Non-invasive positive pressure ventilation in the neonate Peter C. Rimensberger Pediatric and Neonatal ICU University Hospital of Geneva Switzerland

CPAP  intubation + ventilation COIN-trial 610 infants, 25-to-28-weeks’ gestation, randomized to CPAP  intubation + ventilation at 5 minutes after birth In the year 2008: BPD incidence = 35% < 29 wks COIN-trial, NEJM 2008

Elastic work of breathing Adult Infant (Reduced Compliance) Volume (%VC) Pressure Thorax Lungs Chest wall Work = P * V ACB: Move the chest wall from the resting position AXC: Overcome resistive forces

Inward distortion of the rib cage on the volume displaced by the diaphragma  Innefficient ventilation and waist of work

Thoraco-abdominal Asynchrony (the noncoincident motion of the rib cage and abdomen during breathing) If the rib cage is sucked in or retracted as abdominal excursions occur (e.g., in upper airway obstruction), or the abdomen is retracted as the rib cage expands (e.g., diaphragmatic paralysis) Prisk GK Pediatric Pulmonology 2002; 34:462–472

Thoracoabdominal Asynchrony  Synchrony NCPAP NIPPV 25 weeks: Abdominal (red) & Chest Wall (green) Movements Synchronized NIPPV: Better ventilation Courtesy of Simon Bignall

SNIPPV 1) To avoid the need for endotracheal intubation in preterm infants with respiratory failure Barrington KJ Pediatrics 2001; 107: 638–41 (RCT) De Paoli AG Acta Paediatrica 2003; 92: 70–5 (review and meta-analysis) Khalaf MN Pediatrics 2001; 108: 13–7 (RCT) Santin R Perinatol 2004; 24: 487–93 (prospective observational study) Friedlich P Perinat 1999; 19: 413 (RCT) 2) It has been shown to be particularly effective in decreasing reintubation when compared with nasal CPAP as an extubation mode Barrington KJ Pediatrics 2001; 107: 638–41 (RCT) Khalaf MN Pediatrics 2001; 108: 13–7 (RCT) Friedlich P Perinat 1999; 19: 413 (RCT) 3) SNIPPV has been used as an alternative to continued endotracheal mechanical ventilation after surfactant therapy in 28- to 34-week gestation infants with respiratory distress syndrome Santin R Perinatol 2004; 24: 487–93 (prospective observational study) 4) Work of breathing has also been shown to be decreased with the use of SNIPPV compared to nasal CPAP Kiciman NM Pediatr Pulmonol 1998; 25: 175–81

Reintubation after extubation: A prospective RCT comparing SNIPPV vs NCPAP (Khalaf MN, et al. Pediatrics 2001;108:13-17) Criteria for extubation: 1. MAP = 4-6 cm H2O 2. IMV  25/minute 3. PIP  16 cm H2O 4. PEEP  5 cm H2O 5. FiO2  0.35 6. Aminophylline level  8 mg/L 7. Hematocrit  40% After extubation: 1. SNIPPV: PIP +4, same IMV-PEEP 2. NCPAP: 4- 6 3. FiO2: O2 saturations 90-96% Criteria for re-intubation: 1. pH < 7.25 2. PaCO2 > 60 mmHg 3. PaO2 < 50 mmHg despite a FiO2 of 0.7 4. A single episode of apnea requiring bag and mask resuscitation 5. Frequent ( 3/hr) apnea/bradycardia spells 6. Multiple ( 3/hr) desaturation episodes despite a FiO2 of 1.0

Reintubation after extubation: (Khalaf MN, et al. Pediatrics 2001;108:13-17) SNIPPV (n =34) NCPAP (n =30) p value Age at study (d) 4 (1 - 83) 2.5 (1 106) 0.95 Wt. at study (gm) 1110 55 1200 75 0.32 Pre MAP (cm H 2 O) 4.9 0.2 5.1 0.38 FiO 0.30 0.02 0.01 0.84 AR (cm/H O/L/s) 169 16 205 21 0.18 LC (ml/cmH 0.74 0.8 0.1 0.57 Post pH 7.36 + 0.03 7.34 0.14 CO (mmHg) 37 1.0 40 2.0 0.06 Apnea (n) 2.24 2.03 0.7 Success (n, %) 32 (94) 18 (60) <

A Prospective Observational Pilot Study: SNIPPV as a Primary Mode of Ventilation In Infants > or = 28 Weeks with RDS (Santin RS, et al. J Perinatol 2004;24:487-93) SNIPPV (n=24) CV (n=35) P value Birth weight (grams) * 1582 ± 77 1511 ± 103 0.92 Gestational age (weeks) * 31.2 ± 0.5 31.0 ± 0.4 0.89 Gender (male, n, %) 15 (63) 22(62) 0.88 Antenatal steroids (n, %) 18 (75) 24 (68) 0.90 Apgar at 5 minutes (median) 8 0.87 Age at surfactant instillation (h)* 3.1 ± 1.4 2.7 ± 0.49 0.49 Mean ± SEM

A Prospective Observational Pilot Study: SNIPPV as a Primary Mode of Ventilation In Infants > or = 28 Weeks with RDS (Santin RS, et al. J Perinatol 2004;24:487-93) SNIPPV (n=24) CV (n=35) p value OI pre-surfactant instillation (cm H2O) 6.0 ± 1.0 5.5 ± 0.6 0.67 Duration of endotracheal intubation (days) 0.3 ± 0.0 2.40 ± 0.4 0.001 Duration of SNIPPV (days) 2.8 ± 0.4 3.1 ± 0.7 0.68 Duration of CPAP (days) 0.3 ± 0.3 0.2 ± 0.1 0.71 Duration of nasal cannula (days) 3.8 ± 1.5 5.1 ± 1.3 0.3 Duration of supplemental O2 (days) 8.2 ± 3.3 15.0 ± 3.2 0.04 Duration of parenteral nutrition (days) 8.4 ± 0.8 12.1 ± 1.6 0.02 Length of stay (days) 29.1 ± 3.3 37.5 ± 3.0 OI: Oxygenation Index Mean ± SEM

NIMV versus NCPAP for Respiratory Distress Syndrome: A Randomized, Controlled, Prospective Study Kugelmann A J Pediatr 2007;150:521-6

Infants treated initially with NIPPV needed less ETT ventilation than infants treated with NCPAP. Infants treated with NIPPV had a decreased incidence of BPD compared with those treated with NCPAP Kugelmann A J Pediatr 2007;150:521-6

SURF-N-SAVE STUDY: HYPOTHESIS A RANDOMIZED CONTROLLED TRIAL OF SYNCHRONIZED NASAL INTERMITTENT POSITIVE PRESSURE (SNIPPV) VENTILATION IN RDS (Bhandari V, et al. J Perinatol 2007;27:697-703) SURF-N-SAVE STUDY: HYPOTHESIS Primary mode SNIPPV (defined as its use in the acute phase of RDS, following the administration of the first dose of surfactant) initiated shortly after birth would decrease the incidence of BPD and/or death in smaller premature babies when compared to conventional endotracheal mode of ventilation.

<32 weeks gestational age. 2. Birth weight 600-1250 grams 3. A RANDOMIZED CONTROLLED TRIAL OF SYNCHRONIZED NASAL INTERMITTENT POSITIVE PRESSURE (SNIPPV) VENTILATION IN RDS (Bhandari V, et al. J Perinatol 2007;27:697-703) INCLUSION CRITERIA 1. <32 weeks gestational age. 2. Birth weight 600-1250 grams 3. RDS requiring intubation and surfactant therapy within one hour of birth. The need for intubation /surfactant was based on the following: a. Fi02 > 0.4 to maintain Sa02 > 90%. b. Chest radiograph consistent with RDS EXCLUSION CRITERIA (any one) Nasopharyngeal pathology. Choanal atresia. Cleft lip or palate. Major congenital anomalies, especially thoracic or cardiac defects. Clinical parameters for exclusion ninety minutes after initial surfactant therapy (approximately 2½ hours after birth). Oxygenation index (OI=[(Fi02)(mean airway pressure)]/Pa02) > 9. No indwelling arterial line. More than two isotonic fluid boluses. Continuous medication infusion for blood pressure support. Fi02 > 0.8.

A RANDOMIZED CONTROLLED TRIAL OF SYNCHRONIZED NASAL INTERMITTENT POSITIVE PRESSURE (SNIPPV) VENTILATION IN RDS (Bhandari V, et al. J Perinatol 2007;27:697-703) Primary Outcome: CV SNIPPV P (n=21) (n=20) value Birth weight (grams)* 858 ± 27 915 ± 41 0.24 Gestational age (weeks)* 27.0 ± 0.4 26.9 ± 0.3 0.93 BPD or Deaths (n, %) 11 (52) 4 (20) 0.03 BPD (n, %) 7 (33) 2 (10) 0.04 Deaths (n, %) 4 (19) 2 (10) 0.66 Air leaks (n, %) 1 (5) 1 (5) 1.0 PDA (n, %) 3 (14) 4 (20) 0.70 IVH (n, %) 6 (29) 6 (30) 1.0 PVL (n, %) 1 (5) 2 ( 10) 0.61 Longterm Outcome: Mental or Psychomotor Developmental Intex There were no statistically significant differences in the MDI (mean  SD; CV (n=8) versus SNIPPV (n=7); 88.13  10.32 versus 81.43  17.54) or PDI (88.38 11.87 versus 84.29  19.47) scores in the infants, assessed at a median (25th –75th centile) corrected GA of 22 (20.5-24) months.

CPAP  intubation + ventilation COIN-trial 610 infants, 25-to-28-weeks’ gestation, randomized to CPAP  intubation + ventilation at 5 minutes after birth In the year 2008: BPD incidence = 35% < 29 wks COIN-trial, NEJM 2008

Strategizing SNIPPV - As extubation mode - To control apnea, avoiding extubation - Primary mode (with or without surfactant use): more data needed

Synchronization Principles PSV

SNIPPV: Trigger systems for synchronization Graseby Capsule Infant Flow Advanced Viasys “ SIPAP” Flow sensor Ginevri “ Giulia” SLE 5000 Babylog 8000 NAVA-system sensing of diaphragmatic electrical activity Maquet “Servo-I”

? How to set Ti in a spontaneous breathing patient on a pressure support mode ? Peak Flow 25% “Flow termination criteria” 0 flow 0 flow Flow PIP Tinsp. Ti Te PS above PEEP Pressure PEEP Pressure Control Pressure Support

Termination Sensitivity = Cycle-off Criteria Flow Peak Flow (100%) TS 30% Leak TS 5% Time Tinsp. (eff.) Set maximal Tinsp.

Neural breathing pattern in the preterm (room air, no vent) Sleeping, 30 weeks, 1158 g 1 2 3 Sleeping, 30 weeks, 1158 g Sleeping, 30 weeks, 1205 g Sleeping, 30 weeks, 1205 g Feeding, baby moving 28 weeks, 1486g Baby awake, 28 weeks, 1486g 200 a.u. Beck et al, PAS 2006 10 seconds

Non-invasive neurally adjusted ventilatory assist (NAVA) in rabbits with acute lung injury Beck J et al. Intensive Care Med (2008) 34:316–323

Non-invasive neurally adjusted ventilatory assist (NAVA) in rabbits with acute lung injury Beck J et al. Intensive Care Med 2008; 34:316–323

baby 440 grams

1st experience baby 440 grams

baby 440 grams

baby 440 grams

J.Beck ICM 2008 “NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface”

Conclusions Meta-Analysis: “NIPPV is a useful method of augmenting the beneficial effects of NCPAP in preterm infants…..reassuring absence of the gastrointestinal side-effects that were reported in previous case series.” (Cochrane Collaboration) Issues to be solved Patient selection Indications Synchronization during NIPPV