Impact of Stewardship on Inhaled Nitric Oxide Utilization ...iNO in our institution from the beginning to the end of ﬁscal years 2009–2011, we audited our iNO use across the hospital

RESEARCH ARTICLE

Impact of Stewardship on Inhaled Nitric OxideUtilization in a Neonatal ICUAmir Elmekkawi, MD,a Kiran More, MD,b Jennifer Shea, RRT,a Christina Sperling, RRT,c Zelia Da Silva, RRT,a Michael Finelli, RRT,a Asaph Rolnitsky, MD,d

Robert P. Jankov, MD, PhDa

A B S T R A C T OBJECTIVES: Inhaled nitric oxide (iNO) remains the “gold standard” therapy for hypoxemicrespiratory failure in newborns. Despite good quality evidence to guide iNO use in this population,we observed considerable practice variation, particularly in timing and rate of weaning. Topromote evidence-based practice, we launched an iNO stewardship program in April 2013. Ourobjective was to determine whether iNO stewardship led to changes in iNO utilization and weaning.

METHODS: We conducted a quality improvement project in an outborn quaternary NICU,targeting improved iNO guideline compliance. We compared patterns of iNO utilization between2 cohorts: prestewardship (April 2011–March 2013; retrospective data collection) andpoststewardship (April 2013–March 2015; prospective data collection).

RESULTS: Eighty-seven neonates received 88 courses of iNO in the 2 years prestewardship, and64 neonates received 64 courses of iNO in the 2 years poststewardship. There were no significantdifferences (P . .05) in patient demographics, in the proportion of patients receiving iNO“off-label,” in proportion initiated at the referring hospital, or in outcomes (death or extracorporealmembrane oxygenation). There were significant (P , .05) reductions in median total hours oniNO per patient (47 vs 20; P , .001), in iNO hours per patient from maximum dose to initialwean (28 vs 9; P , .01), and in hours from initial wean to discontinuation (14 vs 8; P , .05).

CONCLUSIONS: The introduction of iNO stewardship was associated with improved adherenceto evidence-based guidelines and an overall reduction in total and per-patient iNO use.

aDivision of Neonatologyand cDepartment of

Critical Care, The Hospitalfor Sick Children, Toronto,Canada; bDepartment of

Neonatology,Christchurch Women’sHospital, Christchurch,

New Zealand; anddDepartment of Newborn

and DevelopmentalPaediatrics, SunnybrookHealth Sciences Centre,

Toronto, Canada

www.hospitalpediatrics.orgDOI:10.1542/hpeds.2016-0003Copyright © 2016 by the American Academy of Pediatrics

Address correspondence to Robert P. Jankov, MD, PhD, Division of Neonatology, The Hospital for Sick Children, 555 University Ave,Toronto, Ontario, Canada M5G 1X8. E-mail: [email protected]

HOSPITAL PEDIATRICS (ISSN Numbers: Print, 2154-1663; Online, 2154-1671).

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Drs Elmekkawi and More codesigned the data collection instrument, collected data, coordinated and supervised data collection, andcodrafted the initial manuscript; Ms Shea collected data and reviewed and revised the manuscript; Ms Sperling codesigned the datacollection instrument and reviewed and revised the manuscript; Ms Da Silva and Dr Rolnitsky reviewed and revised the manuscript; MrFinelli codesigned the data collection instrument, collected data, and reviewed and revised the manuscript; Dr Jankov conceptualizedand designed the study, codesigned the data collection instrument, analyzed data, and codrafted the initial manuscript; and all authorsapproved the final manuscript as submitted.

HOSPITAL PEDIATRICS Volume 6, Issue 10, October 2016 607

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www.hospitalpediatrics.orghttp://dx.doi.org/10.1542/hpeds.2016-0003mailto:[email protected]

Persistent pulmonary hypertension ofthe newborn (PPHN) arises either as aprimary condition or secondary torespiratory distress syndrome, meconiumaspiration, sepsis, or birth asphyxia.1,2

PPHN is characterized by persistentlyraised pulmonary vascular resistanceand arterial pressure, generally associatedwith extrapulmonary right-to-left shuntingleading to hypoxemic respiratory failure(HRF). Before the availability of inhalednitric oxide (iNO), therapy was largelysupportive with extracorporeal membraneoxygenation (ECMO) employed as a finalresort. Improved oxygenation with iNOtreatment in cases of PPHN was firstreported in 1992,3,4 with subsequent largerandomized trials demonstrating asignificant reduction in the need forECMO.5–7 Despite there being no evidenceto suggest that iNO decreases mortality,length of hospital stay or the incidence ofadverse neurodevelopmental outcomesafter PPHN,8–13 iNO has greatly simplifiedthe management of PPHN, with no evidenceof adverse effects, either in the short- orlong-term.12

When inhaled, nitric oxide rapidly reachespulmonary vascular smooth musclewhere it binds to soluble guanylate cyclase,stimulating relaxation. Relative pulmonaryselectivity of this effect is conferred bythe rapid reaction of NO with oxyhemoglobinto produce methemoglobin. Toxicity ofNO may result from direct inhibitoryeffects on platelet function, or via itsproducts and reactive metabolites,including methemoglobin, nitrogen dioxide,and peroxynitrite.14–20 At the dose rangeapplied clinically (# 20 ppm), iNO rarelycauses clinically significant bleeding, orleads to potentially toxic levels of eithermethemoglobin or nitrogen dioxide. Norhas iNO been demonstrated to increaseperoxynitrite formation in the lungs or othertissues of human newborns.13 However, thepotential for such effects and the fact thatiNO is an exceptionally resource-intensivetherapy, argues for administering iNOjudiciously, at the lowest effective doseand for the shortest time possible. Despiteapproval being restricted to term andnear-term infants with PPHN, use in pretermneonates with HRF21 and in neonates with

conditions other than HRF22–25 has beensteadily increasing, despite authoritativerecommendations to the contrary.25–28 Atbest, such practices have major economicconsequences; at worst, have the potentialto cause harm. Lack of adherence toguidelines relating to commencement andweaning of iNO therapy represents anotherpractice with major economic and patientsafety implications29; however, compliancewith guidelines relating to iNO use hasnot been previously examined in the NICUsetting.

Stewardship programs are systematicinterventions aimed at improving adherenceto protocols, promoting better practices,and/or reducing costs. Stewardshipprograms to reduce antimicrobial use arenow common30 and programs targetingblood products,31 pain, and adverse druginteractions32 are also reported. Suchprograms have been successful at reducingvariations in medical care that stem fromhuman- and system-related causes.Motivated by a 65% increase in utilization ofiNO in our institution from the beginning tothe end of fiscal years 2009–2011, weaudited our iNO use across the hospital andobserved significant variation in weaningpractices leading to a longer duration of iNOtherapy than recommended by institutionalguidelines. After consultation with keystakeholders (physicians and respiratorytherapists), we instituted a hospital-wideiNO stewardship program in an effort toreduce unintended variations in practice.The objective of this study was to determinewhether the introduction of stewardshipinfluenced iNO utilization and weaningpractices in the NICU. Specifically, wesought to determine whether stewardshipled to improved compliance with our unit-specific weaning guideline, thus leading toreduced hours of iNO per course oftreatment.

METHODSStudy Design

We performed a combined retrospectiveand prospective cohort study using adeidentified data set. The Quality and RiskManagement Department at The Hospital forSick Children approved this study as aquality improvement project.

Population and Setting

The Hospital for Sick Children is a majorpediatric referral center serving south-central Ontario, Canada, with 3 intensivecare units (neonatal, pediatric, andcardiac). The NICU is a 34-bed (average dailycensus 5 36) quaternary outborn unit with700 to 750 admissions annually within aregionalized tertiary and quaternaryneonatal complex serving ∼80 000 deliveriesannually. All neonates requiring, orpotentially requiring, tertiary-level neonatalcare are retrieved by a dedicated transportteam consisting primarily of nurses andrespiratory therapists, but also physicians.Throughout the period of study, iNO wasinstituted only on attending physician orderand commencement and weaning of iNOwere conducted by respiratory therapistsunder the auspices of a unit-specificguideline. Patients potentially requiringECMO were transferred to the PICU. Thecurrent study included all neonatesadmitted to our NICU from Apri1 1, 2011, toMarch 31, 2015, who received iNO initiatedon transport or after admission to theNICU. Infants with major congenital heartdisease were excluded. The study periodwas divided into 2 epochs: a prestewardshipepoch (April 1, 2011–March 31, 2013) anda poststewardship epoch (April 1,2013–March 31, 2015).

Data Extraction and Analysis

In the prestewardship epoch, weretrospectively identified all patients whoreceived iNO by searching the medicationsand respiratory support tables recorded inour electronic charting software (CIMS,Allscripts Sunrise Clinical Care, Richmond,British Columbia, Canada) for the term“nitric oxide.” Chart data collected for eachpatient included sex, gestational age, andweight at initiation of iNO, underlyingclinical problem leading to initiation of iNO,place of initiation of iNO and outcomes,including the need for ECMO or death.Deidentified data were entered into tablesthat were subsequently queried for qualityimprovement purposes. The total durationof iNO therapy was determined bysubtracting the age (to the nearest hour)at which iNO was initiated from the age (tothe nearest hour) at which iNO was

608 ELMEKKAWI et al


discontinued. The age (to the nearest hour)at which the patient reached 5 ppm wasused to calculate hours for initial wean(from maximum dose – 5 ppm) andhours for final wean (from 5 ppm –discontinuation). Use of iNO wasconsidered off-label if gestational age atinitiation was ,35 completed weeks,postnatal age was .14 days, or if iNOwas used for conditions other than HRF.Patients transferred from the NICU to thePICU for consideration of ECMO or whodied in the NICU while on iNO wereexcluded from analyses of iNO weaningtimes. In the poststewardship epoch,patients commenced on iNO were identifiedand data (as above) were recordedprospectively on a dedicated data form thatwas subsequently transcribed into adeidentified table. Comparisons betweenepochs were conducted by Student’s t test,Mann-Whitney U test or x2, as appropriate,using Sigma Plot (version 12.5, SyStatSoftware, San Jose, CA). A P value of , .05was considered statistically significant.To demonstrate changes in the outcomesmeasure (iNO use) and in process measures(compliance rate), process control chartswere used. An X (individual) chart revealingmonthly iNO use as continuous measureddata. For protocol compliance, a P chartwas used for proportion of conformitiesin a changing sample size. Analysis ofstatistical process control charts was basedon the Institute for Healthcare Improvementrules defining special cause variations.33

Stewardship and GuidelineDevelopment Process

An iNO stewardship program was launchedat The Hospital for Sick Children as ahospital-wide initiative on April 1, 2013,which coincided with the release of arevised institutional guideline for iNO use inthe NICU. The NICU guideline was revised aspart of a process engaging key stakeholders(attending medical staff and respiratorytherapists) that included presentation ofaudit data highlighting practice variation induration on maximum dose of iNO andweaning intervals, consultation to ensureuniversal buy-in to the revised guideline anda description of monitoring and prospectivedata collection as part of the stewardship

process. Substantive changes to the revisedguideline were few, but included thefollowing: (1) consideration of iNO inpatients with an oxygenation index of 15 to20 (the previous guideline recommended$20), (2) recommendations to optimize pHand lung recruitment before commencingiNO (not stated in the previous guideline),(3) a recommendation to avoid any changesin therapy while response to iNO was beingevaluated (not stated in the previousguideline), (4) inclusion of an explicitstatement that iNO should be discontinued ifno response is observed within 1 hour (theprevious guideline simply stated that it ispossible to abruptly discontinue iNO within1 hour of commencement), and (5) theprovision of supplemental flow charts as avisual aid in guiding the initial andsubsequent weans (not present in theprevious guideline; see Figs 1 and 2). Thestewardship process began when initiationof iNO therapy, documented in thecomputerized chart, alerted the primaryand supervising researchers, who with therespiratory therapist/s, followed each caseuntil iNO therapy was discontinued. Theresponsible respiratory therapist managedthe initiation and weaning of iNO accordingto the guideline, in communication with themedical team, and recorded the data. AlliNO-treated patients were captured andfollowed during the poststewardship period.

The stewardship committee was led byrespiratory therapists and includedphysician leads and clinical fellows from theNICU and the PICU/Cardiac critical care unit.Over the 2-year period of study, thecommittee met monthly to review iNO usagedata over the preceding month. Respiratorytherapists collected data for each patient oniNO at the bedside and total weekly hourswas crosschecked against downloadedusage data from the iNO delivery devices. Allinstances of iNO use over the precedingmonth were reviewed by the committeechair, with a particular focus on theindications for use of iNO and the durationof iNO therapy in each case. Compliant usesof iNO were defined as dose and duration ofiNO therapy given in accordance with theguideline, regardless of indication.Treatment courses where initial dose iNOwas continued beyond 1 hour, despite a lack

of response, or where weaning did notoccur within the recommended time frame,despite meeting oxygenation criteria, wereconsidered noncompliant. In cases wherethe indication for use of iNO wasambiguous, or where therapy wasnoncompliant with the guideline for reasonsthat were not clear at the time of themeeting, a chart review was undertaken,which was followed if necessary by adiscussion between the stewardshipphysician and the attending physician. Newinformation derived from the chart reviewand discussion was recorded in the patientdata sheet. All members of the committeeregularly interacted with medical staff,trainees, and respiratory therapists fromtheir respective intensive care units toensure ongoing awareness of the guidelineand to review the criteria forcommencement and weaning of iNO. Generaldata on trends in iNO use were presented tothe attending staff every 6 months at aminimum, which included discussions oncommon reasons for noncompliance withthe guideline. The committee also followedtotal hours of usage, targeting a yearlyhospital-wide reduction from an average of11 938 hours annually in the 2 yearsprestewardship, to 7600 hours annually.Target hours were agreed upon with allstakeholders at the beginning of theprocess.

Flow charts summarizing the revisedguidelines are shown in Fig 1 (institution ofiNO) and Fig 2 (weaning and cessationof iNO). Throughout the period of study(April 1, 2011–March 31, 2015), theguidelines had not changed regardingindications for iNO therapy (no gestationalage or postnatal age restriction wasspecified), maximum dose, criteria forweaning, or weaning intervals. As shown inFigs 1 and 2, the range for the duration ofiNO therapy in a patient responding toiNO and persistently meeting criteria forweaning is 6 hours for the initial wean(20–5 ppm) and 5 to 10 hours for weaningfrom 5 ppm to discontinuation (total timefrom commencement is 11–16 hours).

RESULTS

Hospital-wide iNO use decreased from23 876 hours (n 5 212 courses of therapy)



in the 2 years prestewardship (April2011–March 2013) to 13 663 hours (n 5 209courses of therapy) in the 2 yearspoststewardship (April 2013–March 2015).In the NICU, 89 infants received 90 coursesof iNO in the prestewardship epoch and65 infants received 65 courses of iNO inthe poststewardship epoch. Three patientswere excluded due to a diagnosis of majorcongenital heart disease: 2 in the pre- and1 in the poststewardship epoch. Amongthe 88 and 64 courses of treatment,

respectively, total hours of iNO use were5368 hours (23% of hospital-wide hours)prestewardship and 2540 hours (19% ofhospital-wide hours) poststewardship.There were no significant differences inpatient characteristics between epochs(sex, gestational age, weight, and age atinitiation; Table 1) or in outcomes (need forECMO or death; Table 1). The percentage ofpatients in whom iNO was initiated ontransport or received off-label was alsosimilar between epochs (Table 1). Off-label

iNO use was, in the majority of cases, relatedto prematurity (50% and 61% in pre- andpostepochs, respectively), postnatal age (13%and 17%, respectively), both prematurity andpostnatal age (27% and 17%, respectively),and indications other than HRF (10% and 5%,respectively). The most common reason forcommencing iNO other than HRF was severepulmonary hypertension associated withright ventricular dysfunction, diagnosed byechocardiography. The mean and mediancompleted weeks’ gestational age among

FIGURE 1 Flowchart summarizing recommendations on initiation of iNO, determination of response, safety monitoring, and initiation of weaning.ABG, arterial blood gas; CXR, chest x-ray; FIO2, fraction of inspired oxygen; Hgb, hemoglobin; MRP, most-responsible physician; OI,oxygenation index; SpO2, pulse oxygen saturation.

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premature infants receiving off-label iNO was30 weeks (range 24–34 weeks) in bothepochs. No patients were treated withalternative pulmonary vasodilators beforeiNO, none were exposed to iNO atconcentrations higher than 20 ppm, andnone required sildenafil or other pulmonaryvasodilators to facilitate weaning off iNO.There was no significant change in mortalityor ECMO usage between the groups.

Analyses of total iNO hours per patient, timeto initial wean, and time from initial wean todiscontinuation between epochs are shownin Table 2. Analyses of weaning times

included 75 (85%) patients from theprestewardship epoch and 49 (77%)patients from the poststewardship epoch. Ofthe 13 patients excluded prestewardship,3 were transferred to the PICU forconsideration of ECMO (2 received ECMO)and 10 died in the NICU while on iNO. Of the15 patients excluded poststewardship,8 were transferred to the PICU forconsideration of ECMO (5 received ECMO)and 7 died in the NICU while on iNO. Themost common reason for noncompliancewith the weaning guideline was persistentechocardiographic evidence of severe

pulmonary hypertension with or withoutright ventricular dysfunction. Comparingweaning times between epochs, weobserved a significant reduction in totalhours on iNO per course of treatmentpoststewardship, whether patients wereexcluded from analyses. We also observed asignificant decrease in iNO hours perpatient from maximum dose to initial wean(to 5 ppm) and in hours from 5 ppm todiscontinuation of iNO in thepoststewardship epoch (Table 2). As shownin Fig 3A, there was a persistent reductionof iNO usage from 224 hours/month to

FIGURE 2 Flowchart summarizing weaning recommendations for iNO. FIO2, fraction of inspired oxygen; SpO2, pulse oxygen saturation.



106 hours/month between the pre- andpoststewardship eras. As shown in Fig 3B,monthly percentage compliance with theguideline increased from a mean of 3.2% ofiNO courses prestewardship to 25.8%poststewardship.

DISCUSSION

Despite there being high quality evidenceto inform use of iNO in neonates, ourguideline was being frequently ignored.Concerns surrounding the costly, andperhaps unnecessary, use of iNO led us tore-examine our guideline and to developstrategies to improve adherence. Ourfindings demonstrated that implementationof an iNO stewardship program improvedadherence to guidelines, leading tomeaningful reductions in total and per-patient hours of iNO use. To our knowledge,the current study is the first to examineadherence to evidence-based guidelines inthe context of iNO therapy in the NICU andthe first to describe the impact of astewardship program on utilizationpatterns of iNO. Major drivers of change in

iNO utilization likely included an enhancedawareness of the guideline by front linestaff, increased vigilance by respiratorytherapists regarding opportunities forweaning, the observer (Hawthorne) effectand unmeasured cointerventions (eg,arrival of new staff or discussion ofrational use of iNO at conferences, etc),which modified physician behavior.

Clinical practice guidelines are widelyregarded as key to reducing practice variationand improving the quality of care.29,33 However,to be effective, guidelines must be updatedregularly to reflect current evidence or expertopinion, must be minimally controversial toensure maximum buy-in, and must beimplemented in an environment characterizedby sustained communication and vigilance.The stewardship model has been usedsuccessfully in the pediatric setting topromote safe and evidence-based use ofantimicrobial agents.34 Key elements of ouriNO stewardship program included anidentified staff physician and trainee,widespread dissemination of evidence-based

practice guidelines that were approved by allmembers of the medical and respiratorytherapy team, detailed prospective datacollection, setting targets for total yearlyutilization, regular reviews of iNO use by aninterprofessional stewardship committee,discussion of specific cases with theattending physician, and feedback on generaltrends in iNO use to NICU staff.

Our guidelines did not set limits ongestational age for treatment with iNO.Despite this, our rate of off-label use forprematurity was less than recentlypublished rates, which were as high as50%.21 This disparity likely reflectedinherent differences in our outbornpopulation, which is made uppredominantly of complex term and near-term infants, rather than attitudesdiscouraging use of iNO in the verypreterm. Indeed, the pathophysiology ofHRF in the preterm may be identical to theterm infant with PPHN, making the use ofiNO a logical and potentially usefulextension of therapy, thoughresponsiveness may diminish withdecreasing gestational age.35 Similar toterm infants with PPHN, clinical trialsexamining effects of iNO for HRF inpremature infants have confirmed short-term improvements in oxygenation, but noreduction in mortality.36–40 In the absence ofspecific evidence to guide iNO therapy inthis population, our guidelines for startingdose and weaning of iNO were the same,regardless of gestational age.

A significant minority of our iNO-treatedinfants in both epochs did not have HRF. Inmost cases, iNO was instituted based onechocardiographic evidence of chronicpulmonary hypertension with associatedright ventricular dysfunction. Most suchcases were considered noncompliant inthe current study, due to avoidance ofweaning until repeat evaluation byechocardiogram, which greatly prolongediNO therapy. In patients with poorlyresponsive pulmonary hypertensionand/or right ventricular dysfunction,prolonged treatment with iNO may bejustified; however, use of iNO for suchindications is difficult to incorporate intoweaning guidelines, particularly in a

TABLE 1 Patient Demographics and Outcomes

Prestewardship Poststewardship P

Number of patients 87 64 NA

Sex F/M: 37/50 F/M: 31/33 .55

Gestational age in completed weeks at initiationof iNOa

38 (33–40) 38 (34–40) .88

Day of life at initiation of iNOa 2 (1–5) 2 (2–9) .083

Grams body weight at initiation of iNOa 3080 (1753–3675) 3020 (1931–3500) .75

Off-label use (%) 30 (34) 23 (36) .95

iNO initiated before admission (%) 32 (36) 29 (45) .35

ECMO (%) 2 (2) 5 (8) .11

Died (%) 23 (26) 14 (22) .52

NA, not applicable.a Data are presented as median (interquartile range).

TABLE 2 iNO Utilization

Prestewardship Poststewardship P

Courses of iNO treatment given 88 64 NA

Total iNO hours 5368 2540 NA

Hours/course,a all patients 47 (23–66) 20 (13–46) ,.001

Hours/course,a with exclusionsb 49 (25–66) 22 (14–46) ,.001

Hours from maximum dose to 5 ppma,b 28 (12–51) 9 (5–26) ,.01

Hours from 5 ppm to discontinuationa,b 14 (7–24) 8 (6–15) ,.05

NA, not applicable.a Data are presented as median (interquartile range).b Patients who died on iNO or were transferred to the PICU for consideration of ECMO were excluded.

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population in which iNO is usedpredominantly for oxygenation failure. Ourcurrent approach to such cases is to use iNOas a bridge to other therapies,41 if required,at the lowest dose at which a response isobserved (generally 5 or 10 ppm), while

consulting with experts in themanagement of pulmonary hypertension.

Improving Quality

This study evaluated a process that improvedcost-effectiveness by reducing unnecessary

exposure to a medication, without evidence ofharm, thus enhancing quality of health care.42

Limitations of the Study

Data from the prestewardship epoch wascollected retrospectively, which has many

FIGURE 3 Statistical process control charts. A, X-chart displaying hours of iNO use per month. The green line represents the process mean. Thebroken red line represents the upper control limit (3 SDs from the mean). B, P-chart revealing percentage of iNO courses each monthgiven in compliance with the guideline. The blue line and dots represent the compliance rate with the iNO guideline (in percent) for eachmonth. The continuous green line represents the compliance rate mean for each epoch. The pale red line represents the upper controllimit (3 SDs from the mean).



inherent limitations. In particular, it wasfrequently challenging or impossible todetermine the reasons behind patterns ofiNO utilization that deviated greatly from ourguideline. We observed no significantchange in proportion of infants dying orreceiving ECMO between the pre- andpoststewardship eras, suggesting a lack ofharm related to decreased iNO use.However, we did not prospectively collectdata on other possible consequences ofdecreased iNO utilization, including changesin patterns of muscle relaxant, narcotic andsedative use, or on duration of invasivemechanical ventilation or length of hospitalstay. This work was conducted in a singlequaternary outborn NICU populated byinfants across the gestational agespectrum, among which there wassignificant complexity and heterogeneity;this has potential implications forinterpretation of outcomes reflecting safety(use of ECMO or death), at least in the short-term. Due to the observational design of thisstudy, we cannot be certain that thechanges in iNO utilization over time wereprimarily due to the introduction ofstewardship, rather than a secular trend.A major factor in favor of an importantimpact of stewardship on iNO utilizationpatterns was that our guideline, and themethod by which iNO was prescribed andmonitored, did not change substantivelythroughout the period of study.

Generalizability and Spread

Our experience suggests that thestewardship model can be implemented inany NICU. Toward this goal, national Canadianguidelines guiding practice in neonates werecollaboratively developed and promulgatedunder the auspices of the CanadianAssociation of Pediatric Health Centres.43

A Canadian Association of Pediatric HealthCentres-sponsored national iNO stewardshipnetwork is currently in the planning phase.

CONCLUSIONS

Variation in the use of iNO leading tounnecessary prolongation of therapy carriesa significant economic burden and haspotential to cause harm. Implementation of astewardship program improved adherenceto evidence-based guidelines, leading to

significant and important decreases in totaland per-patient iNO use in our NICU. Weconclude that the stewardship model hasutility in reducing practice variation in iNOuse in the NICU setting and has the potentialto generate new knowledge that will informfuture practice.

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http://www.pediatrics.org/cgi/content/full/133/6/e1753http://www.pediatrics.org/cgi/content/full/133/6/e1753http://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaninghttp://ken.caphc.org/xwiki/bin/view/PaediatricPracticeGuidelinesCollaborative/CAPHC+Guidelines+for+Inhaled+Nitric+Oxide+in+Neonates%3A++Dosing,+Administration+and+Weaning

DOI: 10.1542/hpeds.2016-0003 originally published online September 6, 2016; 2016;6;607Hospital Pediatrics

Michael Finelli, Asaph Rolnitsky and Robert P. JankovAmir Elmekkawi, Kiran More, Jennifer Shea, Christina Sperling, Zelia Da Silva,

Impact of Stewardship on Inhaled Nitric Oxide Utilization in a Neonatal ICU

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DOI: 10.1542/hpeds.2016-0003 originally published online September 6, 2016; 2016;6;607Hospital Pediatrics

Michael Finelli, Asaph Rolnitsky and Robert P. JankovAmir Elmekkawi, Kiran More, Jennifer Shea, Christina Sperling, Zelia Da Silva,

Impact of Stewardship on Inhaled Nitric Oxide Utilization in a Neonatal ICU

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Impact of Stewardship on Inhaled Nitric Oxide Utilization ...iNO in our institution from the beginning to the end of ﬁscal years 2009–2011, we audited our iNO use across the hospital