Nasal Continuous Positive Airway Pressure With Heliox Versus Air Oxygen in Infants With Acute Bronchiolitis: A Crossover

Study Federico Martinón-Torres, Antonio Rodríguez-Núñez and Jose María Martinón-Sánchez Pediatrics 2008;121;e1190; originally published online April 14, 2008; DOI: 10.1542/peds.2007-1840

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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 © 2008 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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PhD Pediatric Emergency and Critical Care Division. noninvasive ventilation. 12 fulfilled inclusion criteria. and may reduce the need for endotracheal intubation.martinon.2 cm H2O. consecutively admitted to the PICU from February 2004 to February 2005 for treatment of severe acute bronchiolitis unresponsive to therapy. saturation improved during the study time with both heliox-nasal continuous pos15705 Santiago de Compostela. What’s Known on This Subject Very little is known. Spain.4%. School of Medicine. During the study period. Improvement in clinical Online. Both techniques are noninvasive. 0031-4005. Hospital Clı ´nico Universitario de Santiago de Compostela. PhD. and heliox therapy through a nonrebreathing reservoir face mask were eligible. bronchiolitis. and arterial oxygen de Pediatria.6%.torres@sergas. Santiago de Compostela. the clinical score fell 1. The purpose of this work was to evaluate the effects of administering either heliox or air oxygen in combination with nasal continuous positive airway pressure in infants with refractory bronchiolitis. ABSTRACT OBJECTIVE. Spain.7 points.1542/peds. clinical score of 7. What This Study Adds This study adds objective support for the use of the combination of heliox and nCPAP in the management of infants with severe bronchiolitis refractory to usual therapies and a starting point for future research on this topic. Measurements were taken at baseline and after 30 minutes of each treatment. PATIENT AND METHODS.4 mm Hg). and arterial oxygen saturation of 88.7%. Clinical score. Unidad de 61. 1098-4275). e1190 ´ N-TORRES et al MARTINO Downloaded from pediatrics.aappublications. Jose Marı ´a Martino ´ n-Sa ´ nchez. nebulized 1 hour. continuous positive airway pressure. and arterial oxygen saturation increased by 7. Baseline mean values were as follows: nasal continuous positive airway Address correspondence to Federico pressure of 7. MD. These positive effects are significantly enhanced when nasal continuous positive airway pressure is combined with heliox instead of air oxygen. We conducted a prospective. Antonio Rodrı ´guez-Nu ´n ˜ ez. A predetermined balanced sequential allocation to either 30 minutes of treatment with nasal continuous positive airway pressure with heliox or to air-oxygen nasal continuous positive airway pressure was performed. cross- www. pediatrics Abbreviations nCPAP—nasal continuous positive airway pressure AO—air oxygen RSV—respiratory syncytial virus M-WCAS—Modified Wood’s Clinical Asthma Score satO2—arterial oxygen saturation tcPCO2—transcutaneous CO2 pressure FIO2—fraction of inspired oxygen Accepted for publication Oct 1. Department of Pediatrics. The potential for its use comes from theory and adult data. PhD. Complejo Hospitalario Universitario de Santiago. Copyright © 2008 by the American Academy of Pediatrics score was double with heliox-nasal continuous positive airway pressure compared with the air-oxygen-nasal continuous positive airway pressure ( single-center. A choupana s.1542/ peds.7 vs 5. There was no difference in arterial oxygen saturation between groups. No adverse effects attributable to either of the study interventions were detected.2 PEDIATRICS (ISSN Numbers: Print. 40 infants with bronchiolitis were admitted to the PICU. Santiago de Compostela. Department of Pediatrics.6 mm Hg. transcutaneous CO2 pressure of Martino ´ n-Torres.7 points. E-mail: itive airway pressure and air-oxygen-nasal continuous positive airway pressure: after federico. 2007 over study in a teaching hospital including infants 1 month to 2 years of age. or transcutaneous CO2 pressure of Ͼ50 mm Hg despite supportive therapy.pediatrics. RESULTS. with the fraction of inspired Cuidados Intensivos Pedia ´ at Indonesia:AAP Sponsored on December 18. transcutaneous CO2 pressure.ARTICLE Nasal Continuous Positive Airway Pressure With Heliox Versus Air Oxygen in Infants With Acute Bronchiolitis: A Crossover Study Federico Martino ´ n-Torres. transcutaneous CO2 pressure decreased 8.12 vs 1.08 points). 2012 . Departmento oxygen at 35. respiratory therapy.2007-1840 Key Words helium-oxygen mixture. interventional. MD. seem safe. No patients required endotracheal intubation. CONCLUSIONS. PhD. Patients with a clinical score (Modified Wood’s Clinical Asthma Score) of Ͼ5. including only some positive but uncontrolled experience published previously by our group. arterial oxygen saturation of Ͻ92%. and the fall in the transcutaneous CO2 pressure was greater with heliox-nasal continuous positive airway pressure compared with air-oxygen-nasal continuous positive airway pressure (9. MD. Spain The authors have indicated they have no financial relationships relevant to this article to disclose. University of Santiago de Compostela. mm Hg. Nasal continuous positive airway pressure improves the clinical score and the CO2 elimination of infants with refractory bronchiolitis.2007-1840 doi:10. MD.

Number 5.12. nebulized L-epinephrine. or transcutaneous CO2 pressure (tcPCO2) Ͼ50 mm Hg despite optimized supportive therapy. No patient required sedation to tolerate heliox and nCPAP. No patient received any nebulized medication other than epinephrine or systemic corticosteroids. wheezing. However.6 RSV infection was confirmed by enzyme-linked immunoadsorbent assay of nasal secretions. Twelve of them (7 boys and 5 girls).org at Indonesia:AAP Sponsored on December 18. and several therapeutic interventions have been assessed. observational. cough. warmed and humidified. as a rescue treatment in infants with refractory acute severe bronchiolitis. PATIENTS AND METHODS Patients and Participants Eligible patients were infants 1 month to 2 years old. nasal continuous positive airway pressure (nCPAP) may improve the respiratory status of children with hypoxemic respiratory failure. May 2008 e1191 Downloaded from pediatrics.for respiratory tract illness in 6-hour intervals at the discretion of 1 of the 3 physicians responsible for the study. the settings for nCPAP and FIO2 were maintained throughout the crossover phase of the study. and hyperinflation of the lungs on chest radiograph. Having completed the crossover phase.14 The study was approved by the school of medicine ethical committee. specifically. admitted to the PICU from February 2004 to February 2005. PEDIATRICS Volume 121. Spain).6 During the study period. Initial optimal nCPAP was what could maintain satO2 Ͼ94% using the lowest fraction of inspired oxygen (FIO2). The heliox mixture was delivered to the patient.2 Although pathophysiology has been well described. Madrid. A central wall supply of dry heliox with a fixed concentration (70% helium and 30% oxygen) was used (Air Liquide Medicinal. We have reported previously in a preliminary uncontrolled study that the combination of heliox and nCPAP as a rescue treatment in infants with refractory bronchiolitis could improve the clinical score. and enhance the CO2 elimination in a safe and noninvasive manner.8–11 Taking existing data for adult patients. and 1 patient had suffered from bronchiolitis in the preceding 2 months. Measurements were taken at baseline and after 30 minutes of each treatment.4 by varying the flow of either AO or heliox.5 months) and a median age of 4 months (range: 2– 8 months). To achieve this.13 together with their theoretical bases. Two patients had underlying heart disease. Madrid.5–7 It has also been shown that noninvasive ventilation and.15 included a mixture of helium at 70% and oxygen at 30%. All of the patients fulfilling inclusion criteria received 30 minutes of treatment with each of heliox and AO via nCPAP. Intervention: Heliox-nCPAP and AO-nCPAP Logistics Gas Supply A central wall supply of dry heliox with a fixed concentration (70% helium and 30% oxygen) was used (Air Liquide Medicinal). the study design did not allow us to determine precisely the separate effects of heliox or nCPAP. After determining these values. patients were either maintained on or established on heliox and nCPAP using our usual protocols depending on patient needs.5–11 the combination of heliox and noninvasive ventilation could be synergistic and useful in pediatric patients. Diagnostic criteria of bronchiolitis included tachypnea. 40 infants with acute bronchiolitis were admitted to our PICU. Study Design We conducted a prospective.3. Nasal and pharyngeal secretions were deliberately removed before treatment in all of the patients. it was then admin- B RONCHIOLITIS IS THE main reason for hospitalization istered at 2. prolonged expiratory time. Brighton. Minimum permitted levels were for nCPAP 5 cm H2O and for FIO2 0. with respiratory syncytial virus (RSV) bronchiolitis and Modified Wood’s Clinical Asthma Score (MWCAS) Ն5. Patients were allocated sequentially to begin their treatment alternately with either heliox and nCPAP or AO-nCPAP.1 It can also cause respiratory insufficiency in approximately half the patients admitted to the PICU with this diagnosis. no proven successful treatment has been demonstrated. administered at 10 to 15 L/min through a nonrebreathing reservoir face mask. and humidified by means of a standard device (MR730 Humidification system.2–4 Heliox therapy may be useful in the treatment of infants with acute viral bronchiolitis. nCPAP was increased at 1 cm H2O increments to a maximum of 12 cm H2O while the FIO2 needed was above 0. All of the patients received 1 dose of nebulized Lepinephrine at the start of the study. The patients had a mean age of 4. chest retraction. either before enrollment or during the study. Spain).14 The aim of the present study was to assess the effects on ventilation and clinical score of administering either heliox with nCPAP or air oxygen with nCPAP. United Kingdom).7 months (2.6 arterial oxygen saturation (satO2) Ͻ92%. fulfilled the inclusion criteria and were enrolled in the study.aappublications. warmed. Moderate-to-severe respiratory distress was defined as an M-WCAS of Ն5. single-center study using a crossover design with predetermined balanced sequential allocation. Fisher & Paykel Healthcare Spain. interventional. rales. Heliox therapy6. in continuous positive airway pressure mode. and written informed parental consent was obtained in all of the cases before enrollment. and heliox therapy at 10 to 15 L/min through a nonrebreathing reservoir face mask for Ն1 hour. Patients with underlying chronic lung disease were excluded.1. clinical. 2 patients had been preterm births without chronic lung disease. Noninvasive Ventilation Equipment The noninvasive ventilation equipment used in this study was the Infant Flow Advance (Electro Medical Equipment Ltd. 2012 . Definitions Nebulized L-epinephrine was 3 mg per dose every 2 to 6 hours.

The sample size of 12 patients using 95% confidence levels allows Ͼ95% power in detecting a difference of Ն1 point on the M-WCAS scale and Ͼ70% power to detect a difference of Ն5 mm Hg in tcPCO2.6% (3.2 mm Hg (4. After treatment.6 (10.12 points (0. the size of the patient.5 mm Hg).4 points). The main outcome measures were the changes in M-WCAS and tcPCO2.62 points (1. be reevaluated.aappublications.2 cm H2O (1. and noninvasive blood pressure) were also monitored in all e1192 ´ N-TORRES et al MARTINO 10 9 M-WCAS 8 7 6 5 Basal AO Heliox FIGURE 1 Clinical score using the M-WCAS expressed as mean and SEM at baseline and after treatment with AO-nCPAP or heliox-nCPAP (either case may be 30 or 60 minutes after baseline.001. After the experimental crossover study phase. after 30 minutes of treatment with heliox-nCPAP or AO-nCPAP. respiratory rate. Any need for sedation was also recorded. Either nasal prongs or a nasal mask were selected for heliox and nCPAP delivery.6 The tcPCO2 was continuously monitored by means of an earlobe transcutaneous technique (Tosca. Vital signs (ECG.3. Chicago. M-WCAS was better with heliox-nCPAP than with AO-nCPAP: 5. The level of statistical significance was P Ͻ .001). All of the patients were followed up for Ն6 months after discharge.3%).001). satO2. respectively (P Ͻ . M-WCAS fell 1. CA]).58 points (0. nCPAP was gradually decreased to 5 cm H2O. time elapsed since admission to PICU until study at Indonesia:AAP Sponsored on December 18. treatment with heliox-nCPAP or AO-nCPAP was considered to fail when satO2 fell below 92% with nCPAP Ͼ10 cm H2O and FIO2 Ͼ0. Data obtained after the crossover phase were analyzed by the Friedman test. When the FIO2 needed was Ͼ0. and satO2 88.3 Downloaded from pediatrics. tcPCO2 persistently Ͼ60 mm Hg.9 points) vs 6. If needed.6. To do this.6 points) vs 1. In these circumstances. need for endotracheal intubation. Switzerland).001. patients either continued with or were started on helioxnCPAP. Electro Medical Equipment Ltd). Irvine. with falls from baseline almost double with heliox-nCPAP than with AO-nCPAP. and satO2 increased by 7. and then heliox-nCPAP was stopped. patients would receive conventional therapy. and by considered for endotracheal intubation and invasive mechanical ventilation. When FIO2 Յ0.05. To deliver the highest amount of helium to the patient. In this phase of the study. 2012 .4. Differences between each treatment were analyzed using the paired t test. The data are expressed as means (SDs). tcPCO2. All of the statistical analyses were performed by using SPSS 12. at 51.7 points (0. if the patient could not tolerate the procedure.001) after administration of both treatments. nCPAP was set initially at 7.2%).7 points) (P Ͻ .08 points (0. reevaluated.0 (SPSS Inc. depending on whether given first or second). Group (sequential) differences were analyzed using the t test for independent variables. and at the discretion of the physician. respectively (P Ͻ . respectively (P Ͻ . Demographic data. and respiratory rate values were recorded at baseline.7 mm Hg (3. Measurements and Outcomes M-WCAS. FIO2 was kept as low as possible while maintaining satO2 Ͼ94%. tcPCO2 61. Linde Medical Sensors. Measurement Levels and Removal From the Study During the crossover phase of the study. or if the patient’s clinical condition deteriorated acutely at any time during the study. and afterward at hourly intervals for 6 hours and then at 8 hour intervals until heliox-nCPAP was discontinued. IL). All of the values improved from baseline after treatment with both heliox-nCPAP and AO-nCPAP.7(1). and considered for endotracheal intubation and invasive mechanical ventilation. of the patients.001). and administration of concurrent therapies were collected for each patient.001 in each case).8%) (P Ͻ .7% (3. After treatment. Data obtained during the first 48 hours were analyzed. nCPAP and FIO2 were adjusted. we followed a previously applied methodology. The satO2 was continuously monitored using pulse oximetry (Radical Masimo SET pulse oximeter [Masimo Corporation. Both groups are significantly different from baseline and also from each other (P Ͻ .Human Interface Nasal equipment specific to the ventilator and generator were used (Infant Flow Generator. tcPCO2 fell 8.9 mm Hg (8. patients were to be returned to conventional therapy. at 9.2 mm Hg).2 mm Hg (10. Fig 1). In clinical scoring. Any adverse event potentially related to the treatment with either heliox-nCPAP or AO-nCPAP was recorded.7 mm Hg) vs 56. nCPAP was increased in 1 cm H2O increments. determined by comfort. duration of heliox therapy. at 2.2 cm H2O) to maintain satO2 Ն94% with FIO2 of 35% (6. Statistical Analysis The distribution of trial variables was assessed using the Shapiro-Wilk test. tcPCO2 Ͻ50 mm Hg and M-WCAS Ͻ5 were maintained for 6 hours.2 mm Hg) (P Ͻ . Charts show means and SEMs. Basel. Patient tolerance of the technique was assessed primarily by the investigator and also by the nurse in attendance. RESULTS Baseline characteristics of our patients were M-WCAS 7.0 points). the same criteria for therapeutic failure were used as in the experimental phase. Fig 2). tcPCO2 levels were better with heliox-nCPAP than with AO-nCPAP. with falls from baseline 80% greater with heliox-nCPAP than with AO-nCPAP.

50 (0. and SatO2 (C) over the first 48 hours of treatment with heliox-nCPAP expressed as mean and SEM.1) 11.7 (1.10) P . Analysis of study subjects in 2 groups.5 (2.6 85 Basal 6h 24 h 48 h Group AOH are patients receiving AO-nCPAP first and then heliox-nCPAP. by Order of Treatment Administered. There were no treatment-related adverse events.361 .70 60 50 40 30 tcPCO 2 .5 41.2) 2. tcPCO2 .70 (1.6 (4.9 days (3.60) 58.8 (3.001).2 points).7 mm Hg). All of the patients enrolled at baseline completed the crossover study phase. Group HAO are patients receiving heliox-nCPAP first and then AO-nCPAP.001. A 10 9 8 7.090 . Mean (SD) 5.0) P . After 60 Minutes) Measurement Age.3 (3. Mean (SD) 5.694 .6 (1. depending on whether given first or second).50 (1.6 (1. Fig 3) with changes from baseline at 48 hours of 3.1 (0.5 (2.6 (6. at 96. respectively. 23.2) 6. reaching statistical significance in M-WCAS and tcPCO2. patients were treated with heliox-nCPAP.2) 52.25) 96.00 (1. % 95 90 88.8) 96. tcPCO2.1 (1. respectively.4) 6.749 .30) 96.179). a The difference was statistically significant (P Ͻ .0) 89. tcPCO2.536 . There was no statistically significant difference in satO2 after treatment between heliox-nCPAP and AO-nCPAP.4 mm Hg (1.00 (13.693 .10 (2.7%).aappublications. The effects of heliox-nCPAP or of AO-nCPAP were similar.6 TABLE 1 Differences Between Groups.1) 54.8) 5. and satO2 all continued to improve (P Ͻ .6) Group HAO (n ϭ 6). May 2008 e1193 .2 SatO2 .20) 51.00) 6. depending on the order in which they received heliox-nCPAP and AO-nCPAP.50 (6.001 in each case).4 mm Hg (6.41 points (1. Mean (SD) 4.8 (5. 2012 PEDIATRICS Volume 121.6) 5.1 (2.70) 96.3 (11.701 . From Baseline to the End of the Crossover Phase (Having Had Both Treatments. tcPCO2 (B). and M-WCAS.00) As Second Treatment (n ϭ 6). final changes from baseline at the end of both treatments showed greater improvement when heliox and nCPAP was the second treatment.879 . mo Baseline M-WCAS Baseline satO2 Baseline tcPCO2 Final M-WCAS Final satO2 Final tcPCO2 Difference in M-WCAS Difference in satO2 Difference in tcPCO2 Treatment duration. Both groups are significantly different from baseline and also from each other (P Ͻ .9%) vs 95.2 M-WCAS B 65 60 55 50 45 40 35 48.7) 63.892 .8 4.80) 52. All of the patients recovered fully without sequelae continuing to develop normally over the follow-up period of 6 to 16 months.008a .787 .6) 8.50 (6.1 (2. respectively (P ϭ .579 . After the crossover phase. and 9% (3. Number 5.00) 6.6 (13.20) 54.8) 6.2 (0. shows that the baseline measurements were similar (Table 1).6 mm Hg).2) at Indonesia:AAP Sponsored on December 18.271 Basal AO Heliox FIGURE 2 Partial pressure of tcPCO2 expressed as mean and SEM at baseline and after treatment with AO-nCPAP or heliox-nCPAP (either case may be 30 or 60 minutes after baseline.9) 59.05. Mean (SD) 5 (2.50 (1.5 (1) 96.2 61.5% (1.7) 1.7 7 6 5 4 3 Basal 6h 24 h 48 h 5.5% (1.7) 5.409 . That Is.2) 7.4 4. FIGURE 3 Changes in clinical score (M-WCAS. mm Hg mm Hg) vs 5.6 (2.9) 7.05).60 (2.7%).5 (6.30 (11. mm Hg TABLE 2 Comparison Between Measurements in the Clinical Score (M-WCAS). A).60 (1. P Ͻ .012a . However. regardless of whether they were given first or second (Table 2).903 . Downloaded from pediatrics. Total duration of heliox-nCPAP treatment was between 3 and 14 days. with a mean of 5. Changes during this period were all statistically significant (Friedman test. and satO2 for Each Treatment (helioxnCPAP or AO-nCPAP) Grouped According to Whether the Treatment Was Given First or Second Measurement M-WCAS heliox-nCPAP M-WCAS AO-nCPAP tcPCO2 heliox-nCPAP tcPCO2 AO-nCPAP satO2 heliox-nCPAP satO2 AO-nCPAP Significance level was P Ͻ .2 98.5 (0.3 days).467 Basal 6h 24 h 48 h C 100 98 98. No patient required endotracheal intubation or mechanical ventilation. d Group AOH (n ϭ 6).80) 95. As First Treatment (n ϭ 6).8 38.

clinical scores are often used as a research tool.15 There are some limitations of this study. Helium. beyond their known limitations. as shown by approximately twice the level of improvement in clinical scores and tcPCO2 levels after 30 minutes of therapy. through its high diffusion coefficient.aappublications. On the other hand. The degree of clinical improvement with heliox and nCPAP after the crossover phase was similar to our previous findings. Changes in the pitch of the voice or of crying because of heliox.16 However. validating initial estimates of the sample size needed to have the power to detect the differences in metrics required. this did allow for the detection of significant changes in key metrics.15 Its use in illness where obstruction in the airways is important is through reduced resistance to gaseous flow and.18.9–11 Furthermore. it has been reported that heliox might cause hypoxia secondary to the development of atelectasis15.40%). The study protocol also sought both to maintain the minimum FIO2 to maximize the proportion of heliox reaching patients’ airways and to ensure that oxygen saturation was Ͼ94%.12. a naturally inert gas with a low molecular weight. can avoid the need for intubation and mechanical ventilation. prevent or relieve atelectasis. suggesting that heliox. such as PICU admission criteria. when nCPAP is used with heliox. it is significantly more efficacious than with AO. thus. Improved oxygenation is most likely to be through nCPAP rather than a differential effect of heliox or AO. or disease stage or in intubation practices. and also. nCPAP with heliox in place of an AO mixture (AO-nCPAP) is clearly more efficacious. and promote heliox distribution within the obstructed airways. avoid airway collapse. with even synergy between the heliox and nCPAP.07%– 2. the existing data in adults. Heliox can also reduce respiratory work. and this particular scoring system has been validated previously and could have reasonably counteracted observer bias. together with the obvious changes in ventilator noise (because of the expiratory branch of the flow generator). Furthermore. A literature review suggests that 25% to 60% of infants with bronchiolitis admitted to a PICU may need intubation and ventilatory support. Furthermore.6. However. There are recent references in the literature to the utility of heliox or noninvasive ventilation in the management of infants with bronchiolitis.5–7. improve alveolar ventilation. none of the 40 patients admitted to our unit in the 12 months of this study required mechanical ventilation.13 and our initial experience in pediatric patients. and increase expiratory flow at the same airway pressures compared with AO. Our results suggest that nCPAP with either gas is a safe and effective treatment as measured clinically (M-WCAS) or by tcPCO2 and by satO2 values. The inert nature of helium is responsible for the few secondary effects not only in our patients but also in general clinical practice. we can widen the pool of patients treated. produces a mixed gas one third as dense as air.6. regardless of the treatments administered. thus.4%) of 231 patients admitted to our unit with acute bronchiolitis and managed according to our protocol has needed intubation and mechanical ventilation (95% exact CI: 0. thereby minimizing ineffective treatment with prompt switching to other treatments. As shown in the baseline data. not seen in our patients. limiting the potential detrimental effects of nCPAP.19 However.14 Changes in oxygen saturation were much smaller than those in the clinical score or in alveolar ventilation. reducing the risk of barotrauma from gas trapping and. may be easily prevented with the concomitant use of nCPAP. The response to heliox is seen rapidly within the first hour and is maintained during treatment. Use of nCPAP may also reduce the needed FIO2 in these children. Given what is understood of each of these treatments. DISCUSSION This is the first crossover study to evaluate 2 different gases (heliox and AO) given with noninvasive positive pressure to infants with unresponsive severe acute bronchiolitis. in completing the study.20–25 Although there may be influencing factors other than heliox and nCPAP treatment. we suggest that heliox-nCPAP is of clear addie1194 ´ N-TORRES et al MARTINO tional benefit. This is consistent with the theory of how heliox works. alone or with nCPAP.14 Our work suggests that nCPAP is efficacious not only in patients unresponsive to conventional treatment but also in those not responding sufficiently to treatment with heliox through a nonrebreathing reservoir face mask. only 1 ( at Indonesia:AAP Sponsored on December 18. of heliox and noninvasive ventilation in combination. differences in RSV status. This last effect may help to improve passive expiratory pulmonary mechanics. increase the elimination of carbon dioxide. when mixed with 21% oxygen (the same concentration as in atmospheric air). there is very little published on the combination of the two. This is remarkable and is consistent with our previous findings. being less significant and less certain than on the elimination of carbon dioxide and on the clinical respiratory state. The techniques used were tolerated well in all of the patients. In none of our patients. yet quickly detect nonresponders. 2012 . given the safety of heliox. in respiratory effort. this potential adverse effect.11. The nCPAP may contribute to decreased inspiratory muscle workload.17. further augmenting the actual helium concentration able to be delivered to the patient.1.6 The level of FIO2 and the pressure of nCPAP were deliberately kept constant during the crossover phase of the study to control for their possible effects in Downloaded from pediatrics. in infants with acute bronchiolitis.15 There are no data in the literature on the specific use. were there any adverse effects related to either heliox or to nCPAP. The number of study subjects was low. enhance carbon dioxide elimination. heliox can improve gaseous exchange. This first hour is important because. removed study blinding. all of the patients in this study fit the usual criteria for endotracheal intubation and for initiation of assisted ventilation.No patient required readmission to the PICU in the 3 months after discharge. the use of nCPAP with heliox or AO enabled intubation to be avoided in all of our patients. On the other hand. consistent with its mechanism of action.14 Between 1999 and 2006.

2004 Soong WJ. ed. Crone RK. PA: Elsevier Science. Tassaux D. Hwang B. Zeng L. et al. 2002. Arch Dis Child.16(3):163–166 Beasley JM. [in French]. 2006. 2002. et al. Shah JP. multicenter study. United Kingdom: John Wiley & Sons.2(3):197–204 Moler FW. Perinatal and Pediatric Respiratory Care. Pollack C. Schonfeld T.26(10):1731–1736 6. 25. Am J Respir Crit Care Med.88(12):1065–1069 Prais D. Acute bronchiolitis: evaluation of evidence-based therapy [in Spanish].aappublications. such as the optimal timing of intervention. Bennet R.55(4):345–354 4. Management of respiratory failure in infants with acute bronchiolitis. the ideal initial and maintenance parameters to use. Issue 1. Israeli RSV Monitoring Group. Moll HA. 1993.112(3 pt 1):548 –552 Downloaded from pediatrics. 2006. Heliox for treatment of exacerbations of chronic obstructive pulmonary disease [Cochrane review]. Rodriguez Nunez A. 2006. Chest. 2003. Wirgart BZ. Minasian CC. ACKNOWLEDGMENT We express our gratitude to John Rodriguez for his valuable input and thoughtful grammar/ style review of the manuscript. Fournier-Favre S. Recommendations. 17. Balagny E. Kozlowska WJ. 1995. In: Czervinske MP.106(3): 474 – 476 Jacobs IN.138(11): 1071–1075 Leclerc F. Effects of nasal continuous positive airway pressure ventilation in infants with severe acute bronchiolitis [in French].otherwise confusing the interpretation of the primary variables of interest: the clinical score and the elimination of carbon dioxide. Prediction of duration of hospitalization in respiratory syncytial virus infection. Martino ´ n-Torres F. Arch Dis Child. 19. Rotzen-Ostlund M. Ltd. 2nd ed. together with the immediate switch from Heliox therapy to either AO-nCPAP or heliox-nCPAP during the crossover. Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. Pettignano MM. Scalfaro P. 1985. Moreover. 12. no rebound effect of heliox withdrawal was detected. REFERENCES 1. or in combination with nCPAP.129(3):676 – 682 8. May 2008 e1195 . Number 5. Severity of illness models for respiratory syncytial virus-associated hospitalisation. Martinon-Sanchez JM. Chichester. 2003:677– 681 Larrar S. Rodriguez-Nunez A. Pediatr Crit Care Med. Blyth TP. Pediatrics. Philadelphia. 1999. 2008. CONCLUSIONS Our data show an outstanding beneficial effect of heliox and nCPAP in infants with severe bronchiolitis. 1981. et al. Hypoxia associated with helium-oxygen therapy in neonates. Continuous positive airway pressure in bronchiolitis. Rodrigo C. Shen G. 20. J Pediatr. 10. Martinon Sanchez JM. Martino ´ n-Torres F. 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