Tine Vanhullebusch

Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis

RATIONALE Intensive care unit (ICU)-acquired weakness is a frequent complication of critical illness. It is unclear whether it is a marker or mediator of poor outcomes. OBJECTIVES To determine acute outcomes, 1-year mortality, and costs of ICU-acquired weakness among long-stay (≥8 d) ICU patients and to assess the impact of recovery of weakness at ICU discharge. METHODS Data were prospectively collected during a randomized controlled trial. Impact of weakness on outcomes and costs was analyzed with a one-to-one propensity-score-matching for baseline characteristics, illness severity, and risk factor exposure before assessment. Among weak patients, impact of persistent weakness at ICU discharge on risk of death after 1 year was examined with multivariable Cox proportional hazards analysis. MEASUREMENTS AND MAIN RESULTS A total of 78.6% were admitted to the surgical ICU; 227 of 415 (55%) long-stay assessable ICU patients were weak; 122 weak patients were matched to 122 not-weak patients. As compared with matched not-weak patients, weak patients had a lower likelihood for live weaning from mechanical ventilation (hazard ratio [HR], 0.709 [0.549-0.888]; P = 0.009), live ICU (HR, 0.698 [0.553-0.861]; P = 0.008) and hospital discharge (HR, 0.680 [0.514-0.871]; P = 0.007). In-hospital costs per patient (+30.5%, +5,443 Euro per patient; P = 0.04) and 1-year mortality (30.6% vs. 17.2%; P = 0.015) were also higher. The 105 of 227 (46%) weak patients not matchable to not-weak patients had even worse prognosis and higher costs. The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge (P < 0.001). CONCLUSIONS After careful matching the data suggest that ICU-acquired weakness worsens acute morbidity and increases healthcare-related costs and 1-year mortality. Persistence and severity of weakness at ICU discharge further increased 1-year mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial

BACKGROUND Patients who are critically ill can develop so-called intensive-care unit acquired weakness, which delays rehabilitation. Reduced muscle mass, quality, or both might have a role. The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered with ClinicalTrials.gov, number NCT00512122) showed that tolerating macronutrient deficit for 1 week in intensive-care units (late parenteral nutrition [PN]) accelerated recovery compared with early PN. The role of weakness was unclear. Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres. METHODS In this prospectively planned subanalysis of the EPaNIC trial, weakness (MRC sum score) was assessed in 600 awake, cooperative patients. Skeletal muscle biopsies, harvested from 122 patients 8 days after randomisation and from 20 matched healthy controls, were studied for autophagy and atrophy. We determined the significance of differences with Mann-Whitney U, Median, Kruskal-Wallis, or χ(2) (exact) tests, as appropriate. FINDINGS With late PN, 105 (34%) of 305 patients had weakness on first assessment (median day 9 post-randomisation) compared with 127 (43%) of 295 patients given early PN (absolute difference -9%, 95% CI -16 to -1; p=0·030). Weakness recovered faster with late PN than with early PN (p=0·021). Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls, similarly with early PN and late PN. The LC3 (microtubule-associated protein light chain 3) II to LC3I ratio, related to autophagosome formation, was higher in patients given late PN than early PN (p=0·026), reaching values almost double those in the healthy control group (p=0·0016), and coinciding with less ubiquitin staining (p=0·019). A higher LC3II to LC3I ratio was independently associated with less weakness (p=0·047). Expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants (p≤0·0006), but was unaffected by nutrition. INTERPRETATION Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting, but allowed more efficient activation of autophagic quality control of myofibres and reduced weakness. FUNDING UZ Leuven, Research Foundation-Flanders, the Flemish Government, and the European Research Council.

Interobserver agreement of medical research council sum-score and handgrip strength in the intensive care unit

Introduction: Muscle weakness often complicates critical illness and is associated with devastating short‐ and long‐term consequences. For interventional studies, reliable measurements of muscle force in the intensive care unit (ICU) are needed. Methods: To examine interobserver agreement, two observers independently measured Medical Research Council (MRC) sum‐score (n = 75) and handgrip strength (n = 46) in a cross‐sectional ICU sample. Results: The intraclass correlation coefficient (ICC) for MRC sum‐score was 0.95 (0.92–0.97). The kappa coefficient for identifying “significant weakness” (MRC sum‐score <48, MRC subtotal upper limbs <24) and “severe weakness” (MRC sum‐score <36) was 0.68 ± 0.09, 0.88 ± 0.07, and 0.93 ± 0.07, respectively. The ICC for left and right handgrip strength was 0.97 (0.94–0.98) and 0.93 (0.86–0.97), respectively. Conclusions: Interobserver agreement on MRC sum‐score and handgrip strength in the ICU was very good. Agreement on “severe weakness” (MRC sum‐score <36) was excellent and supports its use in interventional studies. Agreement on “significant weakness” (MRC sum‐score <48) was good, but even better using the equivalent cut‐off in the upper limbs. It remains to be determined whether this may serve as a substitute. Muscle Nerve 45: 18–25, 2012

16 Kinesitherapie bij de kritiek zieke patiënt

Kinesitherapeuten maken een belangrijk deel uit van het zorgteam van kritiek zieke patienten. De kinesitherapie bij deze patientengroep wordt niet zozeer gestuurd vanuit de medische diagnose van de patient, maar legt eerder de nadruk op problemen van fysiologische en functionele aard. Aangrijpingspunten voor de kinesithe-rapie zijn een juiste beoordeling van de respiratoire toestand (secreties, atelectasen en spierzwakte), het fysieke conditieverlies en daaraan gerelateerde problemen (spierzwakte, gewrichtsstijfheid, verminderde functionele inspanningscapaciteit en activiteiten van het dagelijks leven) en het emotionele aspect. Vroegtijdige fysieke activering is van belang in de preventie en behandeling van fysiek conditieverlies gerelateerd aan kritieke ziekte en is onmisbaar in het proces van reconditionering. Er zijn verscheidene mogelijkheden voor zowel inspanningstraining als voor vroegtijdige mobilisatie voorhanden waarvan het effect is aangetoond. Deze verschillende mogelijkheden kunnen gebruikt worden op basis van de ernst van de kritieke ziekte op een bepaald moment, de comorbiditeit en de medewerking van de patient. De kinesitherapeut is verantwoordelijk voor het implementeren van mobilisatieschema’s en oefenprogramma’s en moet deze voortdurend aanpassen aan de toestand van de patient, steeds in overleg met het team van artsen en verpleegkundigen.