Saturation Targets Are They Achievable? Preventing Intermittent Hypoxemia

Transcription

1 Saturation Targets Are They Achievable? Preventing Intermittent Hypoxemia Professor and Chief Department of Neonatology Tuebingen University Hospital Prof. Poets graduated from Hannover Medical School in June He received his medical training first at the Dept. of Pediatrics, Salzgitter City Hospital, and then, from December 1986 to August 1989, at the Dept. of Pediatric Pulmonology & Neonatoloy, Hannover Medical School, Hannover, Germany. He did a 2-year research fellowship at the Dept. of Pediatric Respiratory Physiology, Brompton Hospital&National Heart & Lung Institute, London, where we worked as a Honorary Pediatric Registrar. After his return to Hannover in August 1991, he completed his medical training and then started to work there as a consultant pediatrician in charge of the Neonatal Intensive Care Unit and the Paediatric Sleep Lab in In the same year, he finished his professorial thesis and was appointed lecturer and, in 1999, extracurricular professor at the Department of Paediatric Pulmonology & Neonatoloy, Hannover Medical School. In 2002, he was appointed Professor and Chief, Department of Neonatology, University Hospital, Tuebingen, Germany. The department includes a Pediatric sleep lab. In 2008, he also became chairman of the newly established Interdisciplinary Center for Craniofacial Malformations at Tuebingen University Hospital. He is also chairman of the Clinical Ethics Committee of Tuebingen University Hospital, and a member of this institution s scientific review board (IRB). Prof. Poets has co-authored over 260 articles cited in PubMed and has contributed to over 120 review articles. He is a member of the Neonatal Society and the European Society for Pediatric Research, and was president of the (German speaking) Society for Neonatology and Paediatric Intensive Care in His main research interests include the control of breathing, obstructive sleep apnea, Sudden Infant Death Syndrome, perinatal epidemiology and outcome research, surfactant research, innate immunity, and the conduct of multicenter clinical trials including neurodevelopmental follow-up. With regard to the latter, he is currently PI of NEuroSIS, a large EU-funded multicenter study on the effectiveness of inhaled steroids in the prevention of BPD, and steering committee member of COT (Canadian Oxygen Trial) and ETTNO (Effects of transfusion thresholds on neurocognitive outcome). NICQ Symposium, inicq Alarm Safety Homeroom, Friday, October 2, 2015 Saturation Targets Are They Achievable? Preventing Intermittent Hypoxemia Objectives: Identify 3 opportunities to standardize care processes, and further test them locally in small PDSA cycles. Identify the potential for completed improvement cycles to improve value defined as quality/cost.

2 Potential conflictsofinterest How to reduce/prevent intermittent hypoxemia (IH) in preterm infants? Dept. of Neonatology University Hospital, Tübingen, Germany Christian F. Poets, MD received a research grant for a project unrelated to his presentation from Chiesi Farmaceutici, Parma, Italy, the manufacturer of caffeine citrate in Europe. Also, one of his local colleagues received a loan of pulse oximeters from Masimo free of charge for an unrelated study. Background IH relevant for neurodevelopment Intervention studies mainly focused on apnea Aim: Review data on effects of IH on outcome and the effectiveness of interventions aimed at reducing IH or preventing re intubation in infants <1500 g; both, while intubated & during spontaneous breathing Background: Effects of IH on outcome COT: recordings of SpO 2 for 68 days in 1019 survivors to 36 wk PMA Analysis of episodes with SpO 2 <80% or pulse rate <80/min. for 10 s Association with primary COT outcome: late death/disability at 18 m corrected age Secondary outcomes: GMFCS 2, cognitive/language delay, ROP grade 3 Characteristics of hypox./bradyc. episodes Associations with outcome length=number of data entries <80%/bpm, each 10s apart October 2,

3 Late death/disability & cognitivs delay vs. %time SpO 2 <80%/PR<80/min. Motor impairment, ROP grade 3 Interaction with COT intervention Effect of IH on outcome is age dependent Summary of data on association IH outcome Risk of adverse outcome (primary and all secondary) increased with the %time infants experienced IH Bradycardia w/o IH did not add much to this risk Severity of IH, expressed as AUC, added little, but duration mattered: only events 1 min. associated with increased risk of adverse outcome Associations stronger at later PN ages and in infants assigned to higher SpO 2 range in COT Prevention: Crossover study, S IMV vs. IMV 18 infants, 777±39 g, 25.1±0.3 wk, 43±6 d old Infant star ventilator, S IMV vs. IMV for 1 h each Less % time <90, <85 or <80% SpO 2 with S IMV Firme, Pediatr Pulmonol 2005;40:9 October 2,

4 Tracheal suctioningwithclosedsystems Suctioning involves loss of PEEP when disconnecting ET tube from ventilator PEEP loss preventable via closed systems? Meta analysis, 3 studies, 241 infants, crossover: RR 0.48 (0.31; 0.74) for SpO 2 <90% with vs. w/o ET tube disconnection during suctioning Only few infants <28 wk; increased dead space? Recent study: effect on SpO 2 <85%, not on <80% Can automatic FiO 2 C reduce IH? Miami Controller %time in target & <80% with 2 target ranges: 88 93% vs % 80 infants (26 wk, 18 d) on IPPV/CPAP & FiO 2 >0.21, 24 h automatic vs. manual FiO 2 C Manual Automatic %time in target 57±16 62±17* %time <80% 2.2 ( ) 0.9 ( )* Nepis. <80%>60s 14 (5 24) 4 (1 11)* T a *p<0.05 Van Kaam, J Pediatr 2015 (epub) Can automatic FiO 2 control (FiO 2 C) reduce IH? Tübingen Controller 4 Center RCT, 34 infants, 2x24 h, %time in target 61 vs. 72% %Time <80%: 2.7% (0 6.3) vs. 1.6% (0 7.7), p<0.01 Keeping infants at high SpO 2 (91 95%)? Higher SpO 2 target = less hypoxic ventilatory depression? COT %time SpO 2 <80% in high vs. low group: 7.1% ( ) vs. 3.7% ( ), p<.001 SUPPORT subgroup: fewer events <80% in high target group, significant from wk 8 12 onwards Hallenberger, Pediatrics 2014;133:e379 Urschitz 2015, unpublished Manual control Automatic control Schmidt, JAMA 2013 DiFiore, J Pediatr 2012 Caffeine citrate: CAP study results Caffeine effective for IH at >34 wk PMA Prim. outcome: Death/NDI OR 0.77 ( ) Less motor impairment at age 5 y: OR 0.66 ( ) for GMCSF vs. 15% with developmental movement coordination disorder: OR 0.71, 95% CI No data on IH Schmidt B, JAMA 2012;307:275- Doyle L, J Pediatr 2014;165:356- Rhein,...Poets, JAMA Pediatr 2014;168:250- October 2,

5 10 vs. 2.5 mg/kg/d caffeine maintenance dose: Re-intubation rates at 48h 234 infants <30 W, IPPV at randomisation at 48 h Mean GA 27.1 (SD 1.4) vs (1.4) wk 40 vs. 10 mg/kg loading dose 15 vs. 30% not extubated (OR 0.51; 95%CI ) mean duration of IPPV (<28 wk): 14 vs. 22 d (p=0.01) BPD (36 wk): 34 vs. 48%, p=0.06 CP/blind/deaf/DQ<75 at 1 y: 6/87 vs. 14/86; OR 0.42 ( ) Steer, Arch Dis Child 2004;89:F499- Gray, J Pediatr Child Health 2011;47:167- Doxapram 15 infants 27 wk (24 30), 27 d (12 60) 6 day, longitudinal cohort study; all on caffeine Doxapram mg/kg/h, i.v. or p.o. N events SpO 2 <80%/h reduced with doxapram **p<0.01 Desaturations/h ** ** pre Doxa 24 h 72 h 6 d Poets, Biol Neon 1999;76:207 IH/bradycardia rates with different nasal positive pressure support systems RCT, crossover, 4 non-synchronized systems 16 infants, median PCA at study 30.6 wk (28-34) System / N SpO 2 <80% or HR<80/h Median Range nippv via standard ventilator Variable Flow CPAP (Aladin) * Variable Flow CPAP + nippv Bubble CPAP non-synchronized *p<0.02 vs. standard ventilator Pantalitschka, Arch Dis Child Fetal Neonatal Ed 2009;94:215- IH rates with different nasal support systems RCT, crossover, SNIPPV, NIPPV, CPAP, 4 h each Synchronisation with pneumotachograph (Giulia) 19 infants 27 wk (25 28); 30 wk (29 31) at study N SpO 2 80%/h (mean/iqr) 10.0 **p<0.01 vs. SNIPPV ** ** SNIPPV NIPPV NCPAP Gizzi, Arch Dis Child Fetal Neonatal Ed 2015;100:F17 NIPPV vs. CPAP to prevent respiratory failure* post extubation? Meta analysis Mixed non synchr. synchronised Effect of gavage vs. bottle feeding 100 p< VLBW, 34 wk GA at study, 80 cross-over nipple vs. tube feeding 60 Desaturation rate (SpO 2 <80%): 13.6/h (bottle) vs. 4.6/h (gavage) 40 Effect at expense of delay in attaining full bottle feeds? 20 *defined as need for additional respiratory support within 7d post extubation Lemyre, Cochrane Neonatal Database 2014 Poets, Acta Paediatr 1997;86: Nipple Tube October 2,

6 Summary More data on interventions for reducing IH needed (with IH as primary outcome) Currently, synchronized (N)IPPV, (higher dose) caffeine, automated FiO 2 control promising Doxapram & higher SpO 2 target range potentially effective, but safety yet unclear Nasal HFOV vs. bi level CPAP RCT, 30 infants <1250 g, >72 h, with CPAP failure Nasal HFOV or bi level CPAP (e.g., Infant Flow) Primary outcome: failure of assigned mode N HFOV (N=14) BL CPAP (N=16) NIV failure N(%) 6 (43) 10 (63) Intub. after 72 h N(%) 5 (36) 5 (31) Intub. after 7 d N (%) 6 (43) 6 (38) HFOV not superior to bi level CPAP to avoid re intubation Mukerji, PAS San Diego 2015, abstr Positioning: 15 head-up tilt Crossover study in 12 infants not on caffeine/cpap, mean GA 31 wk 15 head-up tilt vs. horizontal prone position (24 h) N desaturations to <80%SpO 2 : -49% Little effect (-13%) in more recent studies in infants already treated with caffeine (±CPAP) Caffeine citrate: First study on effects on IH 50 infants <32 wk, randomized to caffeine or placebo No lasting effect of caffeine on bradycardia or desaturation Jenni, Pediatrics 1997;100:622-5 Bauschatz, Acta Paed 2008;97:1743- Reher, Arch Dis Child 2008;93:F Bucher, Eur J Pediatr 1988;147: Will blood transfusion reduce IH/bradycardia? Studies on 2 transfusion thresholds Hb prior to transfusion: 10.9 ( ) g/dl N bradycardia/hypoxemia per h 10 1, ( ) g/dl Median: 7.0 vs. 6.8; n.s. Median: 6.4 vs. 4.6; n.s.,1 pre post pre post Poets, Eur J Pediatr 1997;156:311-6 Westkamp, Biol Neon 2002;92: Caffeine and IH: dose dependent effect 37 SpO 2 recordings in 17 infants, wk 1 6: Inverse relationship between caffeine dose & number of IH events/%time SpO 2 <80/85% Kovatis, PAS San Diego 2015, abstr October 2,

7 Intermittent hypoxemia with volume guarantee (VG) ventilation 24 vent. infants, 25±1.5 wk,>4x SpO 2 <75% in 8h 2x24 h conventional vs. VG ventilation, target =exhaled tidal volume prior to study Only little effect of VG on IH; similar data for volume targeted/ controlled SIMV CV VG N epis<80% 20 s 3.7± ±1.9 Episode duration 78±19 67±11* %time SpO 2 <80% 8.9± ±4.1 %time SpO % 33±7 37±10* Jain, PAS 2015 abstr ; Polimeni, Biol Neon 2005;89:50, Hummler IntCareMed 2006;32:577 Blood transfusion & apnea with intervention Meta analysis, 4 studies, 517 patients No effect on apnea requiring intervention Whyte, Cochrane System Rev 2011, Issue 11. Art. No.: CD October 2,