Dr Palepu GopalDr Palepu GopalHyderabadHyderabad

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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

Critical illness Polyneuropathy (CIP)Critical illness Polyneuropathy (CIP)

Critical illness Myopathy (CIM)Critical illness Myopathy (CIM)

Critical illness (Poly) Neuromyopathy (CINM Critical illness (Poly) Neuromyopathy (CINM

or CIPNM) or CIPNM) (Schweickert et al & Appleton

etal)

Critical Illness Neuromuscular Abnormalities Critical Illness Neuromuscular Abnormalities

(CINMA) (CINMA) (Stevens et al)

ICU Acquired Paresis ICU Acquired Paresis (De Jhonghe et al)3

Prevalence of 46% [95% CI]

Prevalence of CIM

7% after OLTx

36% in status asthmaticus

35% COPD severe acute

exacerbations 4

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INCIDENCE OF ICU INCIDENCE OF ICU ACQUIRED WEAKNESSACQUIRED WEAKNESS

PROGNOSIS OF PROGNOSIS OF ICUAWICUAW

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

Morbidity68% Complete functional recovery

28% Persistent severe disability Latronico N:Curr Opin Crit Care 2005

CINM AND WEANING CINM AND WEANING FAILUREFAILURE

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Garnacho-Montero et al. CCM: 2005

PROBABLEPROBABLE

Severe sepsis/ septic

shock

Multi-organ failure

Prolonged MV

Prolonged bed rest

Increased duration of SIRS

Increased duration of MOF

Hyperglycemia

POSSIBLEPOSSIBLE

RISK RISK FACTORSFACTORS

Age Female gender Severity on

admission Admission APACHE

II Hypoalbuminemia Hyperosmolality Parenteral

nutrition RRT Vasopressors Steroids NMBAs Aminoglycosides

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To determine the prevalence, risk factors, and outcomes of critical illness neuromuscular abnormalities (CINMA)

FindingsFirst, 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 mechanicalventilation 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.

NEUROMUSCULAR DYSFUNCTION IN CRITICAL NEUROMUSCULAR DYSFUNCTION IN CRITICAL ILLNESS -A SYSTEMATIC REVIEWILLNESS -A SYSTEMATIC REVIEW

Rober D. Stevens et al

PATHOGENESIS OF CI PATHOGENESIS OF CI POLYNEUROPATHYPOLYNEUROPATHY

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-CI MYOPATHY-PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Reduced membrane excitabilty

Altered sarcoplasmic reticulum

Decreased contractile protein function

Mitochondrial dysfunction and bio-

energetic failure

Muscle denervation

Muscle atrophy

12Levine et al. NEJM 2008

Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically

Ventilated Humans

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Hermans et al: Crit Care 2010

Decreased diaphragmatic Decreased diaphragmatic force during ventilationforce during ventilation

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J. Cachexia Sarcopenai Muscle 2010

Sepsis : Overlapping of ICUAW & Muscle Wasting Sepsis : Overlapping of ICUAW & Muscle Wasting

CLINICAL FEATURES OF CI CLINICAL FEATURES OF CI POLUNEUROPATHYPOLUNEUROPATHY

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 function16

Flaccid quadriparesis proximal >distal muscles

Failure to wean from mechanical ventilation

Facial muscle weakness is relatively common

Extraocular muscle weakness rare

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EXAMINATIONEXAMINATION

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

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MRC SCALE FOR MUSCLE EXAMINATIONMRC SCALE FOR MUSCLE EXAMINATIONFunctions assessed :Upper extremity: wrist flexion, forearm flexion, shoulder abductionLower extremity: ankle dorsiflexion, knee extension, hip flexionScore for each movement

0–No visible contraction1–Visible muscle contraction, but no limb movement2–Active movement, but not against gravity3–Active movement against gravity4–Active movement against gravity and resistance5–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

UPON SUSPICION…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 DD OF WEAKNESS IN ICUICU

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‘‘M U S C L E S’M U S C L E S’

INVESTIGATIONS IN ICUAWINVESTIGATIONS IN ICUAW

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 DIAGNOSTIC CRITERIA FOR CI POLYNEUROPATHYPOLYNEUROPATHY 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

DIAGNOSTIC CRITERIA CI DIAGNOSTIC CRITERIA CI MYOPATHYMYOPATHY

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 CRITICAL ILLNESS NEUROMYOPATHYNEUROMYOPATHY

CINM is diagnosed when all of the following are

met:

Patient meets criteria for

ICUAW

CIP

probable or definite CIM

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TestTest CIPCIP CIMCIM CINMCINM

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 elevatedprotein levels (,0.8 g litre21)

Normal Normal or slightly elevated proteinlevels (,0.8 g litre21)

Nerve conductionstudies

Reduced CMAP amplitudes; reduced SNAPamplitudes; normal conduction velocities andlatencies

Reduced CMAP amplitudes; normal SNAP amplitudes;normal conduction velocities and latencies

Reduced CMAP amplitudes; reducedSNAP amplitudes; normalconduction velocities and latencies

Electromyography

Spontaneous fibrillation potentials and sharp waves;+long duration, high-amplitude polyphasicMUPs (reinnervation)

Spontaneous fibrillation potentials and sharp waves; shortduration, low-amplitude MUPs with early recruitment

Features of both CIP and CIM

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TestTest CIPCIP CIMCIM CINMCINM

Direct musclestimulation

Nerve: muscle ratio , 0.5; normal direct muscleCMAP amplitude

Nerve:muscle ratio 0.5; reduced direct muscle CMAPamplitude

Variable depending on the relativecomponents of CIP and CIM

Muscle biopsy Features of denervation and reinnervation: smallangulated muscle fibres; target and targetoidfibres; group fibre atrophy; fibre type regrouping

Cachectic myopathy with myofibrillar degeneration; thickfilament myopathy with a selective loss of myosinfilaments; necrotizing myopathy with muscle fibrenecrosis

Both features of CIP and CIM

Nerve biopsy Normal, or motor and sensory nerve axonaldegeneration

Normal Normal, or motor and sensory nerveaxonal degeneration

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MUSCLE BIOPSYMUSCLE 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 LOSS OF MYOSIN - Pathognomonic for CIM

ICU-Acquired Weakness : CHEST. 2007

DIAGNOSTIC STRTAEGY FOR ICUAWDIAGNOSTIC STRTAEGY FOR ICUAW

No proven treatment

Treatment of underlying disease

Treatment and prevention of complications

Optimum Rehabilitation

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PREVENTION OF ICUAWPREVENTION OF ICUAW

Minimisation of risk factors

Intensive insulin therapy??

The NICE-SUGAR study precludes it’s use; supports more liberal blood glucose levels

Electrical muscle stimulation

MODIFIABLE ICUAW -RISK FACTOR MODIFIABLE ICUAW -RISK FACTOR EVIDENCE LEVELSEVIDENCE LEVELS

CHEST.2007:131(6)1641CHEST.2007:131(6)1641

??

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 outcomes33

BENEFITS OF EARLY BENEFITS OF EARLY REHABILITATION PROGRAMMEREHABILITATION PROGRAMME

Morris PE, et al. Crit Care Med, 2008;36:2238-2243

REHAB IN ICUREHAB 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…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

CONCLUSIONCONCLUSION 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

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Thank youThank you

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

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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

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Early Activity is safe &feasible in mechanically intubated patient

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