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).

[1]  C. Roussos,et al.  Predisposing factors for critical illness polyneuromyopathy in a multidisciplinary intensive care unit , 2008, Acta neurologica Scandinavica.

[2]  Scott L. Zeger,et al.  Inter-rater reliability of manual muscle strength testing in ICU survivors and simulated patients , 2010, Intensive Care Medicine.

[3]  G. Van den Berghe,et al.  Interobserver agreement of medical research council sum‐score and handgrip strength in the intensive care unit , 2012, Muscle & nerve.

[4]  M. Elia,et al.  ESPEN guidelines for nutrition screening 2002. , 2003, Clinical nutrition.

[5]  Neuromuscular dysfunction acquired in critical illness: a systematic review , 2007, Intensive Care Medicine.

[6]  C. Bolton,et al.  Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. , 1996, Critical care medicine.

[7]  G. Van den Berghe,et al.  Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. , 2013, The Lancet. Respiratory medicine.

[8]  Elizabeth A Stuart,et al.  Matching methods for causal inference: A review and a look forward. , 2010, Statistical science : a review journal of the Institute of Mathematical Statistics.

[9]  R. Stevens,et al.  Presence and severity of intensive care unit-acquired paresis at time of awakening are associated with increased intensive care unit and hospital mortality* , 2009, Critical care medicine.

[10]  G. Van den Berghe,et al.  Impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients (EPaNIC trial): a study protocol and statistical analysis plan for a randomized controlled trial , 2011, Trials.

[11]  E. Bittner,et al.  Global Muscle Strength But Not Grip Strength Predicts Mortality and Length of Stay in a General Population in a Surgical Intensive Care Unit , 2012, Physical Therapy.

[12]  G. Van den Berghe,et al.  Early versus Late Parenteral Nutrition in Critically Ill Adults , 2011, The New England journal of medicine.

[13]  S. Bagshaw,et al.  Association between frailty and short- and long-term outcomes among critically ill patients: a multicentre prospective cohort study , 2014, Canadian Medical Association Journal.

[14]  Rahul Phadke,et al.  Acute skeletal muscle wasting in critical illness. , 2013, JAMA.

[15]  Thierry Troosters,et al.  Early exercise in critically ill patients enhances short-term functional recovery* , 2009, Critical care medicine.

[16]  Peter Jüni,et al.  An overview of the objectives of and the approaches to propensity score analyses. , 2011, European heart journal.

[17]  F. Leijten,et al.  The Role of Polyneuropathy in Motor Convalescence After Prolonged Mechanical Ventilation , 1995 .

[18]  B. de Jonghe,et al.  Respiratory weakness is associated with limb weakness and delayed weaning in critical illness* , 2007, Critical care medicine.

[19]  Anthonius de Boer,et al.  Systematic differences in treatment effect estimates between propensity score methods and logistic regression. , 2008, International journal of epidemiology.

[20]  Laurent Brochard,et al.  Does ICU-acquired paresis lengthen weaning from mechanical ventilation? , 2004, Intensive Care Medicine.

[21]  T. Similowski,et al.  Diaphragm dysfunction on admission to the intensive care unit. Prevalence, risk factors, and prognostic impact-a prospective study. , 2013, American journal of respiratory and critical care medicine.

[22]  N. Latronico,et al.  Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study , 2007, Critical care.

[23]  G. Van den Berghe,et al.  Early versus late parenteral nutrition in ICU patients: cost analysis of the EPaNIC trial , 2012, Critical Care.

[24]  J. Takala,et al.  Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in patients with SIRS and acute respiratory failure , 2009, Intensive Care Medicine.

[25]  D. Needham,et al.  One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: prospective follow-up of EDEN randomised trial , 2013, BMJ.

[26]  Raphaël Porcher,et al.  Propensity scores in intensive care and anaesthesiology literature: a systematic review , 2010, Intensive Care Medicine.

[27]  James G Wright,et al.  The development of a comorbidity index with physical function as the outcome. , 2005, Journal of clinical epidemiology.

[28]  P. Schmitz,et al.  Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain‐Barré syndrome , 1991, Muscle & nerve.

[29]  I. Vasileiadis,et al.  Maximum inspiratory pressure, a surrogate parameter for the assessment of ICU-acquired weakness , 2011, BMC anesthesiology.

[30]  G. Supinski,et al.  Diaphragm weakness in mechanically ventilated critically ill patients , 2013, Critical Care.

[31]  C. Bolton,et al.  Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis , 2011, The Lancet Neurology.

[32]  G. Van den Berghe,et al.  Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. , 2007, American journal of respiratory and critical care medicine.

[33]  E. Hund Neurological complications of sepsis: critical illness polyneuropathy and myopathy , 2001, Journal of Neurology.

[34]  C. Hough,et al.  Manual muscle strength testing of critically ill patients: feasibility and interobserver agreement , 2011, Critical care.

[35]  M. Polkey,et al.  Clinical predictive value of manual muscle strength testing during critical illness: an observational cohort study , 2013, Critical Care.

[36]  Isabelle Durand-Zaleski,et al.  Paresis acquired in the intensive care unit: a prospective multicenter study. , 2002, JAMA.

[37]  N. Latronico,et al.  What is new in prevention of muscle weakness in critically ill patients? , 2013, Intensive Care Medicine.

[38]  Jesse B. Hall,et al.  Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial , 2009, The Lancet.

[39]  J. Batt,et al.  Intensive care unit-acquired weakness: clinical phenotypes and molecular mechanisms. , 2013, American journal of respiratory and critical care medicine.

[40]  M. Eikermann,et al.  Muscle Weakness Predicts Pharyngeal Dysfunction and Symptomatic Aspiration in Long-term Ventilated Patients , 2013, Anesthesiology.

[41]  Peter C Austin,et al.  The performance of different propensity score methods for estimating marginal hazard ratios , 2007, Statistics in medicine.

[42]  K.,et al.  Reliability of measurements of muscle tone and muscle power in stroke patients. , 2000, Age and ageing.

[43]  S. Bagshaw,et al.  The role of frailty in outcomes from critical illness , 2013, Current opinion in critical care.

[44]  S. Lemeshow,et al.  Acquired weakness, handgrip strength, and mortality in critically ill patients. , 2008, American journal of respiratory and critical care medicine.

[45]  B. de Jonghe,et al.  Intensive care unit-acquired weakness: Risk factors and prevention , 2009, Critical care medicine.

[46]  F Bruyninckx,et al.  Insulin therapy protects the central and peripheral nervous system of intensive care patients , 2005, Neurology.