Non Invasive Ventilation Dr Julian Eason Chair Neonatology Corniche Hospital Abu Dhabi

Corniche Hospital 64 bed NICU, 1000 admission/year High Risk obstetric and Fetal medicine referral centre in UAE

Non-invasive support

History of Preterm infants and RDS 1970’s – nCPAP 1972 – Antenatal Steroids 1980’s – Exogenous Surfactant 1990’s – SIMV and HFOV 2000’s – nCPAP, NIPPV, INSURE 2007 – mINSURE 2007 - HHFNC

Learning Points 1. Recognise that the basic element of all noninvasive strategies is to develop Positive End Expiratory Pressure. 2. Be aware that there are uncertainties in the relative benefits of different types of noninvasive ventilation. 3. Acknowledge that noninvasive strategies to avoid intubation and mechanical ventilation do not prevent the development of bronchopulmonary dysplasia in most infants.

Is CLD in LBW infants preventable? Avery et al, Pediatrics 1987 Survey of 8 level 3 NICU in USA Birth weight 700g to 1500g Columbia New York Used Hudson nCPAP ~ 5 cm H2O soon after birth, half in the Delivery Unit PaCO2 up to 60 mmHg before intubation. The Dr Cheng factor

What’s wrong with Ventilation? Barotrauma / Volutrauma / Rheotrauma / Atelectotrauma Increases resistance to breathing. Injures airways, Increases infection. Risk of hypocarbia. Low PaCO2 ?→ PVL Many doctors don’t really know how to use ventilators when to start which mode how to wean when to stop. Options confusing

PEEP is very effective Helps clear lung fluid at birth Helps establish and maintain lung aeration Improves oxygenation Conserves surfactant Decreases upper & lower airway resistance Improves the compliance of stiff lungs Regularises and slows respiratory rate Reduces apnoea Reduces lung injury and inflammation Reduces energy expenditure Reduces the need for ventilation

Why NIV?

Types of CPAP nCPAP, nSiPAP and nBiPAP Assisted CPAP (NIPPV-SNIPPV) Humidified High Flow Nasal Cannula (HHFNC) HFOV (Oscillation)(via nasal prong)

Comparisons nCPAP v NIPPV - BPD same ?Apnoeas Lemyre B. Cochrane Review 2001 SiPAP v nCPAP - No Difference Ricotti et al, J Matern Fetal Neonatal Med. 2013 HHFNC v nCPAP - Similar Bradley A. Yoder, Pediatrics 2013 Neotech RAM Cannula Versus Conventional Binasal Prong Continuous Positive Airway Pressure (CPAP) to Treat Respiratory Distress in Low Birth Weight Neonates – recruiting 2014 Minnesota

Apnoea’s Lin randomised 34 infants and showed decrease in freq of apnoeas (event/hr) with NIPPV v CPAP Lin CH et al. Pediatric Pulmonol 26 1998 p349-353 Cochrane meta-analysis NCPAP v NIMV 54 infants to 4-6 hours Only one infant on CPAP required intubation Lemyre B. Cochrane Review 2007

NIPPV Post extubation Pooled 3 RCT’s showed dec in extubation failure using NIPPV. More infants on NIPPV remained extubated at 48-72 hours All used sync NIPPV Dec CLD favoured NIPPV Davis PG et al. Cochrane Systematic Review 2007

CPAP

Initial Rx of RDS COIN showed 55-60% infants at 25-26 weeks gestation fail initial CPAP NEJM 2008 Feb 14 358(7) 700-8 Bhandari et al. RCT of infants receiving surfactant compared rapid extubation to NIPPV with ongoing ventilation No difference in duration of intubation or oxygen. Reduced CLD 52% to 25% in NIPPV group No differences at 22 months J Perinatol 27 (2007) p521-526

76 neonates 28-34 weeks randomised at 6 hrs NIPPV or CPAP RCT from India 76 neonates 28-34 weeks randomised at 6 hrs NIPPV or CPAP Failure rate at 48 hours and 7 days less with NIPPV Most benefit in smaller infants not receiving surfactant Kishore M et al. Acta Paediatr 2009 98 p1412-15 Ramanathan 110 infants born before 30 weeks requiring surfactant. NIPPV suggested dec CLD compared to CPAP Ramanathan R et al. J Perinatol 2012 May (5) p336-43

CPAP Failure assingned to: Noninvasive positive pressure ventilation or conventional mechanical ventilation for neonatal continuous positive airway pressure failure. Int J Prev Med. 2014 Aug;5(8):1045-53. 55 Newborns 26-35 weeks CPAP Failure assingned to: NIPPV 40-60 bpm at 20cm IPPV 40-60 bpm PIP 12-20cm 74% CPAP failures improved on NIPPV and not ventilated More failure in low 5 min apgar and inc surfactant use Less LOS and oxygen in NIPPV but not significant

CPAP: Generators

Delivery

High Flow Nasal Cannula (HFNC) Heated humidified high flow nasal cannula (HHHFNC) HHFNC can donate more than 1 l/min flow Used as initial mode of respiratory support or after extubation More comfortable and easy to maintained than CPAP, avoid intubation, easy to clear secretion, less trauma and more liked by nursing staff Garg S, J Clin Neonatol. 2013

Optiflow Nasal Cannula

More people are now using HHFNC but………… “The main drawback of using HHFNC is that the pressure generated is not measurable and cannot be regulated.” Really? Do you think you regulate CPAP?

Use of HHFNC in NICUs J Neonatal-Perinatal Med 2010 A survey of 97 training directors in USA 60% responded. Of these 69% used heated humidified HHFNC. Used flows from 1 to 6 L/min Indications for use varied: to give CPAP, after extubation, nasal injury, weaning CPAP, for apnoea Weaned by reducing the flow No adverse effects reported

Use of HHFNC in Australasian NICUs J Paediatrics and Child Health 2011 Survey to all 167 neonatologists 67% completed questionnaire HHFNC used in 93% of NICU Uses: reduce nasal trauma 91%, CPAP 62% Perceived benefit: easier care of infant and better tolerance by infant. Problem: Rainout in prongs

HHFNC increasingly used because of Simplicity Ease of use – nurses and mothers like it Much easier to move and handle baby Effective Minimal nasal trauma More convenient and effective than head box, Much better than gas bubbled through cold water

Research in high flow therapy: Mechanisms of action Dysart Research in high flow therapy: Mechanisms of action Dysart Respiratory Medicine 2009 Washout of nasopharyngeal dead space lowers CO2 Reduces inspiratory and expiratory resistance in nasopharynx, areducing work of breathing. Improves pulmonary compliance and conductance compared to dry, cool gas. Warm, humidified gas through nasopharynx reduces metabolic work associated with gas conditioning. High flow through nasopharynx increases pressure. This all happens with nCPAP!

The high flow of gas flushes out nasopharyngeal dead space Reduces CO2 Reduces work of breathing

Mouth closed CPAP pressure Mouth open 2 pharyngeal pressures 5 10 Mouth closed Mouth open 2 pharyngeal pressures CPAP pressure De Paoli Arch Dis Child F & N 2005; 90(1):F79-F81.

Pharyngeal pressure compared with set CPAP pressure with mouth open and closed Mouth closed Pharyngeal pressure (cmH2O) Mouth open 3 4 5 6 7 8 Set CPAP pressure (cm H2O) De Paoli Arch Dis Child F & N 2005; 90(1):F79-F81.

So n CPAP has……… Low and variable pharyngeal pressure A high gas flow through nasopharynx nCPAP and HHFNC are very similar HHFNC is easier and has less nasal trauma

Overall outcomes from four RCTs of nCPAP vs HHFNC Nasal trauma significantly reduced (except Chinese trial) Similar extubation failure rates for CPAP and HHFNC. No significant differences in mortality and morbidity.

NIPPV May be more effective than nasal CPAP in treating apnoea without influencing long-term outcomes Ramanathan 2012 A trial of NIPPV can be considered to reduce the risk of extubation failure in babies failing on CPAP

Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation Cochrane Database Syst Rev. 2014 Sep 4;9:CD003212 Lemyre B, Davis PG, De Paolli AG, Kirpalani H. NIPPV reduces the incidence of symptoms of extubation failure and need for reintubation within 48 hours to one week more effectively than NCPAP; however, it has no effect on chronic lung disease or mortality. Synchronisation may be important in delivering effective NIPPV. The device used to deliver NIPPV may also be important; however, there are insufficient data to support strong conclusions. NIPPV does not appear to be associated with increased gastrointestinal side effects.

A RCT of HHFNC vs NIPPV for RDS To compare rate of intubation < 35 weeks, >1000g with RDS HHFNC (n = 38) 1 – 5 L/min NIPPV with SLE ventilator (n = 38) Result: no significant difference in intubation rate and morbidities Conclusion: HHFNC may be as effective as NIPPV in preventing intubation in primary treatment of RDS Kugleman Ped Pulm 2014

When to Ventilate Perinatal depression Hypoxaemia requiring >40%O2 Acute hypoventilation with rising CO2 Frequent apnoeas with intervention Severe distress ?<26 weeks Clinical Judgement

Conclusions There are few differences between nCPAP and HHFNC and nIPPV. HHFNC is easier for nurses, and mothers, and and causes less nasal trauma. NIPPV is perhaps more promising demonstrating better success after extubation Use which suits you, the babies and staff.

Thank you

European Consensus Guidelines for RDS Management (2013 Update) {Endorsed by European Association of Perinatal Medicine) Babies with RDS should be given a natural surfactant Early Rescue Surfactant Rx if there is evidence of RDS or for ELBW infants whose mothers had not received AS or those intubated for stabilization. < 26 wks with FiO2 >0.30 and >26 wks with FiO2 > 0.40 should be considered for early, rescue Surfactant Poractant alfa 200 mg/kg is better than 100 mg/kg Consider INSURE and early extubation to NCPAP/NIPPV Caffeine should be considered for all babies < 1250 g BW, who are on NCPAP/ NIPPV Sweet DG et al. Neonatology 2013; 103:353-368

NIPPV: Settings

Simple HHFNC Guidelines Prongs about 50% of nostril diameter Gas heated to 37oC and 100% humidity Flow 2 to 8 L/min for neonates Mouth not actively closed Blended oxygen to achieve SpO2 Wean by reducing FiO2 then flow rate When flow <2 L/min consider off HHFNC Failure criteria same as for CPAP

Future neonatal nCPAP and HFNC research Investigate flow into nose on nCPAP vs HFNC Calculate nasopharyngeal dead space Investigate whether HFNC and nCPAP alter pCO2 Investigate effect of mouth position on gas flow with nCPAP and HFNC Determine the optimal nasal gas flow?

The use of CPAP is well established The use of CPAP is well established. There is evidence of a reduction in Chronic Lung Disease in some studies. Its practical application can be challenging and problems do occur. It has reduced our use of delivery room surfactant and also the amount of rescue surfactant. Despite the fact that we have studies demonstrating improved survival in infants receiving Surfactant, these were mechanically ventilated infants. We have seen no worse outcomes with the increasing use of CPAP. CPAP however is not the only way to generate PEEP and prevent alveolar atelactasis. The introduction of Humidified High Flow Nasal Cannulae as well as Synchronised Nasal Intermittent Positive Pressure Ventilation has increased our choices and brought out our biases to one treatment or another. Current studies show similar outcomes and certainly no harm can be demonstrated. This talk tries to help with understanding the differing physiological mechanisms allowing us to achieve acceptable stability in our premature population.

The Treatment of Idiopathic Respiratory Distress Syndrome with Continuous Positive Airway Pressure. NEJM June 1971 Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Bradley A. Yoder, Pediatrics 2013 Use of HHFNC in Australasian NICUs J Paediatrics and Child Health 2011 Does HHFNC create Pharyngeal Pressure? Wilkinson J Perinatology 2008 A RCT of HHFNC vs NIPPV for RDS. Kugelman. Ped Pulm 2014

Optiflow?

RCT HFNC v CPAP in prems - Collins trial Infants <32 wk n=132 with 59 <28 wk. Post extubation, treated with caffeine CPAP 8 cm H2O if FiO2 >0.3 otherwise 7 cm H2O HFNC @ 8 L/min with Vapotherm No escalation or weaning protocol Composite outcome: Bad apnoea, or PaCO2 >66 mg, or FiO2 increased >15%, or intubated – within 7 days of starting

“No significance differences for composite outcome” Primary outcome (Bad apnoea, or PaCO2 >66 mg, or FiO2 >15%, or intubated in first 7 days) HFNC nCPAP n 67 65 “Failure” 1st week 22% 34% Intubated 1st week 10% 12% “No significance differences for composite outcome” Collins J Peds 2012

Secondary outcomes HFNC nCPAP n 67 65 Reintubated any time 21% 25% Nasal trauma score 3 (7) 12 (11) BPD 36 wk 36% 43% Severe IVH 3% 6% Days to full feeds 12.9 (0.7) 12.3 (0.7) Died 1.5% 4% Conclusion: No significant difference all outcomes between HFNC or NCPAP after extubation except HFNC significantly less nasal trauma. Collins J Peds 2012

423 infants 28 to 42 weeks CPAP as either 1ry therapy or post-extubation Excluded <1000g, <28 wks, air leak, abnormalities Randomised to: CPAP either bubble, ventilator, or SiPAP HFNC either Vapotherm, F & P or Comfort Flo. 1ry outcome - intubation <72 h from start of treatment

Outcomes CPAP n = 216 HFNC n = 211 p Early failure 8.2% 10.8% NS Days any PPS 4 (2-8) 6 (3-11) <0.001 Days ventilated 2 (1-4) 2 (1-5) Days O2 8 (5-24) 10 (5 – 27) BPD in infants <33 w 16% 20% Air leak 2% 1% Nasal trauma 9% <0.05 Death Conclusion: For this population of infants > 28 wk, HFNC had similar efficacy and safety to nCPAP and less nasal trauma.

Infants <32 w post-extubation randomised to: HFNC  at 5-6 L/min or NCPAP at 7 cm H2O. 1ry outcome = failure within 7 days.   Those who failed HFNC could have CPAP 7 cmH2O. Infants where CPAP failed were re-intubated.  300 infants required to show non-inferiority of HFNC with 90% power

Outcomes HFNC CPAP P value 1ry Outcome 34% 25% NS Death 3% 4% BPD – O2 36 w 39% 42% Pneumothorax 1% Reintubated 18% Days resp support (median) 34 38 Days oxygen (median) 49 Nasal trauma 19% 53% <0.001 IVH, PDA, home oxygen, NEC no signif differences