TRAJECTORY OF NEUROMUSCULAR RECOVERY AFTER CRITICAL ILLNESS

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1 TRAJECTORY OF NEUROMUSCULAR RECOVERY AFTER CRITICAL ILLNESS Prof. Nicola Latronico Director, Department of Anesthesia, Critical Care and Emergency University of Brescia, Italy

2 THE MAIN QUESTION RECOVERY OF MUSCLE STRENGTH OR PHYSICAL FUNCTION?

3 1. ICU- ACQUIRED WEAKNESS 2. PHYSICAL DYSFUNCTION

4 A framework for diagnosing and classifying intensive care unit- acquired weakness Stevens RD, et al. Crit Care Med 2009; 37[Suppl.]:S299 S308 The term ICU- acquired weakness (ICUAW) designates clinically detected weakness in crikcally ill pakents in whom there is no plausible ekology other than crikcal illness. Physical examinakon shows diffuse, flaccid, symmetric weakness involving all extremikes and the diaphragm with relakve sparing of the cranial nerves.

5 CriTcal Illness Polyneuropathy Latronico N, et al. Lancet 1996; 347:

6 CriTcal Illness Myopathy onset of sepsis wrist 3 weeks later Tibialis anterior muscle elbow Tibialis anterior muscle Quadriceps muscle Latronico N, Bolton CF. Lancet Neurol 2011; 10:

7 CIP and CIM Latronico N, Tomelleri G, Filosto M. Curr Opin Rheumatol 2012; 24:

8 Paresis acquired in the intensive care unit: a prospectve multcenter study De Jonghe B, et al. JAMA 2002; 288: Among the 95 pakents who achieved saksfactory awakening, the incidence of ICU- acquired paresis was 25.3%. DuraKon of mechanical ventlaton afer day 1 was significantly longer in pakents with ICUAP compared with those without (18.2 vs 7.6 days).

9 Mean durakon of paresis afer awakening (day 1) in ICUAP survivors was 44.6 (79.2) days, with a median durakon of 21 days. De Jonghe B, et al. JAMA 2002; 288:

10 24 pakents with ICUAP 7 died; 1 lost to follow- up 16 pakents alive 12 at home (3 a:er hospital discharge) 4 long- term care facility MRC score > 48 ICUAP De Jonghe B, et al. JAMA 2002; 288:

11 Acquired Weakness, Handgrip Strength, and Mortality in CriTcally Ill PaTents Ali NA, et al. Am J Respir Crit Care Med 2008; 178: MRC & handgrip dynamometry 25.7% had ICUAP (a force value of <11 kg- force for males and <7 kg- force for females) ICUAP was independently associated with hospital mortality (OR 7.8; 95% CI ). ICU- and hospital- free days were also significantly reduced in ICUAP subjects.

12 Acute Outcomes and 1- Year Mortality of Intensive Care Unit acquired Weakness. A Cohort Study and Propensity- matched Analysis. Hermans G, et al. Am J Respir Crit Care Med 2014; 190: As compared with matched not- weak pakents, weak pakents had a lower likelihood for live weaning from MV (hazard rako [HR], [ ]; P = 0.009), live ICU (HR, [ ]; P = 0.008) and hospital discharge (HR, [ ]; P = 0.007). In- hospital costs per pakent (130.5%, 15,443 Euro per pakent; P = 0.04) was also higher.

13 ICUAW & MORTALITY ICU mortality (P = 0.355) and hospital mortality rate (P = 0.075) were not different. Mortality afer 1 year was higher in weak than in not- weak pakents (30.4% vs. 17.2%; P = 0.015). This likelihood of late death was even higher for pakents with a more severe degree of persistent weakness. Hermans G, et al. Am J Respir Crit Care Med 2014; 190(12):

14 Impact of ICU- acquired weakness on post- ICU physical functoning: a follow- up study Wieske L, et al. CriBcal Care 2015; 19: 196 ICU pakents, mechanically venklated 2 days ICUAW with MRC ICU, hospital and 6- month mortality Physical funckoning using the Short- Form Health Survey physical funckoning domain.

15 Wieske L, et al. CriBcal Care 2015; 19: 196

16 ICU AND POST- ICU MORTALITY Survival curves for pakents with (black line) and without (grey line) ICUAW starkng at final ICU discharge unkl end of follow- up; that is, 6 months afer final ICU discharge. Wieske L, et al. CriBcal Care 2015; 19: 196

17 POST- ICU MORTALITY AND PHYSICAL FUNCTIONING Overall mortality was 46% for pakents with ICU- AW and (15% for pakents without ICU- AW (P < 0.01). When adjusted for confounders, ICU- AW was associated with higher post- ICU mortality unkl 6 months afer ICU discharge (HR 3.6; 95% CI, 1.3 to 9.8; P = 0.01) The physical funckoning domain score was significantly lower in pakents with ICU- AW. Afer adjuskng for confounders, ICU- AW was associated with a decrease of 16.7 points on the PF domain score (95% CI, to - 3.1; P = 0.02) Wieske L, et al. CriBcal Care 2015; 19: 196

18 1. ICU- ACQUIRED WEAKNESS 2. PHYSICAL DYSFUNCTION

19 Lancet 2009; 373: A strategy for whole- body rehabilitakon, consiskng of interrupkon of sedakon and physical and occupakonal therapy in the earliest days of crikcal illness, was safe and well tolerated, and resulted in berer funckonal outcomes at hospital discharge, a shorter durakon of delirium, and more venklator- free days compared with standard care.

20 Probability of return to independent funckonal status in intervenkon and control groups Schweickert WD, et al. Lancet 2009; 373:

21 There was no significant difference in absolute MRC examination or hand-grip strength scores between groups. Schweickert WD, et al. Lancet 2009; 373:

22 FuncKonal Disability 5 Years afer Acute Respiratory Distress Syndrome Herridge MS, Tansey CM, Maré A, et al. N Engl J Med 2011;364:

23 FuncKonal Disability 5 Years afer Acute Respiratory Distress Syndrome Herridge MS, Tansey CM, Maré A, et al. N Engl J Med 2011;364: At 5 years, the median distance walked in 6 minutes was 76% of the distance in an age- matched and sex- matched control populakon. At 5 years, the mean score on the physical component of the SF- 36 remained approximately 1 SD below the mean score for an age- matched and sex matched control populakon

24 Physical ComplicaTons in Acute Lung Injury Survivors: A Two- Year Longitudinal ProspecTve Study Fan E, et al Crit Care Med 2014; 42: MMT of extremity (MRC) Hand grip Respiratory muscle strength (MIP); Anthropometrics (weight, BMI, mid-arm circumference, triceps skin fold thickness, and arm muscle area); 6-minute walk distance (6MWD); HRQOL (Physical Function Subscale [PFS] of SF 36 Health Survey).

25 ProporTon of patents with ICUAW declined over Tme 36% at hospital discharge 22% at 3 months post- ALI 15% at 6 months 14% at 12 months 9% at 24 months DuraKon of bed rest was the single risk factor most consistently associated with muscle weakness throughout longitudinal follow- up Fan E, et al Crit Care Med 2014; 42:849-59

26 Fan E, et al Crit Care Med 2014; 42:849-59

27 MMT = manual muscle strength teskng, MIP = maximal inspiratory pressure, 6MWD = 6- min walk distance, SF- 36 PFS = Short Form- 36 Physical FuncKon Subscale score, AMA = arm muscle area. Fan E, et al Crit Care Med 2014; 42:849-59

28 Given that muscle strength recovers more quickly than physical funckon and HRQOL, ALI survivors persistent limitakons in physical funckon and HRQOL are unlikely to be due to ICUAW alone, with many other factors (e.g., cognikve and mental health morbidity, home environment, and caregiver support) likely playing an important role in determining physical limitakons and disability. Fan E, et al Crit Care Med 2014; 42:849-59

29 Risk Factors for Physical Impairment acer Acute Lung Injury in a NaTonal, MulTcenter Study Needham DM, et al Am J Respir Crit Care Med 2014; 189: A prospeckve, longitudinal study of 6- and 12- month physical outcomes (muscle strength, 6- minute- walk distance, and Short Form [SF]- 36 Physical FuncKon score) for 203 survivors of ALI.

30 6 months 12 months MMT (MRC) 92% (SD 8%) * 93% (SD 9%)** 6MWD 64% (SD 22%) 67% (SD 26%) SP- 36 PFS 61% (SD 36%) 67% (SD 37%) There was significant associakon and stakskcal interackon of mean daily dose of coracosteroids and ICU length of stay with impairments in physical outcomes. Needham DM, et al. Am J Respir Crit Care Med 2014; 189: * 8% had ICUAW ** 6% had ICUAW

31 The results for the muscle strength outcome measure revealed less impairment than for the 6MWT and SF- 36 PF measure. Factors other than strength alone contribute to impairments in physical funckoning (6MWT) and quality of life (SF- 36 PF), including issues of muscle endurance, cardiopulmonary funcaon, and psychological status. The ordinal MRC sum- score has a ceiling effect that does not occur with the 6MWT and SF- 36 outcome measures. Needham DM, et al. Am J Respir Crit Care Med 2014; 189:

32 NOBODY CAN UNDERSTAND HOW TIRED I FEEL

33 PERIPHERAL OR CENTRAL CAUSES, OR BOTH? Weakness is remarkably persistent, even though the muscle strength and mass have returned to baseline. Peripheral (CIP/CIM, small fiber pathology, mononeuropathies, pain, heterotopic joint ossificakon) and central causes (cognikve impairment, depression, PTSD) can interact in causing weakness. Latronico N, Piva S, McCredie V. Long term implicabons of ICU acquired weakness. In: The legacy of critcal illness. A textbook of post- ICU medicine. Stevens R, Hart N, Herridge M (Eds). Oxford University Press, 2014, Chapter 24, pp ISBN:

34 CONCLUSIONS ICU- acquired neuromuscular dysfunckon is common and is clinically relevant Recovery of muscle strength is faster than recovery of physical funckon ObjecKve (MRC, hand grip, 6MWD) and subjeckve (SF- 36) measures of muscle strength and physical funckon are equally important Recovery of muscle strength and physical funckon is mulk- dimensional

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