feudtner

Christakis

Connell

. Pediatric deaths attributable to complex chronic conditions: a population-based study of Washington State, 1980-1997. Pediatrics. 2000;106(1 pt 2):205–209.

13.

Pasquali

Burstein

, et al. Association of center volume with mortality and complications in pediatric heart surgery. Pediatrics. 2012;129(2):e370–e376.

14.

Gupta

Jacobs

Pasquali

, et al. Epidemiology and outcomes following in-hospital cardiac arrest after pediatric cardiac surgery. Ann Thorac Surg. 2014;98(6):2138–2144.

15.

Pasquali

Jacobs

, et al. Measuring hospital performance in congenital heart surgery: a comparison of administrative and clinical registry data. Ann Thorac Surg. 2015;99(3):932–938.

16.

Lee

Donovan

Austin

, et al. Comparison of coding of heart failure and comorbidities in administrative and clinical data for use in outcomes research. Med Care. 2005;43(2):182–188.

17.

Pollack

Patel

Ruttimann

UE. PRISM

III : An updated pediatric risk of mortality score. Crit Care Med. 1996;24(5):743–752.

18.

Shann

Pearson

Slater

Wilkinson

. Paediatric index of mortality (PIM): a mortality prediction model for children in intensive care. Intensive Care Med. 1997;23(2):201–207.

19.

Jeffries

Soto-Campos

Katch

Gall

Rice

Wetzel

. Pediatric index of cardiac surgical intensive care mortality risk score for pediatric cardiac critical care. Pediatr Crit Care Med. 2015;16(9):846–852.