ICU Acquired Weakness
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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
![ Prevalence of 46% [95% CI]
Prevalence of CIM
7% after OLTx
36% in status asthmaticus
35% COPD severe acute exacerbations
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ICU Acquired Weakness
- 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
- 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