Musculoskeletal

Rhabdomyolysis: workup and management

Clinical Overview and When to Suspect Rhabdomyolysis

— Traumatic/compressive: crush injury, prolonged immobilization ("found down"), compartment syndrome, electrical injury, lightning strike

— Exertional: unaccustomed strenuous exercise, military recruits, CrossFit, marathon, status epilepticus, severe dystonia, NMS, serotonin syndrome, malignant hyperthermia

— Drug/toxin: statins (esp. + fibrate, macrolide, CYP3A4 inhibitor), cocaine, methamphetamine, alcohol, heroin, colchicine, daptomycin, propofol infusion syndrome

— Infectious: influenza, Legionella, Coxsackie, EBV, HIV, leptospirosis, pyomyositis

— Metabolic/endocrine: hypokalemia, hypophosphatemia, DKA, HHS, hypothyroidism, McArdle disease and other inherited myopathies in recurrent cases

— Ischemic: arterial occlusion, prolonged tourniquet, sickle crisis

Board pearl: A "found down" elderly patient with AKI, hyperkalemia, and metabolic acidosis is rhabdomyolysis until CK proves otherwise — order CK before chasing a primary renal diagnosis.

Definition: Skeletal muscle injury releasing intracellular contents (myoglobin, CK, K+, phosphate, urate, LDH) into circulation, classically defined by CK >5× ULN (>1,000 U/L) plus clinical context, though many use CK >5,000 for "significant" rhabdo with AKI risk.

Core pathophysiology: ATP depletion → failure of Na+/K+ and Ca²⁺ pumps → intracellular Ca²⁺ overload → activation of proteases, phospholipases → sarcolemmal disruption → myoglobinuric AKI via tubular obstruction, direct nephrotoxicity, and renal vasoconstriction.

High-yield etiologies to anticipate on Step 3:

When to suspect even without classic triad: Any patient found down >2 hours, post-seizure, post-cocaine binge, post-extreme exercise, statin user with new myalgia, or unexplained AKI with hyperkalemia out of proportion.

Classic triad — myalgia, weakness, tea-colored urine — present in <10%. Most patients lack all three; rely on labs.

Presentation Patterns and Key History

— Exertional rhabdo: focal proximal muscle pain (thighs, shoulders, back) 24–72 h after intense activity; often in hot/humid conditions or sickle cell trait carriers

— Crush/immobilization: dependent extremity pain, paresthesias, swelling after hours-to-days down; often coexisting hypothermia, pressure ulcers

— Drug-induced: diffuse myalgias in a statin user starting weeks 4–12, often after adding a new CYP3A4 inhibitor (clarithromycin, diltiazem, grapefruit) or fibrate

— Toxic ingestion: agitation, hyperthermia, seizures with cocaine/meth; ask about synthetic cannabinoids and PCP

— Infectious: preceding flu-like illness, fever, then severe myalgias

— Duration of immobilization, last witnessed normal

— Exact medication list including OTC, supplements, energy drinks, recent antibiotic courses

— Substance use including bath salts, opioids, ETOH binges

— Family history of recurrent rhabdo, anesthesia reactions (suggests RYR1/MH or metabolic myopathy)

— Recent vaccinations, infections, heat exposure, military training

— Prior episodes (recurrent rhabdo → workup for CPT II deficiency, McArdle, phosphorylase b kinase, RYR1)

— Anuria or oliguria → assume AKI present

— Calf or forearm "rock-hard" swelling → compartment syndrome

— Altered mental status with hyperthermia → NMS, serotonin syndrome, MH, heat stroke

Step 3 management: When a patient reports a second lifetime episode of unexplained rhabdo, order outpatient referral to neuromuscular/genetics and consider ischemic forearm exercise test or genetic panel — recurrent disease is not just bad luck.

Symptom triad (rare and unreliable): muscle pain, weakness, dark/tea-colored urine. Dark urine reflects myoglobinuria, not hematuria — urine dipstick is heme-positive but microscopy shows no RBCs.

Common symptom clusters by etiology:

Targeted history (Step 3 voice — these change disposition):

Red-flag history demanding rapid action:

Physical Exam Findings and Hemodynamic Assessment

— Volume status is the most important physical finding — assess mucous membranes, JVP, skin turgor, capillary refill, orthostatics. Most rhabdo patients are profoundly volume-depleted (third-spacing into injured muscle can sequester >10 L).

— Temperature: hyperthermia in heat stroke, NMS, MH, serotonin syndrome, sympathomimetic toxicity

— Mental status: depressed in toxic/metabolic causes, agitated in stimulant toxicity

— Tenderness, swelling, induration — often focal (gluteal, paraspinal, calf in "found down")

— Decreased strength out of proportion to pain

— Skin: pressure necrosis, bullae, electrical entry/exit wounds, livedo

— Pain out of proportion, pain with passive stretch, paresthesias, pallor, pulselessness (late), poikilothermia

— Tense, "wood-hard" compartment is the earliest reliable sign

— Pulses are typically preserved until very late — do not be falsely reassured

— Measure compartment pressures if exam is equivocal: ΔP = diastolic BP − compartment pressure; ΔP <30 mmHg = fasciotomy

— Tachycardia from hypovolemia

— Hypotension from volume depletion ± distributive shock in sepsis-associated rhabdo

— ECG features of hyperkalemia: peaked T waves, PR prolongation, QRS widening, sine wave — treat empirically if widened QRS while awaiting K+

— Focal deficits suggest stroke causing immobilization rather than primary rhabdo

— Rigidity (NMS, MH), clonus + hyperreflexia (serotonin syndrome), seizure activity

Key distinction: Compartment syndrome can be the cause of rhabdomyolysis (crush injury) or the consequence of it (massive muscle edema after fluid resuscitation). Re-examine compartments every 2–4 h during aggressive IVF resuscitation — escalating opioid requirement is a warning sign.

General appearance:

Musculoskeletal exam:

Compartment syndrome assessment — high stakes:

Cardiovascular/hemodynamic:

Neuro exam:

Diagnostic Workup — Initial Labs, Urinalysis, ECG

— Diagnostic threshold: >5× ULN, typically >1,000 U/L; risk of AKI rises sharply above 5,000 U/L and is substantial above 15,000–20,000 U/L

— Peaks 24–72 h after injury, half-life ~36 h; falls predictably ~40%/day — failure to fall suggests ongoing injury or compartment syndrome

— CK-MB elevated proportionally (~1–3% of total) — do not misdiagnose MI; troponin is the discriminator

— Dipstick positive for blood, microscopy with few/no RBCs = myoglobinuria pathognomonic clue

— Pigmented (brown) granular casts

— Urine pH often <6.5 — acidic environment promotes myoglobin precipitation

— Hyperkalemia (released from cells; worsened by AKI) — most lethal early complication

— Hyperphosphatemia

— Hypocalcemia (Ca²⁺ binds to damaged muscle and precipitates with phosphate)

— Hyperuricemia

— Elevated BUN/Cr — AKI in 10–55%

— Anion-gap metabolic acidosis from lactate, urate, sulfate

— Look for hyperkalemia changes; treat empirically with IV calcium gluconate if QRS widening before K+ resulting

— Long QT from hypocalcemia

— Troponin (rule out cardiac injury, especially in electrical/crush)

— LFTs — AST/ALT often elevated from muscle, not liver; AST > ALT, normal GGT

— CBC, coags — DIC can complicate severe rhabdo

— LDH, aldolase (supportive, not required)

— Lactate, ABG/VBG, serum osmolality if toxic ingestion

CCS pearl: Order on arrival: CK, BMP, Mg, phos, Ca (ionized), UA with micro, urine myoglobin, troponin, LFTs, CBC, coags, lactate, ECG. Then reassess BMP and CK every 6–12 h to trend response.

Creatine kinase (CK-total):

Urinalysis:

Basic metabolic panel — anticipate the "rhabdo electrolyte profile":

ECG — obtain immediately:

Other initial labs:

Diagnostic Workup — Advanced and Etiology-Specific Studies

— Serum myoglobin clears rapidly (half-life 1–3 h) — a negative serum myoglobin does not exclude rhabdo

— Urine myoglobin more sensitive but not required for diagnosis when CK and clinical picture are clear

— Toxicology screen (cocaine, amphetamines, PCP, synthetic cannabinoids)

— TSH (hypothyroid myopathy)

— HbA1c, glucose, ketones (DKA, HHS)

— HIV, influenza PCR, EBV, Coxsackie, Legionella urinary antigen if infectious prodrome

— Autoimmune myositis workup (ANA, anti-Jo-1, anti-SRP, anti-HMGCR for statin-associated immune-mediated necrotizing myopathy) when CK fails to normalize off statin or weakness persists

— Generally not needed for diagnosis

— MRI most sensitive for muscle edema; reserve for localizing occult injury, suspected pyomyositis, or pre-biopsy planning

— CT if abdominal/pelvic compartment syndrome suspected (e.g., paraspinal rhabdo with retroperitoneal extension)

— Renal ultrasound if AKI to exclude obstruction

— Ischemic forearm exercise test: fails to produce lactate rise in McArdle (myophosphorylase deficiency)

— Acylcarnitine profile, urine organic acids (fatty acid oxidation defects, CPT II)

— Genetic panel for RYR1, CACNA1S, CPT2, PYGM, PFKM

— Muscle biopsy if genetics nondiagnostic and suspicion remains

— Equivocal exam, sedated/intubated patient, deep compartments (gluteal, paraspinal) — measure with Stryker or arterial-line transducer technique

Board pearl: A young athletic patient with second episode of exertional rhabdo, especially with a "second wind" phenomenon during exercise → think McArdle disease; the diagnostic clue is flat venous lactate with rising ammonia on ischemic forearm test.

Confirming myoglobinuria specifically:

Searching for the cause when not obvious:

Imaging:

Recurrent or unexplained rhabdo — metabolic myopathy workup:

When to do compartment pressures:

Risk Stratification and First-Line Management Logic

— CK >5,000 U/L at presentation or rising

— Initial Cr elevation, oliguria

— Hyperkalemia, hyperphosphatemia, hypocalcemia

— Acidosis (pH <7.3, bicarb <19)

— Sepsis, dehydration, crush injury, NSAID/ACEi/ARB co-exposure

— Older age, CKD baseline, diabetes

— Inputs: age, sex, cause, initial Cr, Ca, CK, phos, bicarb

— Score ≥6 → high risk for RRT or death; useful for ICU triage decisions

— Discharge consideration: young, well-appearing, exertional rhabdo, CK <5,000 and falling after IVF challenge, normal renal function, normal electrolytes, reliable follow-up within 24–48 h

— Floor admission: CK 5,000–20,000, normal Cr, stable electrolytes, no comorbidities

— ICU/step-down: CK >20,000, AKI, refractory hyperkalemia, hemodynamic instability, compartment syndrome, ongoing inciting cause

— Aggressive IV crystalloid — the only therapy with consistent evidence to prevent AKI

— Remove inciting cause (stop statin, treat seizure, cool the hyperthermic patient, evacuate compartment)

— Correct life-threatening electrolyte abnormalities (K+ first)

— Monitor urine output (target 200–300 mL/h) — place Foley if not making urine reliably

— Trend CK every 6–12 h until clearly falling

— Normal saline classically used but risks hyperchloremic acidosis at high volumes

— Lactated Ringer's or balanced crystalloid is reasonable and preferred by many; avoid LR concern with hyperkalemia is overblown (K+ ~4 mEq/L)

— Bicarbonate and mannitol are NOT routinely indicated — see chunk 7

Step 3 management: Even a "low CK" patient (3,000–5,000) with new AKI or hyperkalemia needs admission and aggressive IVF — the trajectory matters more than the absolute number.

Predictors of AKI and need for inpatient admission:

McMahon score (validated risk score for renal replacement or death):

Disposition logic:

Core treatment principles applied immediately:

Fluid choice debate:

Pharmacotherapy and Fluid Resuscitation — First-Line Regimen

— Begin 1–2 L isotonic crystalloid bolus in the ED for adult without contraindication

— Then maintenance infusion 200–500 mL/h titrated to urine output 200–300 mL/h (≈3 mL/kg/h)

— Continue until CK <5,000 U/L and falling, typically 24–72 h

— In crush injury: start IVF before extrication if possible; 10–15 mL/kg/h initially, then taper

— Monitor for volume overload — strict I/Os, daily weights, lung exam; reduce rate in oliguric AKI or HF

— Rationale: myoglobin precipitates in acidic urine; alkalinizing to urine pH >6.5 theoretically helps

— Evidence does not show benefit over saline alone

— If used: isotonic sodium bicarbonate (150 mEq in 1 L D5W) at 200 mL/h; stop if urine pH not >6.5 after 4–6 h, or if serum pH >7.5, ionized Ca falls, or symptomatic hypocalcemia

— Avoid in oliguric/anuric AKI

— Calcium gluconate 1–2 g IV if ECG changes (membrane stabilization)

— Insulin 10 U IV + D50 25 g (shift); albuterol nebulizer (shift)

— Sodium bicarbonate if acidemic

— Definitive removal: loop diuretics if making urine; dialysis if refractory or anuric

— Avoid K+-binding resins (patiromer, SZC) as primary therapy in acute crisis — too slow

— Do NOT replace asymptomatic hypocalcemia — Ca²⁺ rebounds during recovery and can cause hypercalcemia from release from injured muscle

— Replace only if symptomatic (tetany, seizures) or if needed to treat hyperkalemia

Board pearl: Bicarbonate and mannitol are not first-line; early, aggressive isotonic crystalloid is the only therapy with proven mortality benefit.

IV fluids — the cornerstone:

Urinary alkalinization (controversial, not routine):

Mannitol: Not recommended outside crush-injury protocols; theoretical osmotic diuretic and free-radical scavenger, but evidence is weak and risks of hyperosmolality and AKI exist

Hyperkalemia management — act fast:

Hypocalcemia:

Treat underlying cause: benzodiazepines for stimulant toxicity/serotonin syndrome, dantrolene for MH/NMS, cooling for heat stroke, stop statin/fibrate

Procedural and Extracorporeal Management

— Standard AEIOU indications: Acidosis refractory, Electrolytes (hyperkalemia refractory), Intoxication (not applicable here), Overload (volume), Uremia

— Anuria/severe oliguria unresponsive to volume challenge

— Symptomatic uremia

— Modality: intermittent hemodialysis preferred in stable patients; CRRT in hemodynamically unstable or massive ongoing CK release

— Note: Dialysis does not effectively clear myoglobin (large molecule), though high-cutoff/high-flux membranes and CRRT can remove some — not the indication; dialysis is for the complications (K+, acidosis, volume), not for CK itself

— Indications: ΔP <30 mmHg, clinical compartment syndrome, or absolute compartment pressure >30 mmHg in obtunded patient

— Emergent surgical consult; do not delay for imaging

— Common sites: anterior compartment of leg, forearm volar, gluteal, paraspinal

— Postoperative wound care is morbid — wet-to-dry dressings, delayed primary closure or skin grafting; risk of infection, nerve injury, chronic disability

— Establish IV access before releasing crushed limb to pre-treat anticipated K+ surge and hypotension

— Pre-extrication IVF, consider calcium and bicarbonate at moment of release

— Tourniquet only if life-threatening hemorrhage

CCS pearl: A crush victim being extricated from rubble — order IV NS at 1 L/h started before extrication, IV calcium gluconate at hand, ECG monitor, and CBC/BMP/CK STAT on arrival; have nephrology on standby. Anticipate hyperkalemic arrest at the moment of compression release.

Renal replacement therapy (RRT) — when:

Fasciotomy for compartment syndrome:

Crush injury extrication protocol:

Hyperbaric oxygen: Not standard; reserved for crush injury with limb ischemia in selected centers

Plasmapheresis/specialized myoglobin removal: Investigational (cytokine-adsorbing filters like CytoSorb in some ICUs); not standard of care

Special Populations — Elderly and Renal/Hepatic Impairment

— Most common scenario: "long lie" after fall, stroke, hypoglycemia, or syncope → prolonged immobilization rhabdo

— Higher baseline CKD reduces renal reserve — AKI develops at lower CK levels

— Volume management is a tightrope: aggressive IVF risks pulmonary edema and HF exacerbation; start with 500 mL boluses, reassess lung exam, JVP, and oxygenation every 30–60 min

— Lower threshold for ICU and invasive monitoring

— Always investigate why they fell — cardiac arrhythmia, orthostatic hypotension, occult infection, medication review (anticholinergics, sedative-hypnotics)

— Pressure injuries: full skin exam, document stage; involve wound care

— Pre-existing CKD → higher AKI and ESRD risk

— Calculate AKI on CKD using KDIGO criteria; small absolute Cr rise (0.3 mg/dL) is meaningful

— Earlier nephrology consult; dialysis access planning

— Avoid nephrotoxins: NSAIDs, iodinated contrast unless essential, aminoglycosides

— Cannot use urine output as marker; rely on K+, acidosis, volume

— May need extra HD sessions for K+ and volume control

— AST/ALT elevations confound — get GGT to distinguish hepatic from muscle source

— Coagulopathy increases bleeding risk if fasciotomy needed

— Drug clearance considerations for sedatives, opioids during ICU stay

— Statin + fibrate, statin + macrolide (clarithromycin, erythromycin), statin + amiodarone, statin + diltiazem/verapamil — review at every transition

— Colchicine + statin is a notorious combination

— Daptomycin requires weekly CK monitoring; hold for CK >5× ULN with symptoms or >10× without

Step 3 management: For an elderly "found down" patient with rhabdo, standing orders include telemetry, orthostatic vitals, medication reconciliation, PT/OT consult, fall-risk evaluation, and social work — discharge without addressing root cause guarantees readmission.

Elderly:

CKD patients:

Dialysis-dependent ESRD:

Hepatic impairment:

Polypharmacy concerns in elderly:

Special Populations — Pregnancy, Pediatrics, and Athletes

— Rare but reported in hyperemesis gravidarum, eclamptic seizures, prolonged labor, amphetamine use, and HELLP-associated muscle injury

— Fluid resuscitation as in nonpregnant; monitor fetal status continuously

— Avoid ACEi/ARBs for hypertension; methyldopa, labetalol, nifedipine preferred

— Hyperkalemia management as usual; sodium polystyrene category C, generally avoided

— Imaging: prefer ultrasound; avoid ionizing radiation when possible

— Less common; consider viral myositis (especially influenza B → benign acute childhood myositis with calf pain, antalgic gait, transient CK elevation, excellent prognosis)

— Other causes: trauma, sickle disease, DMD/BMD (look for Gowers sign, calf pseudohypertrophy), inherited metabolic myopathies, NMS from antipsychotics

— Fluid dosing: 20 mL/kg bolus, then 2–3× maintenance titrated to UOP 2–3 mL/kg/h

— Recurrent pediatric rhabdo demands metabolic and genetic workup

— Exertional rhabdo in unaccustomed exercise (boot camp, spin class, eccentric exercise), hot environments, dehydration, NSAID use, supplements (creatine generally safe; ephedra, DMAA dangerous)

— Sickle cell trait carriers at elevated risk for exertional collapse and rhabdo, especially with altitude/heat

— Return-to-play criteria (American College of Sports Medicine):

— Asymptomatic with normal labs and CK <5× ULN: gradual return after 72 h rest

— Severe cases (CK >100,000, AKI, hospitalization, FH metabolic myopathy, persistently elevated CK at 2 weeks): further workup before return

— Stop statin; if persistently elevated CK and weakness after 4–6 weeks off → consider immune-mediated necrotizing myopathy (anti-HMGCR Ab), requires immunosuppression

Board pearl: A child with calf pain refusing to walk one week after influenza, with CK 3,000 and normal renal function = benign acute childhood myositis — supportive care, hydration, recovery in days; do not over-investigate.

Pregnancy:

Pediatrics:

Athletes and military recruits:

Statin-associated rhabdo in healthy adults:

Complications and Adverse Outcomes

— Most feared early complication; affects 10–55% of hospitalized rhabdo patients

— Mechanisms: tubular obstruction by myoglobin casts, direct tubular toxicity from heme iron and free radicals, renal vasoconstriction from hypovolemia

— Recovery typical but 5–10% require permanent dialysis; baseline CKD predicts non-recovery

— Early hyperkalemia → arrhythmia, sudden cardiac death

— Early hypocalcemia → tetany, QT prolongation, seizures

— Hyperphosphatemia, hyperuricemia → contribute to AKI

— Late hypercalcemia (recovery phase) as deposited Ca²⁺ mobilizes from healing muscle — usually transient, supportive management

— May be cause or consequence; can occur 24–48 h after IVF resuscitation

— Untreated → permanent nerve injury, Volkmann contracture, limb loss

— Severe rhabdo releases thromboplastin-like substances from muscle

— Monitor PT/PTT, fibrinogen, platelets, d-dimer

— Manage with FFP, cryoprecipitate, platelets for bleeding; treat underlying cause

— Chronic kidney disease — even after "recovery," GFR may not return to baseline

— Functional disability from compartment syndrome

— Recurrence in metabolic myopathies

Key distinction: Early phase = hyperkalemia, hypocalcemia, AKI. Recovery phase = hypercalcemia, polyuria, sometimes hypophosphatemia and hypokalemia from refeeding — stop calcium and phosphate supplements as patient transitions.

Acute kidney injury:

Electrolyte cascades:

Compartment syndrome:

DIC:

Hepatic dysfunction: mild transaminitis common; severe liver injury rare and suggests alternative diagnosis (heat stroke, shock liver)

ARDS: Often from underlying cause (sepsis, aspiration during "found down") rather than rhabdo itself

Cardiac arrhythmias: from K+, Ca²⁺ shifts, underlying ischemia

Death: Mortality 5–10% overall; up to 20–30% with severe AKI requiring dialysis; higher with crush, sepsis, multi-organ failure

Long-term sequelae:

When to Escalate Care — ICU, Consults, and Inpatient Triage

— Hemodynamic instability or vasopressor requirement

— Hyperkalemia refractory to medical therapy, or requiring continuous monitoring during dialysis

— AKI requiring CRRT

— Severe acidosis (pH <7.2)

— Hyperthermia (heat stroke, NMS, MH) requiring active cooling

— Compartment syndrome requiring serial pressure measurements

— Massive CK (>50,000–100,000) with anticipated multi-organ involvement

— Crush syndrome with ongoing extrication or multi-trauma

— DIC with bleeding

— Mechanical ventilation needed (rare unless underlying cause)

— CK 10,000–50,000 without AKI but with stable hyperkalemia

— Need for q4–q6h electrolyte monitoring

— Recent ECG changes that have resolved

— Most patients with CK 5,000–20,000, no AKI, stable electrolytes, responsive to IVF

— Nephrology: AKI, refractory hyperkalemia, anticipated RRT, CKD baseline

— Surgery/orthopedics: compartment syndrome, crush injury, fasciotomy planning

— Toxicology: unknown ingestion, polysubstance, NMS/serotonin syndrome

— Cardiology: persistent ECG changes, elevated troponin out of proportion

— Neurology/neuromuscular: recurrent rhabdo, suspected metabolic myopathy

— Rheumatology: suspected inflammatory myopathy with persistent CK off statin

— Genetics: confirmed or suspected inherited myopathy

— PM&R: functional rehab after prolonged immobilization or fasciotomy

— Need for CRRT not available locally

— Pediatric or pregnant patient with severe disease

— Complex multi-trauma crush injury

CCS pearl: On the CCS interface, when patient develops oliguria despite 6 L IVF and Cr rises from 1.0 → 2.5, call nephrology consult, place dialysis catheter, and admit to ICU — do not keep escalating fluids into anuric kidneys; that creates the next problem (pulmonary edema).

ICU admission criteria:

Step-down/telemetry:

Floor admission:

Consultations to consider:

Transfer to tertiary center if:

Key Differentials — Same-Category (Muscle and Pigmenturia Mimics)

— Also dipstick-positive blood with no RBCs on microscopy

— Distinguish by low haptoglobin, elevated indirect bilirubin, schistocytes, elevated LDH, normal CK

— Causes: TTP, HUS, autoimmune hemolytic anemia, mechanical hemolysis (prosthetic valve), G6PD crisis, transfusion reaction, march hemoglobinuria

— Polymyositis, dermatomyositis, immune-mediated necrotizing myopathy: subacute proximal weakness, CK often 2,000–20,000, normal renal function, autoantibody-positive (anti-Jo-1, anti-Mi-2, anti-HMGCR, anti-SRP)

— Skin findings (heliotrope, Gottron papules) in dermatomyositis

— EMG, MRI muscle, biopsy distinguish from acute rhabdo

— McArdle disease (myophosphorylase deficiency): exercise intolerance, "second wind"

— CPT II deficiency: rhabdo after prolonged exercise/fasting/cold

— Pompe, Tarui: other glycogen storage diseases

— Mitochondrial myopathies

— Duchenne, Becker: elevated CK from infancy; rhabdo can be precipitated by exercise or anesthesia

— Family history, calf pseudohypertrophy, Gowers sign

— Myalgia without CK elevation

— Myopathy with mild CK rise

— Rhabdomyolysis (CK >10× ULN)

— Immune-mediated necrotizing myopathy (persists off statin, anti-HMGCR positive)

Key distinction: Hemoglobinuria = dipstick blood positive, no RBCs, low haptoglobin, normal CK. Myoglobinuria = dipstick blood positive, no RBCs, normal haptoglobin, elevated CK. Always order both haptoglobin and CK in pigmenturia.

Hemoglobinuria from intravascular hemolysis:

Inflammatory myopathies:

Inherited metabolic myopathies (often recurrent):

Muscular dystrophies:

Statin-associated muscle symptoms (SAMS) spectrum:

Drug-induced myopathies without massive CK: corticosteroids (atrophy, normal CK), zidovudine, hydroxychloroquine, colchicine

Exertional heat illness without rhabdo: core temp >40°C with neuro changes, but CK normal-to-mild

Key Differentials — Other-Category Causes of Presenting Features

— Beeturia: red urine after beet ingestion in iron-deficient or genetically susceptible patients; dipstick negative

— Porphyria: acute intermittent porphyria with abdominal pain, neuropsychiatric symptoms, urine darkens on standing/light exposure

— Drugs: rifampin, phenazopyridine (orange), methyldopa, levodopa, metronidazole

— Hematuria from GU source: dipstick positive with RBCs on micro

— Concentrated urine from dehydration

— Tumor lysis syndrome: elevated K+, phos, uric acid, LDH; normal CK; hematologic malignancy context

— Acute interstitial nephritis: drug exposure, eosinophilia, WBC casts; CK normal

— Glomerulonephritis: active urine sediment with RBC casts; CK normal

— Sepsis-associated AKI: infection focus, lactate elevated; can coexist with rhabdo

— Cardiorenal/hepatorenal: clinical context distinct

— MI: troponin discriminates

— Hypothyroidism: mild-moderate CK rise, slow reflex relaxation, TSH high

— Macro-CK (rare lab artifact)

— IM injection, recent vigorous exercise (mild rises, <5× ULN)

— Race/sex: Black males have higher baseline CK

— Polymyalgia rheumatica: age >50, proximal pain/stiffness, elevated ESR/CRP, normal CK

— Fibromyalgia: chronic, widespread, normal labs

— Trichinellosis: muscle pain, periorbital edema, eosinophilia, normal-to-mild CK

— Tetanus, strychnine poisoning: spasms without massive CK

— Guillain-Barré: ascending weakness, areflexia, normal CK

— Hypokalemic periodic paralysis: flaccid weakness, low K+, normal-to-mild CK rise

Board pearl: In a patient with elevated CK, AKI, and hyperkalemia after starting chemotherapy for lymphoma — order uric acid, phos, LDH before assuming rhabdo; tumor lysis syndrome is the lookalike that demands rasburicase and different management.

Causes of dark/red urine without true pigmenturia:

Causes of AKI with hyperkalemia that mimic rhabdo:

Causes of elevated CK without rhabdo:

Causes of muscle pain without rhabdo:

Causes of weakness mimicking rhabdo:

Secondary Prevention and Discharge Medication Planning

— Statin-induced:

— Discontinue offending statin

— After CK normalizes and symptoms resolve, rechallenge with low-dose pravastatin, fluvastatin, or rosuvastatin (lower myopathy risk)

— Avoid interacting drugs (gemfibrozil — switch to fenofibrate; avoid clarithromycin/erythromycin — use azithromycin)

— If true intolerance: ezetimibe, PCSK9 inhibitors (alirocumab, evolocumab), bempedoic acid, inclisiran

— Check anti-HMGCR antibodies if CK fails to normalize after 4–6 weeks off statin

— Exertional: gradual return-to-activity protocol; hydration; avoid NSAIDs and stimulants during exercise; acclimatize to heat; sickle trait counseling

— Substance-related: addiction treatment referral, motivational interviewing, naloxone prescription if opioid use, buprenorphine/methadone for OUD, contingency management for stimulants

— Seizure-related: optimize AED regimen, neurology follow-up

— NMS: avoid offending antipsychotic permanently; if antipsychotic essential, clozapine or quetiapine preferred with slow titration after 2-week washout

— MH: medical alert bracelet, family genetic counseling, anesthesia records flagged permanently

— Hold/discontinue: statins (temporarily), nephrotoxic NSAIDs, ACEi/ARB if AKI not resolved

— Resume ACEi/ARB only after Cr returns to baseline

— Adjust renally-cleared medications based on discharge GFR

— BMP and CK in 1 week

— Outpatient nephrology if AKI didn't fully resolve

— Recognize warning signs: dark urine, severe muscle pain, decreased urination

— Stay hydrated, avoid intense unaccustomed exercise during recovery (4–6 weeks)

— Med list updates and pharmacy alerts

Step 3 management: Don't reflexively put a statin patient back on the same statin at the same dose — that's a malpractice setup. Document shared decision-making, dose reduction, drug-drug interaction review, and follow-up CK at 4–6 weeks before resuming any statin.

Etiology-specific prevention is the highest-yield Step 3 task:

Discharge medication review (deprescribe and adjust):

Follow-up labs to send patient home with:

Patient education:

Follow-Up, Monitoring Parameters, and Rehab/Counseling

— CK every 6–12 h until clearly trending down, then daily

— BMP, Mg, phos, Ca every 6–12 h initially; daily once stable

— Strict I/Os, daily weights

— Continuous telemetry for first 24–48 h or until K+ normalizes

— Serial compartment exams in at-risk patients

— Urine output goal 200–300 mL/h (3 mL/kg/h)

— CK <5,000 and falling (some institutions discharge at higher levels if trajectory clear)

— Cr at or near baseline, or stable and trending toward baseline

— Electrolytes normalized

— Ambulating, tolerating oral intake

— Cause identified and addressed

— Reliable follow-up arranged

— PCP visit in 1–2 weeks with repeat BMP, CK

— Nephrology in 2–4 weeks if any residual AKI

— Recheck Cr at 3 months — even "recovered" rhabdo-AKI patients are at elevated long-term CKD risk per KDIGO

— Physical therapy for deconditioning, especially after prolonged ICU stay or fasciotomy

— Occupational therapy for ADLs

— Speech therapy if dysphagia after intubation

— Substance use: warm handoff to SUD treatment

— Exertional: graded return-to-exercise plan over 4–6 weeks

— Statin: shared decision-making conversation documented

— Sickle trait athlete: education, hydration, gradual conditioning, no heat extremes

— Recurrent unexplained: genetic counseling

— Influenza vaccine annually (preventing flu-associated rhabdo)

— Depression in patients with substance use, chronic disability post-fasciotomy

Board pearl: A patient who had AKI from rhabdo, even if Cr "normalizes," has 2–3× increased risk of future CKD and cardiovascular events — schedule 3-month and 12-month renal function checks and counsel on lifelong nephrotoxin avoidance.

Inpatient monitoring during admission:

Discharge criteria:

Outpatient follow-up cadence:

Rehabilitation:

Counseling specific to etiology:

Vaccinations:

Mental health screening:

Ethical, Legal, and Patient Safety Considerations

— Elder abuse or neglect: elderly "found down" for prolonged periods at home raises concern; mandatory reporting in most US states to Adult Protective Services

— Child abuse: pediatric rhabdo with bruising, suspicious mechanism, or unexplained injury → CPS report

— Workplace injury: crush from industrial accident → workers' compensation documentation, OSHA reporting requirements

— Mass casualty/disaster: earthquake, building collapse — crush syndrome protocols, triage, mass-casualty ethical frameworks

— Hazing-related: military, athletic — institutional reporting

— Sedated or intubated patient needing fasciotomy: obtain consent from surrogate; if life- or limb-threatening and no surrogate available, emergency exception applies — document carefully

— Capacity assessment in stimulant-intoxicated patient refusing care — capacity is task-specific; involve psych or ethics if persistent refusal threatens life

— Discharge with inadequate follow-up → readmission with recurrent AKI

— Medication reconciliation errors: resuming statin without dose adjustment or DDI check

— Failure to communicate AKI history to PCP → future contrast study or NSAID prescription causes harm

— Use standardized handoff tools (SBAR, I-PASS), electronic discharge summary within 48 h, pending labs/results communicated, and closed-loop referrals

— Central line placement risks (pneumothorax, infection, malposition) — use ultrasound, follow checklists, post-procedure CXR

— Disequilibrium syndrome in first dialysis sessions for severe uremia — short, gentle initial runs

— Document compartment exam findings serially with time stamps

— Document fluid balance, urine output trends

— Document medication reconciliation and reasoning behind statin/ACEi decisions

— Premature return after exertional rhabdo can cause recurrence and death; follow ACSM guidelines and document shared decision-making

Step 3 management: When discharging a "found down" elderly patient, always file an APS referral if circumstances are unclear, arrange home safety evaluation, and ensure a primary care visit within 7 days — these are testable, billable, and ethically required.

Mandatory reporting and legal context:

Informed consent edge cases:

Transition-of-care risks (high-yield Step 3 theme):

Patient safety in dialysis initiation:

Documentation pearls:

Sports and military "return-to-play" liability:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: If CK is rising on day 3–4 of admission despite IVF, the patient has either ongoing injury (missed compartment syndrome, ongoing toxin exposure) or a new event — re-examine, re-image, repeat tox screen.

CK kinetics: Peaks 24–72 h, falls ~40%/day, half-life 36 h. Persistent or rising CK despite IVF → ongoing injury, compartment syndrome, or new event.

AKI risk threshold: CK >5,000 markedly increases risk; >15,000 very high; <5,000 low (but not zero).

Urine output target: 200–300 mL/h (3 mL/kg/h).

Dipstick blood (+) with no RBCs: myoglobinuria or hemoglobinuria — order CK and haptoglobin.

Hyperkalemia in rhabdo: treat empirically based on ECG; don't wait for K+ result if QRS wide.

Hypocalcemia in early rhabdo: don't replace unless symptomatic — risk of rebound hypercalcemia.

AST elevated > ALT with normal GGT in rhabdo — muscle source, not liver.

Compartment syndrome: ΔP <30 mmHg → fasciotomy. Pulses preserved until late.

McArdle disease: "second wind," flat lactate on ischemic forearm test, rising ammonia.

NMS triad: fever, rigidity, autonomic instability + antipsychotic exposure → dantrolene, bromocriptine, stop offending drug.

MH: halogenated anesthetics + succinylcholine → dantrolene; RYR1 mutation; family counseling.

Serotonin syndrome: clonus, hyperreflexia, hyperthermia + serotonergic drug → cyproheptadine, benzodiazepines.

Crush syndrome: start IVF before extrication, anticipate hyperkalemic arrest at release.

Statin + fibrate (especially gemfibrozil), statin + macrolide, statin + colchicine — high-risk combos.

Daptomycin: weekly CK monitoring; hold if CK >10× ULN.

Propofol infusion syndrome: prolonged high-dose propofol → rhabdo, metabolic acidosis, cardiac failure; risk factors include pediatric ICU, vasopressor use.

Sickle cell trait + exertion + heat → exertional rhabdo and sudden death; military and athletic context.

Influenza B in children → benign acute childhood myositis (calf pain, refusing to walk).

Anti-HMGCR antibodies: immune-mediated necrotizing myopathy; persists after statin discontinuation; needs immunosuppression.

Dialysis does not clear myoglobin meaningfully — RRT is for K+, acidosis, volume.

Hyperthermia syndromes mnemonic: MH (anesthesia), NMS (antipsychotics, days-weeks), serotonin syndrome (SSRI + MAOI, hours), heat stroke (environment), thyroid storm, sympathomimetic toxicity.

Board Question Stem Patterns

Key distinction: When CK and urine dipstick both abnormal → rhabdo. When dipstick abnormal but CK normal → hemolysis. When AKI + hyperK + hyperuric + lymphoma → tumor lysis, not rhabdo.

The "found down" elderly stem: 78-year-old found on bathroom floor 18 h after fall, BUN/Cr 60/3.2, K 6.4, dark urine, dipstick +blood without RBCs. Answer: IV NS bolus, calcium gluconate for K+, ECG, CK level, address fall cause. Don't be distracted by "is this AKI a kidney problem?" — it's rhabdo.

The statin + macrolide stem: 65-year-old on simvastatin started clarithromycin for sinusitis 10 days ago, now diffuse myalgia, weakness, CK 28,000. Answer: Stop both drugs, IV crystalloid, monitor K+/Cr; counsel on DDI; alternative agent for next sinusitis (azithromycin) and consider switching to rosuvastatin or pravastatin after recovery.

The crush extrication stem: Earthquake victim trapped under debris for 6 h, rescue imminent. Answer: Start IV NS before extrication, ECG monitor, have calcium gluconate at bedside, prepare for hyperkalemia; expect AKI; ICU disposition.

The exertional athlete stem: 19-year-old military recruit at boot camp in summer, presents day 2 with thigh pain, cola-colored urine, CK 65,000, Cr 1.4. Answer: Aggressive IV crystalloid, admit, monitor for compartment syndrome; counsel on hydration and sickle trait testing if not done.

The recurrent rhabdo stem: 22-year-old with 3rd episode of exertional rhabdo, family history of similar episodes. Answer: Workup for metabolic myopathy — ischemic forearm test, genetic panel for McArdle, CPT II, RYR1.

The NMS stem: 35-year-old started haloperidol 5 days ago, now temp 40°C, rigid, BP 180/110, HR 130, CK 35,000. Answer: Stop haloperidol, cooling, IV fluids, dantrolene or bromocriptine, ICU.

The propofol infusion syndrome stem: ICU patient on high-dose propofol >48 h develops metabolic acidosis, rhabdo, brady-arrhythmia. Answer: Stop propofol immediately, switch to alternative sedation (midazolam/dexmedetomidine), supportive care.

The pigmenturia mimic stem: Patient with cola urine, dipstick +blood, no RBCs, but CK normal. Answer: Hemoglobinuria — check haptoglobin, LDH, smear; consider TTP, AIHA, mechanical hemolysis.

The tumor lysis lookalike: Lymphoma patient post-chemo with AKI, hyperK, hyperphos, hyperuric. Answer: Tumor lysis, not rhabdo — rasburicase, allopurinol, IVF.

The compartment syndrome stem: Increasing pain, opioid requirement, tense calf, ΔP 22 mmHg. Answer: Emergent fasciotomy — do not wait for further imaging.

One-Line Recap

Rhabdomyolysis is a clinical-laboratory diagnosis (CK >5× ULN with consistent context) whose mortality is driven by hyperkalemia and AKI, and whose only proven therapy is early, aggressive isotonic IV crystalloid titrated to a urine output of 200–300 mL/h while the inciting cause is identified and removed.

Board pearl: When in doubt — give fluids, check the ECG, find the cause, and trend the trajectory.

Diagnostic essentials: CK >1,000 (clinically significant >5,000); urine dipstick (+) blood without RBCs = myoglobinuria; expect hyperK, hypoCa, hyperphos, hyperuric, anion-gap acidosis, AST > ALT with normal GGT; trend CK every 6–12 h.

First-line management: Isotonic crystalloid 1–2 L bolus then 200–500 mL/h titrated to UOP 200–300 mL/h; treat hyperkalemia empirically with calcium gluconate, insulin/D50, albuterol, bicarbonate, dialysis if refractory; do NOT routinely use bicarbonate infusion or mannitol; do NOT replace asymptomatic hypocalcemia.

Don't-miss complications: Compartment syndrome (ΔP <30 → fasciotomy), AKI requiring RRT (dialysis is for K+/volume/acidosis, not myoglobin clearance), DIC, late rebound hypercalcemia, recurrent disease in inherited myopathies.

Step 3 longitudinal pearls: After discharge, recheck CK and BMP in 1 week, nephrology at 2–4 weeks if AKI, repeat Cr at 3 and 12 months given elevated CKD risk; deprescribe nephrotoxins; for statin-induced, restart only a low-risk statin (pravastatin/rosuvastatin) after DDI review and document shared decision-making; for "found down" elderly, file APS referral if neglect suspected and arrange home safety and fall-prevention evaluation; for exertional rhabdo athletes, follow ACSM return-to-play criteria with graded protocols.