Nasal respiratory Support: The best Option for Resource Restricted (and Rich) Countries?

Transcription

1 Nasal respiratory Support: The best Option for Resource Restricted (and Rich) Countries? Rangasamy Ramanathan, MD. Professor of Pediatrics Division Chief, Division of Neonatology Program Director, NPM Fellowship Program Director, LAC+USC NICU LAC+USC Medical Center Keck School of Medicine University of Southern California, LA, CA. SAILING THE SEVEN SEAS, Cape Town, SA

2 Non-Invasive Ventilation: What is it? Rangasamy Ramanathan, M.D. Conflict of Interest Disclosures: u Inventor of RAM NC and I have a Joint Patent with Neotech Products, Inc. u Inventor and Patent Holder of RamSmeeta Ventilator u If I receive any honorarium, I donate to charity that helps Mothers, Newborns and Children globally. u I do not intend to discuss unapproved/ investigative use of commercial product(s)/device(s) in my presentation. u I do not teach how to Intubate; I only teach how to Extubate.

3 What is NIV?: 3 of 5 Modes of NIV NIV NCPAP SIPAP Mimics CPAP NIPPV Mimics Invasive Ventilation 1. Bubble CPAP 2. Ventilator CPAP 3. Infant Flow Driver- Flow Generator High Flow NC: Pressure is neither measured nor controlled Infant Flow Driver: 1. PIP ~10 2. Delta Pr. ~ High Flow Rates 4. Longer I.T. Ventilator: 1. Higher PIP 2. Delta Pr. ~ Flow Limited 4. Shorter I.T. Back Up Rate is provided

4 What is NIV?: 4 th Mode Noninvasive High Frequency Ventilation (NHFV) NHFOV NHFJV NIV: 5 th Mode NIV-NAVA

5 HFNC: Fisher & Paykel vs. Vapotherm and Pharyngeal Pressures in PT Infants (n=9) Variable and unpredictable At 8 lpm, mean pressures were between 4.1 to 4.9 with a SD of 2.2, meaning that 95% of the time, pressures were between 0 and 9 cmh 2 O Collins CL et al (Melbourne). J Pedaitr and Child Health 49: ; 2013

6 High Flow Nasal Cannula: Cannupap : Scalp Emphysema, Pneumo-orbitis & Pneumocephalus Case Report: 26 wks, 901 g Dol #20: Extubated to 4 LPM HFNC Skull X-Ray and CT Scan: Scalp Emphysema & Orbital Air DOL#36: Weaned to 2 LPM. Noted to have Scalp Crepitus and eye swelling Jasin LR et al (Dayton, Ohio) J Perinatology 28: ; 2008

7 High Flow Nasal Cannula: Cannupap : Tension Pneumocephalus Case Report 27wks, 710 g, Dol # 2-5 Extubated to 4 LPM HFNC. DOL#12: Restarted on HFNC. HC increased by 2.5 cm from DOL CT Scan & MRI: Tension Pneumocephalus Iglesias-Deus et al (Pontevedra, Spain) Arch Dis Child Fetal Neonatal Ed 102: F173-F175, October 18, 2016.

8 HHHFNC vs. NCPAP: Forest plots showing results of metaanalyses for Extubation Failures (3 RCTs, GA < 32 wks; n=585) No Difference in BPD Daish H, Badurdeen S. (Middlesex, UK) Arch Dis Child 99:880-2; Sept 2014

9 HFNC use is associated with Higher Risk of Death or BPD & Longer LOS in ELBW Infants (n= 2,487) CPAP HFNC HFNC + CPAP BW GA any time, % LOS, d Multiple regression analysis was used to adjust for the differences between groups In ELBW Infants Taha DK et al. (CHOP) J Pediatrics March 2016

10 HFNC for Primary Respiratory Support in Preterm Infants (n= 564; GA > 28 weeks) [HIPSTER Trial] Multinational, RCT-Non-Inferiority design- Australia & Norway HFNC vs. NCPAP; No Surf. Rx; BW: 1737 vs 1751 g; GA: 32 vs 32 wks Trial stopped early per DSM Committee because of a significant difference in primary outcome of failure within 72 hours of randomization Treatment Failure: HFNC vs. NCPAP: 25.5% vs 13.3% [p<0.001] Conclusions: When used for primary support for preterm infants with respiratory distress, HFNC resulted in a significantly higher rate of treatment failure than did CPAP. In VLBW Infants Roberts CT et al. NEJM 375: , Sept 2016

11 HFNC vs. NCPAP for Primary Respiratory Support in Preterm Infants (n= 272/460; GA > 28 weeks) HFNC (N=133) NCPAP (N=139) P/ RD (95%CI) 1.0 BW, g GA, weeks AS 62% 54% 0.32 randomization, h 05 ( ) 0.5 ( ) 0.32 RDS 54% 42% 0.11 Proportion on primary support ncpap HFNC Rx Failure <72 h 26.3% 7.9% <0.0001/ 18.4% (9.7, 27.1) Time to Rx Failure, h 3 (1-8) 22 (2-34) 0.04 / -19 (-1.9, -36.1) Time, h Rx Failure in <32 wks 37.9% % 10.3% % Study was stopped after a planned interim analysis showing a significantly higher Rx failure with HFNC. HFNC: 5-7 LPM; NCPAP: 5 cm H 2 O Murki S et al. (Mumbai & Hyderabad) Neonatology Jan 23, 2018

12 NIPPV vs. NCPAP in the Delivery Room in VLBW Infants <1500 g (n=221) NCPAP (n=102) NIIPV (n=119) P Value Birth weight, g, mean (SD) 887 (319) 906 (290) 0.65 Gestational age, wks, mean (SD) 27.1 (3.0) 27 (2.6) 0.72 DR intubation, n (%) 87 (85) 37 (31) <0.001 DR Emergency Intubation, n ( %) 69 (68) 34 (29) <0.001 Chest compressions, n (%) 32 (31) 13 (11) <0.001 Median 5 min APGAR, (IQR) 6 (5,8) 7 (6,8) Air Leak Syndrome on first chest radiograph, n (%) 3 (3) 2 (2) 0.33 Incidence of severe IVH, n (%) 7 (6) 5 (4) NS Invasive ventilation at 24 hours of age, n (%) 67 (66) 45 (38) <0.001 Duration of invasive ventilation in days, median (IQR) 11 (1,39) 2 (0,28) 0.01 Surfactant Rx, n (%) 92 (90) 105 (88) 0.64 Biniwale M, Wertheimer F. Resuscitation 116:33-38, May 2017

13 NIPPV vs. NCPAP in the Delivery Room in VLBW Infants <1500 g (n=221): Intubation rates at different Gestational ages from weeks A * * Percentage * * * Face mask group NIPPV Group 20 * * B Gesta onal age in weeks Biniwale M, Wertheimer F. Resuscitation 116:33-38, May 2017

14 NIPPV vs. NCPAP in the Delivery Room in Infants > 1500 g (n=769) Outcome NCPAP (n=375) NIPPV (n=394) P Value Birth weight, g Mean (SE) 2899 (+ 380) 2786 (+ 360) 0.03 DR intubation, n (%) 55 (14.7) 28 (7.1) <0.001 Chest compressions, n (%) 9 (2.4) 5 (1.3) Median 5 min APGAR, (IQR) 8 (7, 9) 8 (7, 9) NS Air Leak Syndrome on first chest radiograph, n (%) Invasive ventilation at 24 hours of age, n (%) Median duration of invasive ventilation in days, (IQR) 18 (4.8) 15 (3.8) (17.3) 30 (7.6) < (1, 5) 1 (1, 3) Wang E, Wertheimer F, Biniwale M, Ramanathan R. PAS meetings, Baltimore

15 NCPAP in the Delivery Room & Failures Unidimentional approach, applicable to an aerated lung that is not water-logged 67# 7 RCTs # 46# 34.4% in the DR 52# # 33# 29.8# te Pas-07 Morley-08 Rojas-09 CURPAP-10 SUPPORT-10 VON-11 Neocosur-12 te Pas-07 COIN-08 Rojas-09 CURPAP-10 SUPPORT-10 VON-11 Neocosur-12 BW 1290 (392) 964 (212) 1293 (324) 913 (200) 835 (188) 1053 (252) 1196 (195) GA 29.5 (1.9) 26.9 (1.0) 29.3 (1.4) 27 (0.97) 26.2 (1.1) 28.1 (1.1) 29.8 (2.4)

16 NCPAP in the Delivery Room & Early Failures (emv in the 1 st <5 days) RCTs emv-1st 5 days of life COIN-08 Rojas-09 SUPPORT-10 CURPAP-10 VON-11 Gopel-11 Kanmaz-13 COIN-08 Rojas-09 SUPPORT-10 CURPAP-10 VON-11 Gopel-11 Kanmaz-13 BW 964 (212) 1293 (324) 835 (188) 913 (200) 1053 (252) 975 (244) 1093 (270) GA 26.9 (1.0) 29.3 (1.4) 26.2 (1.1) 27 (0.97) 28.1 (1.1) 27.5 (0.8) 28 (2) Modified from Fischer HS, Buhrer C. Pediatrics 132:e1351-e60;2013

17 Effect of Avoiding Early MV (1 st 5 days of Life) on Death or BPD (7 RCT): A small but significant impact on preventing BPD Fischer HS, Buhrer C. Pediatrics 132:e1351-e60;2013

18 Si-PAP vs. NCPAP: RCT (n=1,009; <1,000 grams BW; GA < 30 weeks) [A trial comparing noninvasive ventilation strategies in preterm infants] Si-PAP (n=504) NCPAP (n=503) p BW, g mean (SD) 802 (131) 805 (127) NS GA 26.1 (1.5) 26.2 (1.5) NS Re-Intubated postrandomization 59.5 % 61.8 % NS Prior Intubation 46.5 % 45.4 % 0.70 Caffeine Rx 82.9 % 82.9 % NS Survived with BPD 33.9 % 31 % 0.32 Death or 36 wks PMA 38.4 % 36.7 % 0.56 NIPPV= 53% of Centers used Si-PAP; Suggested Settings: PIP 9-10; Vent: PIP 2-4 above PEEP; Max PIP 18; Rate 10-40; IT s; No data on Surfactant Rx Kirpalani H et al. NEJM 369:611-20; August, 2013

19 Si-PAP vs. NCPAP: RCT: Suggested Settings for NIPPV Table S1. Suggested Initiating and Maximal Settings for Respiratory Support by Group. Si-PAP Settings NIPPV ncpap Initial Max Initial Max Rate (breaths per minute) N/A N/A PIP(cm H 2 O) 10 above PEEP or 2-4 > vent PIP or 9-10 on infant flow advance or SiPAP 18 N/A N/A PEEP(cm H 2 O) 5-6 or same as when intubated or same as when intubated 8 FiO 2 (percent) SaO % SaO % Ti Seconds N/A N/A Flow (litres per minute) Kirpalani H et al. NEJM 369:611-20; August, 2013

20 Si-PAP vs. NCPAP: RCT: Devices used for NIPPV (>50% used Si-PAP machines to deliver NIPPV ) Table S3. Ventilator Types: Relative Frequency of Use.* Ventilator Type NIPPV ncpap Babylog 8000/ % 18% Bird VIP/VIP Gold 9% 1% Bubble ncpap % Evita 4/XL 7% 2% Infant Flow % Infant Flow Advance 10% 7% Servo 300/900C/I 5% 1% Viasys Sipap 43% 31% Supplementary Appendix: This appendix has been provided by the authors to give readers additional information about their work Others 5% 8% Kirpalani H et al. NEJM 369:611-20; August, 2013

21 Bi-PAP vs. NCPAP: RCT (n=540; GA < 30 weeks; < 2 weeks old; 8 NICUs; ) Bi-PAP (n=270) NCPAP (n=270) p BW, g mean (<28 wks; n=334) NS BW, g mean (>28 wks; n=236) NS Re-Intubated within 48 hours 21 % 20 % 0.97 Re-Intubated within 7 days 34 % 31 % 0.65 BPD - O 36 wks PMA 50 % 54 % 0.18 Bi-PAP: PIP 8; PEEP 4; IT 1.0 s. Rate 30 bpm; NCPAP= CPAP 6. Primary outcome: Failure of extubation within 48 hrs of randomization; Infant Flow Advance by CareFusion Victor S, Roberts SA et al. (UK) Pediatrics 138:e , Aug 2016

22 NIV: What About NIPPV? Controls / Limits 1. Baseline CPAP level (PEEP) 2. A sigh level of CPAP (PIP) 3. Duration of high pressure (inspiratory time = 4-5 x Time Constant) 4. Number of sighs (rate) 5. Flow rate 2. PIP 1. PEEP Insp. Time 20/6 x 40 x 0.5s

23 snimv vs. NIMV vs. NCPAP: Decrease in Inspiratory Effort during 40 bpm (n=16 PT; BW g) Synchronized NIPPV Non-Synchronized NIPPV Respiratory unloading was more striking at higher snimv rates; Synchronization DID NOT affect Vt, Phase angles, Apnea or Hypoxemic spells Chang HY et al. (Bancalari, Miami) Pediatric Research 69: 84-89; 2011

24 NCPAP vs. NIPPV: Failures needing Intubation (10 RCT) % 60# 50# 49# 44# 40# 41# 39# 40# 37# 34# 30# 20# 10# * 5# NIPPV Failures 5-25% * 15# 15# * 6# * 25# * 6# 18.9# NCPAP# NIPPV# 25# * P <0.05 * * 17# 10# 42# 29# * 13# 0# Ramanathan399# Barrington301# Khalaf301# Kugelman307# More?308# Kishore309# Lista310# Meneses311# Ramanathan312# Oncel32016# Modified from Ramanathan R. J Perinatol 30: S67-72; Sept, 2010

25 NCPAP vs. NIPPV: Need for Intubation and Invasive MV: A Meta-Analysis of 5 studies Significant Decrease in the Need for Invasive ventilation. Risk Ratio 0.44; 95% CI: 0.33, 0.59 Li W, et al. (Chongqing, China) Pediatric Pulmonology 50: ; 2015

26 NCPAP vs. NIPPV: BPD (8 RCT) RCTs using INSURE + NIPPV: Less BPD % * 2 * P <0.05 * 10 INSURE+NIPPV * Barrinton-01 Khalaf-01 Kugelman-07 Bhandari-07 Moretti-08 Kishore-09 Meneses-11 Ramanathan-12 NCPAP NIPPV Modified from Ramanathan R. J Perinatol 30: S67-72; Sept, 2010

27 NCPAP vs. Synchronized or Non-Synchronized NIPPV: Extubation failures. Systematic Review and Meta-analysis efigure 1. NIPPV vs. CPAP: Respiratory failure; subgroup analysis by method of NIPPV Ferguson KN et al. (Melbourne) JAMA Pediatrics 171(2): ; Feb 2017

28 Primary Nasal HFOV vs. NCPAP in Preterm Infants with RDS after Curosurf 200 mg/kg via INSURE (n=76; GA wks) NHFOV (N=37) NCPAP (N=39) BW, g GA, weeks AS 35.1% 38.5% Ventilator Medin-HFOV bcpap Mortality 5.4% 7.7% Air leaks IVH 10.8% 7.7% BPD 8.1% 12.8% A large RCT in 300 preterm infants has been just completed. [Zhu et al. China] P Need for Invasive Ventilation Need for Invasive Ventilation: 24.3% vs. 56.4% P<0.01 Zhu X et al. (Chongqing, China) Pediatric Pulmonology 52: ; June 2017

29 Suggested Settings for Nasal HFV Ventilator Suggested Initial HFV settings Suggested Initial IMV settings 3100A VDR4 or Bronchotron Drager VN500 or Babylog 8000 Frequency: 8-10 Hz I:E ratio: 1:2 or 1:1 Paw: Similar to IMV or CPAP Amp/ P: 2 x Paw Frequency: 5-8 Hz I:E ratio: 1:1 Paw: Similar to IMV or CPAP Frequency: 6-10 Hz Amp/ P: 2 x Paw I:E ratio: 1:1 Paw: Similar to IMV or CPAP No conventional breaths Optional NIPPV breaths Frequency 6-20 bpm PIP as needed to move chest Optional NIPPV breaths Frequency 6-20 bpm PIP: above Paw as needed to move chest Leoni Plus / Stephanie /Sophie Variable I:E ratio Same as Above HFJ Life Pulse Jet Frequency: 4 Hz Valve On time: 0.03 s Same as Above Lower Frequency and Longer Inspiratory Time Modified from Yoder BA et al. Seminars in Fetal & Neonatal Medicine 21: ; 2016

30 Interventions to Improve Rates of Successful Extubation in Preterm Infants: A Systematic Review & Meta-analysis Preventing Extubation Failures Risk Ratio [95% CI] NNT [95% CI] NCPAP vs Head-Box 0.59 [ ] 6 [3-9] NCPAP vs HFNC 1.11 [ ] Methylxanthines 0.48 [ ] 4 [2-7] DOXAPRAM 0.80 [ ] NIPPV vs NCPAP 0.70 [ ] 8 [5-13] NS-NIPPV or Bi-PAP vs NCPAP 064 [ ] 8 [4-50] SNIPPV vs NCPAP 0.25 [ ] 4 [2-5] NS-NIPPV or snippv vs NCPAP 0.28 [ ] 4 [2-5] Conclusions and Relevance: Preterm Infants should be extubated to non-invasive respiratory support. Caffeine should be used routinely. NIPPV is superior to NCPAP Ferguson KN et al. (Melbourne) JAMA Pediatrics 171(2): ; Feb 2017

31 Changes in Ventilation Modes and O 2 use and Lung Function at 8 yrs of Age (n=225) 1997 (n=151) 2005 (n=170) BW, g <0.05 GA, weeks NS AS, % <0.05 Surfactant Rx, % # <0.05 # Postnatal Steroids, % ** <0.05** ET Ventilation, Median-days NCPAP, Median-days ^ <0.05^ BPD- O weeks, % 46 43^ 56 <0.05^ FEV 1, % of predicted value # [NONE WERE ON NIPPV] Doyle LW et al. (Melbourne) NEJM 377: ; July 2017 p <0.05 # FEV 1 :FVC, % of predicted value * <0.05* --Despite substantial increases in the use of less invasive ventilation (NCPAP ONLY) there was no decrease in BPD and no improvement in Lung function at 8 yrs of age.

32 NIPPV Initiation & Weaning: NIPPV to NCPAP to Low Flow NC Initial Settings: 20/6 x 0.5s x 40 bpm When FiO 2 is < 0.40, PCO 2 < 60* and ph > 7.25: v Wean PIP and then PEEP, and then Rate v Off NIPPV when PIP < 15, PEEP 5, Rate ~ 20 & FiO 2 < 0.30 to NCPAP v Off NCPAP when CPAP < 5 to Low Flow NC (< 2 LPM) Minimal Duration for each mode: ~ 24 hrs; CPAP until wks PMA to promote Lung growth *Hypercapnia activates the glottic dilator muscles and opens the larynx in neonates. [Wozniak JA et al. J Appl Physiol 75: ; 1993]

33 Take Home Messages 1. Start with NIPPV/NCPAP in the delivery Room 2. Sustained Inflation < 30 wks 3. Early Caffeine in the DR? 4. minsure for RDS + NIPPV 5. Continue NIPPV in Preterm Infants ~ 32 weeks PMA 6. Wean to NCPAP ~ weeks PMA 7. Wean to Low Flow NC (< 2 LPM) ~ 33 weeks PMA 8. Future: snippv, NAVA+NIV, NHFV, NIV + ino Thank you