ICU ACQUIRED WEAKNESS

DEFINITION

• ICU-ACQUIRED WEAKNESS (ICUAW) ; CLINICALLY DETECTED WEAKNESS IN CRITICALLY ILL

PATIENTS IN WHOM THERE IS NO PLAUSIBLE ETIOLOGY OTHER THAN CRITICAL ILLNESS.
• 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

 CLASSIFICATION

•CRITICAL ILLNESS POLYNEUROPATHY (CIP)

•CRITICAL ILLNESS MYOPATHY (CIM)
•CRITICAL ILLNESS (POLY) NEUROMYOPATHY ( C I N M OR C I P N M )
(SCHWEICKERT ET A L & A P P LETO N ETAL)

•CRITICAL ILLNESS NEUROMUSCULAR ABNORMALITIES (C INMA)

(STEVENS ET AL)

•I C U ACQUIRED PARESIS
(DE J H O N G H E ET AL)
 EPIDEMIOLOGY OF ICU-AW

• PREVALENCE OF 46% [95% CI] PREVALENCE OF CIM

• 7% AFTER OLTX

• 36% IN STATUS ASTHMATICUS

• 35% COPD SEVERE ACUTE EXACERBATIONS

 PROGNOSIS OF ICU-AW

• I C U A W AN INDEPENDENT RISK FACTOR FOR ;

▪ INCREASED DURATION OF M V
▪ INCREASED WEANING DURATION
▪ INCREASED I C U AND HOSPITAL L O S
▪ INCREASED IN-HOSPITAL MORTALITY

•MORTALITY 45% WITHIN HOSPITAL ADMISSION, 20% MORE DIE IN 1STYEAR OF DISCHARGE

•MORB ID ITY 68% COMPLETE FUNCTIONAL RECOVERY, 28% PERSISTENT SEVERE DISABILITY

Latronico N : Cu r r Op i n Crit Care 2005

Garnacho-Montero et al. CCM: 2005
 RISK FACTOR
PROBABLE POSSIBLE
•SEVERE SEPSIS/ SEPTIC SHOCK •AGE
•F E M A L E G E N D E R
•MULTI-ORGAN FAILURE •S E V E R I T Y ON A D M I S S I O N
•A D M I S S I O N APACHE II
•PROLONGED MV •H Y P O A L B U M I N E M I A
•H Y P E R O S M O L A L I T Y
•PROLONGED BED REST •PA R E N T E R A L N U T R I T I O N
•RRT
•INCREASED DURATION OF SIRS •V A S O P R E S S O R S
•S T E R O I D S
•INCREASED DURATION OF MOF
•N M B A S
•HYPERGLYCEMIA •A M I N O G L Y C O S I D E S
N E U RO M U S C U L A R DYSFUN CT ION IN CRITICAL
I L L N E S S -A S Y S T E M AT I C R E V I E W
Rober D. Stevens et al

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
 PATHOGENESIS OF
POLYNEUROPATHY CI

❑ 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

 CI MYOPATHY-
PATHOPHYSI OLOG
Y
 Reduced membrane excitabilty

Altered sarcoplasmic reticulum

Decreased contractile protein function
 Mitochondrial dysfunction and bio-
energetic failure

Muscle denervation

Muscle atrophy
Rapid Disuse Atrophy of Diaphragm
Fibers in Mechanically
Ventilated Humans

Levine et al. NEJM 200812

 DECREASED
DIAPHRAGMATIC
FORCE DURING
VENTILATION

Hermans et al: Crit Care 2010

13
14
E PSIS : OVERLAPPING OF ICUAW & MUSCLE
WASTING

J. Cachexia Sarcopenai Muscle 2010

 CLINICAL FEATURES OF CI
Usually develops in patients
POLUNEUROPATHY
ICU stay for 2 weeks or

more Prolonged weaning

 Limb muscle weakness
from MV and
atrophy
 Reduced or absent deep tendon reflexes

 Loss of peripheral sensation to light touch & pin

prick
 Relative preservation of cranial nerve function

16

FLACCID QUADRIPARESIS PROXIMAL >DISTAL
MUSCLES

 Failure to wean from mechanical ventilation

 Facial muscle weakness is relatively common

 Extraocular muscle weakness rare

17
EXAMINATION

▪ 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 response
limb but normal grimacing
▪ Extra-ocular muscle involvement is very rare
▪ Reflexes may be present, diminished or absent
MRC SCALE FOR MUSCLE EXAMINATION
Functions assessed :
Upper extremity: wrist flexion, forearm flexion, shoulder abduction
Lower extremity: ankle dorsiflexion, knee extension, hip flexion
Score for each movement
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
19
UPON SUSPICION…

▪ 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

DD OF WEAKNESS IN
ICU

‘M U S C L E S’

21
 I NVESTI GATI ONS I N
I CUAW
 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
DIAGNOSTIC CRITERIA FOR CI
POLYNEUROPATHY
 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
 DI AGNOSTI C CRI TERI A
CI MYOPATHY
 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)
 CRITICAL ILLNESS
NEUROMYOPATHY

CINM is diagnosed when all of the following are

met:
✓ Patient meets criteria for
✓ICUAW
✓CIP
✓probable or definite CIM
25
TES
CIP CIM CINM
T
Creatine kinase Normal or Elevated in the Normal or elevated
elevate mildly majority (usually 10
d 000 IU litre)
CSF Normal cell counts; Normal Normal or slightly
normal or slightly elevated protein
elevated levels (,0.8 g litre21)
protein levels (,0.8 g
litre21)
Nerve conduction Reduced CMAP Reduced CMAP Reduced CMAP
studies amplitudes; reduced amplitudes; normal amplitudes; reduced
SNAP SNAP amplitudes; SNAP amplitudes;
amplitudes; normal normal conduction normal
conduction velocities velocities and conduction velocities
and latencies and latencies
latencies

Electromyography Spontaneous Spontaneous Features of both CIP

fibrillation potentials fibrillation potentials and CIM
and sharp waves; and sharp waves;
+long duration, high- short
amplitude polyphasic duration, low-
MUPs amplitude MUPs with
(reinnervation) early recruitment 26
Test CIP CIM CINM
Direct muscle Nerve: muscle ratio , Nerve:muscle ratio Variable depending
stimulation 0.5; normal direct 0.5; reduced direct on the relative
muscle muscle CMAP components of CIP
CMAP amplitude amplitude and CIM

Muscle biopsy Features of Cachectic myopathy Both features of CIP

denervation and with myofibrillar and CIM
reinnervation: small degeneration; thick
angulated muscle filament myopathy
fibres; target and with a selective loss
targetoid of myosin
fibres; group fibre filaments; necrotizing
atrophy; fibre type myopathy with
regrouping muscle fibre
necrosis

Nerve biopsy Normal, or motor and Normal Normal, or motor and

sensory nerve axonal sensory nerve
degeneration axonal degeneration

27
MUSCLE BIOPSY

▪ Definitive diagnosis of muscle involvement

▪ Muscle fiber atrophy ( esp. type II ),occasional
fiber necrosis, regeneration, and decreased
or absent reactivity in myofibrillar ATP
staining
▪ LOSS OF MYOSIN - Pathognomonic for CIM
D I A G N O S T I C S T RTA E GY F O R I C UAW

ICU-Acquired Weakness : C H E S T. 2007


NO PROVEN
TREATMENT
 Treatment of underlying disease

 Treatment and prevention of complications

 Optimum Rehabilitation

30
P R E V E N T I O N O F I C UAW
 Minimisation of risk factors

 Intensive insulin therapy??

 The NICE-SUGAR study precludes it’s use;

supports more liberal blood glucose levels

 Electrical muscle stimulation

 M O D I F I A B L E I C UAW - R I S K FA C T O R
EVIDENCE LEVELS
?

CHEST.2007:131(6)1641
 B E N E F I T S O F E A R LY R E H A B I L I TAT I O
 Minimizing complication of bed rest
PROGRAMME
 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
Morris PE, et al. Crit Care Med, 2008;36:2238-232343
 REHAB IN ICU
 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
SO…
 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
 CONCLUSION
 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
Thank you
METHODOLO
GY




•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

B 39
a
RESUL
 TS
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

Early Activity is safe &

feasible in mechanically intubated patient

40
 INCREASED INCIDENCE OF SUCCINYL CHOLINE
INDUCED CARDIAC ARREST IN PATIENTS
WITH A >2 WEEK STAY IN ICU