Quick Recap
Renal System, Protocol 6/7. Includes Malignant Hyperthermia as a distinct trigger requiring specific antidotal therapy.
1. Definition & Presentation
Rhabdomyolysis = acute skeletal muscle breakdown releasing muscle fiber contents (enzymes, myoglobin) into the blood. Classic triad: acute muscle pain, proximal weakness, myoglobinuria (dark urine) developing over hours to days — but FEWER THAN 10% of patients present with the FULL triad. Do not require all three to suspect/diagnose rhabdomyolysis — the diagnosis is often made incidentally in a weak patient with muscle pain or dark urine found to have markedly elevated CK.
2. Etiology by Category
Category | Examples |
Traumatic | Crush syndrome, compartment syndrome, prolonged immobilization ("found down"), electrical/burn injury, vascular compression to muscle |
Nontraumatic, exertional | Marked exertion in an untrained individual, eccentric exercise, hyperthermia, prolonged convulsive status epilepticus, metabolic/other myopathies |
Nontraumatic, nonexertional | Drug exposure, toxin exposure, infections (viral, sepsis), electrolyte disorders, immune/inflammatory myopathies |
Common drugs associated: statins, colchicine, amiodarone, daptomycin. First-generation antipsychotics can cause acute CK elevation in the context of neuroleptic malignant syndrome specifically (a related but distinct hyperthermic/rigidity syndrome). Prolonged propofol exposure carries rhabdomyolysis risk (propofol infusion syndrome, see Status Epilepticus protocol's PRIS discussion for the overlapping mechanism).
3. Diagnosis
No strict consensus CK cutoff — most sources describe acute rhabdomyolysis in the range of 10,000 to over 200,000.
Myoglobin vs CK kinetics — an important, often-missed distinction:
- Myoglobin rises EARLIER and normalizes EARLIER than CK — when the patient's dark urine CLEARS, this indicates myoglobin normalization and CESSATION of active muscle breakdown, a useful real-time bedside marker
- CK LAGS behind myoglobin, PEAKS at 3-5 days, and slowly declines over the following 6-10 days
- Frequent serial CK measurements are NOT clinically helpful given this lag and slow decline — do not chase a falling-but-still-elevated CK number as a treatment endpoint; the peak/trajectory pattern is expected and does not itself indicate ongoing injury or treatment failure
- Better real-time monitoring parameter: urine myoglobin, OR blood detected on urinalysis dipstick WITHOUT red blood cells on microscopy (the urinalysis heme-based assay cross-reacts between hemoglobin and myoglobin, so a heme-positive/RBC-negative urinalysis is a useful, immediately available surrogate for ongoing myoglobinuria)
4. Immediate Stabilization (ABCDE)
Circulation — aggressive isotonic fluid resuscitation is the central therapy (protects renal function by maintaining tubular flow and diluting myoglobin/reducing intratubular cast formation, the presumed mechanism of myoglobin-induced AKI). Rate should be aggressive but individualized to cardiac/renal status — general critical care fluid resuscitation principles apply, titrated to urine output and avoiding volume overload in patients with concurrent cardiac/renal limitations.
Disability/Exposure: actively screen for compartment syndrome in traumatic/crush-related rhabdomyolysis — a surgical emergency requiring fasciotomy if present, distinct from and in addition to the systemic rhabdomyolysis management.
Checklist:
5. Electrolyte Complications
Most common abnormalities: hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, metabolic acidosis — monitor and manage each per their respective protocols (see Hyperkalemia protocol for full detail; note that rhabdomyolysis-driven hyperkalemia is a classic "transcellular shift + tissue release" cause referenced in that protocol).
Hypocalcemia mechanism: phosphate released from damaged muscle chelates ionized calcium (see the chelation mechanism described generally in Washington Manual electrolyte chapters) — typically does NOT require aggressive calcium repletion unless symptomatic or causing ECG changes, since calcium often self-corrects (and can even rebound to hypercalcemia) during the recovery phase as calcium is released from damaged muscle and deposited calcium-phosphate complexes are mobilized.
Cardiac dysrhythmias can arise from these electrolyte abnormalities — close telemetry monitoring is essential.
6. Acute Kidney Injury
AKI develops in approximately 15-50% of rhabdomyolysis cases and may require temporary RRT (see AKI and CRRT Indications protocols for full management framework). Mechanism: myoglobin-induced direct tubular toxicity, intratubular cast formation/obstruction, and renal vasoconstriction — all mitigated by early, aggressive volume resuscitation, which is why fluid therapy is the single most important preventive intervention rather than a secondary consideration.
7. Immune Myopathy — Critical Differential Diagnosis
Immune myopathies can present with rhabdomyolysis but typically have a more SUBACUTE course (days-weeks rather than the more acute hours-to-days presentation of typical rhabdomyolysis) — this distinction matters enormously because immune myopathies require STEROID or other immunomodulatory treatment, NOT the purely supportive care that addresses typical rhabdomyolysis. Actively consider this differential, especially with a subacute onset, proximal weakness pattern, or lack of an obvious precipitant (trauma, exertion, toxin/drug) — missing this diagnosis and treating with supportive care alone delays appropriate immunosuppressive therapy.
8. Malignant Hyperthermia (MH) — A Distinct, Anesthesia-Specific Trigger
Definition: hypermetabolic crisis in a malignant-hyperthermia-susceptible (MHS) individual exposed to inhaled volatile anesthetics or succinylcholine. Autosomal dominant inheritance, most commonly RYR1 gene mutations (also SCN4A, CACNL2A, CACNA1S, and specific chromosomal loci).
A prior history of tolerating anesthesia does NOT exclude MH — the reaction can be idiosyncratic and may not occur with every exposure in a susceptible individual, an important point when taking anesthesia history in a patient presenting with unexplained rhabdomyolysis post-procedure.
Early signs: rapid rise in EtCO2 RESISTANT to minute ventilation adjustments (the earliest and most specific sign), tachycardia, rapidly rising hyperthermia, diffuse muscle rigidity, masseter spasm, falling SpO2 (from the high CO2 burden).
Pathophysiology: in MHS individuals, these anesthetic agents cause persistently elevated cytoplasmic calcium in muscle cells -> sustained contraction, inability to relax the contractile apparatus -> anaerobic metabolism, lactic acidosis, Na-K ATPase pump failure -> myocyte rhabdomyolysis.
Management (time-critical, anesthesia-team-led): immediate discontinuation of the triggering agent, dantrolene sodium (specific antidote, inhibits calcium release from the sarcoplasmic reticulum), active cooling, aggressive supportive care for the resulting rhabdomyolysis/hyperkalemia/acidosis per the general protocol above, and post-crisis genetic counseling/MHS testing referral for the patient and potentially family members.
9. Investigations
CK (understanding its lag/peak/decline kinetics, Section 3), urine myoglobin or heme-positive/RBC-negative urinalysis (better real-time marker), electrolytes (K+, phosphate, calcium, uric acid) trended serially, renal function, ABG (metabolic acidosis assessment), ECG/telemetry (arrhythmia surveillance), CPK trend if immune myopathy suspected alongside EMG/muscle biopsy per neurology input, creatine kinase and additional workup (ANA, myositis panel) if immune myopathy is a genuine consideration.
10. Organ Support
Aggressive isotonic fluid resuscitation (the primary intervention); RRT for AKI per standard indications if it develops (see AKI and CRRT protocols); telemetry monitoring; standard ICU supportive care; fasciotomy (orthopedic/surgical) for confirmed compartment syndrome.
11. Consultation Matrix
Consultation | Trigger | Timing |
Nephrology | AKI development, RRT consideration | As indicated |
Orthopedic/Trauma Surgery | Suspected compartment syndrome | Immediate |
Neurology | Subacute presentation raising immune myopathy concern | As needed |
Anesthesia/MH Hotline | Suspected malignant hyperthermia | Immediate, time-critical |
12. Monitoring Framework
Serial electrolytes (especially K+, phosphate, calcium) more frequently than CK, urine myoglobin/dipstick trend as the practical real-time marker, telemetry for arrhythmia, renal function trend, urine output response to fluid resuscitation, temperature monitoring if MH is a consideration.
13. Complications
AKI (15-50% of cases), hyperkalemia-related arrhythmia, compartment syndrome (traumatic cases), disseminated intravascular coagulation (severe cases), missed immune myopathy diagnosis leading to delayed appropriate immunosuppression. Prevention: early aggressive fluid resuscitation, prompt trigger identification/removal, active compartment syndrome screening in traumatic mechanism, maintaining immune myopathy as an active differential rather than defaulting to supportive-care-only management. Rescue: RRT for AKI, fasciotomy for compartment syndrome, dantrolene for MH, immunosuppression for confirmed immune myopathy.
14. Escalation & De-escalation
Escalate: worsening AKI/refractory electrolyte abnormalities -> RRT; suspected compartment syndrome -> emergent surgical evaluation/fasciotomy; MH signs during anesthesia -> immediate dantrolene and MH protocol activation.
De-escalate: CK trending down along its expected 3-5 day peak/6-10 day decline trajectory, urine clearing (myoglobin normalizing), electrolytes stable, renal function stable/improving -> liberalize fluid rate, transition to standard monitoring.
15. ICU Discharge Criteria
Urine clear (myoglobin normalized), electrolytes stable, renal function stable or on an established recovery/RRT trajectory, no ongoing compartment syndrome concern, trigger addressed/removed, immune myopathy workup completed if it was a genuine consideration.
16. Documentation & Medicolegal Checklist
17. Key Guidelines
Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve. 2015;51(6):793-810 — primary diagnostic algorithm reference.
18. Controversies
Optimal fluid resuscitation rate/type (isotonic saline vs balanced solutions, and the role of urine alkalinization with bicarbonate) remains debated — urine alkalinization theoretically reduces myoglobin cast nephrotoxicity but lacks strong RCT support and carries its own risks (worsening hypocalcemia, alkalosis). The precise CK threshold warranting the most aggressive intervention is not standardized given the wide reported range (10,000 to >200,000) across sources. Immune myopathy differentiation from typical rhabdomyolysis remains clinically challenging in ambiguous-onset cases, and the threshold for pursuing EMG/biopsy workup varies by institutional practice.
19. References
- Silvestri NJ. Rhabdomyolysis, Malignant Hyperthermia, and Critical Illness Myopathy. Washington Manual of Critical Care, 4th ed, 2025 (Ch. 62).
- Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve. 2015;51(6):793-810.
- Al-Lozi MT, Pestronk A, Yee WC, Flaris N, Cooper J. Rapidly evolving myopathy with myosin-deficient muscle fibers. Ann Neurol. 1994;35(3):273-279.
See also: Acute Kidney Injury, Hyperkalemia (Renal System) for the downstream complications this protocol most commonly triggers; Guillain-Barré Syndrome and Myasthenic Crisis (Neurology System) for the broader neuromuscular weakness differential.