Improving Weaning Automation (WEAN Study)

, 2013 Improving Weaning Automation (WEAN Study) François LELLOUCHE, MD, PhD Centre de recherche de l Institut Universitaire de Cardiologie et de Pneumologie de Québec

CONFLICTS OF INTEREST - Research contracts with Drager medical (5000can$ for travel expenses for the Canadian study on SmartCare-WEAN study) - Research contracts with Hamilton medical to conduct Intellivent evaluation (Salary of the research assistant) - Program of research on automated ventilation and oxygen therapy: Canadian for Innovation(Fonds des Leaders)/FRSQ grants

PLAN Too many modes! Evidence-based for new modes? Why automated modes should be promoted? SmartCare: automated weaning with pressure support Clinical evaluation of SmartCare (WEAN study)

VPC VAC+ VAPS IPAP PC NAVA Automode BILEVEL ASB VACI VCRP CPAP PAC Autoflow VS AI VPAC VA VAC VC VIV SmartCare PA PACI VS-PPV TC PSV SIMV VAIV VPL PAV PRVC VPS ASV PPS ATC EPAP VACI+ Intellivent MMV VS-AI-Vt mini APRV APV BIPAP VPC SPAP Advanced closed loop during mechanical ventilation. Lellouche&Brochard, Best Pract Res 2009

Dual mode within a breath (VAPS) Dual modes breath to breath (VCRP, Autoflow, Volume Assist) Automode Proportionnal Assist Ventilation (PAV) Adaptative Support Ventilation (ASV) Automatic Tube Compensation (ATC) Airway Pressure Release Ventilation (APRV) Respiratory care 2004

ii. Nasogastric tube iii. Amplifier unit NAVA (Sinderby et al., Nature 1999) + + - + - + - + - + - + - - i. Electrode array + + + + + + + + iv. Signal processing unit v. Ventilator unit

PAV (Younes ARRD 1992) Pressure support ventilation and proportional assist ventilation during weaning from mechanical ventilation. Aguirre-Bermeo H, Bottiroli M, Italiano S, Roche-Campo F, Santos JA, Alonso M, Mancebo J. Med Intensiva. 2013 Oct 18. [Epub ahead of print]

Why automated modes should be promoted? NEJM 2000 ARMA Study 6 vs 12 ml/kg de PIT Health care system under pressure Aging population Failure of the knowledge transfert Weaning/protective ventilatory strategy AUTOMATED KT Machines superiors for simple tasks AUTOMATED SYSTEMS

Rationale for weaning automation Weaning protocols are efficient (Ely NEJM 1996, Saura ICM 1996, Kollef CCM 1997, Marelich 2000) and recommended (Mc Intyre Chest 2001, Boles ERJ 2007)..but many obstacles (Ely AJRCCM 1999, Vitacca ICM 2001) to implement weaning protocols trainings on a regular basis required, problems with new protocols and new practices acceptance Great amount of data on weaning (physiological studies & RCT): Esteban, Brochard, Mancebo, Ely, Epstein, Tobin

Dojat et al. Int J Clin Monit Comput 1992 Automated Weaning: SmartCare Ventilator in PSV 1) Automated adaptation of PSV level 2) Automated weaning protocol automatic decrease of the PSV automatic SBT Message in case of successful SBT Patient Monitor Patient Monitor Alarms Control Control Patient Input Automated pressure support Output Automated Weaning RR, TV, EtCO 2 Automatic Weaning System SmartCare Processing

Level of Pressure support (cmh 2O) Example of Weaning with «SmartCare» 18 16 14 12 10 8 6 4 2 0 Minimum level of PS Adaptation Automated reduction of the PSV level Message: «separation from ventilator» PEEP must be 5 cmh 2 O Observation «Automated SBT» Maintain 0:00 0:28 0:57 1:26 1:55 2:24 2:52 E X T U B A T I O N Time (h:min)

70 60 50 40 30 20 12 10 5 0 1 10 hours Diagnostic Respiratoire/Niveau with d assistance SmartCare Sur-Assistance AUTOMATED WEANING PHASES SBT# 1 SBT#2 SBT#3 Sous-Assistance 210 automated evaluations of the patient RR (c/min) PSV (cmh 2 O) PEEP (cmh 2 O) 43 automated adjustment of the PS level 3 automated SBT Adaptation Observation Message No SBT 1 automated message to consider extubation 2 3 4 5 6 7 8 9 10 CONSIDER SEPARATION Temps (h)

INITIAL CLINICAL EVALUATIONS OF SMARTCARE (prototype = NéoGanesh) Dojat et al. AJRCCM 1992 Maintain of the patients in the comfort zone 95% of time 19 patients Dojat et al. AJRCCM 1996 Good performances of the system to predict extubation success/failures 38 patients Dojat et al. AJRCCM 2000 Efficiency of the system to maintain the patients in a comfort zone Reduction of time with high P 0.1 56 modifications of PSV/24 hrs vs 1 modification PSV/24 hrs 10 patients Bouadma, Lellouche et al. Intensive Care Med 2005 Possibility to ventilate patients with the system during prolonged periods (up to 12 days)-pilot study for multicenter RCT 42 patients

YES 1 st Multicenter Randomized Study 144 patients included, 5 centres Mixed population Automated weaning VS Usual protocolized weaning Weaning possible if all following criteria are present: - Improvement of condition having led to intubation - Absence of uncontrolled severe infection - Correction of metabolic disorders - Adequate hemoglobin level - No hemodynamic instability - PaO 2 > 8.5 kpa with FIO 2 0.40 and PEEP 5 cmh 2 O Mechanical ventilation Question at least 2 times a day: Weaning possible? YES Initiation of weaning Stop or lowering of sedation Level of Pressure Support : 20 cmh 2 O NO NO PS level 20 cmh 2 O above PEEP > 60 minutes? YES Spontaneous breathing test feasible if after 60' Question at least 2 times a day: with PS 20 cmh Spontaneous breathing test feasible? 2 O, PEEP 5 cmh 2 O (all must be present): Adaptation - Respiratory rate 30/' of PS - Tidal volume 6 ml/kg YES and/or - No hemodynamic instability NO - SpO 2 90% and FIO 2 0.40 PEEP level - No other contra-indication Spontaneous breathing test during 30' First choice: Pressure support 10 cmh 2 O, ± PEEP 5 cmh 2 O Extubation criteria (all must be Other choices: - T-piece trial present) - Respiratory rate 30/' - CPAP, flow 30 l/min. PEEP 5 cmh 2 O - Pulse < 120/' Extubation criteria present? - Syst. ABP < 180 and > 90 mmhg - No hemodynamic instability - PaO 2 8.5 kpa and FIO 2 0.40 - ph > 7.30 YES NO Extubation possible? - Level of consciousness Primary end point: OK - Efficient swallowing - Efficient cough NO YES Patient weaned but extubation not possible EXTUBATION Weaning process can begin if: The cause of the respiratory failure is partially or completely controlled, including a SpO2 90% under FIO2 0.5 and PEEP 5 cm H2O Hemodynamic stability (Systolic Blood Pressure between 90 and 160mm Hg + Pulse Weaning time between 60 and 125 /minute + absence of uncontrolled arrhythmias) Temperature < 39 C Haemoglobin 8 g/dl (inclusion first extubation) Absence of significant hydro-electrolytes abnormalities Patients can follow simples orders and there is not need for high dose of sedatives For neurological patients: Glascow Coma Scale > 8, Intra-Cranial Pressure < 20 mmhg, Cerebral Perfusion Pressure > 60 mmhg Those patients who accomplish these criteria will follow a spontaneous breathing test (2 hours T tube or Pressure Support Ventilation with 7 cm H2O of pressure support and Positive End Expiratory Pressure 5 cm H2O). No tolerance to spontaneous breathing test will be considerer if: Respiratory Rate > 35 bpm + clinical manifestation * Hypoxemia (PaO2 < 60 mmhg under O2 flow 4 L/min) Acidosis (ph 7.3) * Clinical manifestations: Systolic Blood Pressure 160 mmhg or 90 mmhg, Heart Rate 140 bpm or augmentation of 25% of baseline, new arrhythmia, lower conscience level, sweating or agitation. 1. Patients will be extubated if they successfully complete the 2 hours spontaneous breathing trial and they have an adequate cough 2. For patients that do not tolerate the spontaneous breathing test, weaning will continue on Pressure Support Ventilation. Pressure Support will be adjusted to achieve a respiratory frequency of 25-30 bpm and a good clinical adaptation. Pressure Support will be diminished as soon as possible following patient s clinical tolerance. Patients will be extubated if tolerating low Pressure Support levels (next to 10 cm H2O) with low PEEP levels ( 5 cm H2O) if clinical tolerance and cough are adequate.

Lellouche et al, AJRCCM 2006,174:894-900

Randomized Controlled Trial Monocentric, medical patients 102 patients included High levels of PEEP... Rose, Intensive Care Medicine 2008

Population: Critically ill adults requiring MV> 24 h - Early stage of the weaning process - When patients first tolerate PS (PS Trial) - Patients who are not already weaned (SBT successfully completed) 9 centres Interventions: Automated Weaning (SmartCare ) vs. Protocolized Weaning (paper-based protocol) Common features: PS mode, opportunities for SBTs, PEEP/FiO 2 chart, sedation protocol, extubation/reintubation criteria, criteria for NIV for post-extubation respiratory distress. Primary Outcome: Compliance and acceptance with the weaning & sedation protocols Secondary Outcomes: weaning and mechanical ventilation duration, mechanical ventilation complications Burns et al., AJRCCM 2013

Baseline Characteristics Automated Weaning (n=49) Protocolized Weaning (n=43) p-value Age (year), mean (std) 62.0 (13.8) 65.9 (13.6) 0.18 Female, n (%) 18 (36.7%) 20 (46.5%) 0.34 Duration of MV before randomization (days), median (IQT) 6 (3-10) 5 (2-8) 0.14 Apache II, mean (std) 23.5 (6.3) 23.9 (8.3) 0.78 MODS, mean (std) 5.0 (2.6) 5.0 (2.2) 0.93 COPD, n (%) 10 (20.4%) 13 (30.2%) 0.28 Central neurologic disorder, n (%) 7 (14.3%) 5 (11.6%) 0.71 Classification, n (%) non operative 36 (73.5%) 30 (69.8%) emergent post-op 8 (18.0%) 5 (11.6%) 0.51 elective postop 5 (10.0%) 7 (16.3%) Cointerventions at randomization, n (%) Continuous/intermittent sedation 32 (66.7%) 33 (76.7%) 0.29 Continuous/intermittent narcotics 35 (72.9%) 29 (67.4%) 0.57 Inotropes or vasopressors 9 (18.8%) 4 (9.3%) 0.24 Enteral/parenteral nutrition 43 (89.6%) 36 (83.7%) 0.41 Antibiotics 37 (77.1%) 32 (74.4%) 0.77 Pulmonary artery catheter 0 1 (2.3%) 0.47 Dialysis (intermittent or continuous) 3 (6.3%) 4 (9.3%) 0.70 Neuroleptic medications 5 (10.4%) 6 (14.0%) 0.61

Peri-randomization mechanical ventilation setting Automated Weaning (n=49) Protocolized Weaning (n=43) p-value Mode of ventilation before PST, n (%) PC 2 (4.1%) 5 (11.6%) 0.25 SIMV + PS 1 (2.0%) 3 (7.0%) 0.34 PRVC 6 (12.2%) 0 0.03 PS 34 (67.3%) 25 (58.1%) 0.36 AC 7 (14.3%) 10 (23.3%) 0.27 PST duration (min), mean (std) 105.2 (86.6) 104.8 (131.7) 0.98 Ventilator settings after successful PST PS (above PEEP) cm H 2 O, mean (std) 15.9 (4.1) 16.0 (4.1) 0.93 Set PEEP, mean (std) 6.5 (1.7) 6.4 (1.6) 0.70 FiO 2, mean (std) 0.40 (0.07) 0.44 (0.09) 0.02

PRIMARY OUTCOME Compliance and Acceptance Weaning and Sedation Protocols Automated Weaning (n=49) Protocolized Weaning (n=43) P Value COMPLIANCE - Weaning Protocol Days with protocol violations (%) Average hours off protocol (median, IQR) Proportion of hours with protocol violation (%) 29.0 (8.6) 21.3 (± 9.9) 2.2 (± 5.6) 18.0 (3.5) 17.8 (± 7.4) 2.6 (±1.1) 0.01 0.77 0.56 COMPLIANCE - Sedation Protocol Total missing SAS or RASS scores, n (%) Missing SAS or RASS on weaning protocol Extreme SAS or RASS scores Extreme SAS or RASS scores on protocol 302 (14.7) 69 (22.8%) 66 (4.1%) 29 (3.3%) 467 (14.9) 184 (39.4%) 120 (4.7%) 69 (3.9%) 0.86 <0.0001 0.36 0.44 Weaning Protocol Acceptance (0-10 scale) Physician acceptance score (mean, std) RT acceptance scores (mean, std) 7.4 (± 2.5) 7.2 (± 2.6) 8.1 (± 2.3) 8.1 (± 1.8) 0.01 <0.0001 Sedation Protocols Acceptance (0-10 scale) RN acceptance score - SAS (mean, std) RN acceptance score - RASS (mean, std) 7.9 (± 1.9) 8.0 (± 1.7) 7.6 (± 2.4) 8.4 (± 1.9) 0.47 0.06

SECONDARY OUTCOMES Automated Weaning (n=49) Protocolized Weaning (n=43) p-value Time to first extubation, days, mean (sd) 3.9 (3.3) 8.1 (9.2) 0.02 Time to successful ext., days, mean (sd) 4.8 (3.4) 10.5 (11.1) 0.01 Total duration of MV, days, mean (sd) 11.5 (5.8) 15.4 (12.0) 0.13 ICU length of stay, days, mean (sd) 9.7 (7.8) 15.3 (12.8) 0.04 Hospital length of stay, days, mean (sd) 28.0 (26.0) 31.3 (18.1) 0.54 Nosocomial pneumonia, n (%) 5 (10%) 6 (14.0%) 0.56 Reintubation, n (%) 9 (18%) 11 (25.6%) 0.38 Requirement for NIV, n (%) 4 (8.2%) 6 (14%) 0.50 Self extubation, n (%) 0 1 (2.6%) 0.48 ICU mortality, n (%) 9 (18.4%) 9 (20.9%) 0.80

Burns et al., AJRCCM 2013

RT acceptance (0-10 scale) median (IQR) Physician acceptance (0-10 scale) median (IQR) Time to first extubation, median (IQR) Time to successful ext., median (IQR) Time to successful completion of an SBT median (IQR) Total duration of mechanical ventilation, median (IQR) ICU length of stay, median (IQR) Tracheostomy, count (%) Prolonged mechanical ventilation at 21 days, n (%) AW n=20 7 (5, 8) 8 (5, 9) 4 (2, 10) 4 (3, 10) 0 (0, 2) 10 (8, 20) 10 (5, 16) 4 (20.0) 1 (6.7) HH p-value HME p-value PW n=17 8 (8, 10) 8 (7, 9) 4 (2, 6) 4 (2, 4) 2.5 (1.5, 4) 9 (6, 17) 6 (5, 9) 1 (5.9) AW PW n=29 n=26 < 0.0001 8 8 0.80 (7, 9) (8, 9) Sub-study 0.07 9 9 0.12 Impact of humidification (7, 10) (8, 10) 0.77 3 device 9 on 0.004 (i) (2, 5) acceptance (3,16) 0.25 (ii) 4 outcome 14 0.007 (2, 7) (3, 22) 0.048 1 4 < 0.0001 (0, 3) CLUSTERS: (2, 10) 0.28 11 6 centres 18.5used HH 0.049 (8, 17) in both (11, 29) groups 0.28 6 22 0.008 (5, 12) 3 centres (6, 28) used HME 0.35 4 in both 14groups 0.003 (13.8) (53.9) 0.005 0 1 0 6 (28.6) Burns et al., AJRCCM 2013, Appendix E11

Automated weaning (SmartCare) vs local weaning protocols in post-surgical patients Randomized Controlled Trial Post-op patients with MV > 9 hours 300 patients included 94±144 hours (SmartCare) 118±165 hours (Protocols) (P=0.18) Schadler, AJRCCM 2012

Randomized controlled trial 48 patients who failed SBT Mixed population Monocentric Liu, Chinese Med J 2013

Lellouche et al., AJRCCM 2006 Rose et al., Intensive Care Medicine 2008 Liu et al., Chinese med J 2013 Schadler et al., AJRCCM 2012 Burns et al., AJRCCM 2013 In the context of increasing gap between needs and supply to manage patients on MV, All these studies can be considered «positive» : = better (or same outcome) with less human interventions

Evidence-Based Meta-analysis SmartCare versus Non-automated Weaning Strategies for Critically Ill Adults: A Systematic Review and Meta-analysis. Karen EA Burns, Francois Lellouche, Rosane Nisenbaum, Martin Lessard and Jan O. Friedrich Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children. Rose L, Schultz MJ, Cardwell CR, Jouvet P, McAuley DF, Blackwood B. Cochrane Database Syst Rev. 2013 Jun 6;6:CD009235. doi:0.1002/14651858.cd009235.pub2.

Why automated modes should be promoted? Mai 2000 NEJM ARMA Study 6 vs 12 ml/kg de PIT Health care system under pressure Aging population Failure of the knowledge transfert Weaning/protective ventilatory strategy AUTOMATED KT Machines superiors for simple tasks AUTOMATED SYSTEMS EVIDENCE from RCTs +++

LIMITATIONS OF SMARTCARE -Limitations of pressure support ventilation: In specific populations (Neuro/cardiac): T-Tube > PSV Patient-ventilator asynchronies in COPD patients -Only one parameter automatically set (PSV level) next generation = Fully Automated Ventilators Intellivent (Arnal ICM 2012, Lellouche ICM 2013), EWS (Schadler J Monit Comput 2013) -Use of HH with Smartcare can lead to EtCO 2 sensor errors -Specific features should be avoided (night rest option) -Only one manufacturer provides this «mode» (but accessible to all. no patent )

Conclusions: - Many reasons to use automated weaning - Evidence favoring Automated weaning: => Smartcare > to protocolized weaning with PSV => WEAN study: SmartCare VS. protocolized weaning with HIGH compliance rate -> promising results for clinically important outcomes - Larger RCT are needed.. automated weaning&ventilation will become standard of care - The next generation of ventilators will be (are) Fully Automated (Intellivent, Evita Weaning Systems)

Thank you!