AN OFFICIAL ATS CLINICAL PRACTICE GUIDELINE: THE DIAGNOSIS OF INTENSIVE CARE UNIT ACQUIRED WEAKNESS. Online Supplement

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1 AN OFFICIAL ATS CLINICAL PRACTICE GUIDELINE: THE DIAGNOSIS OF INTENSIVE CARE UNIT ACQUIRED WEAKNESS Online Supplement Institution information: Eddy Fan 1,2 Roy G. Brower 2 Fern Cheek 4 Linda Chlan 5 Rik Gosselink 6 Nicholas Hart 7 Margaret S. Herridge 1 Ramona O. Hopkins 8,9 Catherine L. Hough 10 John P. Kress 11 Nicola Latronico 12 Marc Moss 13 Dale M. Needham 2,3 Mark M. Rich 14 Robert D. Stevens 15 Chris Winkelman 16 Doug W. Zochodne 17 Naeem A. Ali 18 1 Interdepartmental Division of Critical Care Medicine, University Health Network, University of Toronto, Toronto, Canada; 2 Outcomes After Critical Illness and Surgery (OACIS) Group, Division of Pulmonary and Critical Care Medicine and 3 Department of Physical Medicine and Rehabilitation, Johns Hopkins University, Baltimore, MD, ; 4 The Ohio State University, Columbus, OH, ; 5 School of Nursing, University of Minnesota, MN, ; 6 Department of Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium; 7 Lane Fox Respiratory Unit, St Thomas Hospital, Guy s & St Thomas NHS Foundation Trust, King s Health Partners, London, UK; Psychology Department and Neuroscience Center, Brigham Young University, Provo, UT, ; 9 Department of Medicine, Pulmonary and Critical Care, Intermountain Medical Center, Murray, Utah, ; 10 Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, ; 11 Division of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, ; 12 Department of Anesthesia and Critical Care, University of Brescia, Brescia, Italy; 13 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Aurora, CO, ; 14 Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH, ; 15 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, ; 16 School of Nursing, Case Western Reserve University, Cleveland, OH, ; 17 Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; 18 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, E0

2 TABLE OF CONTENTS Table E1: Membership of Guidelines Development Committee Table E2: Literature Search Strategy Table E3: Evidence Table Figure E1: Literature Review Flow-of-Information Table E4: Selected Studies Table E5: Question #1 Relevant Studies Table E6: Question #2 Relevant Studies Table E7: The Medical Research Council (MRC) scale for evaluating peripheral muscle strength Table E8: Studies Using a Composite MRC Score for the Diagnosis of Table E9: Question #3 Relevant Studies Table E10: Voting results for iterative discussions and recommendations E1

3 Table E1: Membership of Guidelines Development Committee Committee member Country Area of expertise Naeem Ali (non-voting) Roy Brower Linda Chlan Eddy Fan Rik Gosselink Nicholas Hart Margaret Herridge Ramona Hopkins Catherine Hough John Kress Nicola Latronico Marc Moss Dale Needham Mark Rich Robert Stevens Chris Winkelman Doug Zochodne Fern Cheek (non-voting) Canada Belgium England Canada Italy Canada Critical Care Medicine Critical Care Medicine Critical Care Nursing Critical Care Medicine Physical Therapy Critical Care Medicine Critical Care Medicine Neurosciences, Psychology Critical Care Medicine Critical Care Medicine Neurological Critical Care Medicine Critical Care Medicine Critical Care Medicine Neurology Neurological Critical Care Medicine Critical Care Nursing Neurology Research Librarian E2

4 Table E2: Literature search strategy The strategy below was developed to be inclusive of all tests used in identifying critically-ill patients with ICU-acquired weakness. It was designed as a starting point and did not preclude the use of other terms. We searched Medline (1950-March 10, 2009), Cochrane Database of Systematic Reviews (up until March 2009), EMBASE (1980-March 2009), and EBSCO (1982- March 2009). Question: How is ICU-acquired weakness defined in the published literature? 1. ("Neuromuscular Diseases/diagnosis"[Mesh] OR "Neuromuscular Diseases/radiography"[Mesh] OR "Neuromuscular Diseases/radionuclide imaging"[mesh] OR "Neuromuscular Diseases/ultrasonography"[Mesh]) 2. ( Neurologic manifestations [Mesh]) 3. (((((((("Intensive Care Units"[Mesh] OR "Critical Care"[Mesh]) OR "Respiratory Distress Syndrome, Adult"[Mesh]) OR "Multiple Organ Failure"[Mesh]) OR "Systemic Inflammatory Response Syndrome"[Mesh]) OR "Respiration, Artificial"[Mesh]) OR "Acute Lung Injury"[Mesh]) OR "Ventilator Weaning"[Mesh]) OR "Ventilator Weaning"[Mesh]) OR "Critical Illness"[Mesh] 4. #1 and #3 5. #2 and #3 6. #4 or #5 7. Limited to Humans E3

5 Table E3: Evidence table: Physical therapy in patients with Bibliography: 1. Ali NA, O Brien JM, Hoffman SP, Phillips G, Garland A, Finley JC, Almoosa K, Hejal R, Wolf KM, Lemeshow S, et al. Acquired weakness, handgrip strength, and mortality in critically ill patients. Am J Respir Crit Care Med 2008; 178: Nordon-Craft A, Schenkman M, Ridgeway K, Benson A, Moss M. Physical therapy management and patient outcomes following ICU-acquired weakness: a case series. J Neurol Phys Ther 2011; 35: Quality of Evidence Assessment-- No. of Study Limitations Inconsistency Indirectness Imprecision Quality of Studies design Evidence Discharge home (as opposed to discharge to a rehabilitative or long-term medical facility) 2 Case No serious No serious No serious Serious 1 Very low series limitations inconsistency indirectness (critical outcome) --Summary of Findings-- In the first case series of 35 patients with, 6 patients were able to be discharged home (17%) following their critical illness. In the second case series of 19 patients with who underwent physical therapy, 6 patients were able to be discharged home (32%) following their critical illness. RR 1.84, 95% CI Mortality 2 Case series No serious limitations No serious inconsistency No serious indirectness Serious 1 Very low (critical outcome) The severity of illness was similar in the case series (a SOFA score of 8 in the first case series and 6 in the second case series). In the first case series of 35 patients with, 11 patients died (31%). In the second case series of 19 patients with who underwent physical therapy, 2 patients died (11%). RR 0.33, 95% CI The severity of illness was similar in the case series (a SOFA score of 8 in the first case series and 6 in the second case series). Abbreviations: = Intensive care unit-acquired weakness; SOFA = Sequential Organ Failure Assessment. 1 Imprecision: The two series included only 54 patients collectively and, therefore, the confidence intervals for the estimates are wide. E4

6 Figure E1: Literature Review Flow-of-Information Electronic Database Literature Search CENTRAL, CINAHL, EMBASE, EBSCO, MEDLINE Total citations = 26,707 Excluded by review of title and duplicates removed Total articles = 26,288 Combined Iterative Search Total citations = 419 Excluded by review of abstract Total articles = 306 Full Article Retrieved for Detailed Review Total citations = 113 Met Eligibility Criteria Total citations = 31 Did not meet eligibility criteria: No reproducible methods (53) Duplicate publication (6) Not adults (1) Unclear diagnostic tests (9) Case report or case series (n<3) (12) Hebrew language, not translated to English (1) Total articles = 82 E5

7 Table E4: Selected Studies Thirty-one relevant studies were selected during our systematic review of the literature: 1. Latronico, N., G. Bertolini, B. Guarneri, M. Botteri, E. Peli, S. Andreoletti, P. Bera, D. Luciani, A. Nardella, E. Vittorielli, B. Simini, and A. Candiani Simplified electrophysiologicalal evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study. Crit Care. 11:R Lefaucheur, J. P., T. Nordine, P. Rodriguez, and L. Brochard Origin of ICU acquired paresis determined by direct muscle stimulation. J Neurol Neurosurg Psychiatry. 77: Bednarik, J., Z. Lukas, and P. Vondracek Critical illness polyneuro: the electrophysiologicalal components of a complex entity. Intensive Care Med 29: Trojaborg, W., L. H. Weimer, and A. P. Hays Electrophysiological studies in critical illness associated weakness: or neuropathy--a reappraisal. Clin Neurophysiol. 112: Tennila, A., T. Salmi, V. Pettila, R. O. Roine, T. Varpula, and O. Takkunen Early signs of critical illness polyneuropathy in with systemic inflammatory response syndrome or. Intensive Care Med 26: Larsson, L., X. Li, L. Edstrom, L. I. Eriksson, H. Zackrisson, C. Argentini, and S. Schiaffino Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels. Crit Care Med. 28: Hough, C. L., K. P. Steinberg, B. T. Thompson, G. D. Rubenfeld, and L. D. Hudson Intensive care unit-acquired neuro and corticosteroids in survivors of persistent ARDS. Intensive Care Med 35: De Jonghe, B., T. Sharshar, J. P. Lefaucheur, F. J. Authier, I. Durand-Zaleski, M. Boussarsar, C. Cerf, E. Renaud, F. Mesrati, J. Carlet, J. C. Raphael, H. Outin, and S. Bastuji-Garin Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 288: Leijten, F. S. S., D. C. J. Poortvliet, and A. W. De Weerd The neurological examination in the assessment of polyneuropathy in mechanically ventilated patients. European Journal of Neurology 4: Amaya-Villar, R., J. Garnacho-Montero, J. L. Garcia-Garmendia, J. Madrazo-Osuna, M. C. Garnacho-Montero, R. Luque, and C. Ortiz-Leyba Steroid-induced in patients intubated due to exacerbation of chronic obstructive pulmonary disease. Intensive Care Med. 31: Guarneri, B., G. Bertolini, and N. Latronico Long-term outcome in patients with critical illness or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry 79: Hermans, G., A. Wilmer, W. Meersseman, I. Milants, P. Wouters, H. Bobbaers, F. Bruyninckx, and B. G. van den Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir.Crit Care Med 175: Garnacho-Montero, J., R. Amaya-Villar, J. L. Garcia-Garmendia, J. Madrazo-Osuna, and C. Ortiz-Leyba Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. Crit Care Med 33: Ali, N. A., J. O'Brien, S. P. Hoffmann, G. Phillips, A. Garland, J. C. Finley, K. Almoosa, R. Hejal, K. M. Wolf, S. Lemeshow, J. Connors, and C. B. Marsh Acquired Weakness, Handgrip Strength and Mortality in Critically Ill Patients. Am.J.Respir.Crit.Care Med. 178: Witt, N. J., D. W. Zochodne, C. F. Bolton, F. Grand'Maison, G. Wells, G. B. Young, and W. J. Sibbald Peripheral nerve function in and multiple organ failure. Chest. 99: Nanas, S., K. Kritikos, E. Angelopoulos, A. Siafaka, S. Tsikriki, M. Poriazi, D. Kanaloupiti, M. Kontogeorgi, M. Pratikaki, D. Zervakis, C. Routsi, and C. Roussos Predisposing factors for critical illness polyneuro in a multidisciplinary intensive care unit. Acta Neurol Scand. 118: Khan, J., T. B. Harrison, M. M. Rich, and M. Moss Early development of critical illness and neuropathy in patients with severe. Neurology 67: Van den Berghe, G., K. Schoonheydt, P. Becx, F. Bruyninckx, and P. J. Wouters Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 64: Bednarik, J., P. Vondracek, L. Dusek, E. Moravcova, and I. Cundrle Risk factors for critical illness polyneuro. J Neurol. 252: Velazquez, P. L., J. A. Jara Gonzalez, and C. G. Sanchez [Peripheral nerve conduction studies in patients with multiple organ failure]. Rev Neurol. 36: de Letter, M. A., P. I. Schmitz, L. H. Visser, F. A. Verheul, R. L. Schellens, D. A. Op de Coul, and F. G. van der Meche Risk factors for the development of polyneuropathy and in critically ill patients. Crit Care Med 29: Garnacho-Montero, J., J. Madrazo-Osuna, J. L. Garcia-Garmendia, C. Ortiz-Leyba, F. J. Jimenez-Jimenez, A. Barrero- Almodovar, M. C. Garnacho-Montero, and M. R. Moyano-Del-Estad Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients. Intensive Care Med 27: Thiele, R. I., H. Jakob, E. Hund, S. Tantzky, S. Keller, M. Kamler, U. Herold, and S. Hagl Sepsis and catecholamine support are the major risk factors for critical illness polyneuropathy after open heart surgery'. Thorac Cardiovasc Surg. 48: E6

8 24. Tepper, M., S. Rakic, J. A. Haas, and A. J. Woittiez Incidence and onset of critical illness polyneuropathy in patients with septic shock. Neth.J.Med 56: Coakley, J. H., K. Nagendran, G. D. Yarwood, M. Honavar, and C. J. Hinds Patterns of neurophysiological abnormality in prolonged critical illness. Intensive Care Med. 24: Mohr, M., L. Englisch, A. Roth, H. Burchardi, and S. Zielmann Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gram-negative. Intensive Care Med 23: Schwarz, J., J. Planck, J. Briegel, and A. Straube Single-fiber electromyography, nerve conduction studies, and conventional electromyography in patients with critical-illness polyneuropathy: evidence for a lesion of terminal motor axons. Muscle Nerve. 20: Rich, M. M., S. J. Bird, E. C. Raps, L. F. McCluskey, and J. W. Teener Direct muscle stimulation in acute quadriplegic. Muscle Nerve. 20: Leijten, F. S., A. W. De Weerd, D. C. Poortvliet, V. A. De Ridder, C. Ulrich, and J. E. Harink-De Weerd Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med 22: Leijten, F. S., J. E. Harinck-de Weerd, D. C. Poortvliet, and A. W. De Weerd The role of polyneuropathy in motor convalescence after prolonged mechanical ventilation. JAMA 274: Campellone, J. V., D. Lacomis, D. J. Kramer, A. C. Van Cott, and M. J. Giuliani Acute after liver transplantation. Neurology. 50: E7

9 Table E5: Question #1 Relevant Studies In which critically ill patient groups does ICU-acquired weakness occur with a clinically significantly increased frequency? (Descriptive) Reference # Study goal Type of patients (No) 4. Trojaborg Describe spectrum Patients with of CINMA in weakness and patients with prolonged mechanical ventilation Type of study Test(s) Outcome/Results Comments Case Series MMT/EMG/NCS Normal humans for controls; did not use as controls MMT not reported 5. Tennila Determine incidence of CINMA with severe Case series EMG/NCS Did not report controls MMT not reported 8. De Jonghe Determine with mechanical ventilation MMT 24/95 with 13. Garnacho- Montero Determine morbidity of CIP in with severe EMG/NCS 34/64 with CINMA 14. Ali Determine morbidity of 15. Witt Determine the electrophysiological abnormalities in with mechanical ventilation with severe MMT 35/136 had MMT/EMG/NCS 30/43 had abnormal NCS 16. Nanas Determine clinical risk factors for MMT 50/474 had 17. Khan Determine in Sepsis Patients with Sepsis MMT/EMG/NCS 23/48 had 22. Garnacho- Montero Determine in Sepsis Patients with MV and Sepsis (73) EMG/NCS 50/73 with CINMA 24. Tepper Determine in Septic Shock with Septic shock (22) MMT/EMG/NCS 19/22 with 27. Schwarz Determine in SIRS with Sepsis/SIRS (9) EMG/NCS 5/9 with CINMA ICU, intensive care unit;, ICU-acquired weakness; CINMA, critical-illness associated neuromuscular abnormality; MMT, manual muscle testing; EMG, electromyography; NCS, nerve conduction studies; DMS, direct muscle stimulation. E8

10 Table E6: Question #2 Relevant Studies What tests are used to identify ICU-acquired weakness and how are they applied in critically ill patients? (Descriptive) Reference # Study goal Type of patients (No) 1. Latronico General ICU Adult ICU patients patients with elevated SAPS2 scores Type of study Test(s) Outcome/Results Comments EMG/NCS; CMAP <2 SD normal proposed as a screening test 28/92 with abnormal EMG. EMG done on admit and serially per week No correlation with MMT. Screening test 2. Lefaucher Determine if DMS has utility in aiding diff dx of Critically ill patients on the ventilator for >7 days and Case series EMG/NCS/DMS 26/30 with normal stimulation, but evidence of Utility of DMS evaluated, no controls 3. Bednarik Determine EPS abnormalities in MOF Critically ill patients with 2 OF MMT/EMG/NCS/DMS at ICU day 3 and week 5 after enrollment 26/46 patients with Only patients completing study are reported 4. Trojaborg Describe spectrum of CINMA in patients referred for Patients with weakness and prolonged mechanical ventilation Case series MMT/EMG/NCS 100% with CIM; applied after referral for clinical weakness Normal human subjects for controls; did not use ICU patients as controls 5. Tennila Determine incidence of CINMA with severe Case series EMG/NCS Did not report controls MMT not reported 6. Larsson Describe AQM Consecutive patients with weakness Case series EMG/NCS/MMT All subjects with disease; no controls 7. Hough Prospective assessment of cases with reported ARDS patients Charting, report of MMT and EMG/NCS 43/128 with CINM, predominant CIM; EMG done after clinical weakness documented 11 subjects received EMG/NCS 8. De Jonghe Determine with mechanical ventilation MMT 24/95 with 9. Leijten Compare exam to EMG findings in patients at risk for with MV>7 days and age <75 MMT/EMG/NCS at ventilator day /71 with CINMA 10. Amaya- Villar Determine incidence of Acute in critically ill COPD patients treated with steroids Patients requiring MV for COPD who are treated with steroids MMT/ EMG 9/26 patients with 11. Guarneri Determine the longterm recovery of Patient diagnosed with after ICU stay MMT/50m walk test 33% recovered by 3 months E9

11 12. Hermans Report of in patients treated in RCT of IIT Critically ill patients remaining in Medical ICU for at least 7 days Weekly limited EMG 188/420 developed Fibrillation potential defined 13. Garnacho- Montero Determine morbidity of CIP in with severe and MV use >7days EMG/NCS performed at onset of ventilator liberation 34/64 with CINMA 14. Ali Determine morbidity of 15. Witt Determine the electrophysiological abnormalities in 16. Nanas Determine clinical risk factors for 17. Khan Determine in Sepsis with mechanical ventilation with severe with mechanical ventilation Patients with Sepsis MMT 35/136 had MMT/EMG/NCS 30/70 had abnormal NCS MMT 44/185 had MMT/EMG/NCS 23/48 had 18. Van den Berghe Report of in patients treated in RCT of IIT Critically ill patients remaining in Surgical ICU for at least 7 days Weekly limited EMG 74/405 developed Fibrillation potential defined 19. Bednarik Determine EPS abnormalities in MOF Critically ill patients with 2 OF MMT/EMG/NCS/DMS at ICU day 3 and week 5 after enrollment 17/61 developed and 35/61 developed 20. Velazquez Report of patients presenting with weakness Critically ill patients with >2 OF MMT/EMG/NCS after presentation with weakness 7/18 patients with CINMA Additional controls 21. de Letter Assess incidence of Critically-ill patients requiring mechanical ventilation > 3 days MMT/NCS/MMT 32/98 with Twice weekly neurologic exams, EMG/NCS Day 4, 11 and Garnacho- Montero Determine morbidity of CIP in with severe and MV use > 10days EMG/NCS performed at day 10 and 21 after mechanical ventilation 50/73 with CINMA 23. Thiele Description of CIP after cardiac surgery Cardiac surgery patients with > 7 days stay Cases received EMG/NCS 4/7 CIP cases died in hospital Controls were other nonaffected patients who stayed in ICU>7 days. 24. Tepper Determine with Septic MMT/EMG/NCS 19/22 with E10

12 in Septic Shock shock (22) 25. Coakley Describe Neuromuscular abnormalities in Septic patients in ICU for 7 days MMT/Muscle Biopsy/EMG/NCS 22/23 patients had abnormal Bx and/or EMG Only 23 of 62 eligible patients enrolled 26. Mohr Description of the development of CIP in MOF Critically ill patients with MOF >4 days MMT/EMG/NCS 7/33 patients with All were septic 27. Schwarz Determine in SIRS with Sepsis/SIRS (9) EMG/NCS 5/9 with CINMA 28. Rich Describe syndrome of acute quadriplegic in ICU for >14 days and evidence of weakness Case series NCS/EMG/DMS performed after clinical manifestation 14 patients described 29. Leijten Determine morbidity of CIP in prolonged critical illness with MV>7 days and age <75 MMT/EMG/NCS at ventilator day /38 patients with 30. Leijten Determine morbidity of CIP in prolonged critical illness with MV>7 days and age <75 MMT/EMG/NCS at ventilator day /50 patients with 31. Campellone Determine the AQM after liver transplantation Consecutive liver transplant patients MMT in all, EMG/NCS in those with weakness; 5 with muscle Bx 7/100 with ICU, intensive care unit;, ICU-acquired weakness; CINMA, critical-illness associated neuromuscular abnormality; MMT, manual muscle testing; EMG, electromyography; NCS, nerve conduction studies; DMS, direct muscle stimulation. E11

13 Table E7: The Medical Research Council (MRC) scale for evaluating peripheral muscle strength Score Response 0 No contraction 1 Flicker or trace of contraction 2 Active movement, with gravity eliminated 3 Active movement against gravity 4 Active movement against gravity and resistance 5 Normal power When MMT evaluates strength in 3 muscle groups of 4 limbs each scored between 0 and 5, the maximum total score is 60. Motions tested: shoulder abduction, arm flexion, wrist extension, hip flexion, leg extension and ankle dorsiflexion. Exam procedures: For each muscle group, the movement is first performed passively, to clarify with the patient what movement is expected. Shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion are typically tested bilaterally to determine distribution and asymmetry. For each muscle group, first, the ability to move against gravity is tested. (MRC 3) Dependent of the resulting action, resistance is added (MRC 4/5) or gravity is eliminated (MRC 0-2). Diagnostic criteria for from the Brussels Round table expert panel(11) can be defined as new diffuse, flaccid and symmetric weakness (defined below) with a clear onset after the development of critical illness. a. MRC sum score <48 or 80% of maximum possible score persisting at least 24 hours b. Some evidence of weakness in all examined limbs c. Cranial nerve function intact (preserved eye opening and facial grimace) All 3 required E12

14 Table E8: Studies Using a Composite MRC Score for the Diagnosis of Study Author (Year) Muscles Tested MRC Threshold for Leijten (1995) All muscle groups of all extremities < 4/5 in each muscle tested Leijten (1997) Proximal and distal muscle groups 4/5 in at least both legs Campellone (1998) Proximal and distal muscle groups 3/5 in at least 1 muscle group De Letter (2001) Wrist extension, elbow flexion, < 26/30 (87%)* shoulder abduction, ankle plantar flexion, knee extension, hip flexion De Jonghe (2002) Wrist extension, elbow flexion, < 48/60 (80%)* shoulder abduction, ankle dorsiflexion, knee extension, hip flexion Lefaucheur (2006) Same as De Letter (2001) above < 48/60 (80%)* Guarneri (2008) Proximal and distal muscle group < 4/5 in muscles tested exam in all 4 limbs Ali (2008) Same as De Letter (2001) above < 4/5 in all muscles tested Nanas (2008) Same as De Letter (2001) above < 48/60 (80%)* Abbreviations:, ICU-acquired weakness; MRC, Medical Research Council * Percent of the total MRC score defining in the included study E13

15 Table E9: Question #3 Relevant Studies How is electrophysiological testing used in critically-ill patients when making the diagnosis of ICU-acquired weakness? (Descriptive) Reference # Study goal Type of patients (No) 1. Latronico General ICU Adult patients with elevated SAPS2 scores Type of study Test (standard) Outcome/Results Comments EMG/NCS; CMAP <2 SD normal proposed as a screening test 28/92 with abnormal EMG. EMG done on admit and serially per week No correlation with MMT. Screening test 2. Lefaucher Determine if DMS has utility in aiding diff dx of Critically ill patients on the ventilator for >7 days and Case series EMG/NCS/DMS 26/30 with normal stimulation, but evidence of Utility of DMS evaluated, no controls 3. Bednarik Determine EPS abnormalities in MOF 4. Trojaborg Describe spectrum of CINMA in patients referred for Critically ill patients with 2 OF Patients with weakness and prolonged mechanical ventilation MMT/EMG/NCS/DMS at ICU day 3 and week 5 after enrollment 26/46 patients with Case series MMT/EMG/NCS 100% with CIM; applied after referral for clinical weakness Only patients completing study are reported Normal human subjects for controls; did not use as controls 7. Hough Prospective assessment of cases with reported ARDS patients Charting, report of MMT and EMG/NCS 43/128 with CINM, predominant CIM; EMG done after clinical weakness documented 11 subjects received EMG/NCS 8. De Jonghe Determine with mechanical ventilation MMT/NCS 24/95 with had EMG/NCS All subjects with persistent weakness for 7 days received NCS/EMG 12. Hermans Report of in patients treated in RCT of IIT Critically ill patients remaining in Medical ICU for at least 7 days Weekly limited EMG 188/420 developed Fibrillation potential defined 13. Garnacho- Montero Determine morbidity of CIP in with severe and MV use >7days EMG/NCS performed at onset of ventilator liberation 34/64 with CINMA 17. Khan Determine in Sepsis Patients with Sepsis MMT/EMG/NCS 23/48 had 18. Van den Berghe Report of in patients treated in RCT of IIT Critically ill patients remaining in Surgical ICU for at least 7 days Weekly limited EMG 74/405 developed Fibrillation potential defined 19. Bednarik Determine EPS abnormalities in MOF Critically ill patients with 2 OF MMT/EMG/NCS/DMS at ICU day 3 and week 5 after enrollment 17/61 developed and 35/61 developed 22. Garnacho- Montero Determine morbidity of CIP in with severe and MV use > 10days EMG/NCS performed at day 10 and 21 after mechanical ventilation 50/73 with CINMA 28. Rich Describe syndrome of acute quadriplegic in ICU for >14 days and evidence of weakness Case series NCS/EMG/DMS performed after clinical manifestation 14 patients described 29. Leijten Determine morbidity of CIP in prolonged critical illness with MV>7 days and age <75 MMT/EMG/NCS at ventilator day /38 patients with E14

16 30. Leijten Determine morbidity of CIP in prolonged critical illness with MV>7 days and age <75 MMT/EMG/NCS at ventilator day /50 patients with ICU, intensive care unit;, ICU-acquired weakness; CINMA, critical-illness associated neuromuscular abnormality; MMT, manual muscle testing; EMG, electromyography; NCS, nerve conduction studies; DMS, direct muscle stimulation. E15

17 Table E10: Voting results for iterative discussions and recommendations Cooperative patients requiring prolonged mechanical ventilation should undergo MMT when feasible. % yes response % LOWER QUALITY EVIDENCE 56.3 In favor 93.8 UNCERTAIN BENEFITS VS 31.3 Strongly in favor 62.5 HARM DIFFERENCES IN VALUES 43.8 Against 0 UNCERTAIN BENEFITS VS COSTS 25.0 Weak recommendation for We suggest Cooperative patients experiencing difficulty with ventilator weaning from an unknown cause should undergo MMT when feasible. % yes response % LOWER QUALITY EVIDENCE 50.0 In favor UNCERTAIN BENEFITS VS 31.3 Strongly in favor 50.0 HARM DIFFERENCES IN VALUES 37.5 Against 0 UNCERTAIN BENEFITS VS COSTS 31.3 Weak recommendation for We suggest Cooperative patients with severe should undergo MMT when feasible. % yes response % LOWER QUALITY EVIDENCE 50.0 In favor 87.5 UNCERTAIN BENEFITS VS 31.3 Strongly in favor 50.0 HARM DIFFERENCES IN VALUES 37.5 Against 0 UNCERTAIN BENEFITS VS COSTS 37.5 Weak recommendation for We suggest Uncooperative patients at high-risk for because of prolonged mechanical ventilation should undergo EMG/NCS when available. % yes response % LOWER QUALITY EVIDENCE 75.0 In favor 50.0 UNCERTAIN BENEFITS VS 68.8 Strongly in favor 18.8 HARM DIFFERENCES IN VALUES 62.5 Against 31.3 UNCERTAIN BENEFITS VS COSTS 81.3 No recommendation Uncooperative patients with difficult ventilator weaning from an unknown cause should undergo EMG/NCS when available % yes response % LOWER QUALITY EVIDENCE 68.8 In favor 62.5 UNCERTAIN BENEFITS VS 68.8 Strongly in favor 12.5 HARM DIFFERENCES IN VALUES 68.8 Against 31.3 UNCERTAIN BENEFITS VS COSTS 75.0 Weak recommendation for We suggest Uncooperative, but stable patients at high risk for because of severe should undergo EMG/NCS when available % yes response % E16

18 LOWER QUALITY EVIDENCE 62.5 In favor 37.5 UNCERTAIN BENEFITS VS 68.8 Strongly in favor 12.5 HARM DIFFERENCES IN VALUES 68.8 Against 31.3 UNCERTAIN BENEFITS VS COSTS 81.3 No recommendation E17