School of Rehabilita?on Science Reaching Further Time is Muscle Michelle Kho, PT, PhD Canada Research Chair in Cri?cal Care Rehabilita?on and Knowledge Transla?on McMaster University, Hamilton, ON Clinician Scien?st, Physiotherapy Dept., St. Joseph s Healthcare, Hamilton, ON Cri?cal Care Canada Forum, October 30, 2014 In this talk, I will address 3 ques7ons: Why? What is the evidence for early muscle weakness in the ICU? How? When should we start treatments for muscle weakness? What s next? How do we advance the field? khome@mcmaster.ca 1
When should we start to think about muscles in the ICU? Finfer S and Vincent JL. Cri?cal Care Challenge. NEJM. April 2014. Prospec7ve 1 and 5- year follow- up study of 109 ICU survivors SeYng: 4 Canadian ICUs Popula?on: Adult pa?ents with ARDS Clinical Course ICU Admission ICU Discharge Outcomes: Primary 6 minute walk test Pulmonary func?on tests Health- related quality of life 6 minute walk distance 3 months 6 months 12 months N=83 281 m 49% predicted N=82 396 m 64% predicted N=83 422 m 66% predicted 60 months N=64 436 m 76% predicted Herridge et al, NEJM. 2003. 348:683-93;Herridge et al., NEJM. 2011. 364:1293-304. khome@mcmaster.ca 2
Time is muscle. In acute MI,?me is muscle The golden hour of trauma. In people with stroke,?me is brain But what about cri-cal care? hbp://www.trinityhealth.org/?meismuscle/home- images/images/home_07.jpg WHAT IS THE EVIDENCE FOR EARLY MUSCLE WEAKNESS IN THE ICU? khome@mcmaster.ca 3
1. Quadriceps muscle cross sec7onal area decreases quickly in the ICU Puthucheary et al., JAMA. 2013. 310(15):1591-600. 2. Within 7 days of ICU admission, involuntary quadriceps force is very low ~ day 7 Vivodtzev et al., Cri?cal Care. 2014. 18:431. khome@mcmaster.ca 4
3. Pa7ents developing ICUAW have longer LOS & MV, higher costs, and higher 1- year mortality Last MRC in ICU > 48 Last MRC in ICU 36 to 47 Last MRC in ICU <36 ICUAW = ICU- acquired weakness MRC = Medical Research Council Hermans et al., AJRCCM. 2014; 190(4):410-420. WHEN SHOULD WE START TREATMENTS FOR MUSCLE WEAKNESS? khome@mcmaster.ca 5
Interven7ons to improve physical func7on post- ICU In- ICU Post- ICU Post- Hospital Ineffec7ve Therapies Effec7ve Therapies Interven7on Type: n Exercise / Physical therapy; n Non- exercise X = measurement 7me point Calvo- Ayala et al., Chest. 2013; 144(5):1469 1480 Barriers to ICU rehabilita7on? Poten7al Barrier Evidence Mechanical Ven?la?on No life- threatening adverse events 1 Vasopressors/ Inotropes Not a contraindica?on to star?ng early rehabilita?on 2 Dialysis Mobility may improve CRRT filter life 3 Femoral catheter in situ No safety events 4,5 Seda?on Sedated pa?ents can do some ac?ve cycling 6 1 Li et al., Arch PM & R. 2013. 94:551-61. 2 Pohlman et al., Crit Care Med 2010; 38:2089 2094. 3 Wang et al. Cri?cal Care 2014, 18:R161 4 Damluji et al., J Crit Care. 2013;28(4):535.e9-15. 5 Perme et al. Cardiopulmonary Phys Ther Journal. 2013, 24(2), 12-17. 6 Kho et al., AJRCCM. 2014. 189. A3880. khome@mcmaster.ca 6
Of 1,110 pa7ents and 5,267 PT treatment sessions in MICU, adverse events were rare Overall Event Rate = 0 to 1.9 events per 1,000 PT sessions No cardiorespiratory arrests, or removal of ETT or trach, dialysis/ pheresis catheters, or CVCs. Sricharoenchai et al. Journal of Cri?cal Care. 2014. 29:395 400. Adult pa7ents mechanically ven7lated > 24 h Ini7a7on of Ac7ve Mobiliza7on interven7on; All RCTs unless specified Chen et al., 2011 Bur7n et al., 2009 Schweickert et al., 2009 Morris et al., 2007 (Prospec7ve cohort) Chen et al., 2012 Nava et al., 1998 Porta et al., 2005 Orange = Resp ICU Blue = Medical ICU Blue / Red = Med Surg ICU Chiang et al., 2006 (Quasi RCT) Incident ICU Admission 2 Weeks 4 Weeks >4 Weeks Li et al., Archives of Physical Medicine and Rehabilita?on. 2013. 94:551-61). khome@mcmaster.ca 7
Primary Outcome: ICUAW @ awakening MRC score <48/60 (unblinded) R Daily NMES Quadriceps & peroneals 55 min/ session N=70 3/24 (13%) p=0.04 N=142 Day 2 ICU admission; APACHE II >=13 Control N=72 11/28 (39%) Routsi et al., Crit Care. 2010. 14:R74. Primary Outcome: Lower extremity strength @ hospital discharge Medical ICU R N=36 Daily NMES Quadriceps, 7bialis anterior, gastrocnemius N=16 Usual Care N=18 28 (2) N= 12 27 (3) N= 17 p=0.07 Kho et al., Journal of Cri?cal Care. 2014. In press. khome@mcmaster.ca 8
Medical ICU R N=104 Daily interrup7on of seda7on + Early OT/PT 7d/wk N=49 Primary Outcome: Independent func?onal status @ hospital discharge (6 ADLs + independent walking) 59% (29/49) p=0.02 Daily interrup7on of seda7on + Standard 35% (19/55) care OT/PT N=55 Schweickert et al., Lancet. 2009. 373: 1874-82. Primary Outcome: Tower Test 3 months post- ICU Cogni7ve Therapy + Early PT N=43 10.0 [8.0-11.0] N=18 R N=87 Early PT N=22 11.0 [11.0-12.0] N=14 p=0.20 Single center Medical (n=53) Surgical (n=34) Usual Care N=22 10.0 [8.8-12.0] N=12 Normal = 7 to 13 Higher scores = beter Brummel et al., Intensive Care Med. 2014. 40(3):370-9. khome@mcmaster.ca 9
Primary Outcome: 6 minute walk test @ 12 months (model es?mates) Medical/ Surgical ICU Intensive exercise in ICU, on ward, and post- ICU N=74 409.6 (22.9) m N=41 R N=150 Standard care N=76 404.9 (23.0) m N=38 p=0.884 Denehy et al. Crit Care. 2013, 17:R156. Summary of early interven7on RCTs Interven7on ICU start Primary Outcome Results 55 min daily NMES 1 2 days Fewer pa?ents with ICUAW @ ICU awakening 60 min daily NMES 2 4 days No difference in lower extremity muscle strength @ hospital d/c Daily OT and PT 3 1.5 days of MV More pa?ents func?onally independent at hospital d/c BID Cogni?ve and 3 days No difference in Tower test @ 3 daily PT 4 months Intense exercise 5 auer 5 days No difference in 6MWT @ 1 year 1 Crit Care. 2010. 14:R74. 2 Journal of Cri?cal Care. 2014. In press. 3 Lancet. 2009. 373: 1874-82. 4 Intensive Care Med. 2014. 40(3):370-9. 5 Crit Care. 2013, 17:R156. khome@mcmaster.ca 10
Pilot Studies can inform future trials Interven7on ICU start Primary Outcome Results 55 min daily NMES 1 2 days Fewer pa?ents with ICUAW @ ICU awakening 60 min daily NMES 2 4 days No difference in lower extremity muscle strength @ hospital d/c Daily OT and PT 3 1.5 days of MV More pa?ents func?onally independent at hospital d/c BID Cogni?ve and 3 days No difference in Tower test @ 3 daily PT 4 months Intense exercise 5 auer 5 days No difference in 6MWT @ 1 year 1 Crit Care. 2010. 14:R74. 2 Journal of Cri?cal Care. 2014. In press. 3 Lancet. 2009. 373: 1874-82. 4 Intensive Care Med. 2014. 40(3):370-9. 5 Crit Care. 2013, 17:R156. Continuum of physical activity Bedrest Completely Passive Completely Ac7ve Increasing physical ac7vity and pa7ent engagement in rehab khome@mcmaster.ca 11
Non- voli7onal interven7ons Interven7on ICU start Primary Outcome Results 55 min daily NMES 1 2 days Fewer pa?ents with ICUAW @ ICU awakening 60 min daily NMES 2 4 days No difference in lower extremity muscle strength @ hospital d/c Daily OT and PT 3 1.5 days of MV More pa?ents func?onally independent at hospital d/c BID Cogni?ve and 3 days No difference in Tower test @ 3 daily PT 4 months Intense exercise 5 auer 5 days No difference in 6MWT @ 1 year 1 Crit Care. 2010. 14:R74. 2 Journal of Cri?cal Care. 2014. In press. 3 Lancet. 2009. 373: 1874-82. 4 Intensive Care Med. 2014. 40(3):370-9. 5 Crit Care. 2013, 17:R156. Outcome assessors blinded to interven7on Interven7on ICU start Primary Outcome Results 55 min daily NMES 1 2 days Fewer pa?ents with ICUAW @ ICU awakening 60 min daily NMES 2 4 days No difference in lower extremity muscle strength @ hospital d/c Daily OT and PT 3 1.5 days of MV More pa?ents func?onally independent at hospital d/c BID Cogni?ve and 3 days No difference in Tower test @ daily PT 4 3 months Intense exercise 5 auer 5 days No difference in 6MWT @ 1 year 1 Crit Care. 2010. 14:R74. 2 Journal of Cri?cal Care. 2014. In press. 3 Lancet. 2009. 373: 1874-82. 4 Intensive Care Med. 2014. 40(3):370-9. 5 Crit Care. 2013, 17:R156. khome@mcmaster.ca 12
Outcomes focused on func7on Interven7on ICU start Primary Outcome Results 55 min daily NMES 1 2 days Fewer pa?ents with ICUAW @ ICU awakening 60 min daily NMES 2 4 days No difference in lower extremity muscle strength @ hospital d/c Daily OT and PT 3 1.5 days of MV More pa?ents func?onally independent at hospital d/c BID Cogni?ve and 3 days No difference in Tower test @ daily PT 4 3 months Intense exercise 5 auer 5 days No difference in 6MWT @ 1 year 1 Crit Care. 2010. 14:R74. 2 Journal of Cri?cal Care. 2014. In press. 3 Lancet. 2009. 373: 1874-82. 4 Intensive Care Med. 2014. 40(3):370-9. 5 Crit Care. 2013, 17:R156. Outcome 7ming Interven7on ICU start Primary Outcome Results 55 min daily NMES 1 2 days Fewer pa?ents with ICUAW @ ICU awakening 60 min daily NMES 2 4 days No difference in lower extremity muscle strength @ hospital d/c Daily OT and PT 3 1.5 days of MV More pa?ents func?onally independent at hospital d/c BID Cogni?ve and 3 days No difference in Tower test @ daily PT 4 3 months Intense exercise 5 auer 5 days No difference in 6MWT @ 1 year 1 Crit Care. 2010. 14:R74. 2 Journal of Cri?cal Care. 2014. In press. 3 Lancet. 2009. 373: 1874-82. 4 Intensive Care Med. 2014. 40(3):370-9. 5 Crit Care. 2013, 17:R156. khome@mcmaster.ca 13
Summary of the state of the science Strengths Interven?ons started within 1 st week of ICU Use of pilot trials to inform future research Con?nuum of interven?ons Methodological rigor Future considera7ons Interven?on feasibility Recruitment Delivery (?me req d) Reproducibility Common outcome measures Pa?ent- important outcomes Longer follow up post- ICU HOW DO WE ADVANCE THE FIELD? khome@mcmaster.ca 14
CYCLE: Cri7cal Care Cycling to Improve Lower Extremity Strength CYCLE Prepara?on phase TryCYCLE: Phase II open label study CYCLE pilot: Phase II randomized pilot CYCLE RCT: Phase III randomized trial ICAN Rehab Survey development: pt, family, clinician sa?sfac?on with rehabilita?on CYCLE- R Systema?c Review Uni- CYCLE Retrospec?ve chart audit 1 center, 33 pt prospec?ve cohort Design the interven?on; select outcomes; assess fidelity, safety, sa?sfac?on, and acceptability 5 center, 60 pt pilot RCT Feasibility Mul?center RCT CYCLE$ Economic evalua?on BICYCLE Behavioural Interven?on for Knowledge Transla?on In cri7cal care, 7me is muscle: Why? What is the evidence for early muscle weakness in the ICU? Muscle weakness starts within the 1 st week of ICU As early as possible How? When should we start treatments for muscle weakness? Consider feasibility, longer- term outcomes What s next? How do we advance the field? khome@mcmaster.ca 15