ICU-acquired weakness (critical illness myopathy/polyneuropathy) · ICU Topics

Cinematic ICU scene of a deconditioned ICU survivor performing bedside active-assisted limb exercises with a physiotherapist and an MRC strength chart, clinical-blue lighting, medical educational, no faces, no text — FigureICU-acquired weakness — the critical illness myopathy and polyneuropathy — strikes 25-50% ventilated beyond a week: the sepsis, the immobility, the hyperglycaemia, the steroids. Prevent with the glycaemic control, the early mobilisation, and the sedation lightening; diagnose with the MRC sum-score below 48.

[3]

Types of ICU-acquired weakness

CIM (myopathy)

Muscle involvement

Primary myopathy (muscle fibre dysfunction)
More common than CIP in ICU
Electrophysiology: reduced CMAP amplitude, normal sensory studies
Muscle biopsy: myosin filament loss, muscle fibre atrophy/necrosis
Associated with: corticosteroids, NMBAs, sepsis, hyperglycaemia

CIP (polyneuropathy)

Nerve involvement

Axonal sensorimotor polyneuropathy
Electrophysiology: reduced CMAP and SNAP amplitudes (axonal pattern)
Often coexists with CIM (CINM — critical illness neuromyopathy)
Associated with: sepsis, multi-organ failure, prolonged ICU stay

[4]

Diagnosis

Clinical — MRC score

[2]

Electrophysiology

Diagnostic approach

Clinical assessment

MRC score <48/60 in a cooperative patient who has been in ICU for >7 days. Weakness is diffuse, symmetrical, and spares facial muscles (unlike GBS or MG). Areflexia/hyporeflexia may be present but is not required.

Exclude other causes

GBS (acute ascending paralysis, CSF albuminocytological dissociation), MG (fatigable weakness, positive AChR antibody), electrolyte disturbance (check K, Mg, Ca, phosphate), spinal cord lesion (sensory level, sphincter involvement), prolonged effects of NMBAs.

Electrophysiology (nerve conduction studies + EMG)

CIM: reduced CMAP amplitude, normal SNAP (sensory), myopathic EMG changes. CIP: reduced CMAP AND SNAP (axonal), denervation on EMG. CINM: features of both. Electrophysiology differentiates CIM from CIP.

Muscle biopsy (rarely needed)

Reserved for research or diagnostic uncertainty. Shows: myosin filament loss (selective loss of thick myosin filaments — characteristic of CIM), fibre atrophy, fibre necrosis, fatty degeneration.

[1]

Prevention

ICUAW prevention — the modifiable risk factors

Glycaemic control — the #1 modifiable factor

Hyperglycaemia directly causes muscle dysfunction (osmotic damage, oxidative stress, protein catabolism). Target: 6-10 mmol/L. Avoid severe hyperglycaemia (>10). NICE-SUGAR trial: moderate control (6-10) better than tight (4.4-6.1) — tight control risks hypoglycaemia. Insulin infusion for persistently elevated glucose.

Minimise sedation

Daily sedation interruption (SAT) + spontaneous breathing trial (SBT). Use light sedation (RASS -1 to 0). Avoid benzodiazepines (increase delirium and immobilisation). Prefer dexmedetomidine or propofol. Immobilisation causes rapid muscle wasting — 1.5-2% per day.

Early mobilisation

PASSIVE range of motion from day 1. Sit on edge of bed when haemodynamically stable. Stand/walk when possible (within 72h if safe). Requires coordinated effort: nursing, physiotherapy, medical staff. Reduces ICUAW, delirium, and ventilator days.<Cite id="3" />

Minimise corticosteroids and NMBAs

Corticosteroids cause myopathy (especially high-dose, prolonged use). NMBAs cause prolonged weakness (especially with concurrent steroids — ‘acute quadriplegic myopathy’). Use the shortest duration possible. Monitor with train-of-four if using NMBAs.

Nutrition

Adequate protein: 1.2-1.5 g/kg/day. Avoid overfeeding (refeeding syndrome, hyperglycaemia). Start enteral nutrition early (within 48h). Check phosphate, magnesium, potassium before starting feed. Do NOT restrict protein — muscle catabolism is already maximally stimulated by critical illness.

[2]

Risk factors

ICU-acquired weakness risk factors

25-50%

Ventilated >7 days

Develop ICUAW

Hyperglycaemia

Most modifiable risk factor

1.5-2%/day

Muscle loss

Per day of bed rest in ICU

~50%

Incomplete recovery

At 1 year post-ICU

[2]

Clinical pearls

High-yield ICUAW points for the CICM/FFICM exam

ICUAW affects 25-50% of patients ventilated >7 days.[1]
MRC score <48/60 = diagnostic threshold (6 muscle groups, bilateral, 0-5 scale).
Hyperglycaemia is the #1 modifiable risk factor — target 6-10 mmol/L.[6]
CIM vs CIP: differentiated by nerve conduction studies (CIM: normal sensory, CIP: abnormal sensory).
Corticosteroids + NMBAs together dramatically increase risk ('acute quadriplegic myopathy').
Early mobilisation (within 72h) reduces ICUAW and delirium.[3]
Minimise sedation — immobilisation causes rapid muscle wasting (1.5-2%/day).
Facial muscles are SPARED in ICUAW (unlike GBS or MG) — if facial weakness present, reconsider diagnosis.
Muscle biopsy: selective loss of thick myosin filaments (characteristic of CIM).
Outcomes: prolonged ventilation, increased mortality, long-term disability.
No specific treatment — prevention is key. No evidence for: steroids, NMBAs, electrical stimulation (conflicting evidence).
Recovery: starts within weeks of ICU discharge but may take months-years. ~50% have incomplete recovery at 1 year.
Nutrition: adequate protein (1.2-1.5 g/kg/day) — but avoid overfeeding.
Daily SAT + SBT pairing reduces ventilation days → fewer days immobilised → less ICUAW.

Red flags

Pathophysiology — how critical illness damages nerve and muscle

Educational schematic of ICU-acquired weakness: sepsis immobility hyperglycaemia steroids NMBA driving critical illness polyneuropathy axonal injury and critical illness myopathy myosin loss — FigureICUAW pathophysiology — systemic inflammation, immobility, hyperglycaemia and drugs converge on axonal injury (CIP) and myosin loss (CIM).

ICU-acquired weakness is not a single disease but the convergent end-result of several parallel injury pathways triggered by systemic inflammation, immobility, metabolic derangement, and drug toxicity. Three overlapping mechanisms dominate: critical illness myopathy (skeletal-muscle fibre dysfunction), critical illness polyneuropathy (axonal peripheral-nerve injury), and — when both coexist, as they do in over half of electrophysiologically-confirmed cases — critical illness neuromyopathy (CINM).[1]

Muscle (CIM)

Myocyte injury

Catabolic state: resistance to insulin/IGF-1 + ↑ TNF-α/IL-1/IL-6 → ubiquitin-proteasome and autophagy-lysosome proteolysis of contractile proteins
Preferential loss of THICK (myosin) filaments → selective myosin loss (hallmark histology); later type II fibre atrophy
Sodium-channel dysfunction + membrane depolarisation → inexcitable sarcolemma (reduced/absent CMAP on direct muscle stimulation)
Mitochondrial dysfunction (impaired oxidative phosphorylation, ↓ ATP) → energy failure, impaired Ca²⁺ handling, oxidative stress
Triggered by: immobilisation, corticosteroids, NMBAs, hyperglycaemia, sepsis

Nerve (CIP)

Axonal degeneration

Distal, symmetrical, AXONAL (not demyelinating) sensorimotor polyneuropathy
Microvascular dysfunction → endoneurial ischaemia + increased blood-nerve-barrier permeability
Sepsis/inflammation → activation of Schwann cells, mitochondrial injury, energy failure of the axon
Electrophysiology: reduced CMAP AND SNAP amplitudes (both motor AND sensory affected — the key discriminator from CIM)
Triggered by: sepsis, multi-organ failure, prolonged stay; axonal degeneration is the dominant lesion

Combined (CINM)

Most common in practice

Coincident myopathy + polyneuropathy — found in >50% of electrophysiologically-confirmed ICUAW
Sensory studies often "normal-ish" in pure CIM but abnormal in CINM — direct muscle stimulation resolves ambiguity
Clinically indistinguishable from isolated CIM/CIP at the bedside — needs electrophysiology to separate
Worse functional outcomes and slower recovery than either alone
Risk profile = union of CIM and CIP risks (sepsis + steroids + NMBAs + immobility + hyperglycaemia)

[1] [2]

The unifying pathophysiology — three convergent injury pathways

1. Membrane depolarisation and inexcitability. In CIM the sarcolemma becomes electrically inexcitable: sodium-channel dysfunction and a sustained partial depolarisation of the resting membrane potential render the muscle fibre unable to fire, even when the motor nerve is intact. This explains why CMAP amplitude falls (or vanishes) on stimulation, and why the weakness can be profound yet largely reversible as the membrane repolarises during recovery.[9]

2. Muscle atrophy and contractile-protein loss. Critical illness triggers resistance to insulin and IGF-1 alongside a surge of TNF-α, IL-1β and IL-6. The balance shifts to net catabolism: the ubiquitin-proteasome and autophagy-lysosome pathways degrade contractile protein, with a strikingly selective loss of thick myosin filaments (the histological hallmark of CIM). Quadriceps cross-sectional area can fall 1.5-3% per day in the first ICU week.[2]

3. Critical illness polyneuropathy. In parallel, sepsis and microvascular dysfunction produce a distal, symmetrical, axonal (non-demyelinating) sensorimotor polyneuropathy. Endoneurial oedema and ischaemia, breakdown of the blood-nerve barrier, and Schwann-cell mitochondrial injury drive length-dependent axonal degeneration. The result is denervation of muscle — which in turn amplifies the myopathy (a "two-hit" neuromuscular injury).[1]

The pathophysiological cascade — from sepsis to weakness

Trigger: systemic inflammation (sepsis, MODS, ARDS)

Cytokine storm (TNF-α, IL-1β, IL-6), microcirculatory failure, oxidative stress, and mitochondrial dysfunction are the upstream drivers. Sepsis is the single strongest risk factor for ICUAW.

Catabolic dominance in muscle

Insulin/IGF-1 resistance + cytokine-driven proteolysis (ubiquitin-proteasome, autophagy-lysosome) → net breakdown of myofibrillar protein, preferential loss of thick myosin filaments, and type II fibre atrophy.

Sarcolemmal inexcitability

Sodium-channel dysfunction and partial membrane depolarisation render muscle fibres electrically silent → reduced/absent CMAP. This is reversible and underlies the rapid fluctuation seen early in recovery.

Axonal degeneration in nerve (CIP)

Microvascular ischaemia, blood-nerve-barrier breakdown, and Schwann-cell mitochondrial failure produce distal axonal sensorimotor polyneuropathy → secondary muscle denervation.

Amplifiers: immobility, drugs, glucose

Bed rest alone causes ~1.5-2% quadriceps loss/day. Corticosteroids + NMBAs synergise to cause "acute quadriplegic myopathy". Hyperglycaemia damages nerve (osmotic/oxidative) and muscle (protein catabolism).

Clinical phenotype: diffuse, flaccid, symmetric weakness

Limbs > trunk > face (facial sparing). Hyporeflexia/areflexia. Respiratory muscle involvement → failed weaning. Sensation intact or only mildly impaired (unlike the marked weakness).

[1] [11]

CIP vs CIM vs CINM — discriminating the overlap at the bedside

Pure CIM and pure CIP are conceptually distinct but overlap so frequently in practice that CINM is the most common reality. The distinction matters for prognosis and for understanding trial populations, but the management is identical: there is no specific treatment for any of the three — only prevention and rehabilitation.[1]

[9]

Diagnosis in depth — the ATS framework

The 2014 American Thoracic Society guideline defines ICUAW as symmetrical, diffuse, clinically detected weakness developing during critical illness that cannot be explained by a pre-existing condition. The MRC sum score is the core bedside criterion, with electrophysiology as confirmation when feasible and exclusion of mimics as mandatory.[10]

Diagnostic algorithm (ATS 2014)

Step 1 — Suspect ICUAW

Any patient ventilated >48-72 h, or with sepsis/MODS, prolonged sedation, steroid + NMBA exposure, or difficulty weaning from ventilation. Screen actively — ICUAW is under-recognised.

Step 2 — Cooperative? Perform MRC sum score

Arouse the patient (RASS ≥ -1), ensure no residual NMBA effect (train-of-four ≥ 4/4), then score 6 muscle groups bilaterally (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, ankle dorsiflexion) 0-5 each. MRC <48/60 (and definitely <36) = ICUAW. Average of bilateral scores if asymmetric.

Step 3 — Uncooperative? Use surrogate measures

Hand-grip dynamometry (<11 kg female / <27 kg male = weakness), MRC of available groups, or wait for cooperation. New inability to lift arms off the bed, weak hand squeeze, or facial weakness ALL away from ICUAW.

Step 4 — Exclude mimics (mandatory)

Guillain-Barré (acute ascending, areflexic, CSF albuminocytological dissociation, may involve face), myasthenia gravis (fatigable, ocular/bulbar, +AChR/MuSK Ab), electrolyte disorder (K⁺, Mg²⁺, Ca²⁺, phosphate), spinal cord lesion (sensory level, sphincter signs), prolonged NMBA effect (train-of-four), steroid myopathy, motor neuron disease.

Step 5 — Electrophysiology (confirm + phenotype)

Nerve conduction studies + needle EMG differentiate CIM (normal SNAP, ↓CMAP, myopathic EMG) from CIP (↓SNAP + ↓CMAP, denervation) and identify CINM. Direct muscle stimulation (tibialis anterior) is the most specific discriminator when sensory studies are confounded.

Step 6 — Muscle biopsy (rarely needed)

Reserved for research or genuine diagnostic uncertainty. Hallmark of CIM: selective loss of thick myosin filaments, fibre atrophy, and (in severe cases) fibre necrosis with fatty replacement.

[10] [11]

Diagnostic thresholds — the numbers to know

<48/60

MRC sum score

Diagnostic of ICUAW

<11 kg

Grip strength (F)

Dynamometry threshold — female

<27 kg

Grip strength (M)

Dynamometry threshold — male

>48 h

Ventilation

When to start screening

[8]

Risk factors in depth

[8]

ICUAW risk — the numbers to quote in a viva

25-50%

Prevalence

Ventilated >7 days

Up to 67%

Septic shock

Highest-risk subgroup

~50%

Incomplete recovery

At 1 year post-ICU

2-3x

Mortality

With ICUAW vs without

[2] [8]

Prevention — the ABCDEF bundle applied to ICUAW

Because no treatment reverses established ICUAW, prevention is the entire game. The SCCM ICU Liberation ABCDEF bundle is the single best-evidenced, multidisciplinary strategy and addresses every major modifiable risk factor.[12]

ICUAW prevention — the ABCDEF bundle, component by component

A — Assess and manage pain

Untreated pain drives immobility, hyperglycaemia (stress response) and delirium. Use CPOT (intubated) or NRS (extubated). Analgesia-first sedation reduces opioid and benzodiazepine burden.

B — Both SAT and SBT

Daily spontaneous awakening trial + spontaneous breathing trial. Shorter ventilation = less ventilator-induced diaphragm dysfunction and less immobility. Pair the two (SAT-and-SBT protocol) for synergy.

C — Choice of sedation

Prefer dexmedetomidine or propofol over benzodiazepines. Target light sedation (RASS -1 to 0). Avoid prolonged deep sedation, which is an independent risk factor for ICUAW.

D — Delirium assessment and management

Monitor with CAM-ICU or ICDSC. Prevent delirium (pain control, light sedation, sleep, mobilisation, family). Delirium and ICUAW are tightly linked — both reflect and worsen critical illness.

E — Early mobility

The single most effective ICUAW-specific intervention. Passive ROM day 1 → in-bed cycling → sit on edge of bed → stand → walk, as soon as haemodynamically safe (often within 72 h, even while ventilated). Coordinated nursing + physiotherapy + medical staff.

F — Family engagement and empowerment

Family presence and participation in mobilisation and care; flexible visiting; ICU diaries. Reduces sedation needs, supports rehabilitation, and addresses PICS-F.

[12] [13]

Glycaemic control — the Leuven story and its correction

The link between hyperglycaemia and ICUAW was cemented by Van den Berghe (2001, NEJM): intensive insulin therapy (target 4.4-6.1 mmol/L) in surgical ICU patients halved the incidence of critical illness polyneuropathy/myopathy and reduced mortality. This drove widespread adoption of "tight" glucose control.[5]

NICE-SUGAR (2009, NEJM) then showed that the same tight target increased mortality and severe hypoglycaemia compared with moderate control (target ≤10 mmol/L). The synthesis: moderate glycaemic control (6-10 mmol/L) — avoiding both severe hyperglycaemia (which causes ICUAW) and hypoglycaemia (which causes brain injury) — is the current standard. Insulin infusion titrated to a glucose of 6-10 mmol/L remains the single most evidence-supported ICUAW prevention measure after early mobilisation.[6]

Recovery timeline and prognostic factors

Recovery from ICUAW is variable and often incomplete. CIM (membrane repolarisation + refeeding of muscle) tends to recover faster than CIP (axonal regrowth at ~1 mm/day). The MRC sum score at ICU discharge is the single best early predictor of long-term function.[2]

Recovery trajectory — how ICUAW recovers over time (click each)

Rehabilitation phase

Functional gains accelerate with active rehabilitation. Many patients regain independent ambulation if weakness was predominantly myopathic. Axonal regrowth (CIP) continues slowly.

[2]

Key trials and evidence

van den Berghe 2001 — Intensive insulin therapy (Leuven surgical) (PMID 11794168)

[2]

Exam practice

SAQ — ICU-acquired weakness

10 minutes · 10 marks

A 67-year-old man with severe community-acquired pneumonia and septic shock has been in ICU for 9 days. He required vasopressors for 3 days, has received hydrocortisone 200 mg/day for 5 days, a 48-hour cisatracurium infusion for ARDS, and remains mechanically ventilated. Sedation has been weaned and he is now cooperative (RASS 0). On examination he has flaccid, symmetric limb weakness; facial strength is normal. His glucose has ranged 8-16 mmol/L despite an insulin infusion. Train-of-four shows 4/4 twitches.

[7]

SAQ — CIP versus CIM: differentiating the electrophysiology

10 minutes · 10 marks

A 54-year-old woman with severe ARDS from H1N1 influenza has been ventilated for 12 days. She received hydrocortisone 200 mg/day for 7 days and a 48-hour cisatracurium infusion. Sedation has been weaned; she is cooperative (RASS 0) but has flaccid, symmetric limb weakness and has failed two spontaneous breathing trials despite radiological resolution of her pneumonia. MRC sum score is 36/60. Nerve conduction studies show reduced compound muscle action potential (CMAP) amplitudes in all limbs with normal conduction velocities and normal distal latencies.

[10]

SAQ — Preventing and rehabilitating ICU-acquired weakness

10 minutes · 10 marks

A 62-year-old man is admitted to ICU with septic shock from a perforated diverticulum. He is intubated, on noradrenaline 0.3 mcg/kg/min, and has been started on hydrocortisone 200 mg/day for refractory vasoplegia. His glucose is 14 mmol/L. He is sedated with propofol and fentanyl. Outline your strategy to prevent ICU-acquired weakness and to rehabilitate him if it occurs.

[3]

Additional clinical pearls — examiner depth

Beyond the basics — deeper ICUAW points for the CICM/FFICM exam

CINM (combined) is the most common phenotype — pure CIM and pure CIP are conceptually distinct but overlap in >50% of electrophysiologically-confirmed cases.[1]
The SNAP is the key discriminator: normal SNAP = CIM; reduced SNAP + reduced CMAP = CIP (axonal). Nerve conduction velocity is normal in both (the lesion is axonal, not demyelinating).[10]
Direct muscle stimulation (tibialis anterior) is the gold standard when sensory studies are confounded — it reclassifies many "CIP" cases as CIM/CINM. Inexcitable muscle on direct stimulation = CIM.[9]
Selective loss of thick myosin filaments on muscle biopsy is the histological hallmark of CIM — examiners love this detail.
Membrane (sarcolemmal) depolarisation and inexcitability explain why CIM can cause profound yet rapidly reversible weakness — the membrane repolarises as the illness resolves.[11]
CIP is AXONAL, not demyelinating — so conduction velocities are preserved and recovery depends on axonal regrowth (~1 mm/day), explaining the slow, often incomplete recovery.
Sepsis is the single strongest risk factor for ICUAW overall; hyperglycaemia is the most modifiable.[2]
Acute quadriplegic myopathy = the classic steroid + NMBA combination injury — high-yield for vivas. Cause selective myosin loss and fibre atrophy.
Van den Berghe (2001) showed intensive insulin halves ICUAW; NICE-SUGAR (2009) showed the very tight target increases mortality — synthesis = moderate control (6-10 mmol/L).[5][6]
Schweickert (2009, Lancet) is the landmark early-mobilisation RCT: 59% vs 35% return to independent function at discharge in ventilated patients.[7]
ICUAW causes failed weaning: De Jonghe showed ICU-acquired paresis independently prolongs weaning — when weaning fails and infection/cardiac causes are excluded, calculate the MRC score.[8]
The ABCDEF bundle (SCCM ICU Liberation) addresses every major modifiable ICUAW risk; the ICU Liberation Collaborative (>15,000 patients, Pun 2019) showed higher bundle completeness improves survival.[12][13]
~30-50% have incomplete recovery at 1 year — ICUAW is a major contributor to PICS and failure to return to work. The MRC score at ICU discharge predicts long-term function.[2]
Facial sparing distinguishes ICUAW from Guillain-Barré and myasthenia (which involve ocular/bulbar muscles). Areflexia is common but not required.
CIM recovers faster than CIP: CIM membrane inexcitability reverses in weeks; CIP axonal regrowth takes months-years at ~1 mm/day.[2]
Always exclude mimics before diagnosing ICUAW: GBS (CSF albuminocytological dissociation), MG (+AChR/MuSK), electrolyte disorder (K⁺, Mg²⁺, Ca²⁺, phosphate), spinal cord lesion, prolonged NMBA effect (check train-of-four).[10]
Ventilator-induced diaphragm dysfunction (VIDD) is a distinct but overlapping entity — rapid diaphragm atrophy from inactivity during mechanical ventilation contributes to failed weaning.
There is NO specific treatment for established ICUAW — no evidence for steroids, NMBAs, or (consistently) for electrical muscle stimulation. Prevention + rehabilitation are the only effective strategies.[4]
The ATS 2014 guideline standardised ICUAW diagnosis (MRC <48 in a cooperative patient after excluding other causes, confirmed by electrophysiology) — cite this in an exam answer.[10]
MRC sum score requires a cooperative patient (RASS ≥ -1) and exclusion of residual NMBA (train-of-four ≥ 4/4). If uncooperative, use hand-grip dynamometry (<11 kg F / <27 kg M) or wait.
Survival ≠ recovery: the ICU quality target is now functional recovery, and ICUAW is the dominant physical-domain gap between the two.[14]

Red flags — what must not be missed

ICUAW — the traps and must-not-miss points

Corticosteroids + NMBAs together cause acute quadriplegic myopathy — avoid the combination where possible; if unavoidable, use the shortest duration and monitor train-of-four.
Hyperglycaemia is the #1 modifiable risk factor — target 6-10 mmol/L; both Van den Berghe (2001, benefit) and NICE-SUGAR (2009, harm of over-tight control) shape current practice.[5][6]
Facial weakness REJECTS the diagnosis of ICUAW — think GBS (areflexia, CSF dissociation) or myasthenia (fatigable, ocular/bulbar) instead.[10]
ICUAW causes failed weaning — when weaning fails and infection/cardiac causes are excluded, calculate the MRC score (De Jonghe).[8]
No specific treatment exists — prevention (ABCDEF bundle, glycaemic control, early mobilisation) and rehabilitation are the only effective strategies. Do not "treat" with steroids or NMBAs.[4]
~30-50% have incomplete recovery at 1 year — set expectations; the MRC score at ICU discharge predicts long-term function and discharge destination.[2]
MRC <48/60 is associated with prolonged ventilation, higher mortality, and long-term disability — it is not a benign finding.[1]
Always exclude residual NMBA (train-of-four) and electrolyte disorder (K⁺, Mg²⁺, Ca²⁺, phosphate) before attributing weakness to ICUAW.[10]
The ABCDEF bundle works — the ICU Liberation Collaborative (Pun 2019) showed higher bundle completeness improves survival across >15,000 patients.[13]

References

[1]Stevens RD, Marshall SA, Cornblath DR, Hoke A, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Critical care medicine, 2009.PMID 20046114
[2]Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. New England Journal of Medicine, 2014.PMID 25014703
[3]Tipping CJ, Harrold M, Holland A, Romero L, et al. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive care medicine, 2017.PMID 27864615
[4]Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G, et al. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database of Systematic Reviews, 2014.PMID 24477672
[5]van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. New England Journal of Medicine, 2001.PMID 11794168
[6]NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. New England Journal of Medicine, 2009.PMID 19318384
[7]Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. The Lancet, 2009.PMID 19446324
[8]De Jonghe B, Bastuji-Garin S, Sharshar T, Outin H, et al. Does ICU-acquired paresis lengthen weaning from mechanical ventilation? Intensive care medicine, 2004.PMID 14767593
[9]Lefaucheur JP, Nordine T, Rodriguez P, et al. Origin of ICU acquired paresis determined by direct muscle stimulation. Journal of neurology, neurosurgery, and psychiatry, 2006.PMID 16306155
[10]Fan E, Cheek F, Chlan L, Gosselink R, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. American Journal of Respiratory and Critical Care Medicine, 2014.PMID 25496103
[11]Latronico N, Shehu I, Guarneri B Use of electrophysiologic testing. Critical care medicine, 2009.PMID 20046116
[12]Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF Bundle in Critical Care. Critical Care Clinics, 2017.PMID 28284292
[13]Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, et al. Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Critical care medicine, 2019.PMID 30339549
[14]Hiser SL, Casey K, Nydahl P, Hodgson CL. Intensive care unit acquired weakness and physical rehabilitation in the ICU. BMJ, 2025.PMID 39870417

[3]

Types of ICU-acquired weakness

CIM (myopathy)

Muscle involvement

Primary myopathy (muscle fibre dysfunction)
More common than CIP in ICU
Electrophysiology: reduced CMAP amplitude, normal sensory studies
Muscle biopsy: myosin filament loss, muscle fibre atrophy/necrosis
Associated with: corticosteroids, NMBAs, sepsis, hyperglycaemia

CIP (polyneuropathy)

Nerve involvement

Axonal sensorimotor polyneuropathy
Electrophysiology: reduced CMAP and SNAP amplitudes (axonal pattern)
Often coexists with CIM (CINM — critical illness neuromyopathy)
Associated with: sepsis, multi-organ failure, prolonged ICU stay

[4]

Diagnosis

Clinical — MRC score

[2]

Electrophysiology

Diagnostic approach

Clinical assessment

Exclude other causes

Electrophysiology (nerve conduction studies + EMG)

Muscle biopsy (rarely needed)

Reserved for research or diagnostic uncertainty. Shows: myosin filament loss (selective loss of thick myosin filaments — characteristic of CIM), fibre atrophy, fibre necrosis, fatty degeneration.

[1]

Prevention

ICUAW prevention — the modifiable risk factors

Glycaemic control — the #1 modifiable factor

Minimise sedation

Early mobilisation

Minimise corticosteroids and NMBAs

Nutrition

[2]

Risk factors

ICU-acquired weakness risk factors

25-50%

Ventilated >7 days

Develop ICUAW

Hyperglycaemia

Most modifiable risk factor

1.5-2%/day

Muscle loss

Per day of bed rest in ICU

~50%

Incomplete recovery

At 1 year post-ICU

[2]

Clinical pearls

High-yield ICUAW points for the CICM/FFICM exam

ICUAW affects 25-50% of patients ventilated >7 days.[1]
MRC score <48/60 = diagnostic threshold (6 muscle groups, bilateral, 0-5 scale).
Hyperglycaemia is the #1 modifiable risk factor — target 6-10 mmol/L.[6]
CIM vs CIP: differentiated by nerve conduction studies (CIM: normal sensory, CIP: abnormal sensory).
Corticosteroids + NMBAs together dramatically increase risk ('acute quadriplegic myopathy').
Early mobilisation (within 72h) reduces ICUAW and delirium.[3]
Minimise sedation — immobilisation causes rapid muscle wasting (1.5-2%/day).
Facial muscles are SPARED in ICUAW (unlike GBS or MG) — if facial weakness present, reconsider diagnosis.
Muscle biopsy: selective loss of thick myosin filaments (characteristic of CIM).
Outcomes: prolonged ventilation, increased mortality, long-term disability.
No specific treatment — prevention is key. No evidence for: steroids, NMBAs, electrical stimulation (conflicting evidence).
Recovery: starts within weeks of ICU discharge but may take months-years. ~50% have incomplete recovery at 1 year.
Nutrition: adequate protein (1.2-1.5 g/kg/day) — but avoid overfeeding.
Daily SAT + SBT pairing reduces ventilation days → fewer days immobilised → less ICUAW.

Red flags

Pathophysiology — how critical illness damages nerve and muscle

Muscle (CIM)

Myocyte injury

Catabolic state: resistance to insulin/IGF-1 + ↑ TNF-α/IL-1/IL-6 → ubiquitin-proteasome and autophagy-lysosome proteolysis of contractile proteins
Preferential loss of THICK (myosin) filaments → selective myosin loss (hallmark histology); later type II fibre atrophy
Sodium-channel dysfunction + membrane depolarisation → inexcitable sarcolemma (reduced/absent CMAP on direct muscle stimulation)
Mitochondrial dysfunction (impaired oxidative phosphorylation, ↓ ATP) → energy failure, impaired Ca²⁺ handling, oxidative stress
Triggered by: immobilisation, corticosteroids, NMBAs, hyperglycaemia, sepsis

Nerve (CIP)

Axonal degeneration

Distal, symmetrical, AXONAL (not demyelinating) sensorimotor polyneuropathy
Microvascular dysfunction → endoneurial ischaemia + increased blood-nerve-barrier permeability
Sepsis/inflammation → activation of Schwann cells, mitochondrial injury, energy failure of the axon
Electrophysiology: reduced CMAP AND SNAP amplitudes (both motor AND sensory affected — the key discriminator from CIM)
Triggered by: sepsis, multi-organ failure, prolonged stay; axonal degeneration is the dominant lesion

Combined (CINM)

Most common in practice

Coincident myopathy + polyneuropathy — found in >50% of electrophysiologically-confirmed ICUAW
Sensory studies often "normal-ish" in pure CIM but abnormal in CINM — direct muscle stimulation resolves ambiguity
Clinically indistinguishable from isolated CIM/CIP at the bedside — needs electrophysiology to separate
Worse functional outcomes and slower recovery than either alone
Risk profile = union of CIM and CIP risks (sepsis + steroids + NMBAs + immobility + hyperglycaemia)

[1] [2]

The unifying pathophysiology — three convergent injury pathways

The pathophysiological cascade — from sepsis to weakness

Trigger: systemic inflammation (sepsis, MODS, ARDS)

Cytokine storm (TNF-α, IL-1β, IL-6), microcirculatory failure, oxidative stress, and mitochondrial dysfunction are the upstream drivers. Sepsis is the single strongest risk factor for ICUAW.

Catabolic dominance in muscle

Sarcolemmal inexcitability

Axonal degeneration in nerve (CIP)

Microvascular ischaemia, blood-nerve-barrier breakdown, and Schwann-cell mitochondrial failure produce distal axonal sensorimotor polyneuropathy → secondary muscle denervation.

Amplifiers: immobility, drugs, glucose

Clinical phenotype: diffuse, flaccid, symmetric weakness

Limbs > trunk > face (facial sparing). Hyporeflexia/areflexia. Respiratory muscle involvement → failed weaning. Sensation intact or only mildly impaired (unlike the marked weakness).

[1] [11]

CIP vs CIM vs CINM — discriminating the overlap at the bedside

[9]

Diagnosis in depth — the ATS framework

Diagnostic algorithm (ATS 2014)

Step 1 — Suspect ICUAW

Any patient ventilated >48-72 h, or with sepsis/MODS, prolonged sedation, steroid + NMBA exposure, or difficulty weaning from ventilation. Screen actively — ICUAW is under-recognised.

Step 2 — Cooperative? Perform MRC sum score

Step 3 — Uncooperative? Use surrogate measures

Step 4 — Exclude mimics (mandatory)

Step 5 — Electrophysiology (confirm + phenotype)

Step 6 — Muscle biopsy (rarely needed)

Reserved for research or genuine diagnostic uncertainty. Hallmark of CIM: selective loss of thick myosin filaments, fibre atrophy, and (in severe cases) fibre necrosis with fatty replacement.

[10] [11]

Diagnostic thresholds — the numbers to know

<48/60

MRC sum score

Diagnostic of ICUAW

<11 kg

Grip strength (F)

Dynamometry threshold — female

<27 kg

Grip strength (M)

Dynamometry threshold — male

>48 h

Ventilation

When to start screening

[8]

Risk factors in depth

[8]

ICUAW risk — the numbers to quote in a viva

25-50%

Prevalence

Ventilated >7 days

Up to 67%

Septic shock

Highest-risk subgroup

~50%

Incomplete recovery

At 1 year post-ICU

2-3x

Mortality

With ICUAW vs without

[2] [8]

Prevention — the ABCDEF bundle applied to ICUAW

ICUAW prevention — the ABCDEF bundle, component by component

A — Assess and manage pain

Untreated pain drives immobility, hyperglycaemia (stress response) and delirium. Use CPOT (intubated) or NRS (extubated). Analgesia-first sedation reduces opioid and benzodiazepine burden.

B — Both SAT and SBT

C — Choice of sedation

Prefer dexmedetomidine or propofol over benzodiazepines. Target light sedation (RASS -1 to 0). Avoid prolonged deep sedation, which is an independent risk factor for ICUAW.

D — Delirium assessment and management

Monitor with CAM-ICU or ICDSC. Prevent delirium (pain control, light sedation, sleep, mobilisation, family). Delirium and ICUAW are tightly linked — both reflect and worsen critical illness.

E — Early mobility

F — Family engagement and empowerment

Family presence and participation in mobilisation and care; flexible visiting; ICU diaries. Reduces sedation needs, supports rehabilitation, and addresses PICS-F.

[12] [13]

Glycaemic control — the Leuven story and its correction

Recovery timeline and prognostic factors

Recovery trajectory — how ICUAW recovers over time (click each)

Rehabilitation phase

Functional gains accelerate with active rehabilitation. Many patients regain independent ambulation if weakness was predominantly myopathic. Axonal regrowth (CIP) continues slowly.

[2]

Key trials and evidence

van den Berghe 2001 — Intensive insulin therapy (Leuven surgical) (PMID 11794168)

[2]

NICE-SUGAR 2009 — Glucose control in ICU (PMID 19318384)

[2]

Schweickert 2009 — Early mobilisation in ventilated patients (PMID 19446324)

[2]

De Jonghe 2004 — ICU-acquired paresis and weaning (PMID 14767593)

[2]

Pun 2019 — ABCDEF bundle in >15,000 ICU patients (PMID 30339549)

[1]

Exam practice

SAQ — ICU-acquired weakness

10 minutes · 10 marks

[7]

SAQ — CIP versus CIM: differentiating the electrophysiology

10 minutes · 10 marks

[10]

SAQ — Preventing and rehabilitating ICU-acquired weakness

10 minutes · 10 marks

[3]

Additional clinical pearls — examiner depth

Beyond the basics — deeper ICUAW points for the CICM/FFICM exam

CINM (combined) is the most common phenotype — pure CIM and pure CIP are conceptually distinct but overlap in >50% of electrophysiologically-confirmed cases.[1]
The SNAP is the key discriminator: normal SNAP = CIM; reduced SNAP + reduced CMAP = CIP (axonal). Nerve conduction velocity is normal in both (the lesion is axonal, not demyelinating).[10]
Direct muscle stimulation (tibialis anterior) is the gold standard when sensory studies are confounded — it reclassifies many "CIP" cases as CIM/CINM. Inexcitable muscle on direct stimulation = CIM.[9]
Selective loss of thick myosin filaments on muscle biopsy is the histological hallmark of CIM — examiners love this detail.
Membrane (sarcolemmal) depolarisation and inexcitability explain why CIM can cause profound yet rapidly reversible weakness — the membrane repolarises as the illness resolves.[11]
CIP is AXONAL, not demyelinating — so conduction velocities are preserved and recovery depends on axonal regrowth (~1 mm/day), explaining the slow, often incomplete recovery.
Sepsis is the single strongest risk factor for ICUAW overall; hyperglycaemia is the most modifiable.[2]
Acute quadriplegic myopathy = the classic steroid + NMBA combination injury — high-yield for vivas. Cause selective myosin loss and fibre atrophy.
Van den Berghe (2001) showed intensive insulin halves ICUAW; NICE-SUGAR (2009) showed the very tight target increases mortality — synthesis = moderate control (6-10 mmol/L).[5][6]
Schweickert (2009, Lancet) is the landmark early-mobilisation RCT: 59% vs 35% return to independent function at discharge in ventilated patients.[7]
ICUAW causes failed weaning: De Jonghe showed ICU-acquired paresis independently prolongs weaning — when weaning fails and infection/cardiac causes are excluded, calculate the MRC score.[8]
The ABCDEF bundle (SCCM ICU Liberation) addresses every major modifiable ICUAW risk; the ICU Liberation Collaborative (>15,000 patients, Pun 2019) showed higher bundle completeness improves survival.[12][13]
~30-50% have incomplete recovery at 1 year — ICUAW is a major contributor to PICS and failure to return to work. The MRC score at ICU discharge predicts long-term function.[2]
Facial sparing distinguishes ICUAW from Guillain-Barré and myasthenia (which involve ocular/bulbar muscles). Areflexia is common but not required.
CIM recovers faster than CIP: CIM membrane inexcitability reverses in weeks; CIP axonal regrowth takes months-years at ~1 mm/day.[2]
Always exclude mimics before diagnosing ICUAW: GBS (CSF albuminocytological dissociation), MG (+AChR/MuSK), electrolyte disorder (K⁺, Mg²⁺, Ca²⁺, phosphate), spinal cord lesion, prolonged NMBA effect (check train-of-four).[10]
Ventilator-induced diaphragm dysfunction (VIDD) is a distinct but overlapping entity — rapid diaphragm atrophy from inactivity during mechanical ventilation contributes to failed weaning.
There is NO specific treatment for established ICUAW — no evidence for steroids, NMBAs, or (consistently) for electrical muscle stimulation. Prevention + rehabilitation are the only effective strategies.[4]
The ATS 2014 guideline standardised ICUAW diagnosis (MRC <48 in a cooperative patient after excluding other causes, confirmed by electrophysiology) — cite this in an exam answer.[10]
MRC sum score requires a cooperative patient (RASS ≥ -1) and exclusion of residual NMBA (train-of-four ≥ 4/4). If uncooperative, use hand-grip dynamometry (<11 kg F / <27 kg M) or wait.
Survival ≠ recovery: the ICU quality target is now functional recovery, and ICUAW is the dominant physical-domain gap between the two.[14]

Red flags — what must not be missed

ICUAW — the traps and must-not-miss points

Corticosteroids + NMBAs together cause acute quadriplegic myopathy — avoid the combination where possible; if unavoidable, use the shortest duration and monitor train-of-four.
Hyperglycaemia is the #1 modifiable risk factor — target 6-10 mmol/L; both Van den Berghe (2001, benefit) and NICE-SUGAR (2009, harm of over-tight control) shape current practice.[5][6]
Facial weakness REJECTS the diagnosis of ICUAW — think GBS (areflexia, CSF dissociation) or myasthenia (fatigable, ocular/bulbar) instead.[10]
ICUAW causes failed weaning — when weaning fails and infection/cardiac causes are excluded, calculate the MRC score (De Jonghe).[8]
No specific treatment exists — prevention (ABCDEF bundle, glycaemic control, early mobilisation) and rehabilitation are the only effective strategies. Do not "treat" with steroids or NMBAs.[4]
~30-50% have incomplete recovery at 1 year — set expectations; the MRC score at ICU discharge predicts long-term function and discharge destination.[2]
MRC <48/60 is associated with prolonged ventilation, higher mortality, and long-term disability — it is not a benign finding.[1]
Always exclude residual NMBA (train-of-four) and electrolyte disorder (K⁺, Mg²⁺, Ca²⁺, phosphate) before attributing weakness to ICUAW.[10]
The ABCDEF bundle works — the ICU Liberation Collaborative (Pun 2019) showed higher bundle completeness improves survival across >15,000 patients.[13]

References

[1]Stevens RD, Marshall SA, Cornblath DR, Hoke A, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Critical care medicine, 2009.PMID 20046114
[2]Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. New England Journal of Medicine, 2014.PMID 25014703
[3]Tipping CJ, Harrold M, Holland A, Romero L, et al. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive care medicine, 2017.PMID 27864615
[4]Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G, et al. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database of Systematic Reviews, 2014.PMID 24477672
[5]van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. New England Journal of Medicine, 2001.PMID 11794168
[6]NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. New England Journal of Medicine, 2009.PMID 19318384
[7]Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. The Lancet, 2009.PMID 19446324
[8]De Jonghe B, Bastuji-Garin S, Sharshar T, Outin H, et al. Does ICU-acquired paresis lengthen weaning from mechanical ventilation? Intensive care medicine, 2004.PMID 14767593
[9]Lefaucheur JP, Nordine T, Rodriguez P, et al. Origin of ICU acquired paresis determined by direct muscle stimulation. Journal of neurology, neurosurgery, and psychiatry, 2006.PMID 16306155
[10]Fan E, Cheek F, Chlan L, Gosselink R, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. American Journal of Respiratory and Critical Care Medicine, 2014.PMID 25496103
[11]Latronico N, Shehu I, Guarneri B Use of electrophysiologic testing. Critical care medicine, 2009.PMID 20046116
[12]Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF Bundle in Critical Care. Critical Care Clinics, 2017.PMID 28284292
[13]Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, et al. Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Critical care medicine, 2019.PMID 30339549
[14]Hiser SL, Casey K, Nydahl P, Hodgson CL. Intensive care unit acquired weakness and physical rehabilitation in the ICU. BMJ, 2025.PMID 39870417