This document discusses critical illness-acquired weakness (ICUAW), including its prevalence, risk factors, outcomes, and diagnostic criteria. The main points are: First, ICUAW occurs in approximately 50% of adult ICU patients receiving prolonged mechanical ventilation or those with sepsis/multiple organ failure. Second, while hyperglycemia is associated with ICUAW, studies have not consistently supported other accepted risk factors like glucocorticoids or neuromuscular blockers. Third, ICUAW increases duration of mechanical ventilation and hospitalization, and may cause long-term neuromuscular weakness, though it does not reliably predict mortality. Diagnosis is challenging due to heterogeneity. Early rehabilitation and mobil

1. DDrr PPaalleeppuu GGooppaall
HHyyddeerraabbaadd
1

2. ICU-acquired weakness (ICUAW) is ‘clinically detected
weakness in critically ill patients in whom there is no
plausible aetiology other than critical illness.
 Sir Wiliam Oslerof 19th century
‘Rapid loss of flesh’ in prolonged sepsis
 As critical care becomes more advanced,
more cases of neuropathy and myopathy
in ICUs being recognized
Stevens RD et al Critical Care Med 2009; 37 (Suppl.): S299–S308

3.  Critical iillllnneessss PPoollyynneeuurrooppaatthhyy ((CCIIPP))
 CCrriittiiccaall iillllnneessss MMyyooppaatthhyy ((CCIIMM))
 CCrriittiiccaall iillllnneessss ((PPoollyy)) NNeeuurroommyyooppaatthhyy ((CCIINNMM oorr
CCIIPPNNMM)) (Schweickert et al & Appleton etal)
 CCrriittiiccaall IIllllnneessss NNeeuurroommuussccuullaarr AAbbnnoorrmmaalliittiieess
((CCIINNMMAA)) (Stevens et al)
 IICCUU AAccqquuiirreedd PPaarreessiiss (De Jhonghe et al)
3

4.  Prevalence of 46% [95% CI]
 Prevalence of CIM
7% after OLTx
36% in status asthmaticus
35% COPD severe acute exacerbations
4

5. 5
IINNCCIIDDEENNCCEE OOFF IICCUU
AACCQQUUIIRREEDD WWEEAAKKNNEESSSS

6. PPRROOGGNNOOSSIISS OOFF
IICCUUAAWW
 ICUAW an independent risk factor for
 Increased duration of MV
 Increased weaning duration
 Increased ICU and hospital LOS
 Increased in-hospital mortality
 Mortality 45% within their hospital admission
20% more die in 1styear of discharge
 Morbidity 68% Complete functional recovery
28% Persistent severe disability
Latronico N:Curr Opin Crit Care 2005

7. CCIINNMM AANNDD WWEEAANNIINNGG
FFAAIILLUURREE
7
Garnacho-Montero et al. CCM: 2005

8. PPRROOBBAABBLLEE
 Severe sepsis/ septic shock
 Multi-organ failure
 Prolonged MV
 Prolonged bed rest
 Increased duration of SIRS
 Increased duration of MOF
 Hyperglycemia
PPOOSSSSIIBBLLEE
RRIISSKK
FFAACCTTOORRSS
 Age
 Female gender
 Severity on admission
 Admission APACHE II
 Hypoalbuminemia
 Hyperosmolality
 Parenteral nutrition
 RRT
 Vasopressors
 Steroids
 NMBAs
 Aminoglycosides

9. To determine the prevalence, risk factors, and outcomes of critical illness
neuromuscular abnormalities (CINMA)
Findings
First, found in approximately 50% of adult ICU patients who receive prolonged
mechanical ventilation, have sepsis or multiple organ failure.
Second, five of six reports found an association between CINMA and higher serum
glucose levels, yet existing studies do not consistently support several other
generally accepted risk factors for CINMA such as exposure to glucocorticoids or
neuromuscular blocking drugs.
Third, although CINMA does not reliably predict ICU mortality in unadjusted models,
it consistently and significantly increased duration of mechanical
ventilation and hospitalization, and it may be linked with long-term neuromuscular
weakness.
Last, there is considerable heterogeneity in the way CINMA is diagnosed, and
CINMA subtypes are not well differentiated.
9
NEUROMUSCULAR DDYYSSFFUUNNCCTTIIOONN IINN CCRRIITTIICCAALL
IILLLLNNEESSSS --AA SSYYSSTTEEMMAATTIICC RREEVVIIEEWW
Rober D. Stevens et al

10. PPAATTHHOOGGEENNEESSIISS OOFF CCII
PPOOLLYYNNEEUURROOPPAATTHHYY
 Reduced O2 and nutrient delivery to the axon
Macrocirculatory impairment -
hypotension, myocardial depression, vasodilatation
Microcirculatory impairment -endothelial dysfunction,
increased permeability ,tissue edema & shunting
 Impaired mitochondrial O2 utilisation and ATP generation
 A LMW neurotoxin injuring the nerve axon (LPS, IL-2R )
 Hyperglycemia induced axonal injury
 Sodium channel inactivation membrane inexcitability

11. CCII MMYYOOPPAATTHHYY--
PPAATTHHOOPPHHYYSSIIOOLLOOGGYY
 Reduced membrane excitabilty
 Altered sarcoplasmic reticulum
 Decreased contractile protein function
 Mitochondrial dysfunction and bio-energetic failure
 Muscle denervation
 Muscle atrophy

12. Rapid Disuse Atrophy of Diaphragm
12 Levine et al. NEJM 2008
Fibers in Mechanically
Ventilated Humans

13. Hermans et al: Crit Care 2010
13
Decreased ddiiaapphhrraaggmmaattiicc
ffoorrccee dduurriinngg vveennttiillaattiioonn

14. 14

15. Sepsis : Overlapping of ICUAW && MMuussccllee WWaassttiinngg
J. Cachexia Sarcopenai Muscle 2010

16. CCLLIINNIICCAALL FFEEAATTUURREESS OOFF CCII
PPOOLLUUNNEEUURROOPPAATTHHYY
Usually develops in patients
ICU stay for 2 weeks or more
Prolonged weaning from MV
 Limb muscle weakness and atrophy
 Reduced or absent deep tendon reflexes
 Loss of peripheral sensation to light touch & pin prick
 Relative preservation of cranial nerve function
16

17.  Flaccid quadriparesis proximal >distal muscles
 Failure to wean from mechanical ventilation
 Facial muscle weakness is relatively common
 Extraocular muscle weakness rare
17

18. EEXXAAMMIINNAATTIIOONN
 Sensory and reflex exam is limited by
 examiner-patient interaction
 altered sensorium
 Limb edema
 Generally symmetrical motor deficits in all limbs
 Range from local Paresis to true quadriplegia
 Painful stimulation  Limited to absent limb response
but normal grimacing
 Extra-ocular muscle involvement is very rare
 Reflexes may be present, diminished or absent

19. MMRRCC SSCCAALLEE FFOORR MMUUSSCCLLEE EEXXAAMMIINNAATTIIOONN
Functions assessed :
Upper extremity: wrist flexion, forearm flexion, shoulder abduction
Lower extremity: ankle dorsiflexion, knee extension, hip flexion
Score for each movement
1199
0–No visible contraction
1–Visible muscle contraction, but no limb movement
2–Active movement, but not against gravity
3–Active movement against gravity
4–Active movement against gravity and resistance
5–Active movement against full resistance
Maximum Normal score: 60 (four limbs, max of 15 points per limb)
Minimum score: 0 (quadriplegia) Kleyweg RP et al. Neurology 1988

20. UUPPOONN SSUUSSPPIICCIIOONN……
 Exclude preexisting neuromuscular condition
 Assessment of premorbid functional status
 Consider conditions like acute spinal cord
injury, MND, GBS, and muscular dystrophy
 These may emerge during critical illness

21. DDDD OOFF WWEEAAKKNNEESSSS IINN
IICCUU
21
‘‘MM UU SS CC LL EE SS’’

22. INVESTIGATIONS IINN IICCUUAAWW
 Muscle/nerve biopsy only if there is diagnostic
uncertainty; not specifically for the diagnosis of
CIP, CIM, CINM
 If there is no improvement after 1-2 weeks
 If the weakness is very severe
 Blood tests: electrolytes, CK, ESR, auto-antibodies,
LP, ENMG, MRI of brain/spinal cord

23. DIAGNOSTIC CCRRIITTEERRIIAA FFOORR CCII
PPOOLLYYNNEEUURROOPPAATTHHYY
 1. Patient meets the criteria for ICUAW
 2. CMAP amplitudes are decreased to <80% of
the lower limit of normal in >2 nerves
 3. SNAP amplitudes are decreased to <80% of
the lower limit of normal in >2 nerves
 4. Normal or near normal nerve conduction
velocities
 5. The absence of a decremental response on
RNS

24. DIAGNOSTIC CCRRIITTEERRIIAA CCII
MMYYOOPPAATTHHYY
 1.Patient meets the criteria for ICUAW
 2.SNAP amplitudes on nerve conduction studies are
>80% of the lower limit of normal in >2 nerves
 3.EMG in >2 muscle groups showing typical
myopathic changes
 4. Direct muscle stimulation demonstrating reduced
excitability
 5. Muscle histology consistent with myopathy
 Diagnostic criteria for CIM : Probable CIM (1, 2, 3 or 4;
or 1 and 5) and Definite CIM (1, 2, 3 or 4, 5)

25. CCRRIITTIICCAALL IILLLLNNEESSSS
NNEEUURROOMMYYOOPPAATTHHYY
CINM is diagnosed when all of the following are
met:
 Patient meets criteria for
ICUAW
CIP
probable or definite CIM
25

26. TTeesstt CCIIPP CCIIMM CCIINNMM
Creatine kinase Normal or mildly
elevated
Elevated in the
majority (usually 10
000 IU litre)
Normal or elevated
CSF Normal cell counts;
normal or slightly
elevated
protein levels (,0.8 g
litre21)
Normal Normal or slightly
elevated protein
levels (,0.8 g litre21)
Nerve conduction
studies
Reduced CMAP
amplitudes; reduced
SNAP
amplitudes; normal
conduction velocities
and
latencies
Reduced CMAP
amplitudes; normal
SNAP amplitudes;
normal conduction
velocities and
latencies
Reduced CMAP
amplitudes; reduced
SNAP amplitudes;
normal
conduction velocities
and latencies
Electromyography Spontaneous
fibrillation potentials
and sharp waves;
+long duration, high-amplitude
polyphasic
MUPs (reinnervation)
Spontaneous
fibrillation potentials
and sharp waves;
short
duration, low-amplitude
MUPs with
early recruitment
Features of both CIP
and CIM
26

27. TTeesstt CCIIPP CCIIMM CCIINNMM
Direct muscle
stimulation
Nerve: muscle ratio ,
0.5; normal direct
muscle
CMAP amplitude
Nerve:muscle ratio
0.5; reduced direct
muscle CMAP
amplitude
Variable depending
on the relative
components of CIP
and CIM
Muscle biopsy Features of
denervation and
reinnervation: small
angulated muscle
fibres; target and
targetoid
fibres; group fibre
atrophy; fibre type
regrouping
Cachectic myopathy
with myofibrillar
degeneration; thick
filament myopathy
with a selective loss
of myosin
filaments; necrotizing
myopathy with
muscle fibre
necrosis
Both features of CIP
and CIM
Nerve biopsy Normal, or motor and
sensory nerve axonal
degeneration
Normal Normal, or motor and
sensory nerve
axonal degeneration
27

28. MMUUSSCCLLEE BBIIOOPPSSYY
 Definitive diagnosis of muscle involvement
 Muscle fiber atrophy ( esp. type II ),occasional
fiber necrosis, regeneration, and decreased
or absent reactivity in myofibrillar ATP
staining
 LLOOSSSS OOFF MMYYOOSSIINN - Pathognomonic for CIM

29. DDIIAAGGNNOOSSTTIICC SSTTRRTTAAEEGGYY FFOORR IICCUUAAWW
ICU-Acquired Weakness : CHEST. 2007

30.  No proven treatment
 Treatment of underlying disease
 Treatment and prevention of complications
 Optimum Rehabilitation
30

31. PPRREEVVEENNTTIIOONN OOFF IICCUUAAWW
 Minimisation of risk factors
 Intensive insulin therapy??
 The NICE-SUGAR study precludes it’s use;
supports more liberal blood glucose levels
 Electrical muscle stimulation

32. MMOODDIIFFIIAABBLLEE IICCUUAAWW --RRIISSKK FFAACCTTOORR
EEVVIIDDEENNCCEE LLEEVVEELLSS
CCHHEESSTT..22000077::113311((66))11664411
??

33.  Minimizing complication of bed rest
 Facilitating the weaning from ventillatory support
 Reduced ICU length of stay
 Reduced hospital length of stay
 Promoting improved function
 Improving patients quality of life
 Cost saving
 No adverse outcomes
33
BBEENNEEFFIITTSS OOFF EEAARRLLYY
RREEHHAABBIILLIITTAATTIIOONN PPRROOGGRRAAMMMMEE
Morris PE, et al. Crit Care Med, 2008;36:2238-2243

34. RREEHHAABB IINN IICCUU
 Harms of Proloned bed rest and inactivity
Skin ulceration
Compression neuropathies
Joint ossification
Deconditioning
Low mood
 Underatke Incremental level of activity
 Physical activity, mobilisation and exercise therapy:
safe and useful
 Passive and active limb movements, cycle ergometry,
electrical muscle stimulation all helpful

36. SSOO……
 ICUAW a major contributor to functional
impairment
 Slow and incomplete recovery
 Aggressive treatment of conditions like sepsis
 Attenuate factors like severe hyperglycemia
 Early mobilisation
 Intermittent and minimal sedation
 Multidisciplinary care

37. CCOONNCCLLUUSSIIOONN
 ICUAW is a common cause of prolonged MV and
delayed return to physical self-sufficiency
 Lack of standard diagnostic criteria
 A number of risk factors associated with
development of weakness during critical illness
 Treatment is largely supportive
 More aggressive use of physiotherapy early in
the course of disease and ambulation leads to
better outcome
37

38. TThhaannkk yyoouu

39. Methodology
 Prospective cohort study
 103 patients/1449 activity events
 Mechanically ventilated patients for > 4 days
 Airway: Tracheotomy & endotracheal tube
 Measured recorded activity events & adverse events
 Activity events included:
 Sit on bed, Sit in chair, Ambulate
 Adverse events defined as:
 Fall to knees,
 Tube removal,
 SBP > 200 mmHg, SBP < 90mmHg,
 O2 desaturation < 80% &
 Extubation
Bailey P, et al. Crit care Med, 2007;35:139-145
39

40. Results
 Activity events included:
 Sit on bed (233 or 16%)
 Sit in chair (454 or 31%)
 Ambulate (762 or 53%)
With an ET in place:
 Sit on bed, chair or ambulate (593)
 Ambulate (249 or 42%)
Adverse events
 < 1% activity related adverse events (no extubations
occurred)
69% all to ambulate at > 100 feet at ICU discharge
40
Early Activity is safe &
feasible in mechanically intubated patient

42.  Increased incidence of succinyl choline induced
cardiac arrest in patients with a >2 week stay
in ICU