What s new in neonatal resuscitation?

Transcription

1 What s new in neonatal resuscitation? Anup Katheria, M.D. Director, Neonatal Research Institute Sharp Mary Birch Hospital for Women & Newborns

2 Disclosures I have no financial Disclosures.

3 Overview Delivery room monitoring Adjunctive therapies during resuscitation

4 Delivery room Monitoring Current assessment of clinical status unreliable (ie. variability in Apgar scores). Additional tools may be able to alert providers to make changes during resuscitation.

5 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

6 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

7 EKG in the Delivery Room 7 th edition of the NRP guidelines recommends the use of a cardiac monitor in infants that need resuscitation.

8 Evidence for EKG EKG in newborns provides an earlier heart rate than pulse oximetry (Iglesias B et al, An Pediatr 2016, Petrozzino et al, J Investig 2008, Katheria et al, Pediatrics 2012) Pulse oximetry measures a lower heart rate compared with EKG (Von Voderen et al, J Pediatr 2015, Kamlin et al, J Pediatr 2008)

9 Correlation between heart rate (HR) as measured by pulse oximetry (PO) (x-axis) or ECG (y-axis) during resuscitation in the delivery room in very preterm infants. Beatriz Iglesias et al. Arch Dis Child Fetal Neonatal Ed 2017

10 How Does it Effect Resuscitation? It is unclear what the effect of an earlier more reliable heart rate in the first few minutes has on the resuscitation of premature newborns.

11 Data Acquisition System Camera EKG Blender Oximete r Biopac MP150 Data Acq. System TOTS Laptop Airway Pressure

12 EKG Study Randomized 40 premature infants (<32 weeks) to having the EKG blinded and unblinded to the neonatal team. Changes in heart rate, oxygen saturations, FiO2, and mean airway pressure were recorded.

13 Results EKG Non-Displayed (n=20) EKG Displayed (n=20) P-value Time to Visible Heart Rate Time to Heart Rate by EKG Time to Heart Rate by Pulse Oximeter Time to Saturation by Pulse Oximeter 114 +/- 39 (Pulse Oximeter) 66 +/- 20 (EKG) < / / / / / /

14 EKG Non-Displayed (n=20) EKG Displayed (n=20) P-value Time to Place CPAP 30 +/- 40 (n =20) 38 +/- 6 (n=19) 0.69 PPV started 106 +/- 144 (n=17) 77 +/- 116 (n=16) 0.55 Number of Infants Intubated (%) 6 (30) 6 (30) 0.99 Time to Intubation 350 +/ / FiO 2 Increase n, (%) 18 (90) 18 (90) 0.99 Time FiO 2 Changed 148 +/ / Pressure Increased n (%) 5 (20) 8 (45) 0.54 Time Pressure Changed 66 +/ /

15 Data When PO and EKG Working

16 Conclusions EKG provides an earlier, and more accurate heart rate No difference in interventions with blinded or unblinded EKG Earlier EKG placement before pulse oximeter placement may effect other interventions, but needs further study

17 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

18 CO2 monitoring During facemask ventilation helps determine airway patency and leak during positive pressure ventilation. (Finer 2010, Schmoelzer, 2015) Can be qualitative or quantitative.

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20 Studies to date No difference in the occurrence of hypocapnia or hypercapnia on admission blood gas. Kong et al J peds 2013, Murthy et al Early Hum Dev 2012 No difference between quantitive or qualitative CO2 monitor at birth on admission blood gas. Hawkes et al J peds 2016

21 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

22 Respiratory Function Monitoring Most commonly seen in NICU on ventilators. Displays breathing pattern, tidal volumes, flow and pressure waves, and percentages of gas leak. Guide positive pressure ventilation in newborn resuscitation

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24 Studies to date During mask ventilation of preterm infants results in significantly less leak, more mask adjustments and a lower rate of excessive tidal volume given. Schmolzer et al J Peds 2012 Improves ventilation with masks compared with nasal tubes during stabilization of preterm infants. Van Vonderen J Peds 2015 However, the use and interpretation of RFM can be technically challenging for many inexperienced users. Milner et al J Peds 2015

25 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

26 Near InfraRed Spectroscopy (NIRS) NIRS at birth can reduce cerebral hypoxia. RCT by Pichler et al J Peds 2016 Unclear whether low delivery room NIRS can correlate with abnormal outcomes.

27 Fuchs H et al, Brain oxygenation monitoring during neonatal resuscitation of very low birthweight infants, J peri

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29 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

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31 Combined Monitoring in premature newborns during resusctation EEG (3 leads) NIRS (StO 2 )

32 Application of Sensors Previous studies had to use cup electrodes, scrubbing and gel before placement (Pichler, 2013). We used Hydrogel-based adhesive electrodes after wiping the forehead quickly after delivery.

33 Application of leads

34 Overall IVH and death in first 72 hours HR SpO2 StO2 aeeg MAP

35 Severe IVH/death in first 10 minutes

36 Cerebral StO2 in first 10 minutes StO2 > 66 Sens 88, Spec 86, AUC=0.94, p< StO2 (no or low grade) StO2 (Severe IVH) Minutes of life

37 Delivery Monitoring Standard: Pulse oximetry ECG Colorimetric CO 2 detector Research: Quantitative CO 2 NIRS EEG Respiratory Function Monitors Electrical Impedance Tomography (EIT)

38 Electrical Impedance Tomography Uses electrodes around the thorax to measure voltage differences. Using the differences one can measure impedence of the underlying tissue and generate an image.

39 Before and after surfactant therapy Chatziioannidis et al, Hippokratia Jul-Sep; 15(3):

40 Future Directions DG Tingay et al. An Individualized Approach to Sustained Inflation Duration at Birth Improves Outcomes in Newborn Preterm Lambs. Am J Physiol Lung Cell Mol Physiol 309 (10), L1138-L Sep 25. DG Tingay et al. Effectiveness of Individualized Lung Recruitment Strategies at Birth: An Experimental Study in Preterm Lambs. Am J Physiol Lung Cell Mol Physiol 312 (1), L32-L Nov 23.

41 Adjunctive Therapies

42 Caffeine Use at Birth Caffeine is a potential drug of choice for BPD in low birth weight infants. It is one of the most commonly used drugs in the NICU (Clark et al, 2006) It remains a highly cost effective therapy (Dukhovny D et al, 2011).

43 Survey of Providers in USA for the timing of caffeine administration st Hour 2-12 Hours Hours 2-3 Days Apnea/Extubation VON small baby collaborative N=44 units

44 Benefits of Caffeine Therapy CAP Trial: Multicenter RCT vs Placebo Days Mechanical Vent/O 2, BPD +/ Neutral Neurodevelopmental Outcome No reduction in death or NDI at 4 yo Improvement in behavioral motor scores (Doyle et al, J Pediatr 2014) Schmidt B, et al. N Engl J Med 2006, 2007 Schmidt B, et al JAMA 2012

45 Hemodynamic Effects of Caffeine HR, BP, SV, LVO Not studied during early transition Soloveychick V, et al. J Peri 2009

46 Review the Timing Trials Early Caffeine (1-2d) Late Caffeine (>3 d) P-values or (CI) Dobson et al, 2014 (N=62,056) BPD PDA Lodha et al, 2015 (N=5101) Death or BPD ( ) PDA ( ) Gupte et al, 2016 (N=160) BSID-III Composite < Cognitive <70 Language < Motor <

47 Pilot Trial of Early vs Routine Caffeine <29 weeks gestational age infants (N=21) were randomized to intravenous caffeine citrate (20 mg/kg) either before 2 hours of age (early) or at 12 hours of age (routine). No significant difference in the need for intubation (early 27% vs late 70%, p=0.08), or vasopressors (0 vs 20%, p=0.21) by 12 hours of life. Early caffeine was associated with improved blood pressure (p=0.03) and systemic blood flow (superior vena cava flow, p=0.04 and right ventricular output, p=0.03). Katheria Am J Perinatology 2015

48 European Experience In some of the studies evaluating the LISA technique for surfactant application, very early use of caffeine in the delivery room was part of the overall strategy to maintain spontaneous ventilation. Kribs et al, Seminars in Fetal and Neonatal Medicine Jun 2016, Kribs et al, Non intubated Surfactant Application vs Conventional Therapy in Extremely Preterm infants: A Randomized Controlled Trial: JAMA Pediatr 2015)

49 Pilot study (N=30) infants Evaluate the respiratory effects of 10 mg of caffeine administered immediately after birth in delivery room compared to the NICU.

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51 Early (DR) Caffeine?? Improve spontaneous ventilation and reduce need for invasive support Has hemodynamic benefits Needs a larger trial powered to look at such effects

52 Inhaled Nitric Oxide (ino) as an adjunct gas to Neonatal Resuscitation in Premature Infants: A Pilot double blind randomized controlled safety trial. Slides courtesy of Sekhar et al Presented at PAS San Francisco May 9, 2017

53 Background: ino In situations where neonatal transition is impaired addition of a pulmonary vasodilator such as inhaled NO may improve the VQ mismatch, reduce the pulmonary vascular resistance, increase the blood flow and reduce the need for excess oxygen. ino has been shown to decrease PVR in premature animal models during hypoxemia. ino has never been attempted in human neonatal resuscitation.

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55 Secondary outcomes Variable ino Placebo P Value IVH Gr 2 0/12 (0%) 3/13 (23%) 0.22 ROP > Stage 2 1/10 (10%) 3/11 (27%) 0.59 PDA requiring treatment 0/11 (0%) 6/12 (50%) Mechanical Ventilation (days) 3 (0, 7)* 3 (0, 15.5)* 0.98 NIV# (days) 20 (6, 25)* 19 (6, 26.5)* 0.9 BPD (oxygen at 36 weeks) 3/11 (27%) 3/12 (25%) 1.0 Late onset sepsis 0/11 (0%) 1/12 (8%) 1.0 Length of stay (days) 76 (43, 113)* 67 (48.5, 88)* 0.58 Mortality 2/13 (15%) 1/13 (8%) 1.0 *Median (interquartile range) #NIV= non- invasive ventilation (HFNC >2lpm, CPAP, NIPPV)

56 Early (DR) Nitric Oxide Reduce need for supplemental oxygen? Is the decrease heart rate related to improved cardiac output? Less need for PDA treatment? Needs a larger trial powered to look at such effects

57 DR/Resuscitation Interventions Monitoring (HR, CO 2, NIRS, EEG, EIT)- Hard to demonstrate improved outcomes in RCTs but likely beneficial in certain cases (airway obstruction, initiation/avoidance of interventions (starting PPV, or avoiding chest compressions) Caffeine/Nitric Oxide DR administration may have greater benefits, needs more study

58 Neil Finer, MD Paul Wozniak, MD Deb Poelter, PhD Maurcio Maldonando, MD Deb Petruzzelli, RN Melissa Brown, RRT Wade Rich, RRT Kathy Arnell, RN Kasim Hassen, RRT Danielle Lazarus, RRT Jane Steen, RN Stephanie Freeman, RRT Thank You!!