Nasal CPAP in Neonatology: We Can Do Better

Transcription

1 Nasal CPAP in Neonatology: We Can Do Better

2 COI Disclosure I do not have any conflict of interest, nor will I be discussing any off-label product use. This class has no commercial support or sponsorship, nor is it co-sponsored.

3 Objectives 1. Identify the major clinical factors associated with the Development of bronchopulmonary dysplasia (BPD). 2. Describe the role of non-invasive respiratory support in Premature Infants. 3. Discuss the evidence for improved efficacy of nasal CPAP in premature infants.

4 Nasal CPAP in 2018 Presently The Standard of Respiratory Care Domestically? Variance in how nasal CPAP is applied (interfaces) Variance in how long nasal CPAP is used Variance in the kind of nasal CPAP used Variance in culture Presently the Standard of Respiratory Care in Global Health?

5 Why Nasal CPAP: Pulmonary Embryology and BPD Risk Fetal Risks IUGR and lung development Inflammation Postnatal Risks Airway overdistension: Injury Alveolar overdistension: Injury Underdistension: Atelectotrauma Inflammation

6 Placental Vasculopathy Premature Neonate Maternal Chorioamnionitis Increased Pressure/Flow Airway Inhomogeneity Compliance Immature Cells Antioxidant Deficiency Compliant Chest Wall Surfactant Deficiency Volutrauma Atelectasis (Atelectatrauma) Oxidant Stress Aberrant Gene Expression Where should we aim the Silver Bullet? Inflammation Arrested Lung Development Acute Lung Injury Pulmonary Edema Airway + + Injury = BRONCHOPULMONARY DYSPLASIA

7 Transitional Phases in Respiratory Management Respiratory Management in Premature Infant < 28 weeks Intubate? Chronic Care on Nasal CPAP Through 32 to 33 weeks PMA No Fail ncpap? Yes Extubate quickly (< 7days) Yes Fail CPAP? No Continue to evaluate for extubation (7-28 days) Yes No Fail CPAP? Protracted Mechanical Ventilation

8 Nasal CPAP in 2018: Can We Do Better?

9 CPAP in 2018 > CPAP in Developing Countries > CPAP Strategies Bubble versus Ventilator CPAP Others > Other Non-Invasive Strategies > Additional CPAP Strategies Seattle-PAP

10 Malawi Medical Journal :131 College of Medicine Silver Jubilee Special Issue Low-cost CPAP to reduce neonatal mortality Research Article (PLOS ONE) Efficacy of a low-cost bubble CPAP system intreatment of respiratory distress in a neonatal ward in Malawi Kondwani Kawaza, Heather E. Machen, Jocelyn Brown, Zondiwe Mwanza, Suzanne Iniguez, Al Gest, E. O Brian Smith, Maria Oden, Rebecca R. Richards-Kortum, Elizabeth Molyneux Kawaza K et al. Malawi Med J :131

11 Nasal CPAP in Malawi Kawaza K et al. Malawi Med J :131

12 Nasal CPAP in Malawi Kawaza K et al. Malawi Med J :131

13 Simone Martin et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F495-F504

14 Copyright BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved. Bubble CPAP versus Ventilator CPAP and Failure Simone Martin et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F495-F504

15 Bubble Nasal CPAP in the US Lee KS, Dunn MS, Fenwick M and Shennan. Biol neonate, :69-75

16 Bubble Nasal CPAP in the US Lee KS, Dunn MS, Fenwick M and Shennan. Biol neonate, :69-75

17 Bubble Nasal CPAP in the US Lee KS, Dunn MS, Fenwick M and Shennan. Biol neonate, :69-75

18 Schmolzer et al

19 CPAP Efficacy: BPD Schmolzer et al

20 CPAP Efficacy: The Big Three Schmolzer et al

21 Nasal CPAP failure rates > SUPPORT Trial (24-27 weeks) 83% > COIN Trial (25-28 weeks) 59% > VON trial (26-29 weeks) 48%

22 Alternatives to Nasal CPAP > Is all CPAP created equal? > NIPPV or others > HHHFNC

23 Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation Cochrane Database of Systematic Reviews 1 FEB 2017 DOI: / CD pub3

24 Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation Cochrane Database of Systematic Reviews 1 FEB 2017 DOI: / CD pub3

25 Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation Cochrane Database of Systematic Reviews 1 FEB 2017 DOI: / CD pub3

26 Kirpalani H et al. N Engl J Med 2013;369: Secondary Outcomes.

27 Original Article Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants Calum T. Roberts, M.B., Ch.B., Louise S. Owen, M.D., Brett J. Manley, Ph.D., Dag H. Frøisland, Ph.D., Susan M. Donath, M.A., Kim M. Dalziel, Ph.D., Margo A. Pritchard, Ph.D., David W. Cartwright, M.B., B.S., Clare L. Collins, M.D., Atul Malhotra, M.D., Peter G. Davis, M.D., for the HIPSTER Trial Investigators N Engl J Med Volume 375(12): September 22, 2016

28 Baseline Characteristics of the Mothers and Infants. Roberts CT et al. N Engl J Med 2016;375:

29 Primary Outcome, Intubation within 72 Hours, and Outcomes in the Subgroup and Per-Protocol Analyses. Roberts CT et al. N Engl J Med 2016;375:

30 Reasons for Treatment Failure and Other Secondary Outcomes. Roberts CT et al. N Engl J Med 2016;375:

31 Reasons for Failure > Process Failure Operational Fear of nasal trauma > CPAP Failure Not all CPAP is alike Innovative changes in nasal CPAP

32 Interim Summary > Nasal CPAP and NIPPV have equivalent outcomes > Nasal CPAP > Nasal CPAP failure is common Process failure It s the culture CPAP failure -?Better CPAP Strategies

33 Changing tube orientation

34 Bubble Nasal CPAP

35 Seattle PAP and the Lung

36 Seattle PAP versus Nasal CPAP DiBlasi, Pediatr Res 2010 DiBlasi et al. Pediatr Res 67:

37 Oxygenation, Ventilation, and Work of Breathing in Lavaged Juvenile Rabbits on Seattle-PAP DiBlasi et al. Pediatr Res 67:

38 Study 1 > To test the hypothesis that Seattle PAP would be associated with a lower PRP than Bn-CPAP > Study Design <32 weeks gestation 6-72 h of age stable 2 h epochs on Bn-CPAP, Seattle PAP and Bn-CPAP > Measure PRP, TcPCO2 and many other secondary endpoints

39 Measurement of Pes over an Epoch 39

40 Measurement of Pes during Quiet Breathing 40

41

42 Summary statistics for the demographic and clinical data Study subjects, n (%) All entered, n=40 Used in analyses, n=27 Female 26 (65) 18 (67) Race Asian 1 (2) 1 (3) Black 11 (28) 8 (30) White 28 (70) 18 (67) Ethnicity Hispanic 9 (23) 7 (26) Ampicillin and Gentamicin 27 (68) 18 (67) Surfactant 19 (48) 18 (67) Birth Weight, g Mean ± SD 1298 ± ± 246 Median Gestational Age, wks Mean ± SD 29.4 ± ± 1.7 Median Age at start of study, h Mean ± SD 45 ± ± 13

43 Inter-Epoch Comparisons of Effort of Breathing PRP cmh 2 O/min ΔP es cmh 2 O RR breaths/min AUC/Breath cmh2o x min x 103 AUC/min cmh2o Epoch (+90.0) 1.44 (+0.79) 67.1 (+19.9) 9.58 (+4.01) 0.65 (+0.38) Epoch (+79.4) 1.33 (+0.73) 73.8 (+22.0) 8.10 (+3.75) 0.58 (+0.35) Epoch (+111.7) 1.53 (+0.98) 68.6 (+19.0) 9.70 (+4.49) 0.69 (+0.47) ANOVA (F, P) Friedman ( c 2, P) 0.54 (0.586) 2.50 (0.092) 3.01 (0.058) 5.93 (0.005) 3.50 (0.038) 4.67 (0.097) 7.41 (0.025) 6.74 (0.034) (0.002) 7.19 (0.028) Data are presented as means ±SD computed from median values for each epoch for each patient, except for respiratory rates, for which epoch mean RRs were assessed. Shaded areas denote differences between epochs. Data were analyzed using ANOVA. 43

44 GEE Model Fit Variable/Factor Postnatal age at study (days) PRP cmh 2 O/min P es cmh 2 O/min RR breaths/min AUC per Breath x 10 3 cmh 2 O x min AUC per min cmh 2 O/min 0.19 (±0.09) 0.29 (±0.10) (±4.86) 0.35 (±0.15) 0.24 (±0.10) Ampicillin and Gentamicin administration (±0.23) (±0.16) (±6.32) (±0.13) (±0.17) Epoch (±0.05) 0.06 (±0.05) (±3.48) 0.20 (± 0.08) 0.10 (±0.04) Epoch (±0.09) 0.14 (±0.05) (±4.23) 0.20 (± 0.08) 0.15 (±0.06) Data are expressed as means ± SE Baseline: GA 29.6 wk, age 2 d, no surfactant, amp. or gent., Epoch 2 (Sea Bn-CPAP). Different from baseline infant P-value < 0.05 Different from baseline infant P-value < Transcutaneous PCO 2 measurements did not change between Epochs No significant interactions found between GA (wk) or prior administration of surfactant

45 GEE Model Fit Data are expressed as means ± SE Baseline: GA 29.6 wk, age 2 d, no surfactant, amp. or gent., Epoch 2 (Sea Bn-CPAP). Transcutaneous PCO 2 measurements did not change between Epochs No significant interactions found between GA (wk) or prior administration of surfactant

46 Summary > Study patients were stable, relatively mature and large at study commencement > There were no adverse events during the 6 h study period and no serious adverse events attributable to the Seattle-PAP > In this sample of patients that were clinically stable, ΔPes, AUC and AUC per unit time were lower during the Seattle- PAP epoch than the epochs on standard bubble nasal CPAP 46

47 Conclusions to Pilot Study > In this pilot study of stable patients unlikely to fail nasal CPAP the results suggest that respiratory support with Seattle-PAP is safe and leads to a lower work/effort of breathing > Safety and efficacy of this promising respiratory support tool awaits clinical trials in the developed and developing world > Subsequent Efficacy Multi-Center Trial started in 2/1017 > To date approximately 75 patients have been enrolled and almost 50 are off of study 47

48 Overall Conclusions for Premature Neonates > Transitioning to non-invasive support is critical and problematic > No compelling evidence for approaches other than nasal CPAP > Nasal CPAP fails frequently > Failure is related to; Bad Process CULTURE! Suboptimal CPAP for Respiratory Mechanics > Seattle PAP is a promising CPAP device and Efficacy Domestic Trials are ongoing > International Trials are planned