Recovery after Critical Illness: Looking inside the muscles What s New In ICU? May 2017 Edinburgh David Griffith Royal Infirmary of Edinburgh @Griffith_DM
Looking inside the muscles Is this an important issue? What effect does critical care have on muscle function? What happens after ICU? Can we fix it?
Our patients tell us if we ask Before ICU able to do moderate exercise, walking, and swimming Immediately after discharge I was lucky if I could walk 20 paces A major concern but also a motivating factor was that I was worried I might not be able to drive as a profession My body wasn t responding as quickly as might be needed to ensure both my safety and that of my passengers
ICU top 10 research priorities How can the physical consequences of critical illness (such as muscle wasting, weakness, nerve damage) be prevented and what is the best way to support recovery from these after intensive care? When should physical rehabilitation start and what rehabilitation methods during and after critical illness achieve the best outcomes for patients? http://www.jla.nihr.ac.uk/priority-setting-partnerships/intensive-care/top-10-priorities/
Walking distance after ARDS Herridge MS et al. N Engl J Med 2011
Surviving ICU is exhausting APPETITE FATIGUE Visual analogue scale score Visual analogue scale score 3 months 12 months 3 months 12 months ore Griffith et al (in preparation) 2017 PAIN ore JOINT STIFFNESS
and impacts on quality of life A B Griffith et al (in preparation) 2017 C D Q4 (n=33) (4.8) Q4 (n=34) 5 (3.6)
ICU acquired weakness Kress et al NEJM 2014 Stevens et al Crit Care Med 2009 Clinically detected weakness in critically ill patients in whom there is no plausible aetiology other than critical illness
Risk factors for neuromuscular complications Illness severity Sepsis / inflammation Organ failure Immobilisation Glucose Hermans et al Critical Care 2015 Kress et al NEJM 2014
Batt et al 2017 ICM
Muscle composition Puthucheary et al 2013 JAMA
Muscle composition OpenStax Anatomy and Physiology Published May 18, 2016
Muscle composition Levine et al NEJM 2008
Muscle composition Inhibition of protein synthesis Resting muscle Mitochondrial damage Reactive oxygen species Decreased ATP production Reduced satellite cell number Inflammation Immobilisation Endocrine stress responses Denervation Ubiquitin proteasome system (UPS) upregulation Cytokines Oxidative stress Dysregulated Autophagy
Peripheral nerve dysfunction Distal axonal sensory-motor polyneuropathy. Reduced compound muscle AP Reduced sensory nerve AP Normal conduction velocity Axonal neuropathy (not always!)
Peripheral nerve dysfunction Membrane depolarisation defect channelopathy? Microcirculatory dysfunction Ischaemia / accumulation of toxic metabolites? Hyperglycaemia
Muscle membrane in-excitability Sodium channels OpenStax Anatomy and Physiology Published May 18, 2016
Excitation contraction uncoupling Calcium channels OpenStax Anatomy and Physiology Published May 18, 2016
Bio-energetic failure OpenStax Anatomy and Physiology Published May 18, 2016
Pre-existing muscle disease? Baseline physical function Critical illness Neuromuscular damage ICUAW
The ageing muscle Baseline physical function Reduction in muscle mass 40% reduction between years 20 and 80 Reduction in muscle strength But mismatch between strength rand mass reduction Reduction in muscle quality Fat infiltration Kalyani et al 2014 Lancet Diabetes and Endocrinology
The ageing muscle Right Leg Mid-Femur 1 ElderlyPatient (Patient Th3a) Young Patient (Patient Th15a) 1 Image courtesy of Dr Carolyn Greig PhD Senior Lecturer in Nutrition and Ageing, MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Sport and Exercise Sciences, The University of Birmingham
The ageing muscle Reduction in muscle mass Baseline physical function Bio-energetic failure Mitochondrial dysfunction Oxidative stress Inflammation Axonal degeneration Hormonal changes Repair mechanisms: Reduced satellite cell number and function Kalyani et al 2014 Lancet Diabetes and Endocrinology
Comorbidity Baseline physical function COPD Rheumatoid Arthritis Congestive Cardiac Failure CKD Cirrhosis Kalyani et al 2014 Lancet Diabetes and Endocrinology
Comorbidity Baseline physical function Kalyani et al 2014 Lancet Diabetes and Endocrinology
After ICU Physical Function Score (6 months) ICUAW No ICUAW p 45 (30-70) 75 (50-90) <0.01
After ICU Physical Function Score (6 months) ICUAW No ICUAW p 45 (30-70) 75 (50-90) <0.01 Age 65 (16) 59 (14) 0.03 Septic Shock 35 (58) 26 (36) 0.01 APACHE IV 81 (23) 73 (28) 0.1 Max SOFA 12 (3) 9 (4) <0.01
After ICU Physical Function Score (6 months) ICUAW No ICUAW p 45 (30-70) 75 (50-90) <0.01 Age 65 (16) 59 (14) 0.03 Septic Shock 35 (58) 26 (36) 0.01 APACHE IV 81 (23) 73 (28) 0.1 Max SOFA 12 (3) 9 (4) <0.01 ICUAW associated with decrease of 16.7 (-30.2 to - 3.1) points on the physical functioning scale.
After ICU Strength Quads Mass Electrophysiology CIP CIM UPS mediated proteolysis Mitochondrial number Satellite cell number + + - - - + Dos Santos 2016 AJRCCM
After ICU
After ICU Griffith 2016 Thorax
ICU discharge 3 months Age 50 years Reason for ICU admission Pneumonia (Flu A +ve) Days of mechanical ventilation 9 Comorbidity count 3 Pre-ICU RMI 15 Post-ICU RMI 9
ICU discharge ICU discharge 3 months Difference % Difference 3 months Quadriceps muscle volume (mm 3 ) 111,976 159,660 47,684 +43%
Can we do anything about it? To date, only intensive insulin therapy has been shown to positively affect the prevalence of critical illness acquired weakness; however, this cannot be routinely recommended due to the significant risk of adverse effects, particularly hypoglycemia At this time, we are unable to determine an overall effect on functional exercise capacity, or on health-related quality of life, of an exercisebased intervention initiated after ICU discharge for survivors of critical illness
Looking inside the muscles Is this an important issue? What effect does critical care have on muscle function? What happens after ICU? Can we fix it?
Thanks I C Muscle Team Lisa Salisbury David Hope Lucy Barclay Tim Walsh Rachel Kirkbride Edwin Van Beek Calum Gray Scott Semple Neil Roberts Mike Perrins Jane Crowe Bronwen Connolly Nicholas Hart RECOVER Investigators Tim Walsh Lisa Salisbury Pam Ramsay Jude Merriweather Julia Boyd Guru Huby Suzanne Kean Simon Mackenzie Ashma Krishan Steff Lewis Gordon Murray John Forbes Joel Smith Janice Rattray Alasdair Hull @Griffith_DM
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