Noninvasive ventilation in pediatric intensive care Kimberly Marohn and Jose M, Panisollo Purpose of review Tho use of noninvasive ventilation {NIV) has become increasingly populr in the pediatric intensive care ‘nit PICU] over the last decade, This roview intends lo ettess ovr current knowledge on the uization of ‘noninvasive support in children, especialy focusing on is efficacy and safely profile Recent findings Recent studies endorse the use ofthis therapy in he pediatric inlensve core seling. NIV appears to be ‘sociated with « decrease in the intubation rate in children, Children who are responsive to NV will Lusvelly show improvement in theit physiologic parameters sherly aie the ination ofthis therapy ond this improvement is often susteined. NIV is proving to be a welioleroled cliernative to endotracheal intubation, in patticular in these patients with primary respiratory fallue, postsurgical patienls or with postextubation respiratory disress. Most studs represent single-cenier experience and therefore caution must be exeried ‘when cttempling to generalize their resus ‘Summary NIV appears fo be a weloerated allernative for se inthe pediae population. ts wse is associated with decreased intubation rales, which may lead ¥o @ decrease in the inubotionselated complications. More invesigation is needed to fully evaluate the ramifications of increased use of this technology inthe PICU. rds BIPAP, CPAP, high-low nasal cannula, NIPPV, noninvasive ventilation, pediatric INTRODUCTION Respiratory support delivered through an endotra- cheal tube was, until very recently, the quintessen- tial image of a patient in a pediatric intensive care unit (PICU). The use of noninvasive ventilation (NIV) has become increasingly popular as a suppor- tive therapy in the treatment of acute respiratory failure in both children and adults. The first use of noninvasive techniques in the adult population was in the late 1980s. Use of high-flow nasal cannula (HNC) was developed a decade later, primarily for the neonatal population, These therapies are g ally well tolerated and have resulted in a decrease in the incidence of endotracheal intubation in both adult and pediatric patients with acute respiratory failure (1). Although noninvasive support can he delivered using positive or negative pressure systems, non- invasive positive pressure ventilation (NIPPV) is the most commonly used modality as well as the main focus of most recent studies. A variety of devices have been developed to leliver NIPPV in both the acuteand chronic setting. 4 key element of NIPPV is the interface with the patient, that is, nasal prongs, nasal or face masks or full helmets. 4 com= fortable interface may determine the success of the weww.co-pediatrics.com NIPPV system, especially in the toddler whose cooperation is limited. The most described modes of NIPPV [continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP)} are included in most case series and frequently analyzed together. This diversity of systems adds a layerof difficulty when assessing the current studies in the pediatric population. Furthermore, most of the available studies are single center and retrospec- tive, and are difficult to generalize to the pediatric population as a whole. REVIEW OF THE CURRENT LITERATURE There have been several randomized controlled trials (RCTS) In adults evaluating the use of NIPPV. Secton of Pedaire Creal Care, Yale Unveraty School of Medeine New Haven, Cormectcut, USA Corpspondence to Jose M. Panisela, MO, Section of Crtical Care Medicine, Dopartnent of Padiatics, Yale University Schoa of Medeine, £388 Cedar Sreot PO Box 205064, Now Haven,CT 065206064, USA. Ts +1:208 78S 4651; fax +1 203 785 7186; emak:eeepaancalo @yaleed (Curr Opin Pediatr 2018, 25:280-288 O:10.1097/1K0PO80138978360be Volume 25.» Number 3 + June 2013 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.Noninvasive ventilation Marohn and Panivello KEY POINTS ‘* Noninvasive ventilation including CPAP, BIPAP ond highlow nasal connule is a weltolerated alternative to endorrochea! intubation inthe pediatric intensive care unit, + Patients who respond to the use of noninvasive ventilation typically show improvement shortly er the initiation of theropy. «Use of noninvasive ventilation is essociaied with decreased rate of endotracheal intubation, which may load to decreased incidence of intubation. related complications + Priors of fale of noninvasive verion incide evidence of multiorgan dysfunction, worsenin Teeptoory caidas, underlying diognass ol sepals or oncologic disease and higher oxygen requirement prior to the initiation of theropy. A 2005 meta-analysis by Masip et al. 2| of patients randomized to receive NIPPV vs, conventional therapy for the treatment of cardiogenic pulmonary edema demonstrated an overall 43% reduction in mortality in the NIPPV group as well as a $7% decrease in intubations. NIPPY has also been shown to decrease the need for re-intubation when it has been employed after extubation of adults suffering. from chronic hypercapnic respiratory failure who. have failed conventional spontaneous breathing trials [3]. Reduced ICU mortality and reduced intu- bation rates as well as decreased rate of ventilator associated pneumonia have also been demonstrated consistently in NIPPV used in adults with acute respiratory distress syndrome and hypoxic respirat- ony failure [4,5]. Success of NIPPV appears to he tied to the underlying diagnosis. It has been shown to be particularly effective in adults with a primary respit- atory process or with acute cardiogenic pulmonary edema and less effective in adults with respiratory failure secondary to oncologic or other primary processes, In 2008, Yanez ef al. published the only RCT in the pediatric population to date (see Table 1 for a summary of the recent studies), Fifty patients with acute respiratory failure were randomized to receive ational oxygen therapy alone or con: ventional therapy plus BiPAP. NIPPV significantly reduced the need for endotracheal intubation when compared with the conventional group (28 vs. 60? P- 0,045), Itshould be noted that, despite random ization, the NIPPV group had a lower initial oxy requirement expressed by the PaOa/ either conv. n jaQo Kato, AS in other pediatrics studies, NIPPV. significantly improved some of the physiological parameters, like mespiratory rate and heart rate, but this study was not powered to evaluate changes in mortality or hospital length of stay [I"], There have been several other studies that demonstrate significant reduction in respiratory rate, heart rate, respiratory acidosis and use of accessory muscles shortly after the Table 1. Summary of recent noninvasive ventilation studies Authors Date Sudy Mode individuals Ress Yenez 2008 Randomized contolled __CPAP/PS <10ka, 50 Rate of intubation decreased from rol. [1") ‘ral BiPAP in >10kg 6055 in contol group to 23% in NPV group (P0045). Clinical signs of resiratoy fale improved at 1-2h ofer the inttion oF IPP, Dohne-Shwake 2011 Retrospective chart ‘cea /eS 74 Clinical sign of respiratory fire eral (6) review improved of 1~2h,sustined ot TOh, Predictor of Faure: pH «7.25 1-2h oho the Feta of PPV. James 2011 Retrospective chart (CPAP ond BAP 163 Rete of intubation: 6 of 36 (17%) rel. (78) review of potent wih pimany 10808708 © 2013 Wobors Kluwer Heath | Lippincot Willams & Wilkins respiratory probloms: 15 of 23 (652) of pation wit unde lying oncologic problem Precictors of faire: Unclelying ‘encolegic problem (0.0007), higher FO 1032), higher eespirctory ‘ete ore the inion of NPPV (P=0.012) weww.co-pediatrics.com 291 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.Emergency and critical care medicine Table 1 (Continued) ‘uthers ote Shady ‘Mode # indvidscle Resale Mayordome 2008 Prospective cbsorvational CPAP or PS 11S Shorierlorgih of tay Colunga ‘dy of FICL patients in rpenders (7 va 14.5 deys, tal.) placed on NPV 0.003). Prodictore of NPPV foilre: Higher PRISM score (745 117, P=002) hypoxic espictoy foie (OR 1.1, c12.5-47.8), no decrease in esptctory fate on nition of NIPPV (357 ve 48.9 bpm, P=0.001), Munoz Benet 2010 Retospectve reviow (CPAP or BIPAP 47 Nine pationts required intubation etal. 9] (19%), Reduction ofheaa rose ‘ond PCO? at 2 and 4h, Predictors of NPV folie younger age (4 vs. 7.7 years, 0.04), prance of ARDS, ‘worsening chest rediographe ot 2a and 48h 2012 Rerospactve review of Noxol or il foce 399 Shorter ICU length of soy in pans wih bronchi: CPAP patients who ai nol raquire Tis ploced on NIPPY innubotion 2.38 vs. 5.19 doys, F-0.001), The neroasing alization ria of NIPPY (2.8% per yeor) was associated wth 4% decline in inbotan reles per yeor (P=0.04) loaner 2012 Retrospective reviow of CPAP or BiPAP 65 Shorter ICU longth of ay in fol. [11] pptienls wit bronchio- INPPY responders vs. ifuboted Ts patients (2 ve. 8, P0001] fond in NPPY responders vs ‘nonresponders (I'v. 9.5, 0.001). No diferonce bbetwaen non NIPPY responders ‘ond intubated potions Clinical signs of respiratory failure improved ot 2 and 4h in INPPY responders Jovouhey 2009 Retrospective CPAP or BPAP 97 Decreased incidence of provne- tal [12} Bronchitis ‘iain piers on NIPPV (P02). Bases 2006 — Retoupactve review af Navel BAP 83 ——_NIPPV rele! in reluton in ofl. (13) peciatic astra espretory rote in 77% patients placed on of patients an impeoves NPV in the ED. ‘oxygen sotuation in 88% of patients, Predictor of elu intolerance cf nasal BPAP atk. Complections esprotry rate end oxygen ‘ohuation not measured © cenanert tine period ‘forthe ition oF NIP, Wing 2012 Retrospective chert ENC. B48 Role of intubation decroased in tal. (14) review before ED, unchanged in PICU, ‘5nd ote iitoton oF HENC [ARDS ac repory canoe encom? BAP, bowl pone way prasure Cl, cnfdencs awl CPAP, continues pole oiwoy prose: FD, emergency depotnea HNC, high how nail comdl; NPV, soinvasie pete presuie velco: OF, odds ato, PSMA, pest ko maaly pres sip. 202 www.co-pediatries.com Volume 25» Number 3 + June 2013, Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.Noninvasive ventilation Marahn and Panivella Initiation of NIV, Dohna-Schwake et at. (6] showed that heart rate, respiratory rate, pH, Sa02 and CO improved significantly in the first 2h of NIPPV Interestingly, the patients described in this series had chronic health problems that placed them at @ higher risk of respiratory compromise. Cavari et a, [15] showed a significant reduction of the respirat- ory rate in infants presenting with acute respiratory illness within 3h of initiation of NIPPY, James et a, {7"| demonstrated that, among children managed with NIPPV, those who had a significant reduction in respiratory rate and oxygen requirements in the first 2h of treatment were less likely to require intubation. In this last study, the severity of illness measured by the Pediatric Index of Mortality 2 (PIM2) was similar at presentation; nevertheless the group requiring intubation initially had higher respiratory rate and lower pH. Some of these reports assessed the use of NIPPV asa supportive therapy in children initially managed with conventional mechanical ventilation who develop respiratory dis- tress after extubation, and it appears that NIPPV has been associated with decreased rates of re-intuba- tion [6,7%,16]. It iy clear that NIPPV can be used successfully to improve the respiratory parameters in the short term and, although most studies will infer that these benefits are sustained, potentially reducing the overall need of invasive ventilation, the absence of control groups in these case series makes this final conclusion less certain, NIPPV has been widely used in pediatric emer: geney departments and ICUs for children with respiratory failure because of a variety of causes. A proportion of these children will fail NIV and go on to require intubation, Some authors have examined whether independent predictors of NIV success or failure can be identified. In a large uncontrolled prospective study, Mayoniomo-Colunga et al. [8] showed that, in a general PICU population, severity of illness, hypoxemic respiratory failure and lack of improvement in respiratory rate were independent predictors of NIV failure. James ct al. [7*] found that high respiratory rates at presentation and_ the need to change the NIV mode from CPAP to BiPAP were independent predictors of failure. Similarly Munoz-Bonet et al. [9] reported that the inability to reduce the FiO in the prevence of a high mean airway pressure predicted a poor response to NIV Additionally, a pH less than 7.25 after 1-2 of NIV therapy has also been linked to therapy failure [6] as well as children with evidence of multisystem organ dysfunction (MODS) [7,17]. Children with a primary respiratory problem appear to have overall lower rates of failure of NIPPV and mortality than dren with respiratory failure related to an under- lying oncologic process [18]. Some of the differences 10808708 © 2013 Wobors Kluwer Heath | Lippincot Willams & Wilkins between these studies may reflect the different methods of delivering NIV among different centers and no absolute conclusions can be drawn; nevertheless, these studies provide the clinician a good insight on the usefulness and limitations of NIPPY. Recently, there has been significant effort to evaluate the use of NIPPV in specific disease states, As the use of NIPPV has become increasingly popular, multiple retrospective reviews of the use of NIPPV in bronchiolitis have demonstrated a reduction in the intubation ratey over the last 10 years [10%,1 1,12]. These studies have also shown a decreased length of stay in both the [CU and the hospital among patients who were successfully treated with NIPPV compared with those who required invasive ventilation. This may be because of the fact that patients who required intubation were likely the sicker patients and does not indicate that the use of NIPPV in and of itself shortened their hospital or ICU stay. One hospital permitted the use of NIPPV outside the ICU setting, which may also account for the decrease in the ICU length of stay if patients on NIPPV were Uansfetred to the general wards. The use of NIPPV has also been studied in asth- matic patients in both the pediatric and the adult population, These studies have shown evidence of Improved gas exchange, improved peak flows and reduction in clinical asthma scores with the use of NIPPV compared with conventional therapy with oxygen and bronchodilators [13,19-21]. To date, there have been no studies comparing the asthma scores in patients managed with NIPPV vs. those requiring invasive ventilation. Interestingly, there are two adult trials in asthma and cystic fibrosis that have shown improvement in the delivery of aero- solized bronchodilators when driven by NIPPV [22,23] ‘NIP has had particular success in the manage- ment of chronic respiratory failure among children with neuromuscular disorders who are managed at home with NIV, These children have a decreased rate of [CU admissions because of respiratory infec tions when compared with children who do not use NIV at home [24]. These data are retrospective and to date there have been no RCTs. Additionally, recent reports described the use of NIPPV to support children who developed respiratory distress follow ing extubation after liver transplant and among patients who developed postoperative atelectasis following abdominal surgery [25]. NIPPV has also been used successfully in the treatment of trans. fusion-related acute lung injury and in lung injury occurring ay a result of bone marrow transplant (18,26) weww.co-pediatricscom 298 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.Emergency and critical care medicine A different mode of NIV, HP progressively more common in PICU. Unlike the other modes of NIV support, HENC tends to be reported separately, Developed for adults in 1994, HENC has been a successful alternative to CPAPin the neonatal population, RCTs in the neonatal popu- lation have demonstrated similar intubation rates among infants ventilated with HENC vs. CPAP as well as a decreased risk of intubation with the use of HNC compared with standard nasal cannula [27,28]. However, there are limited data available in the pediatric population. In 2009, Spentzas et al, studied 46 children treated with HFN, showing that it consistently generated positive airway pressures of 442m H,0 and a decreased respiratory distress score at 12h [29], Use of HNC was at the discretion of the attending physician and there was no com- parison group in this study. Retrospective data reviews show a similar reduction in the intubation rates with the introduction of HNFC as have been shown with CPAP and BiPAP [14,3031]. [t appears that HFNC is. a well-tolerated alternative to traditional CPAP and BiPAP for use in the pediatric population. >, is becoming DISCUSSION The use of NIPPV for pediatric acute respiratory failure has increased significantly over the last decade, Despite this popularity, RCTs inthe pediatric population assessing the Impact of NIPPV on mortality, length of stay and associated compli- cations are lacking. Why these studies have not been undertaken Is unclear. It may be that the pediatric intensive care community feels reassured by the adult and neonatal studies and sees NIPPV as part of the continuum of positive pressure support. Review of the available data in children indicates that CPAP, BIPAP and HENC are well-tolerated alternatives to invasive ventilation and those requir- ing mote aggressive support can be intubated safely in the PICU environment. Concurrently with the increased popularity of NIPPY, PICUs in the USA and Europe have consist- ently shown a decrease in the intubation rates. Thisis true in a variety of pediatric populations, including those with primary respiratory illnessand those with, postextubation or postsurgical respiratory distress Only one study has proven this in a prospective, randomized controlled manner, whereas the rest are primarily single-center retrospective reviews that do not include a control or non-NIDPV arm, There- fore, itis possible that a proportion of these children could have improved without any supportive therapy. Furthermore, the use or implementation of NIPPV is in many cases at the discretion of the 294 wwww.co-pedlatries.com attending physician, but the decision is not necess- arilyone of either intubation or NIPPV. [tis likely that XIPPV fsstarted preemptively asa supportive therapy to reduce the work of breathing before the patient’s condition deteriorates to the point of intubation, NIPPV is. generally better tolerated than an endotracheal tube, and children on NIPPV have a decreased need for sedation and other invasive pro- cedures compared with those who are intubated [32]. This leads to a decrease in the adverse effects associated with sedation as well asallowing children to be more comfortable, alert and interactive with their environment. In addition, fewer intubations are expected to be associated with a decrease in intubation-related complications, such as venti- lator-associated pneumonia and airway. trauma: This has been well documented in adults, but there is limited data available in the pediatric population. Use of NIPPY has also been consistently associ- ated with rapid improvement in the markers of impending respiratory failure. Although larger RCTs are required in this area, it appears that responders to NIPPV show improvement relatively early alter implementation, often sustained, potentially pre- venting the need of endotracheal intubation, This is one of the most significant findings in the pediatric literature to date. One potential concern is that the use of NIPPV could delay a necessary intubation and therefore place that patient at risk. The fact that NIPPV, when effective, seems to show its effects early may help the clinician to determine when to escalate the level of care, ‘There will always be a subset of children who. will progress despite support with NIPPV and will require intubation, The available data suggests that children who have more severe respiratory distress on presentation are at higher risk of failing NIPPV trial. Children with an underlying diagnosis of sepsis, malignancy or immunosuppression tend to have a poorer response to NIPPV than those with primary respiratory disease, There is also a popu- lation of patients for whom NIPPV is not an appro- priate therapy because of underlying anatomic or airway anomalies that prevent proper fit of non- invasive interfaces. NIPPV is largely dependent on the patient being able to reliably initiate their own breaths. It is also paramount to have intact airway protective reflexes, so patients with acute severe neurologic conditions are seldom good candidates for NIPPV. Contraindications to the use of NIPPV should include patients with cardiorespiratory arrest, patients with severe hemodynamic instabile ity and patients with an acute severe neurologic compromise or coma except asa temporary measure until the airway can be secured by means of an endotracheal tube. Neonates with apnea should Volume 25.» Number 3 + June 2013 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibitedNoninvasive ventilation Marahn and Panivella be monitored carefully and intubated if apnea does not resolve with initiation of NIPPV. Children with signs of severe respiratory failure and children with sepsis or underlying oncologic diagnoses may be considered candidates for a trial of NIPPV, but should be closely monitored in an intensive care unit. Similarly, patients with progressive neuromus- cular disease who develop acute respiratory failure may be managed with NIPPV, but they should be observed carefully CONCLUSION NIV has become a common supportive therapy in many pediatric intensive care units, Over the last few years, a number of studies have tried to delineate its Use and safety profile, All the available data represent single-center practice and there is a need to replicate these initial results in multicenter, randomized, pro- spective trials with the standardized protocols, so the results can be representative of the current PICU practice. A better and more precise understanding Of the factors that predict NIV success will be import ant to determine realistically the limits of this treat ment modality, avoiding unnecessary risk to patients. There is also the need to understand the adverse effects that NIV may generate independently asa therapy, and not only in comparison with invae sive mechanical ventilation; for example, areas like the nutritional ot psychological impact on children may be worth exploring, Finally, as NIV is used in a variety of settings from acute to chronic support, itis important that we understand what resources are necessary to safely manage these patients, in particu: lar when it Is appropriate to manage them locally outside the PICU setting without compromising the quality of care. Acknowledgements The authors would like to thank Dr George Lister for his thoughtful review of this manuscript. Conflicts of interest There are no conflicts of interest. REFERENCES AND RECOMMENDED READING Pape ot pa er mies, publened win he aru pens ct eve, rake een gma 2 ot spari rerest Stoustanang wert ‘Ational frenes red tots topic can aso De und inthe Curent ‘Nong sere seston is steep 427) 1 Vane U, Yurge M.Emore et A pospectve roma, conttd st tlomonaneveriton pene le spray fae Peace “To dine hs ste oy fandom ccrtiotea Wat of NIPPY 9 petates. ‘Sermons oe esed maton rate nee weed wn NPP 28 ‘simpowemem ene cia sire respracy rare 2 hae vaiton 10808708 © 2013 Wobors Kluwer Heath | Lippincot Willams & Wilkins 2 Mas J Roque M_Sareer Bet a. Nonna Veto ate {adogenie punoray edema Sitenac reer and Mesa MA Ss Bos sae 3130 4 Git Bateman AbraaF st Nera tion a xeanea inate wih cv pear epson lie a engomed ml (ae ta) AJ Respro Care ah 2077 104672" 679 4 Vegan wr Feet Gut AK Te of cay of renimashe beste pes vetiaton In AROS" # COW ed ohot Sy Tek ‘ous 010,508 24 6 Arto Cart 6 Esquina Aca A mute center suvey one n ‘nea poste of anmeeve vein sane lowon oe fepintoy dese snaone Cr ae ed 2007 98.10 25 6 DalraSehwalec Sang e Tehiense ca Norns veiation oa Fecate terse cae unt ey ey, presto of secs Fea Pumorel 2081-46-11 1 domes 8, tare Ch anes Of ef Prey the ices of on: * iauecae ur necneCueedov1 Srtaia 200" ‘ng isan eet arrperne even fh tne Me eos RIPE (lve swat x exrg a NPPV ay eles Scene Sas cloocuneesd nite ani our Batre ote os ae ‘te peas popusten| himorsoho-coinga J edna A Rey Cet a. 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Msntaner PF Alen High ow nasa Stenstveinat 3conpasonovo ooates.) Perel 2970, 99605 Carnie they In ats wih bnchiolts J Ped 2010, 156 508. 654 638. 2 Viooateat 0D. Lanbet OK. Clak.M, Cisensen RO. Comparing wo SI. Les Retr K) Wor. Use oh ow nsalcanuainertsly nets of cetveang Tah ov 935 aby Oy rasa rnd alow Iineres gin angaduts acrtalreniat othe Reale rersve Cae Guiana eaten apospecive (anconzed masked, OSS id Mos 2015 90247 257 ‘Pent 2000.25. “Tish an ocelot even oe asa Weraue onthe use of HENC inthe 29. Speco T Mink tt Pairs AB, ela Chitren win espictry dstess peda peplaton sed th Nigh ou has camaa dinowve Cae Med 2008, 25927 Hibet 6. Co\zeay. Nam Bul H, Vaga® F Seaton curry noinesie es ‘ein Mirena Anestesiol 201278842 846 296 www.co-pediatries.com Volume 25 © Number 3 + lune 2013 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited