1. Effect of Ventilatory Variability on Occurrence of Central Apneas RESPIRATORY CARE MAY 2013 VOL 58 NO 5 Paul F. Nuccio, MS, RRT, FAARC Brigham and Women’s Hospital Boston, MA

2. Background Definitions: PSV = Pressure Support Ventilation NAVA = Neurally Adjusted Ventilatory Assist Periodic breathing What is the research question? Is there a difference in the occurrence of central apnea episodes between patients ventilated with a constant-level PSV vs. NAVA? Is this research question relevant? Central apnea may be associated with significant pathophysiologic changes, including stroke, brainstem lesion, encephalitis, and congestive heart failure.

3. Background What is known about this subject? normal ventilation varies from breath to breath traditional mechanical ventilation may be monotonous close association between arousal from sleep and ventilatory effort Background literature Anesthesiology 2010;112(3):670-681. NAVA resulted in more complexity of airflow and breathing pattern compared with PPV Anesthesiology 2009;110(2):342-350. Variability of pressure support improves lung function Any concerns about COI? None. Dr. Delisle has disclosed a relationship with Fisher & Paykel.

4. Methods What is the study design? Prospective, comparative, crossover study Inclusion criteria Invasive mechanical ventilation Normal consciousness Absence of sedatives and opiates for > 24 hours PSV with FiO2 90%) Exclusion criteria Presence of a central nervous system disorder Glasgow Coma Scale score <11 Hemodynamic instability Renal and/or hepatic insufficiency Ongoing sepsis History of esophageal varices or gastroesophageal bleeding (past 30 days) History of GI symptoms such as vomiting

5. Methods What is the control group? With a crossover study, every patient serves as his or her own control. Is the sample size appropriate? There were a total of 14 patients in the study. Very difficult to draw conclusions from such a small sample size. What are the threats to validity of the design? Small sample size Compare apples to apples? Was the statistical analysis appropriate? Statistical software utilized for analysis Comparisons made using general linear model for repeated measures Wilcoxon test for paired samples Any ethical concerns? The ethics committee of the hospital approved the study, and the subjects or their surrogates gave their informed consent. Potential ethics concerns if one therapy appears to provide more benefit.

6. Study Protocol Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

7. Polysomnography tracings with neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV) in a representative subject. Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

8. Results What are the main results? Study population See table 1 Breathing pattern See table 2 Apneas See table 3 Variability of ventilation See table 4

9. Table 1 - Subjects Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

10. Table 2 - VT, Breathing Frequency, Apneas per Hour, and PETCO2 While Awake and Asleep. Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

11. Table 3 - Oscillatory Behavior of VT, Breathing Frequency, V ̇ E, and PETCO2 During Sleep Stages 2 and 3–4 During PSV in the 10 Patients With Central Apneas. Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

12. Table 4 - VT, f-flow, and EAdi Peak Variability in the 10 Patients With Central Apneas. Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

13. Fig 3 - Variability during pressure support ventilation (PSV). Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

14. Fig 4 - Variability during neurally adjusted ventilatory assist (NAVA). Delisle, S. et al. Respir Care 2013;58:745-753 (c) 2012 by Daedalus Enterprises, Inc.

15. Discussion What do these finding mean? Interesting & provocative study that lacks clear clinical outcomes benefit How should these findings impact practice? Unlikely to have a significant impact on practice How do these findings relate to previous findings from other studies? Similar to other studies

16. Discussion What are the study limitations/concerns? Single center study Small sample size Possible influence of sedation Single level of both NAVA and PSV Potential risk of using NG tubes What additional work is needed in this area? Study findings of physiological effect of NAVA must be confirmed by further clinical studies.

17. Editorial … by Kathy S Myers Moss MEd RRT-ACCS University of Missouri “I commend the authors on their use of a prospective, randomized, controlled trial, the gold standard of experimental research methods. In addition, the research design integrated a crossover method with attention to minimizing residual effects. The statistically significant effect on tidal volume variation is especially noteworthy given the small sample size of 14.’’ “Until well designed studies provide evidence suggesting reduced morbidity, mortality, stay, number of ventilator days, or other desirable clinical outcomes, clinical managers are unlikely to invest in the required software and hardware upgrades necessary to implement NAVA.”

18. Conclusions What are the authors’ conclusions? NAVA was associated with increased ventilatory variability compared to constant level PSV. With NAVA absence of overassistance during sleep coincided with absence of central apneas, suggesting that load capacity and/or neuromechanical coupling were improved by NAVA and that this improvement decreased or abolished central apneas. How do you think this should affect practice? Since NAVA is exclusively an option for one ventilator, widespread use of this technology will continue to be limited. More widespread adoption of this technology will require physiologic outcomes improvements, outcomes such as decreased number of ventilator days, and fewer complications of mechanical ventilation. What is the take-home message? Further clinical investigations are needed to evaluate the impact of NAVA on weaning time and patient outcomes.