Noninvasive respiratory therapiesby a nose? NEO- The Conference for Neonatology February 21, 2014 Disclosures I have no relevant financial relationships to disclose or conflicts of interest to release. I will not discuss unapproved or off label experimental or investigational use of a product, drug or device. Mark C. Mammel, MD mamme001@umn.edu University of Minnesota Children s Hospital Noninvasive respiratory therapieswhy bother? Invasive therapy = intubation, mechanical ventilation Endotracheal tube Airway trauma Impaired mucocilliary clearance Ventilator: VILI Noninvasive respiratory therapies- types Nasal CPAP Nasal IPPV Nasal cannulae Positive pressure device vs. negative pressure physiology Potential for baro, volu, atelectrauma Iatrogenic injury infection Suction devices CPAP Von Reuss and CPAP, 1914 In 1914, Von Reuss described use of CPAP to resuscitate newborn infants: Note the O2 tank, tubing attached to a mask/rubber ball, and water bottle into which the tubing is placed to provide CPAP *Von Reuss AR. Diseases of the Newborn. Berlin,1914
Early CPAP Columbia n Columbia again 500-1500 gm Infants: Variation in CLD 100 90 * 80 70 % 60 New York Boston * 50 40 * 30 * 20 *p<0.0001 10 0 Avery ME et al, 1987 Early CPAP Finer NN, et al. Delivery room continuous positive airway pressure/positive end-expiratory pressure in extremely low birth weight infants: a feasibility trial. Pediatrics 114;651:2004 28 wks No intubation for surfactant only Intubated in NICU for FiO2>0.3, ph < 7.25, apnea To determine whether intervention feasible at this GA range Survival MV Surfactant Indocin %CLD Van Marter et al. Pediatrics 2000;105:1194-1201 CPAP + surfactant What about surfactant?? Most studied intervention in gy neonatology Decreases mortality Early or prophylactic therapy best Should patients get surfactant too? Fig 1. % of infants at each GA requiring intubation for resuscitation in the DR Surfactant & CPAP vs Surfactant & SIMV: INtubation SURfactant Extubation Approach Cochrane review: Stevens TP et all. Updated Aug 22, 2007 6 RCTs from 1994-2006; most infants >1200 gms INSURE at FiO2 <0.45 is associated with: Less need for MV Lower incidence of BPD Decreased air leak syndrome CPAP- the COIN trial International multicenter trial: Nasal CPAP at birth or intubation for very preterm infants (COIN). 2 treatment groups for intervention at 5 min age (25-28 wks GA): CPAP at 8 cmh2o; surfactant, MV if treatment failed Intubate, MV Primary outcomes: Death or CLD @ 36 wks adj Secondary outcomes: intubation, surfactant use, O2 at 28 days; FIO2, air leaks; ICH; duration of MV; hospital days; days to birth weight N=610; Morley CJ et al, NEJM 2008;358:700
COIN Trial COIN Trial Modified from Morley et al, NEJM 2008;358:700 Modified from Morley et al, NEJM 2008;358:700 CPAP- Recent clinical trials SUPPORT Trial NICHD Neonatal Network: CPAP vs Surfactant, and a Lower vs Higher Oxygen Saturation in 24 to 27 Week Preterm Infants (SUPPORT). 4 treatment groups for intervention, saturation monitoring (24-27+6 wks GA): Intubate, surfactant, MV, high S ao 2 (92-96%) Intubate, surfactant, MV, low S ao 2 (85-59%) Primary outcomes: % surviving without CLD @ 36 wks adj, % surviving without severe ROP N=1316; SUPPORT Study Group, NEJM 2010;362:1970 CURPAP trial: Prophylactic or Early Selective Surfactant Combined with ncpap in Very Preterm Infants. 2 treatment groups (25-28wks GA not intubated at birth): Intubate/surfactant/extubate to CPAP CPAP, intubation + surfactant based on clinical indications Primary outcome: Need for MV during first 5 days of life N=208; Sandri S et al, Pediatrics 2010;125:e1042 Vermont Oxford trial: Delivery Room Management Trial of Premature Infants at High Risk for RDS. 3 treatment groups (26-29+6 wks GA): Intubate+surfactant, MV Intubate, surfactant, extubate to CPAP CPAP, intubation + surfactant based on clinical indications Primary outcomes: CLD @ 36 wks adj, Death at 36 wks adj; N=895; terminated early at 648. Dunn MS et al, Pediatrics 2011;128:1069 Modified from SUPPORT Study Group, NEJM 2010;362:1970 SUPPORT Trial CURPAP Trial Modified from SUPPORT Study Group, NEJM 2010;362:1970 Modified from Sandri S et al, Pediatrics 2010;125:e1042
CURPAP Trial VON Trial Modified from Sandri S et al, Pediatrics 2010;125:e1042 PS= prophylactic surfactant; ISX= intubate/surf/extubate; ncpap= DR CPAP Modified from Dunn MS et al, Pediatrics 2011;128:e1069 VON Trial CPAP- Recent clinical trials Early CPAP: Conclusions No differences in death or BPD, other secondary outcomes Possible benefit at <28 wks GA Decreased rate/duration of intubation, surfactant use Decreased postnatal corticosteroids PS= prophylactic surfactant; ISX= intubate/surf/extubate; ncpap= DR CPAP Modified from Dunn MS et al, Pediatrics 2011;128:e1069 High flow nasal cannulae What do they do? Provide oxygen Makes nurses happy More? High flow nasal cannulae Potential mechanisms of action Provide oxygen Provide oxygen Washout of N-P deadspace Decrease N-P resistance Improve lung mechanics with heated, humidified gas Provide positive pressure
Comparison of HFNC with ncpap in treatment of AOP Sreenan et al. Pediatrics, 2001 Methods In Vivo Data CPAP 6cmH 2 O Saline-filled 8Fr Catheter for P es HHNC 6lpm 5lpm 4lpm 3lpm 2lpm 1lpm Data collected after 30 minutes at each new level Data: Vital signs, mean esophageal pressures and arterial blood gas values Modified from Lampland AL et al, J Pediatr 2009;154:177 In vivo Data In vivo Data CPAP 6 6 L/m 5 L/m 4 L/m 3 L/m 2 L/m 1 L/m COV% (inter) 161 209 302 223 841 654 1885 COV% (intra) 122 117 180 143 51 147 99 Modified from Lampland AL et al, J Pediatr 2009;154:177 Modified from Lampland AL et al, J Pediatr 2009;154:177 In Vivo Data Comparison to Sreenan Equation Predictions Randomized comparison of CPAP vs HFNC for O2 weaning 7Actual vs predicted gas flow based on Sreenan equation 6 5 Flow (L/min)_ 4 3 2 1 0 0 0.5 1 1.5 2 2.5 Weight (kg) Flow (lpm) = 0.92 + 0.68 x Weight (kg) Modified from Abdel-Hady H et al, Early Human Dev 2011;87:205
Randomized comparison of CPAP vs HFNC for O2 weaning Randomized comparison of CPAP vs HFNC for post extubation support Duration O2 Rx 5 vs 14 d; respiratory support 10.5 vs 18 d favoring CPAP group Vapotherm at 8L/m: CPAP est at 4-5 cmh 2 O; extubation failure 7 days, nasal trauma Modified from Abdel-Hady H et al, Early Human Dev 2011;87:205 Modified from Collins CL et al, J Pediatr 2013;162:949 Randomized comparison of CPAP vs HFNC for post extubation support Wilkinson D et al, Cochrane Reviews 2012 4 studies of HFNC- insufficient evidence of safety or efficacy After extubation, MAY be higher risk of reintubation No difference in extubation failure rate; less nasal trauma with HFNC More work needed! Modified from Collins CL et al, J Pediatr 2013;162:949 Nasal Ventilation: SiPAP What about SiPAP? Impact on gas exchange, apnea? Randomized 4-period crossover trial of CPAP vs SiPAP Hypothesis: in babies stable on CPAP, SiPAP at the same Paw will produce Similar oxygenation Improved ventilation Nasal Ventilation: SiPAP Physiologic data (continuous): Transcutaneous CO2 Heart rate Respiratory rate Oxygen saturation Physiologic data (intermittent): Cuff blood pressure q 10 minutes Pneumogram Heart rate Oximetry Thoracic impedence Lampland A et al, unpublished data (presented at SPR 2012). Lampland A et al, unpublished data (presented at SPR 2012).
Nasal Ventilation: SiPAP Nasal Ventilation: SiPAP Results: CPAP SiPAP p-value Demographics: HR 168.2 (±12.3) 167.3 (±12.1) 0.4 O 2 Sats 87.4 (±2.9) 87.3 (±3.8) 0.98 GA: 26 5/7 ± 1 6/7 wks Postnatal age: 33 ± 23 d Wt: 1310 ± 373 gms. FiO 2 : 030± 0.30 ± 004 0.04 TCO2 RR FiO2 SBP 54 (±7.1) 47.9 (±9.5) 30.1 (±4.8) 68.4( (±10.4) 53.2 (±6.4) 47.6 (±9.9) 29.4 (±4.3) 69.8( (±10.9) 0.91 0.5 0.99 0.0808 DBP 42.5 (±7.4) 45.1 (±8.8) 0.003* MBP 52.3 (±8.3) 54.4 (±9.1) 0.01* CPAP SiPAP P-value Apnea-10 1.1 (±3.7) 1.2 (±3.1) 0.87 Bradycardia-10 0 (±0.2) 0.1 (±0.3) 0.32 Desaturation-10 2.0 (±2.3) 1.9 (±2.9) 0.95 Apnea-20 0.4 (±1.1) 1.0 (±4.6) 0.45 Bradycardia-20 0.03 (±0.2) 0 (±0) 0.32 Desaturation-20 2.7 (±4.4) 2.9 (±5.0) 0.67 Pooled data, final 20 min each period Lampland A et al, unpublished data (presented at SPR 2012). Randomised Controlled Trial of SiPAP versus CPAP as a primary mode of respiratory support in preterm infants with RDS 2 center trial: 28-31 6/7 weeks - 120 babies enrolled (60 SiPAP, 60 CPAP) Primary outcome: failure of support requiring intubation Randomized by center and GA Wood F et al, unpublished data (presented at SPR 2013). Nasal Ventilation: SiPAP Nasal Ventilation Randomised Controlled Trial of SiPAP versus CPAP as a primary mode of respiratory support in preterm infants with RDS Results: For the very preterm infant, using SiPAP for firstline treatment of RDS does not confer benefit in shortterm respiratory outcomes as compared to CPAP. Preterm morbidities and complications of noninvasive respiratory support were similar irrespective of allocation. IMV, SIMV or HFOV can be delivered through nasal prongs Data limited, no long term outcomes Policlinico Umberto 1, Rome Wood F et al, unpublished data (presented at SPR 2013). Nasal Ventilation Nasal Ventilation NIPPV vs SIMV in piglets. Fewer mechanical support breaths required in NIPPV group; Interstitial inflammation was increased in SIMV group. Modified from Lampland A et al. Crit Care Med 2008;36:183. Modified from Moretti C et al, Early Human Development 1999;56:167
Nasal Ventilation Nasal Ventilation NIPPV after surfactant- a MCRCT. Primary outcome: need for ventilation at 7 days. NIPPV delivered using Avea ventilator or SiPAP device (CareFusion). Rates 30-40, ti 0.5 sec, PEEP 5; PIP = PEEP+10-15. No synchronization. Modified from Ramamanthan R et al, J Perinatol 2012;32:336. Modified from Ramamanthan R et al, J Perinatol 2012;32:336. Nasal Ventilation Nasal Ventilation- Kirpalani et al NIPPV MCRCT- Kirpalani et al 1009 infants from 36 sites NIPPV (synchronized or nonsynchronized) Early and late (post extubation, 1 st 28 days) y) Primary outcome: death or BPD Subgroups, synchronized vs non, NEC Modified from Kirpalani H et al, NEJM 2013;369:611 Modified from Kirpalani H et al, NEJM 2013;369:611 Nasal Ventilation- Kirpalani et al NIPPV- Where do we go from here? Current trials Little support for early or rescue use Problems Too many devices Unclear mechanisms of action To trigger or not to trigger? More work needed Modified from Kirpalani H et al, NEJM 2013;369:611
Larynx and NIV Nasal Support- NAVA In adult humans : laryngoscopic observations NAVA: Neurally-adjusted ventilatory assist nippv levels EAdi: Electrical activity of the diaphragm Laryngeal closure against ventilator insufflations Trigger for noninvasive support? Lung ventilation Gastric distension? Courtesy of J. Beck and CA Sinderby, Toronto, ON Jounieaux, J Appl Physiol, 1995 Nasal Support- NAVA Nasal Support- NAVA PSVG NAVA-int NAVA-ext Modified from of Beck J et al, Intens Care Med 2008;34:316 Modified from of Beck J et al, Pediatr Res 2009;65:663 Noninvasive respiratory therapies- Why bother? Glottal constrictor Glottal l dilator CPAP- the new ventilation? Initial therapy, ± surfactant Similar outcomes to traditional therapy at 24 wks Nasal cannulae- CPAP without prongs? Less nasal trauma, better patient comfort, p No evidence for benefit, may prolong support needs NIPPV- CPAP with a rate- more support with less Potential additional therapy with possible improvement in outcomes compared to CPAP Synchronized vs unsynchronized- major issue SiPAP- voodoo? NAVA- could be the real thing!
Noninvasive Support - By a nose?