Muscle matters: Transforming the care of intensive care unit acquired sarcopenia and myosteatosis

Table 1 Imaging modalities for intensive care unit muscle assessment

Technique	Parameters measured	Advantages	Limitations	Clinical utility
CT scan	Skeletal muscle CSA; muscle attenuation (density)	Accurately quantifies muscle/adipose tissue, visualizes muscle quality, and serves as the reference standard for sarcopenia diagnosis	Requires radiation and ICU transport, unsuitable for frequent reassessments, costly, and limited to opportunistic snapshots	Baseline risk stratification using CT-derived low muscle mass predicts worse outcomes and has been correlated with mortality and ICU length of stay
Ultrasound	Muscle thickness; CSA; echo-intensity (grayscale)	Bedside, portable, radiation-free, low-cost, repeatable for monitoring, and assesses limb and respiratory muscles in real time	Operator-dependent, limited to specific muscles, and affected by edema or obesity	Enables monitoring of muscle wasting, early detection of ICU-acquired loss, and assessment of diaphragm and peripheral muscles to guide rehabilitation
Magnetic resonance imaging	Muscle volume; detailed anatomy and composition	Provides highly accurate muscle volume and fat measurement without radiation	Infeasible in critically ill due to transport, time, cost, and contraindications with ICU devices or instability	Used in research to study muscle architecture; rarely applied clinically in ICU due to logistical constraints
Dual-energy X-ray absorptiometry scan	Lean body mass; appendicular muscle mass via dual X-ray absorption	Gold standard for body composition and precise in diagnosing chronic sarcopenia	Requires transport, affected by fluid shifts, involves low radiation, and unsuitable for ICU monitoring	Useful for nutritional assessment post-ICU or in research; impractical during acute ICU stay
Bioelectrical impedance analysis	Total body water, estimated fat-free mass (via electrical impedance)	Bedside, quick, non-invasive, and portable	Assumes normal hydration; inaccurate with fluid imbalance, vasopressors, edema, or position changes	Limited in ICU; useful for trend tracking by nutrition teams but confounded by fluid shifts

CT: Computed tomography; CSA: Cross-sectional area; ICU: Intensive care unit.

Table 2 Biomarkers for assessing muscle wasting in intensive care unit

Biomarker	What it measures	Advantages	Limitations	Clinical utility
3-MH (urine)	Myofibrillar protein breakdown (release of 3-MH from muscle proteins)	Specific marker of skeletal muscle catabolism and quantifies muscle protein breakdown	Affected by diet and renal function; not routinely available in clinical laboratories	Used in research to quantify muscle breakdown; rarely clinical due to confounders and complexity
Creatinine-based indices (e.g., creatinine height index)	Muscle mass proxy based on creatinine production (muscle-derived creatinine per 24 hours or per body size)	Simple, historically used in nutrition assessment; based on urine or blood creatinine	Assumes stable renal function, confounded by fluid shifts, and insensitive to acute changes	Limited in ICU; low creatinine may indicate low muscle mass but requires caution without renal failure
Muscle enzymes (e.g., CK)	Muscle fiber damage or necrosis (CK leaks into blood with muscle membrane injury)	Widely available; elevated CK indicates acute muscle injury (e.g., rhabdomyolysis)	Not a marker of chronic atrophy; normal CK can mask wasting, while elevations may reflect other injuries	Detects acute muscle injury but not ICU sarcopenia; normal CK with weakness suggests critical illness myopathy over necrosis
Inflammatory markers (CRP, interleukin-6, tumour necrosis factor-α)	Systemic inflammatory response driving catabolic state	Easily measured (e.g., CRP); elevated levels reflect illness severity and catabolic drive	Non-specific; do not assess muscle directly; sustained inflammation promotes muscle breakdown and organ dysfunction	Helps identify patients at risk of muscle loss from catabolic inflammation; highlights need for anti-inflammatory and nutritional strategies, but not a direct muscle metric
Hormonal signals (e.g., IGF-1, cortisol, myostatin)	Anabolic vs catabolic hormonal milieu (IGF-1 promotes muscle synthesis; myostatin inhibits it; cortisol catabolic)	Reflect muscle growth pathway activity; low IGF-1 or high myostatin associate with atrophy in research	Research-only, with specialized assays, complex interactions, and no ICU-specific reference ranges	Studied as therapeutic targets (e.g., myostatin inhibitors, growth hormone axis) in ICU trials; not for routine monitoring

CK: Creatinine kinase; CRP: C-reactive protein; ICU: Intensive care unit; IGF: Insulin-like growth factor; 3-MH: 3-methylhistidine.

Table 3 Functional tests and neuromuscular assessments in the intensive care unit

Assessment method	Description and parameters	Advantages	Limitations	Clinical utility
MRC sum score (manual muscle testing)	Clinician-performed manual strength exam of 6 muscle groups bilaterally (scored 0–5 each; max score 60). ICU-AW defined by MRC < 48	No equipment needed; bedside clinical exam. Standardized scoring system with prognostic significance. Validated for diagnosing ICU-AW when patient is awake	Feasible only in conscious, cooperative patients (often < 50% of ICU patients early on). Subjective effort can vary; inter-rater variability in scoring. Cannot detect subclinical weakness in sedated patients	Primary diagnostic tool for ICU-AW once patient can participate. Identifies patients requiring rehab interventions; a score < 48 correlates with difficulty in weaning and prolonged ICU stay
Handgrip dynamometry	Patient squeezes a handheld dynamometer to measure grip strength (kg force). Typically, the best of 2-3 attempts is recorded for each hand	Objective, numeric measure of strength. Quick (< 1 minute) and reproducible. Can be done in bed; minimal patient movement required (just hand squeeze)	Requires patient arousal and minimal cognitive function. Assesses primarily forearm/hand strength (may not reflect leg weakness). Grip may be impaired by local hand issues (arthritis, injury)	Useful surrogate for global strength; prognostic indicator (low grip strength on ICU admission associated with higher mortality). Can track strength improvements over ICU stay and guide nutrition/physio needs
Electrophysiological studies (nerve conduction studies and EMG)	Nerve conduction studies: Stimulate motor nerves and record muscle action potentials; EMG: Needle electrodes measure muscle electrical activity at rest and contraction. Detects CIP or CIM	Does not require patient cooperation or movement. Can diagnose the presence of neuropathy vs myopathy, aiding etiologic understanding. Highly sensitive to electrical changes in muscle/nerve function	Specialized personnel and equipment needed (not available in all ICUs). Time-consuming and somewhat uncomfortable (needle EMG). Edema and electrical noise in ICU can interfere with signals. Primarily diagnostic, not for routine monitoring of recovery	Confirms ICU-AW and differentiates CIP vs CIM in patients with unexplained or severe weakness. Often employed if weakness is profound or prolonged and other causes need exclusion. Helps prognostication (e.g., pure CIP has different recovery profile than CIM)
Functional mobility tests (e.g., sit-to-stand, 6-minute walk, etc.)	Performance-based tests of muscle function and endurance administered when patient is ambulatory. 5 × sit-to-stand: Time to rise from chair 5 times; 6-minute walk test: Distance walked in 6 minutes, etc.	Directly assesses integrated muscle function, balance, and endurance. Relates to real-world functional outcomes and independence. Useful for discharge planning and rehab goals	Not applicable during acute ICU phase (requires patient to be awake, off most support, and able to stand/walk). Influenced by cardiopulmonary fitness and motivation in addition to muscle strength. Safety concerns if patient is frail (risk of falls)	Employed at ICU discharge or step-down to evaluate recovery. For example, a very low 5 × sit-to-stand performance at ICU discharge indicates ongoing weakness and high rehab needs. These tests connect ICU-acquired muscle deficits to patient-centered outcomes like mobility and quality of life after critical illness

CIM: Critical illness myopathy; CIP: Critical illness polyneuropathy; EMG: Electromyography; ICU: Intensive care unit; ICU-AW: Intensive care unit acquired weakness; MRC: Medical research council.