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Nebulized Hypertonic Saline Without Adjunctive Bronchodilators for Children With Bronchiolitis Shawn Ralston, Vanessa Hill and Marissa Martinez Pediatrics 2010;126;e520; originally published online August 16, 2010; DOI: 10.1542/peds.2009-3105


The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/126/3/e520.full.htmll http://pediatrics.aappublications.org/content/126/3/e520.full.htm

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Nebulized Hypertonic Saline Without Adjunctive Bronchodilators for Children With Bronchiolitis WHAT’S KNOWN ON THIS SUBJECT:  Multiple studies evaluated nebulized hypertonic saline solution as a therapy for viral bronchiolitis in young children. However, the available studies combined hypertonic saline solution with some form of  bronchodilator because of theoretical concerns that hypertonic saline solution may cause bronchospasm. WHAT THIS STUDY ADDS:  This is the first study to investigate systematically the risk of bronchospasm or other significant adverse effects with hypertonic saline solution administered without bronchodilators for viral bronchiolitis.

AUTHORS:  Shawn Ralston, MD,a,b Vanessa Hill, MD,a,b and Marissa Martinez, MDb a 

Department of Pediatrics, University of Texas Health Science 

Center at San Antonio, San Antonio, Texas; and  b Christus Santa  Rosa Children’s Hospital, San Antonio, Texas 

KEY WORDS bronchiolitis, therapy, adverse effects, hypertonic saline solution ABBREVIATION CI—confidence interval Dr Martinez’s current affiliation is QTC Medical Services, San Antonio, TX. www.pediatrics.org/cgi/doi/10.1542/peds.2009-3105 doi:10.1542/peds.2009-3105


Accepted for publication May 28, 2010

OBJECTIVE: The goal was to determine an adverse event rate for nebulized hyper hypertoni tonicc sali saline ne solut solution ion admin administer istered ed witho without ut adjunc adjunctive tive bronchodilators for infants with bronchiolitis. METHODS: This was a retrospective cohort study of the use of nebulized liz ed 3% sal saline ine for chi childr ldren en 2 yea years rs of age who wer were e hos hospit pitali alized zed wit with h  the primary diagnosis of bronchiolitis at a single academic medical center. The medical records of study participants were analyzed for  the use of nebulized 3% saline solution and any documented adverse events related to this therapy. Other clinical outcomes evaluated included respiratory distress scores, timing of the use of bronchodila tors in relation to 3% saline solution, transfer to a higher level of care, and readmission within 72 hours after discharge.

Address correspondence to Shawn Ralston, MD, University of  Texas Health Science Center at San Antonio, Department of  Pediatrics, 7703 Floyd Curl Dr, MSC 7829, San Antonio, TX 78229. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2010 by the American Academy of Pediatrics FINANCIAL DISCLOSURE DISCLOSURE::  The authors have indicated they have  no financial relationships relevant to this article to disclose.

RESULTS: A total of 444 total doses of 3% saline solution were administered, with 377 doses (85%) being administered without adjunctive bronchodilators. Four adverse events occurred with these 377 doses, for a 1.0% adverse event rate (95% confidence interval: 0.3%–2.8%). Adverse events were generally mild. One episode of bronchospasm was doc docume umente nted, d, for a ra rate te of 0.3 0.3% % (95 (95% % con confide fidence nce int interv erval: al: 0.01%– 1.6%). CONCLUSIONS:  The use of 3% saline solution without adjunctive bronchodilators for inpatients with bronchiolitis had a low rate of adverse events in our center. Additional clinical trials of 3% saline solution in bronch bro nchiol ioliti itiss sho should uld eva evalua luate te its eff effect ective ivenes nesss in the abs absenc ence e of adj adjunc unc- tive bronchodilators. Pediatrics  2010;126:e520–e525  2010;126:e520–e525

e520   RALSTON et al

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Vira Virall bronc bronchioli hiolitis tis is the most most-comm -common on reason for hospital admission for infants,, accou fants accounting nting for 20% of hospi hospitaltal1 izations izati ons at   1 year of age ge.. Metaanalys ana lyses es of dat data a on the mos most-u t-used sed  therapies, namely, nebulized albuterol and an d ep epin inep ephr hrin ine, e, fa fail iled ed to de demo monnstrate any effect on relevant clinical

 typical bronchiolitis do not involve bronch bro nchial ial smo smooth oth mus muscle cle hyp hyperr erreespon sp onsi sive vene ness ss,, co conc ncer ern n re rega gard rdin ing g bronchospasm resulting from the use of 3% saline solution among patients with bronchiolitis remains theoretical.

outcomes, in comparison with placebo.2–5 Current clinical practice guidelines do not recommend the routine use of any medication for bronchioli tis  t is..6 Despite the evidence, use of ineffective therapies for bronchiolitis remains high. high.7,8

problematic because investigators coadministered 3% saline solution with bronchodilators, medications that are known to be ineffective in the disease. In only 1 study was any 3% saline solu tion administered without concomi tant bronchodilator treatment; al though only some of the patients in  that study received the medication without witho ut bronc bronchodil hodilator ators, s, bronc bronchoshospasm was not a reported adverse effect fe ct..12 No evi eviden dence ce has est establ ablish ished ed  that 3% saline solution induces bron-

provided by a group of academic pediatric hospitalists employed by the University of Texas Health Science Center at San Antonio, with 15% of medical service inpatients being cared for by physicians in private practice. Yearly admissions with the primary diagnosis of bronchiolitis in this institution ranged between 350–500 350 –500 patients per year over the past 5 years.

chospasm in infant chospasm infantss with bronc bronchioli hiolitis, tis, but its safety when used without ad junctive bronchodilators also has not been established.

years, primary diagnosis diagnosis of acute viral bronchiolitis (International Classification of Diseases, Ninth Revision, code 466.11 or 466.19), and hospitalization on 1 of the 2 medical service floors at Christus Santa Rosa Children’s Hospital. Hospital. The time period was chosen because of the availability of  an exte extensiv nsive e data database base being mai mainn tained  taine d for an ongo ongoing ing qual quality ity improv pr oveme ement nt pro projec ject. t. The 2 med medica icall service floors were chosen for the database because they hospitalized

Several studies reported on the use of  nebuli neb ulized zed 3% sal saline ine sol soluti ution on for infants with bronchiolitis, with the ma jority reporting substantial benefits of   therapy.  thera py.9–12 Evidence suggests that hypertonic saline solution favorably al ters mucociliary clearance in both normal and dis diseas eased ed lun lungs, gs, in mul multip tiple le clinic cli nical al set settin tings gs..13–16 Be Beca caus use e th the e pathophysi patho physiolog ologic ic chara character cteristi istics cs of  bronchiolitis primarily involve airway inflammati inflam mation on with incr increased eased mucus production and mucus plugging, it is logica log icall to thi think nk tha thatt imp improv roved ed muc mucoci ocililiary clearance would be beneficial in bronchiolitis, although there is only indirect evidence that this is true. The only significant adverse effect of  nebulized hypertonic saline solution is

Most available studies on hypertonic saline sal ine sol soluti ution on in bro bronch nchiol ioliti itiss are

This study was undertaken because of   the emerging popularity of nebulized 3% saline solution in our center and  the variable use patterns noted. Our primary goal was to gain more information about the use of this new therapyy in ou ap ourr ce cent nter er,, wi with th a sp spec ecifi ificc ai aim m of  establishi estab lishing ng a rate of adver adverse se reac tions for 3% saline solution used with-

 the risk of bronchospasm. Use of nebulized hypertonic saline solution is es tablished in the asthma literature as a diagnostic test to distinguish individuals with asthma from those without asthma asthm a.17 There is a fairly clear doseresponse respo nse rela relations tionship hip for hyper hypertoni tonicc saline solution and bronchospasm in individuals with asthma. asthma.18 Typical concentrations used in studies of individuals with asthma range from 4.5% to 7%, with widely varying volumes being required requi red to induce bronchospas bronchospasm m.19

out adjunctive bronchodilators, to es tablish the safety of the intervention.

Because the vast majority of patients with bronchiolitis do not have asthma and the pathophysiologic features of 

and wa and wass ap appr prov oved ed by the the Chr Chris istu tuss Santa San ta Ros Rosa a Chi Childr ldren’ en’ss Ho Hospi spital tal research office.

PEDIATRICS PEDIATRI CS Volume 126, Number 3, September 2010

METHODS Study Design

This was a retrospective cohort study of infants hospitalized with bronchioli tis between December 15, 2008, and Marc Ma rch h 15 15,, 200 2009, 9, at Ch Chri rist stus us Sa Sant nta a Ro Rosa sa Children’s Childr en’s Hosp Hospital. ital. This study qualified for exempt status from the University of Texas Health Science Center at San Antonio institutional review board


Study Setting

The Chr Christ istus us San Santa ta Ros Rosa a Chi Childr ldren’ en’ss Hospital is an urban, nonprofit, children’s hospital in San Antonio, Texas (metro (me tropol polita itan n are area a pop popula ulatio tion n of 2 mil mil-lion), which serves a population covered ere d pri primar marily ily by pub public lic ins insura urance nce programs. Inpatient pediatric care is

Inclusion Criteria

Inclusio Incl usion n crit criteria eria were age of    2

 the vast major majority ity of patie patients nts with bronchiolitis in the hospital, had a fixed capacity from year to year, had clear admission criteria (ie, no cardiacc mo dia monit nitor oring ing), ), and had st stabl able e nurse/patient nurse/pat ient ratios and therefor therefore e would provide a stable denominator with little variation in severity of disease eas e for the qua qualit lityy im impro prove vemen mentt project. Exclusion Criteria

Exclusion criteria were the presence of  complicating underly complicating underlying ing illness illnesses es (bronchopulm cho pulmonar onaryy dys dysplas plasia ia or chro chronic nic lung diseas dis ease, e, neur neuromu omuscul scular ar imp impair airment ment,,

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immunodeficiency,, or congenit immunodeficiency congenital al heart disease). Methods

Information was obtained through review vie w of an exi existi sting ng dat databa abase se doc docuumenting menti ng all bronc bronchioli hiolitis tis hospi hospitali talizaza tions on the regular medical service floors. The database was established as pa part rt of a qua quali lity ty im impr prov ovem emen entt project centered on the use of a bronchiolitis chiol itis respi respirato ratory ry dist distress ress scor score. e. The score was adapted from a score report rep orted ed by the Chi Childr ldren’ en’ss Hos Hospit pital al and Medical Center of Cincinnati Cincinnati (F (Fig ig 20 1).. Our mod 1) modific ificati ation on con consis sisted ted of  dropping 1 of the original 5 assessment sections for the score, namely, estimatio estim ation n of an inspi inspirati ration/ex on/expirat piration ion ratio. The protocol specified external nasal suctioning suctioning befor before e scor scoring ing and finding a score of  3 before proceeding to any type of nebulized therapy. Use of the scoring system and/or pro tocol order set was on a voluntary basis. Outcomes

The primary outcomes for this study were the rate of adverse reactions to 3% saline solution and the methods of 

delivery of the therapy (ie, conco delivery concomimi tantly with bronchodilators, within 4 hours after bronc bronchodil hodilator ator admin adminisis tration, or alone). We use the phrase “without adjunctive bronchodilators”  to indicate doses of 3% saline solution  that were administered without preceding bronchodilator administration

section for each score. Although respiratory rato ry thera therapist pistss docum documented ented finding findingss routin rou tinely ely in our ele electr ctroni onicc med medica icall records, the requirement to document a score was new, as was the immediate at e pr prom ompt pt fo forr co comm mmen ents ts on th the e score. sco re. We met wit with h the res respir pirato atory ry  therapis  ther apists ts reg regular ularly ly duri during ng the project, project,

within 4 hours and that did not result in bronc bronchodil hodilator ator admin administr istratio ation n in  the 4 hours immediately after the dose. For study purposes, adverse reactions were defined quite broadly to includ inc lude e any doc docume umente nted d sym sympto ptom m tha thatt was alleged to result from administra tion of the nebulized therapy. This strategy was undertaken deliberately,  to provide the most-liberal assessment of poten potential tial adverse adverse effec effects ts of  nebulized 3% saline solution, because  the goals of the study were to provide

 to promote the scoring system and to encourage increased documentation. In gener general, al, adverse events are underreport rep orted ed in hea health lth car care e set settin tings; gs; the thererefore, for e, we con consid sidere ered d it nec necess essary ary to  take special steps to increase reporting during the study period. We did not prov pr ovid ide e a de defin finit itio ion n of an ad adve vers rse e event to the respiratory therapists, al though we encouraged them to documentt any sym men sympto ptoms ms the theyy tho though ughtt wer were e related rela ted to the administrati administration on of any nebulized therapy.

documenta docume ntatio tion n to sup suppor portt the saf safety ety of  a novel therapy. There was no standardized method of reporting adverse events in response to nebulized therapies in our center. We created a new process for respiratory therapy documentation in the chart in association with the scoring system used for the protocol, with addition of a comment

RESULTS One hundre hundred d fiftyfifty-eight eight patients patients met  the inclusion criteria for the study cohort. Four patients were excluded, 1 because of chronic lung disease of  prema pr ematur turit ityy and st stat atic ic enc enceph ephalalopathy, opat hy, 2 beca because use of diag diagnose nosess of  bronchopulmonary bronchopul monary dys dyspla plasia sia,, and 1 because of trisomy 21 with neuromuscular impairment, which left 154 pa tients constituting the study cohort. The study cohort is described in described  in Table Table 1, with reference to any receipt of 3% saline solution. Sixty-eight Sixty-eig ht (44%) of 154 pati patients ents received cei ved any 3% sal saline ine sol soluti ution. on. All dos doses es of 3% saline solution in the study cohort were 4 mL in volume and nebulized with a 6-L flow of oxygen from a wall source, with the hospital’s standardized configuration. A total of 444 doses dos es of 3% sal saline ine so solut lution ion wer were e docu do cume ment nted ed,, wi with th a me mean an of 6. 6.5 5 doses per patient (median: 4 doses

FIGURE 1 Modified Cincinnati bronchiolitis score.

e522   RALSTON et al

per pat patien ientt [i [inte nterqu rquart artil ile e ra range nge:: 2–10 doses per patient]). Sixty-seven doses (15%) were administered con-

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TABLE 1.   Characteristics of Patients Who Received Any 3% Saline Solution Versus None

Age, mean  SD, moa Male, estimate (95% CI), % Readmitted within 72 h, estimate (95% CI), % Tran Tr ansf sfer erre red d to hi high gher er le level vel of ca care re,, est estim imat ate e (95 (95% % CI CI), ), % Received steroids, estimate (95% CI), % Re ce cei ve ve d antibiotics , es titi ma mate (9 5% 5% CI) , % Rece Re ceiv ived ed ch ches estt ph phys ysio ioth ther erap apy, y, es esti tima mate te (9 (95% 5% CI CI), ), % Re ce cei ve ve d al bu bute ro rol, estim at ate (9 5% 5% CI), % Received Rece ived res respir pirato atory ry scor scoring ing pro protoc tocol, ol, esti estimat mate e (95% CI) CI),, % Initial respiratory score, (95% CI) a Mean respiratory score, (95% CI) a a

Received 3% Saline Solution (N   68)

Did Not Receive 3% Saline Solution (N   86)

5.2  3.9 51.5 (39.8–63.0) 1.5 (0.01–8.6) 2.9 (0. (0.2– 2–10. 10.7) 7) 5.9 (2.9–14.6) 30 .9 .9 (2 1. 1.1 –4 –42 .7 .7 ) 5.9 5. 9 (1 (1.9 .9–1 –14. 4.6) 6) 20 .6 .6 (1 2. 2.6 –3 –31 .8 .8 ) 61.8 (49. (49.9–72 9–72.4) .4) 1 .8 .8 (1 .4 .4–2 .2 .2) 2 .4 .4 (1 .9 .9–2 .8 .8)

7.0  5.2 54.0 (43.6–64.1) 1.2 (0.01–6.8) 2.3 2. 3 (0 (0.14 .14–8 –8.5) .5) 15.1 (8.9–24.3) 4 2. 2.0 (32 .0 .0–52 .4 .4) 2.3 2. 3 (0 (0.1 .14– 4–8. 8.5) 5) 2 0. 0.9 (13 .6 .6–30 .8 .8) 67.8 (57. (57.4–7 4–76.7) 6.7) 0.8 (0.6 –1 –1 .0 .0) 0.9 (0.4 –1 –1 .2 .2)

P   .05.

comitant with or within 4 hours of  administration of any   -adrenergic recept rec eptor or ago agonis nist, t, wi with th 377 dos doses es (85%)) being admi (85% administ nistered ered with without out adjunctive bronchodilators.

Four adverse events, all defined as respiratory in nature, occurred among 377 doses administered administered without ad junctive bronchodilators, for a 1.0% adverse event rate (95% confidence in-

 terval [CI]: 0.3%–2.8%). One additional adverse event was documented for a dose dos e of 3% sal saline ine sol soluti ution on adm admini iniss tered concomitantly with with albuterol, for an overall rate of 1.1% (95% CI: 0.4%– 2.7%) for all doses. All events were respiratory in nature, generally were describe scr ibed d as cou coughi ghing, ng, and are ful fully ly characterized in Tab Table le 2. Wit With h inc inclus lusion ion of only events considered significant enough to result in discontinuation of   the therapy for the remainder of the hospitali hospi talizatio zation n (2 of 377 doses), the adverse event rate was 0.5% (95% CI: 0.02%–2%). Finally, with consideration of only events documented as bronchospasm chos pasm (the potent potential ial adver adverse se effect generating the most concern), the

TABLE 2.   Characteristics of Documented Adverse Adverse Events With 3% Saline Solution Age/Gender

Type of Event

Medication Administered

Recorded by


6 wk /m /male

Bronc ho hos pa pasm (dec re re as as ed ed oxygen saturation and increased respiratory rate documented)

4 mL of 3% saline solution

Respiratory therapist and physician

2.5 2. 5 mo mo/f /fem ema ale

Coug hin Cou hing g dur urin ing g nebulization

4 mL of 3% saline solution

Respiratory Respira tory thera therapist pist

2.5 mo/female (same as above)

Coughing during nebulization

4 mL of 3% saline solution and 2.5 mg of  albuterol

Respiratory Respira tory thera therapist pist

4 mo/male

Excessive coughing

4 mL of 3% saline solution

Respiratory Respira tory thera therapist pist

13 mo/male

Excessive coughing

4 mL of 3% saline solution

Respiratory Respira tory thera therapist pist

Physician was called to bedside by respiratory therapist. Predose and postdose respiratory scores were 5 and 6, respectively. Racemic epinephrine was administered and patient’s condition stabilized, according to physician’s note. Patient was given 1 more dose of 3% saline with predose respiratory score of 5, and no additional scores were obtained. Patient then received scheduled albuterol dose without improvement. Patient’s condition deteriorated over next 8 h, with eventual transfer to ICU. Patient  then received scheduled albuterol, epinephrine, and ipratropium doses and underwent intubation because of “apnea and respiratory failure” within several hours after admission to PICU. Dose was discon discontinued tinued befor before e nebulizat nebulization ion was finished finished,, at discretion of respiratory therapist. Predose respiratory score was 4; subsequently, scoring was discontinued and patient was removed from scoring protocol, at discretion of attending physician (see below). Physician Physici an discon discontinued tinued 3% saline saline admini administrat stration ion after second episode of coughing, which reoccurred despite addition of albuterol. Patient received scheduled albuterol for remainder of hospitalization. Nursing notes continued to document cough during and after nebulizations. No interven intervention tion was perform performed. ed. Predose Predose and postd postdose ose respiratory scores were 4 and 5, respectively. One additional dose of 3% saline was given during hospitalization, without documented adverse event. Patient was discharged within 24 hours after event. No interven intervention tion was perform performed. ed. No No respirat respiratory ory scores were available. Subsequently, patient was given scheduled albuterol and 3% saline administration was discontinued. No further excessive cough during nebulizations was documented.

PEDIATRICS PEDIATRI CS Volume 126, Number 3, September 2010


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adverse event rate was 0.3% (95% CI: 0. 0.01 01%– %–1. 1.6% 6%). ). Al Alll ra rate tess ar are e pr preesented in sented  in Table 3. Table 3. The bronc bronchioli hiolitis tis prot protocol, ocol, which allowed us to track respiratory scores, was used for 98 patients. The institu tional bronchiolitis protocol emphasized siz ed sup suppor portiv tive e car care e onl only, y, and pa-

occurred and we did not attempt to assess systematically the efficacy of the  therapy in this project. Respiratory scores worsened after 3% saline solu tion administration for 2 (1%) of 211 doses dos es adm admini inist stere ered. d. Bot Both h of the these se events, including the scores, are described in scribed  in Table 2. Table 2.

epinephrine. epinephr ine. The pat patient ient in ques questio tion n pro pro-gressed to respiratory failure over the nextt 24 hour nex hours; s; howe however ver,, the docu document mented ed reason for intubation was apnea.

 tients were required to achieve a respiratory score at or above an intervention threshold of 3 to receive any thing other than nasopharyngeal suc tioning and oxygen administration. Forty-tw Fort y-two o patie patients nts (43%) treated according to the protocol received any 3% sal saline ine sol soluti ution. on. Fif Fifty ty-6 -6 pat patien ients ts (57%) (57 %) did not rec receiv eive e any neb nebuli ulized zed  therapies during hospitalization, which indicates that their respiratory scores remained   3. Of the total of  444 doses of 3% saline solution, 211

Respirator Respira toryy sco scores res,, wher where e ava availa ilable, ble, werediff were differen erentt betw between een the pati patients entswho who recei re ceive ved d any 3% sa sali line ne so solut lutio ion n an and d  those  thos e who did not, both on average average and at presentation presentation (Table 1). (Table  1). This is to be expected, expec ted, because patie patients nts were required to reach a cutoff respiratory score scor e befor before e proc proceeding eeding to any nebulized liz ed the therap rapyy and pat patien ients ts who received ceive d any nebuli nebulized zed thera therapy py necessarily would have higher scores. We also noted a small age difference be tween the groups, with the patients in

 tion was docu  tion document mented; ed; this inv involv olved ed a 4-month-old patient for whom a physician was called because of a heart rate of 189 189beat beatss per perminu minute. te.No No int interv erventi entions ons were performed, performed, and the patient experienced an uncomplicated hospitalization, without administration of any additional nebulized therapies. This adverse event was not considered to be related to 3% saline solution for the purposes of this study, because no tachycardia or concern regarding tachycardia was documented before the dose of epinephrine.

were administered to patients being  treated according to the scoring pro tocol, with a mean of 2 doses per pa tient (median: 0 doses per patient [in terquartile range: 0 –2 doses per patien pat ient]) t]).. Of the 211 dos doses es adm admini iniss tered according to the protocol, only 24 (9%) were administered concomi tant with or within 4 hours of a bronchodilato chodi lator. r. Respi Respirato ratory ry scor scores es after 3% saline solution administration improved for 188 (89%) of 211 doses administered; however, we do not necessarily interpret this improvement as resulting from the 3% saline solution, because additional nasal or nasopharyngeal ryng eal sucti suctioning oning and incre increases ases in oxyg ox ygen en de deli live very ry al also so mi migh ghtt ha have ve

 the 3% saline solution group being slightly younger. Rates of use of other  therapies, such as antibiotics or steroid ro ids, s, we were re si simi mila larr be betw twee een n th the e 2 grou gr oups ps.. Ra Rate tess of re read admi miss ssio ion n an and d  transfer to a higher level of care were equivalent for patients who received 3% saline solution and those who did no t no  t (Table 1). (Table  1).

Our study is the first to address directly  the adv advers erse e eff effect ect pro profile file of 3% sal saline ine

One adverse event in response to albu terol administe  terol administered red with 3% sal saline ine solu tion  tio n was documented documented,, as det detaile ailed d in Table 2. No adv advers erse e rea reacti ctions ons to alb albute uterol rol alone were found in the available documentatio ument ation n in our study; however, literatur era ture e find finding ingss sug sugges gestt tha thatt a decrea cr ease se in ox oxyg ygen en sa satu tura rati tion on af afte terr admini adm inistr strati ation on of alb albute uterol rol occ occurs urs in bronc bronchioli hiolittis is..21 Unfo Unfortuna rtunately, tely, at tempts to quantify oxygen saturation leve le vels ls in ou ourr da data taba base se we were re ab aban an-doned because too many valu values es were

solution, used without adjunctive bronchodilators, in bronchiolitis. It is notable  that377 dos doses es of 3% sal saline inesol soluti ution on were administered adminis tered without adjunctive bronchodilators for 68 patients, with a 1.0% adverse event rate. Most of our adverse event ev entss we were re mi mild ld an and d wer were e des descr cribe ibed d as coughing. Two adverse events (0.5% of  all doses administered) resulted in discontinuation of the therapy, and 1 adverse event was classified as bronchospasm and resulted in a physician being called to evaluate the patient. The physi-

found to be missing. The possibility of overreporting of adverse events by respiratory therapists in our study is likely. As stated previously, we actively encouraged reporting during the study period, through several methods, and the fact that all of our adverse events were reported by respiratory therapists supports the contention that respiratory therapists were predisposed to report on the basis of the their ir inv involv olveme ement nt in the pro protoc tocol. ol. Also, given the fact that the interven-

cian who responded to the event documented ment ed sta stabili bilizati zation on of the pati patient ent’s ’s conditio dit ion n af after ter a si singl ngle e dos dose e of ra racem cemic ic

 tion was unblinded, overreporting because of personal bias regarding the use of a novel therapy might be more

TABLE 3.   Adverse Event Rates Rates Associated With Nebulized 3% Saline Solution Administered Without Adjunctive Bronchodilators (N   377) Type of Event A ny ny do cum cumen ente ted d ev even entt Events resulting in discontinuation of   therapy Events characterized as bronchospasm

e524   RALSTON et al

Rate, Estimate (95% CI), % 1.0 (0 1.0 (0.3 .3–2 –2.8 .8)) 0.5 (0.02–2)

0.3 (0.01–1.6)


One ad One adver verse se ev event(3.8 ent(3.8% % of dos doses es ad admi minnistered) associated with a dose of racemic epin epinephr ephrine ine admi adminis nister tered ed   10 minutes after a dose of 3% saline solu-

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likely. In addition, the fact that excessive coughing was the most-common advers adv erse e rea reacti ction on may be ques questio tionab nable, le, becaus bec ause e cou cough gh is enc encoun ounter tered ed fre fre-quently with nebulized therapies and we were unable to provide a standardized definition of excessive coughing.

verse events. However, each of those charts was carefully reviewed for any respiratory therapist documentation in standard locations, and 1 of the advers ve rse e ev even ents ts wa wass id iden enti tifie fied d in th this is manner.

verse event rate would be higher if documentation was incomplete. Finally, becaus ca use e of our st study udy de desi sign, gn, our da data ta cannot be applied to questions regarding the efficacy of 3% saline solution.


The possibility of underreporting also

Our study clearly is limited by its retrospect spe ctiv ive e na natur ture, e, an and d we mi might ght hav have e

must be considered. If the comments section was left blank, then this was interpreted as the absence of an adverse ver se eve event. nt. Fur Furthe thermo rmore, re, pat patien ients ts who received 3% saline solution and were not being treated according to  the protocol (n   26) did not have the added oversight of receiving a score before each dose, which might have served as a prompt to document ad-

missed some doses of hyperto hypertonic nic saline solution because of incompleteness of   the database database,, which was generat generated ed retrospectively rospect ively through chart review and review of pharmac pharmacy, y, respiratory therapy, and nursing electronic records. We were able to report only adverse events  that were were documented documented in the phy physic sician, ian, respiratory therapist, or nursing notes, which leaves the possibility that the ad-

 junctive  junctiv e bro broncho nchodil dilato ators rs for you young ng children hospitalized with bronchi bronchiolitis olitis had a low rate of adverse events in our cen ter.. Additio  ter Additional nal clinic clinical al trials trials of 3% 3% saline saline solution in bronchiolitis should evaluate  the effe effecti ctivene veness ss of 3% sal saline ine sol solutio ution n in  the abs absence ence of adju adjuncti nctive ve bro broncho nchodila dila- tors,  tor s, because because these these medic medicati ations ons are are not routinely routin ely indicat indicated ed in bronchi bronchiolitis olitis,, on  the basis basis of curr current ent eviden evidence. ce.

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The us use e of 3% sa sali line ne so solu luti tion on wi witho thout ut ad ad--


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PEDIATRICS PEDIATRI CS Volume 126, Number 3, September 2010

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Nebulized Hypertonic Saline Without Adjunctive Bronchodilators for Children With Bronchiolitis Shawn Ralston, Vanessa Hill and Marissa Martinez Pediatrics 2010;126;e520; originally published online August 16, 2010; DOI: 10.1542/peds.2009-3105 Updated Services Information &

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