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discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/269712406

An Official American Thoracic Society Clinical

Practice Guideline: The Diagnosis of Intensive
Care Unitacquired Weakness in Adults

ARTICLE in AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE DECEMBER 2014
Impact Factor: 11.99 DOI: 10.1164/rccm.201411-2011ST Source: PubMed

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18 AUTHORS, INCLUDING:

Nicholas Hart Catherine Lee Hough

King's College London University of Washington Seattle
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Robert D. Stevens Chris Winkelman

Johns Hopkins Medicine Case Western Reserve University
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Available from: Nicholas Hart

Retrieved on: 06 August 2015
 AN OFFICIAL ATS CLINICAL PRACTICE GUIDELINE: THE DIAGNOSIS OF
INTENSIVE CARE UNIT ACQUIRED WEAKNESS

Online Supplement

Eddy Fan1,2
Roy G. Brower2
Fern Cheek4
Linda Chlan5
Rik Gosselink6
Nicholas Hart7
Margaret S. Herridge1
Ramona O. Hopkins8,9
Catherine L. Hough10
John P. Kress11
Nicola Latronico12
Marc Moss13
Dale M. Needham2,3
Mark M. Rich14
Robert D. Stevens15
Chris Winkelman16
Doug W. Zochodne17
Naeem A. Ali18
Institution information:
1
Interdepartmental Division of Critical Care Medicine, University Health Network, University
of Toronto, Toronto, Canada; 2Outcomes After Critical Illness and Surgery (OACIS) Group,
Division of Pulmonary and Critical Care Medicine and 3Department of Physical Medicine and
Rehabilitation, Johns Hopkins University, Baltimore, MD, USA; 4The Ohio State University,
Columbus, OH, USA; 5School of Nursing, University of Minnesota, MN, USA; 6Department of
Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium; 7Lane Fox
Respiratory Unit, St Thomas Hospital, Guys & St Thomas NHS Foundation Trust, Kings
Health Partners, London, UK; Psychology Department and Neuroscience Center, Brigham
Young University, Provo, UT, USA; 9Department of Medicine, Pulmonary and Critical Care,
Intermountain Medical Center, Murray, Utah, USA; 10Division of Pulmonary and Critical Care
Medicine, University of Washington, Seattle, WA, USA; 11Division of Pulmonary and Critical
Care Medicine, University of Chicago, Chicago, IL, USA; 12Department of Anesthesia and
Critical Care, University of Brescia, Brescia, Italy; 13Division of Pulmonary Sciences and
Critical Care Medicine, University of Colorado, Aurora, CO, USA; 14Department of
Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH,
USA; 15Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University,
Baltimore, MD, USA; 16School of Nursing, Case Western Reserve University, Cleveland, OH,
USA; 17Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta,
Canada; 18Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Wexner Medical
Center at The Ohio State University, Columbus, OH, USA

E0
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 ICUAW
Table E9: Question #3 Relevant Studies
Table E10: Voting results for iterative discussions and recommendations

E1
Table E1: Membership of Guidelines Development Committee

Committee member Country Area of expertise

Naeem Ali (non-voting) USA Critical Care Medicine

Roy Brower USA Critical Care Medicine
Linda Chlan USA Critical Care Nursing
Eddy Fan Canada Critical Care Medicine
Rik Gosselink Belgium Physical Therapy
Nicholas Hart England Critical Care Medicine
Margaret Herridge Canada Critical Care Medicine
Ramona Hopkins USA Neurosciences, Psychology
Catherine Hough USA Critical Care Medicine
John Kress USA Critical Care Medicine
Nicola Latronico Italy Neurological Critical Care Medicine
Marc Moss USA Critical Care Medicine
Dale Needham USA Critical Care Medicine
Mark Rich USA Neurology
Robert Stevens USA Neurological Critical Care Medicine
Chris Winkelman USA Critical Care Nursing
Doug Zochodne Canada Neurology
Fern Cheek (non-voting) USA Research Librarian

E2
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
Table E3: Evidence table: Physical therapy in patients with ICUAW
Bibliography:
1. Ali NA, OBrien 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; 178:261-268.
2. 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; 35:133-140.

--Quality of Evidence Assessment-- --Summary of Findings--

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 Serious1 Very low In the first case series of 35 patients
series limitations inconsistency indirectness (critical with ICUAW, 6 patients were able
outcome) to be discharged home (17%)
following their critical illness.

In the second case series of 19

patients with ICUAW who
underwent physical therapy, 6
patients were able to be discharged
home (32%) following their critical
illness.

RR 1.84, 95% CI 0.69-4.93

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).
Mortality
2 Case No serious No serious No serious Serious1 Very low In the first case series of 35 patients
series limitations inconsistency indirectness (critical with ICUAW, 11 patients died
outcome) (31%).

In the second case series of 19

patients with ICUAW who
underwent physical therapy, 2
patients died (11%).

RR 0.33, 95% CI 0.08-1.36

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: ICUAW = 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
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

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

Met Eligibility Criteria

Total citations = 31

E5
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. 2007. Simplified electrophysiologicalal evaluation of peripheral nerves in critically ill
patients: the Italian multi-centre CRIMYNE study. Crit Care. 11:R11.
2. Lefaucheur, J. P., T. Nordine, P. Rodriguez, and L. Brochard. 2006. Origin of ICU acquired paresis determined by direct
muscle stimulation. J Neurol Neurosurg Psychiatry. 77:500-506.
3. Bednarik, J., Z. Lukas, and P. Vondracek. 2003. Critical illness polyneuromyopathy: the electrophysiologicalal
components of a complex entity. Intensive Care Med 29:1505-1514.
4. Trojaborg, W., L. H. Weimer, and A. P. Hays. 2001. Electrophysiological studies in critical illness associated weakness:
myopathy or neuropathy--a reappraisal. Clin Neurophysiol. 112:1586-1593.
5. Tennila, A., T. Salmi, V. Pettila, R. O. Roine, T. Varpula, and O. Takkunen. 2000. Early signs of critical illness
polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med 26:1360-
1363.
6. Larsson, L., X. Li, L. Edstrom, L. I. Eriksson, H. Zackrisson, C. Argentini, and S. Schiaffino. 2000. 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. 28:34-45.
7. Hough, C. L., K. P. Steinberg, B. T. Thompson, G. D. Rubenfeld, and L. D. Hudson. 2009. Intensive care unit-acquired
neuromyopathy and corticosteroids in survivors of persistent ARDS. Intensive Care Med 35:63-68.
8. 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. 2002. Paresis acquired in the intensive care unit: a
prospective multicenter study. JAMA 288:2859-2867.
9. Leijten, F. S. S., D. C. J. Poortvliet, and A. W. De Weerd. 1997. The neurological examination in the assessment of
polyneuropathy in mechanically ventilated patients. European Journal of Neurology 4:124-129.
10. Amaya-Villar, R., J. Garnacho-Montero, J. L. Garcia-Garmendia, J. Madrazo-Osuna, M. C. Garnacho-Montero, R. Luque,
and C. Ortiz-Leyba. 2005. Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive
pulmonary disease. Intensive Care Med. 31:157-161.
11. Guarneri, B., G. Bertolini, and N. Latronico. 2008. Long-term outcome in patients with critical illness myopathy or
neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry 79:838-841.
12. Hermans, G., A. Wilmer, W. Meersseman, I. Milants, P. Wouters, H. Bobbaers, F. Bruyninckx, and B. G. van den. 2007.
Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive
care unit. Am J Respir.Crit Care Med 175:480-9.
13. Garnacho-Montero, J., R. Amaya-Villar, J. L. Garcia-Garmendia, J. Madrazo-Osuna, and C. Ortiz-Leyba. 2005. Effect of
critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients.
Crit Care Med 33:349-354.
14. 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. 2008. Acquired Weakness, Handgrip Strength and Mortality in Critically Ill
Patients. Am.J.Respir.Crit.Care Med. 178:261-268.
15. Witt, N. J., D. W. Zochodne, C. F. Bolton, F. Grand'Maison, G. Wells, G. B. Young, and W. J. Sibbald. 1991. Peripheral
nerve function in sepsis and multiple organ failure. Chest. 99:176-184.
16. 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. 2008. Predisposing factors for critical illness polyneuromyopathy in a
multidisciplinary intensive care unit. Acta Neurol Scand. 118:175-181.
17. Khan, J., T. B. Harrison, M. M. Rich, and M. Moss. 2006. Early development of critical illness myopathy and neuropathy
in patients with severe sepsis. Neurology 67:1421-1425.
18. Van den Berghe, G., K. Schoonheydt, P. Becx, F. Bruyninckx, and P. J. Wouters. 2005. Insulin therapy protects the
central and peripheral nervous system of intensive care patients. Neurology 64:1348-1353.
19. Bednarik, J., P. Vondracek, L. Dusek, E. Moravcova, and I. Cundrle. 2005. Risk factors for critical illness
polyneuromyopathy. J Neurol. 252:343-351.
20. Velazquez, P. L., J. A. Jara Gonzalez, and C. G. Sanchez. 2003. [Peripheral nerve conduction studies in patients with
multiple organ failure]. Rev Neurol. 36:15-20.
21. 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.
2001. Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 29:2281-
2286.
22. 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. 2001. Critical illness polyneuropathy: risk factors
and clinical consequences. A cohort study in septic patients. Intensive Care Med 27:1288-1296.
23. Thiele, R. I., H. Jakob, E. Hund, S. Tantzky, S. Keller, M. Kamler, U. Herold, and S. Hagl. 2000. Sepsis and
catecholamine support are the major risk factors for critical illness polyneuropathy after open heart surgery'. Thorac
Cardiovasc Surg. 48:145-150.

E6
24. Tepper, M., S. Rakic, J. A. Haas, and A. J. Woittiez. 2000. Incidence and onset of critical illness polyneuropathy in
patients with septic shock. Neth.J.Med 56:211-214.
25. Coakley, J. H., K. Nagendran, G. D. Yarwood, M. Honavar, and C. J. Hinds. 1998. Patterns of neurophysiological
abnormality in prolonged critical illness. Intensive Care Med. 24:801-807.
26. Mohr, M., L. Englisch, A. Roth, H. Burchardi, and S. Zielmann. 1997. Effects of early treatment with immunoglobulin on
critical illness polyneuropathy following multiple organ failure and gram-negative sepsis. Intensive Care Med 23:1144-
1149.
27. Schwarz, J., J. Planck, J. Briegel, and A. Straube. 1997. 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. 20:696-701.
28. Rich, M. M., S. J. Bird, E. C. Raps, L. F. McCluskey, and J. W. Teener. 1997. Direct muscle stimulation in acute
quadriplegic myopathy. Muscle Nerve. 20:665-673.
29. Leijten, F. S., A. W. De Weerd, D. C. Poortvliet, V. A. De Ridder, C. Ulrich, and J. E. Harink-De Weerd. 1996. Critical
illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med
22:856-861.
30. Leijten, F. S., J. E. Harinck-de Weerd, D. C. Poortvliet, and A. W. De Weerd. 1995. The role of polyneuropathy in motor
convalescence after prolonged mechanical ventilation. JAMA 274:1221-1225.
31. Campellone, J. V., D. Lacomis, D. J. Kramer, A. C. Van Cott, and M. J. Giuliani. 1998. Acute myopathy after liver
transplantation. Neurology. 50:46-53.

E7
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 Type of study Test(s) Outcome/Results Comments

patients (No)
4. Trojaborg Describe spectrum Patients with Case Series MMT/EMG/NCS Normal humans for MMT not
of CINMA in weakness and controls; did not reported
patients with prolonged use ICU patients as
ICUAW mechanical controls
ventilation

5. Tennila Determine ICU patients Case series EMG/NCS Did not report MMT not
incidence of with severe controls reported
CINMA sepsis

8. De Jonghe Determine ICU patients Observational MMT 24/95 with ICUAW

prevalence of with mechanical
ICUAW ventilation

13. Garnacho- Determine ICU patients Observational EMG/NCS 34/64 with CINMA
Montero morbidity of CIP in with severe
sepsis sepsis

14. Ali Determine ICU patients Observational MMT 35/136 had

morbidity of with mechanical ICUAW
ICUAW ventilation

15. Witt Determine the ICU patients Observational MMT/EMG/NCS 30/43 had abnormal
prevalence of with severe NCS
electrophysiological sepsis
abnormalities in
sepsis

16. Nanas Determine clinical ICU patients Observational MMT 50/474 had
risk factors for ICUAW
ICUAW

17. Khan Determine Patients with Observational MMT/EMG/NCS 23/48 had ICUAW
prevalence of Sepsis
ICUAW in Sepsis

22. Garnacho- Determine Patients with Observational EMG/NCS 50/73 with CINMA
Montero prevalence of MV and Sepsis
ICUAW in Sepsis (73)

24. Tepper Determine ICU patients Observational MMT/EMG/NCS 19/22 with ICUAW
prevalence of with Septic
ICUAW in Septic shock (22)
Shock

27. Schwarz Determine ICU patients Observational EMG/NCS 5/9 with CINMA
prevalence of with
ICUAW in SIRS Sepsis/SIRS (9)
ICU, intensive care unit; ICUAW, ICU-acquired weakness; CINMA, critical-illness associated neuromuscular abnormality; MMT, manual
muscle testing; EMG, electromyography; NCS, nerve conduction studies; DMS, direct muscle stimulation.

E8
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 Type of study Test(s) Outcome/Results Comments

patients (No)
1. Latronico General ICU Adult ICU Observational EMG/NCS; CMAP <2 28/92 with No correlation
patients patients with SD normal proposed as abnormal EMG. with MMT.
elevated a screening test EMG done on Screening
SAPS2 scores admit and serially test
per week

2. Lefaucher Determine if DMS Critically ill Case series EMG/NCS/DMS 26/30 with normal Utility of
has utility in aiding patients on the stimulation, but DMS
diff dx of ICUAW ventilator for evidence of evaluated, no
>7 days and myopathy controls
ICUAW

3. Bednarik Determine Critically ill Observational MMT/EMG/NCS/DMS 26/46 patients with Only patients
prevalence of EPS patients with at ICU day 3 and week CIPNM completing
abnormalities in 2 OF 5 after enrollment study are
MOF reported

4. Trojaborg Describe spectrum Patients with Case series MMT/EMG/NCS 100% with CIM; Normal
of CINMA in weakness and applied after human
patients referred for prolonged referral for clinical subjects for
ICUAW mechanical weakness controls; did
ventilation not use ICU
patients as
controls

5. Tennila Determine ICU patients Case series EMG/NCS Did not report MMT not
incidence of with severe controls reported
CINMA sepsis

6. Larsson Describe AQM Consecutive Case series EMG/NCS/MMT All subjects with
patients with disease; no
weakness controls

7. Hough Prospective ARDS patients Observational Charting ICUAW, 43/128 with 11 subjects
assessment of cases report of MMT and CINM, received
with reported EMG/NCS predominant CIM; EMG/NCS
ICUAW EMG done after
clinical weakness
documented

8. De Jonghe Determine ICU patients Observational MMT 24/95 with

prevalence of with ICUAW
ICUAW mechanical
ventilation

9. Leijten Compare exam to ICU patients Observational MMT/EMG/NCS at 35/71 with

EMG findings in with MV>7 ventilator day 7-9 CINMA
patients at risk for days and age
ICUAW <75

10. Amaya- Determine Patients Observational MMT/ EMG 9/26 patients with
Villar incidence of Acute requiring MV myopathy
myopathy in for COPD who
critically ill COPD are treated
patients treated with with steroids
steroids

11. Guarneri Determine the long- Patient Observational MMT/50m walk test 33% recovered by
term recovery of diagnosed with 3 months
CIPNM CIPNM after
ICU stay

E9
12. Hermans Report of CIPNM Critically ill Observational Weekly limited EMG 188/420 developed Fibrillation
in patients treated in patients CIPNM potential
RCT of IIT remaining in defined
Medical ICU myopathy
for at least 7
days

13. Garnacho- Determine ICU patients Observational EMG/NCS performed 34/64 with
Montero morbidity of CIP in with severe at onset of ventilator CINMA
sepsis sepsis and MV liberation
use >7days

14. Ali Determine ICU patients Observational MMT 35/136 had

morbidity of with ICUAW
ICUAW mechanical
ventilation

15. Witt Determine the ICU patients Observational MMT/EMG/NCS 30/70 had
prevalence of with severe abnormal NCS
electrophysiological sepsis
abnormalities in
sepsis

16. Nanas Determine clinical ICU patients Observational MMT 44/185 had
risk factors for with ICUAW
ICUAW mechanical
ventilation

17. Khan Determine Patients with Observational MMT/EMG/NCS 23/48 had ICUAW
prevalence of Sepsis
ICUAW in Sepsis

18. Van den Report of CIPNM Critically ill Observational Weekly limited EMG 74/405 developed Fibrillation
Berghe in patients treated in patients CIPNM potential
RCT of IIT remaining in defined
Surgical ICU myopathy
for at least 7
days

19. Bednarik Determine Critically ill Observational MMT/EMG/NCS/DMS 17/61 developed

prevalence of EPS patients with at ICU day 3 and week ICUAW and 35/61
abnormalities in 2 OF 5 after enrollment developed CIPNM
MOF

20. Velazquez Report of patients Critically ill Observational MMT/EMG/NCS after 7/18 patients with Additional
presenting with patients with presentation with CINMA controls
weakness >2 OF weakness

21. de Letter Assess incidence of Critically-ill Observational MMT/NCS/MMT 32/98 with CIPNM Twice weekly
CIPNM patients neurologic
requiring exams,
mechanical EMG/NCS
ventilation > 3 Day 4, 11 and
days 25

22. Garnacho- Determine ICU patients Observational EMG/NCS performed 50/73 with
Montero morbidity of CIP in with severe at day 10 and 21 after CINMA
sepsis sepsis and MV mechanical ventilation
use > 10days

23. Thiele Description of CIP Cardiac Observational Cases received 4/7 CIP cases died Controls were
after cardiac surgery EMG/NCS in hospital other non-
surgery patients with > affected
7 days stay patients who
stayed in
ICU>7 days.

24. Tepper Determine ICU patients Observational MMT/EMG/NCS 19/22 with

prevalence of with Septic ICUAW

E10
 ICUAW in Septic shock (22)
Shock

25. Coakley Describe Septic patients Observational MMT/Muscle 22/23 patients had Only 23 of 62
Neuromuscular in ICU for 7 Biopsy/EMG/NCS abnormal Bx eligible
abnormalities in days and/or EMG patients
sepsis enrolled

26. Mohr Description of the Critically ill Observational MMT/EMG/NCS 7/33 patients with All were
development of CIP patients with CIPNM septic
in MOF MOF >4 days

27. Schwarz Determine ICU patients Observational EMG/NCS 5/9 with CINMA
prevalence of with
ICUAW in SIRS Sepsis/SIRS
(9)

28. Rich Describe syndrome ICU patients Case series NCS/EMG/DMS 14 patients
of acute in ICU for >14 performed after clinical described
quadriplegic days and manifestation
myopathy evidence of
weakness

29. Leijten Determine ICU patients Observational MMT/EMG/NCS at 18/38 patients with
morbidity of CIP in with MV>7 ventilator day 7-9 CIPNM
prolonged critical days and age
illness <75

30. Leijten Determine ICU patients Observational MMT/EMG/NCS at 29/50 patients with
morbidity of CIP in with MV>7 ventilator day 7-9 CIPNM
prolonged critical days and age
illness <75

31. Determine the Consecutive Observational MMT in all, EMG/NCS 7/100 with
Campellone prevalence of AQM liver transplant in those with weakness; myopathy
after liver patients 5 with muscle Bx
transplantation
ICU, intensive care unit; ICUAW, ICU-acquired weakness; CINMA, critical-illness associated neuromuscular abnormality; MMT, manual
muscle testing; EMG, electromyography; NCS, nerve conduction studies; DMS, direct muscle stimulation.

E11
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 ICUAW from the Brussels Round table expert panel(11)

ICUAW 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
Table E8: Studies Using a Composite MRC Score for the Diagnosis of ICUAW

Study Author (Year) Muscles Tested MRC Threshold for ICUAW

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: ICUAW, ICU-acquired weakness; MRC, Medical Research Council

* Percent of the total MRC score defining ICUAW in the included study

E13
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 Type of study Test (standard) Outcome/Results Comments
(No)
1. Latronico General ICU Adult ICU patients Observational EMG/NCS; CMAP <2 28/92 with No correlation with
patients with elevated SD normal proposed as abnormal EMG. MMT. Screening
SAPS2 scores a screening test EMG done on admit test
and serially per
week

2. Lefaucher Determine if DMS Critically ill patients Case series EMG/NCS/DMS 26/30 with normal Utility of DMS
has utility in aiding on the ventilator for stimulation, but evaluated, no
diff dx of ICUAW >7 days and evidence of controls
ICUAW myopathy

3. Bednarik Determine Critically ill patients Observational MMT/EMG/NCS/DMS 26/46 patients with Only patients
prevalence of EPS with 2 OF at ICU day 3 and week 5 CIPNM completing study
abnormalities in after enrollment are reported
MOF
4. Trojaborg Describe spectrum Patients with Case series MMT/EMG/NCS 100% with CIM; Normal human
of CINMA in weakness and applied after subjects for
patients referred for prolonged referral for clinical controls; did not
ICUAW mechanical weakness use ICU patients as
ventilation controls

7. Hough Prospective ARDS patients Observational Charting ICUAW, 43/128 with CINM, 11 subjects received
assessment of cases report of MMT and predominant CIM; EMG/NCS
with reported EMG/NCS EMG done after
ICUAW clinical weakness
documented

8. De Jonghe Determine ICU patients with Observational MMT/NCS 24/95 with ICUAW All subjects with
prevalence of mechanical had EMG/NCS persistent weakness
ICUAW ventilation for 7 days received
NCS/EMG

12. Hermans Report of CIPNM in Critically ill patients Observational Weekly limited EMG 188/420 developed Fibrillation
patients treated in remaining in CIPNM potential defined
RCT of IIT Medical ICU for at myopathy
least 7 days

13. Garnacho- Determine ICU patients with Observational EMG/NCS performed at 34/64 with CINMA
Montero morbidity of CIP in severe sepsis and onset of ventilator
sepsis MV use >7days liberation

17. Khan Determine Patients with Sepsis Observational MMT/EMG/NCS 23/48 had ICUAW
prevalence of
ICUAW in Sepsis

18. Van den Berghe Report of CIPNM in Critically ill patients Observational Weekly limited EMG 74/405 developed Fibrillation
patients treated in remaining in CIPNM potential defined
RCT of IIT Surgical ICU for at myopathy
least 7 days

19. Bednarik Determine Critically ill patients Observational MMT/EMG/NCS/DMS 17/61 developed
prevalence of EPS with 2 OF at ICU day 3 and week 5 ICUAW and 35/61
abnormalities in after enrollment developed CIPNM
MOF

22. Garnacho- Determine ICU patients with Observational EMG/NCS performed at 50/73 with CINMA
Montero morbidity of CIP in severe sepsis and day 10 and 21 after
sepsis MV use > 10days mechanical ventilation

28. Rich Describe syndrome ICU patients in ICU Case series NCS/EMG/DMS 14 patients
of acute for >14 days and performed after clinical described
quadriplegic evidence of manifestation
myopathy weakness

29. Leijten Determine ICU patients with Observational MMT/EMG/NCS at 18/38 patients with
morbidity of CIP in MV>7 days and age ventilator day 7-9 CIPNM
prolonged critical <75
illness

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30. Leijten Determine ICU patients with Observational MMT/EMG/NCS at 29/50 patients with
morbidity of CIP in MV>7 days and age ventilator day 7-9 CIPNM
prolonged critical <75
illness
ICU, intensive care unit; ICUAW, ICU-acquired weakness; CINMA, critical-illness associated neuromuscular abnormality; MMT, manual muscle
testing; EMG, electromyography; NCS, nerve conduction studies; DMS, direct muscle stimulation.

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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 25.0 Weak recommendation for We suggest
COSTS

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 100.0
UNCERTAIN BENEFITS VS 31.3 Strongly in favor 50.0
HARM
DIFFERENCES IN VALUES 37.5 Against 0
UNCERTAIN BENEFITS VS 31.3 Weak recommendation for We suggest
COSTS

Cooperative patients with severe sepsis 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 37.5 Weak recommendation for We suggest
COSTS

Uncooperative patients at high-risk for ICUAW 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 81.3 No recommendation
COSTS

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 75.0 Weak recommendation for We suggest
COSTS

Uncooperative, but stable patients at high risk for ICUAW because of severe sepsis should
undergo EMG/NCS when available
% yes response %

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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 81.3 No recommendation
COSTS

E17