Kugelman A, Riskin A, Said W, Shoris I, Mor F, Bader D.

Transcription

1 Heated, Humidified High-Flow Nasal Cannula (HHHFNC) vs. Nasal Intermittent Positive Pressure Ventilation (NIPPV) for the Primary Treatment of RDS, A Randomized, Controlled, Prospective, Pilot Study Kugelman A, Riskin A, Said W, Shoris I, Mor F, Bader D. Pediatric Pulmonary Unit and Department of Neonatology, Bnai Zion Medical Center The B&R Rappaport Faculty of Medicine, Haifa, Israel Pediatric Pulmonoloy. March 2014

2 Conflict of Interest Disclosure Vapotherm Inc. supplied the equipment for HHHFNC for our study.

3 Introduction Because mechanical ventilation is associated with morbidity, mainly BPD, the trend today is to minimize the use of mechanical ventilation.

4 Introduction - Nasal Respiratory Support Nasal respiratory support (NRS) Nasal continuous positive airway pressure (NCPAP) * Nasal intermittent positive pressure ventilation (NIPPV) ** NRS was shown to be effective in treating infants in the acute phase of RDS Enables the avoidance of mechanical ventilation in a relatively large number of infants * Ho et al, Cochrane 2000; Morley et al, N Engl J Med 2008; Finer NN et al, N Engl J Med 2010.** Kugelman et al, J Pediatr 2007

5 Introduction - Nasal Respiratory Support While NCPAP is currently the common practice for the initial treatment of RDS, NIPPV is probably more beneficial. * * Total cohort Infants <1500 g Endotracheal Ventilation * Total cohort NCPAP NIPPV Infants <1500 g BPD * * p<0.05 NIPPV is our NICU drug of choice. * Kugelman et al, J Pediatr 2007

6 Introduction - Heated, Humidified High-Flow Nasal Cannula (HHHFNC) HHHFNC is frequently used to deliver oxygen and as a mode of NRS. Few RCT have recently reported that HHHFNC was as good as NCPAP for the early stages of RDS (Yoder et al, Pediatrics 2013) For later treatment post extubation, after endotracheal ventilation and surfactant administration for RDS (Yoder et al, Pediatrics, 2013; Collins et al, J Peds 2012; Manley et al, NEJM 2013) For apnea of prematurity (Sreenan et al, Pediatrics 2001).

7 Introduction - HHHFNC By definition HHHFNC delivers flow rates that exceed patient inspiratory flow rates at various minute volumes. High flows Result in washout of anatomical and physiological dead space Contribute to improved fractions of alveolar gases with respect to carbon dioxide and oxygen. * HHHFNC creates inadvertent PEEP that may contribute to its beneficial effect.**, *** * Dewan et al, Chest 1994, ** Kubicka et al, Pediatrics 2008; *** Sreenan et al, Pediatrics 2001

8 Non Invasive Ventilatory Approach to Treat RDS Delivery Room or NICU Endotracheal Intubation Caffeine INSURE Approach Surfactant Steroids- Selective use Nutrition Vitamin A? MIST Immediate Extubation Extubation at RDS Resolution Nasal Respiratory Support HHHFNC NCPAP Nasal Ventilation (NIPPV/SNIPPV) 1Permissive Hypercapnia 2Adequate Oxygenation Spontaneous Unsupported Breathing (Kugelman A. Ped Pulmonol 2011)

9 Introduction - HHHFNC No randomized prospective study was published yet that Evaluated HHHFNC in the primary treatment of RDS. Compared HHHFNC with NIPPV for the primary treatment of RDS.

10 Hypothesis We hypothesized that: While the ELBW infants (<1000 g) may need NIPPV as NRS for the treatment of RDS, Larger infants may enjoy the comfort benefits associated with HHHFNC while getting comparable respiratory support to NIPPV.

11 Objective To determine the need for endotracheal ventilation in preterm infants treated with early HHHFNC compared with NIPPV for the primary treatment of RDS.

12 Methods: Procedure This was a prospective, randomized, controlled, single center, clinical, pilot study. The study was approved by the IRB in our center. All the parents signed an informed consent. We performed an intention-to-treat analysis, with a sample size calculation of 37 infants in each arm of the study.

13 Methods: Procedure Early NRS (HHHFNC or NIPPV) was initiated in any spontaneously breathing premature infant showing signs of respiratory distress (tachypnea, grunting, nasal flaring, retractions). * If NRS was indicated, the mode was decided randomly between HHHFNC and NIPPV. Cross over between groups was not encouraged but was allowed. * Gittermann et al, Eur J Pediatr 1997

14 Subjects Infants that were born in Bnai Zion Medical Center, Haifa, Israel, during the study period and met the inclusion criteria participated in the study.

15 Inclusion Criteria 1. Gestational age <35 weeks and weight >1000 g. 2. Infants with RDS who needed NRS as initial therapy. 3. Written informed consent.

16 Exclusion Criteria 1. Significant morbidity apart from RDS including: - Cardiac disease (not including PDA) - Congenital malformation - Cardiovascular or respiratory instability because of sepsis, anemia or severe IVH

17 Respiratory Management Endotracheal intubation was performed in the delivery room if: Heart rate did not increase to >100 beats per minute The infant had insufficient spontaneous respiratory effort Marked and increasing dyspnea * Exogenous surfactant ( mg/kg, 1 to 2 doses as needed, Curosurf, Chiesi Farmaceutici, Parma, Italy) was given only as rescue therapy. *Lindner et al, Pediatrics 1999

18 HHHFNC Respiratory Management HHHFNC was delivered by the Vapotherm device (Precision Flow, Vapotherm Inc., Stevensville, MD), using flows between l/m. Flows were started on 1 l/m and increased at intervals of 1 l/m according to: - Clinical condition - Respiratory [retractions, respiratory rate, grunting] - Hemodynamic [blood pressure and heart rate]) - Ventilation (PaCO 2 ) - Oxygenation

19 HHHFNC Respiratory Management FiO 2 was set to keep SpO 2 between 88-92%. The HHHFNC was given via the Vapotherm nasal prongs (outer diameter: 0.2 cm-0.3 cm). Leak was created/allowed by using the nasal prongs no larger than 1/2 the diameter of the nares and no chin rap was allowed.

20 NIPPV Respiratory Management NIPPV was delivered by the SLE 2000 or 5000 (Specialized Laboratory Equipment Ltd., South Croydon, UK) via nasal prongs (INCA, Ackrad Labs, Berlin, Germany). NIPPV was set at a synchronized mode Rate of breaths per minute (according to PaCO 2 ) Inspiratory time of 0.3 seconds PEEP of 6 cmh 2 O PIP of cmh 2 O according to chest excursion and the infant's weight FiO 2 was set to keep SpO 2 between 88-92%.

21 Primary Outcome Measure The percent of infants who failed NRS and needed endotracheal ventilation or were switched to another mode of NRS.

22 Criteria for Failure of Nasal Support * Clinical deterioration [increased respiratory distress] accompanied by at least one of the following or worsening of the following: 1. ph<7.20 and PCO 2 >60 mmhg 2. PaO 2 <50 mmhg or SpO 2 <88% on FiO 2 >50% 3. Recurrent significant apnea requiring repeated stimulation or bag-and-mask ventilation despite the use caffeine or adequate nasal support Switch was allowed in failure of NRS mode or in cases of nasal septal damage. * Kugelman et al, J Pediatr 2007

23 Results

24 Infant Enrollment Delivered infants < 35 weeks 317 Exclusion criteria (<1000 g =22, cardiac anomaly=1, CDH=1) 24 Eligible infants 293 Included in study 76 Did not participate 217 Refusal 2 Technical 3 NIPPV 38 HHHFNC 38 Ventilated in delivery room 15 No respiratory support 197 Ventilated Not Ventilated Ventilated Not Ventilated

25 Demographic Characteristics NIPPV (38) HHHFNC (38) p value Gestational age (weeks) 32.7 ( ) 32.5 ( )* NS** Birth weight (g) NS Infants<1500 g 12 (31%) 13 (34%) NS Male/Female 24/14 26/12 NS Prenatal steroids 19 (50%) 19 (50%) NS Caffeine 14 (36.8%) 15 (39.5%) NS Cardio-Respiratory Status at Study Entry NIPPV (38) NHHHFNC (38) p value FiO ( ) 0.25 ( ) NS SpO 2 (%) 90 (46-100) 92 (70-100) NS PCO 2 (mm Hg) NS ph NS Grunting or retractions (%) 35 (92) 36 (94) NS RR (breaths/min) NS HR (beats/min) NS MBP # (mmhg) NS Start nasal support (hours) NS * Mean+SD or median (range), ** Not significant, # mean blood pressure (No difference between groups for infants <1500 g, 12 on NIPPV, 13 on HHHFNC)

26 Main Findings: Endotracheal Intubation and BPD % * NS Total cohort * 38 Infants <1500 g Endotracheal Ventilation NS 50 NS Total cohort BPD HHHFNC NIPPV NS 16.7 Infants <1500 g * One infant (< 1500 g) met intubation criteria on HHHFNC, was switched to NIPPV and did not need ETT.

27 Clinical Outcomes NIPPV (n=38) HHHFNC (n=38) p value Pneumothorax 0 2 (5.2%) NS Trauma NS # 0 0 NS Mean comfort score 1.36±0.41 (1.25) 1.33±0.50 (1.00) NS MV # Duration (d) * NS NRS # Duration (d) BPD 2 (5.2%) 1 (2.6%) NS IVH 1 (2.6%) 2 (5.3%) NS PDA 4 (10.5%) 9 (23.7%) NS NEC 0 2 (5.3%) NS Sepsis 3 (7.8%) 4 (10.5) NS Time to FF # (d) 11.0 (5-49) 13.0 (96-28) NS (p=0.07) Length of stay (d) 39.5 (9-113) 35.0 (8-91) NS Death 0 0 NS (No difference between groups for infants <1500 g) # NS - nasal septum, MV - mechanical ventilation, NRS nasal respiratory support, IVH - intraventricular hemorrhage, BPD - bronchopulmonary dysplasia, FF - full feeds, * mean+sd or median (range),

28 DISCUSSION

29 Physiology and Practice HHHFNC and NIPPV act physiologically different and need to be set accordingly in a different manner. When using NIPPV we occlude the nares and possibly the mouth to avoid leak and to create a monitored PEEP. In contrast, while on HHHFNC we create purposely a leak, as we can not measure a possible inadvertent PEEP, to avoid air leak.

30 HHHFNC Strategy Because No previous clinical prospective trials were published for the initial treatment of RDS, Concerns for air leak, We chose a safe and a relatively conservative approach in using the HHHFNC. The two strategies for use of HHHFNC, Starting with high flows and then weaning Using a "step-up" approach Were not compared in any study.

31 Study Limitations 1) The mode of support assignment could not be blinded to the medical team. Use of objective failure criteria and management protocols reduce the possibility of a bias that this might have caused. 2) We included for safety issues only infants weighing >1000 g and we had only a small sample size for infants <1500 g. Thus, our results in the VLBW infants should be taken with caution. These infants should be the target population for future studies.

32 Conclusions HHHFNC was found to be as effective as NIPPV in preventing endotracheal ventilation in the initial treatment of RDS in premature infants (<35 weeks GA, with BW >1000 g). The rates of neonatal morbidities were comparable in both modes of NRS.. HHHFNC seems to be safe.

33 Summary Our pilot study provides the basis for further, larger trials of this intervention before it can be concluded that HHHFNC is safe and can serve as primary mode of NRS in premature infants with RDS. Thank you!!!

34 NRS NIPPV (n=38) HHHFNC (n=38) p value Initial flow HHHFNC (l/min) - Maximal flow HHFNC (l/min) - % infants on max. flow - 14/38 (37%) - Time to stop NRS 2.0 ( ) 4.0 ( ) P=0.006 Time to stop O2 3.0 ( ) 5.0 (0-69.0) NS Failed NS 13 (34.2%) 12 (31.6%) NS Intubation 13 (34.2%) 11 (28.9%) NS Duration of MV 4.0 ( ) 3.0 ( ) NS Surfactant 13 (34.2%) 11 (28.9%) NS (No difference between groups for infants <1500 g) # NS - nasal septum, MV - mechanical ventilation, NRS nasal respiratory support, * mean+sd or median (range).

35 Secondary Outcome Measure 1. Clinical features during treatment (hourly): blood pressure, heart rate, respiratory rate, SpO 2, and respiratory status prior to mechanical ventilation if needed according to arterial blood gas (PaO 2, PCO 2, ph), and time to stop nasal support (only oxygen or low nasal cannula flow <1 L/min, and allowed when infants on nasal support were on FiO 2 <30%, had normal blood gases, and no respiratory distress or apnea). 2. Incidence of IVH, duration of mechanical ventilation, incidence of BPD (oxygen at 36 weeks post conceptional age to keep SpO 2 >92%), time until full feeds, and length of stay. 3. Safety: nasal trauma due to NRS, rate of air leak (pneumothorax), gastrointestinal perforation, irritability and discomfort assessed by a validated score given by the nurses at the first 4 hours on NRS. * * Kugelman et al, Acta Pediatr 2008

36 Introduction - HHHFNC HHHFNC may decrease the work of breathing. New devices enable high flows Humidified and warmed air (HHHFNC) Were shown to perform better than a standard HFNC immediately following extubation In maintaining a normal appearing nasal mucosa A lower respiratory effort score Averting reintubation. * HHHFNC probably creates inadvertent PEEP that may contribute to its beneficial effect.**, *** * Woodhead et al, J Perinatol 2006, ** Kubicka et al, Pediatrics 2008; *** Sreenan et al, Pediatrics 2001