Multiorgan Dysfunction Syndrome

Multiorgan dysfunction syndrome is a state of altered function in two or more organs in an acutely ill patient, such that homeostasis cannot be maintained without intervention. It is the usual final path of sepsis, severe trauma, burns, pancreatitis, prolonged shock, major surgery and cardiac arrest. It is the leading cause of death in intensive care.

Mechanisms

• Dysregulated inflammation (cytokine storm) with endothelial injury, glycocalyx shedding and microvascular thrombosis
• Mitochondrial dysfunction and cellular energy failure ("cytopathic hypoxia")
• Immune paralysis and secondary infection
• Gut barrier failure with bacterial and endotoxin translocation
• Ischemia and reperfusion injury, and the effect of therapy (ventilator injury, nephrotoxins, over-resuscitation)

Organ dysfunction is quantified with a sequential score on a scale of 0 to 4 for six systems: respiration (PaO2 to FiO2 ratio), coagulation (platelet count), liver (bilirubin), cardiovascular (mean arterial pressure and vasopressor dose), central nervous system (Glasgow coma score) and renal (creatinine or urine output). An increase of 2 or more points from baseline defines dysfunction.

Mortality rises with the number of failing organs and with duration: about 20 to 30% with one organ, 50 to 60% with three, and over 80% with four or more persisting beyond 4 days. Age, chronic illness and delay in source control are adverse factors. Complications: persistent critical illness, intensive care acquired weakness, cognitive decline, recurrent infection and death.

• Hypotension requiring vasopressors, with mottling and lactic acidosis
• Respiratory failure with hypoxemia and bilateral infiltrates
• Oliguria and rising creatinine
• Jaundice, coagulopathy, bleeding, thrombocytopenia
• Confusion, delirium or coma
• Ileus, intolerance of enteral feeding, stress ulceration and hyperglycemia
• Red flags: rising lactate, new organ failure within 48 hours of presentation, refractory shock, anuria and falling consciousness

1. Serial organ function assessment: the six-organ sequential score on admission and daily.
2. Laboratory tests: lactate, arterial blood gas, creatinine, urea, bilirubin, liver enzymes, platelet count, coagulation tests with fibrinogen and D-dimer, glucose, troponin, procalcitonin and C-reactive protein.
3. Search for the driver: blood cultures, imaging for sources of infection or ischemia (CT chest, abdomen and pelvis), echocardiography, and review of drugs and lines.
4. Monitoring: arterial line, hourly urine output, central venous oxygen saturation and cardiac output measurement as needed.
5. Exclusion of reversible contributors: adrenal insufficiency, thyroid disease, abdominal compartment syndrome, tamponade and drug toxicity.

Differentials: isolated organ failure, chronic organ disease decompensating, and toxic or metabolic syndromes with multi-system effects.

There is no drug specific to the syndrome. Treat the cause early and support each failing organ, while avoiding harm.

1. Source control and antimicrobials: drain, debride or remove the source within 6 to 12 hours. Piperacillin-tazobactam 4.5 g IV every 6 hours (children 100 mg/kg of piperacillin every 8 hours), or meropenem 1 g IV every 8 hours (children 20 mg/kg every 8 hours), given within 1 hour of recognition of sepsis, with narrowing at 48 to 72 hours by culture results.
2. Circulation: balanced crystalloid 30 mL/kg IV in the first 3 hours, then dynamic assessment. Norepinephrine 0.05 to 0.5 micrograms/kg/min IV to a mean arterial pressure of 65 mmHg or higher, vasopressin 0.03 units/min IV as a second agent, and dobutamine 2.5 to 20 micrograms/kg/min IV for low cardiac output. Hydrocortisone 50 mg IV every 6 hours for ongoing high vasopressor need.
3. Lungs: ventilation with tidal volume 6 mL/kg predicted body weight, plateau pressure 30 cmH2O or lower, positive end-expiratory pressure titrated to oxygenation, prone positioning when PaO2 to FiO2 is under 150, and extracorporeal membrane oxygenation in refractory cases.
4. Kidneys: avoid nephrotoxins, and start renal replacement therapy for refractory hyperkalemia (over 6.5 mmol/L), severe acidosis (pH under 7.1), fluid overload with respiratory compromise, or uremic complications. Continuous therapy suits unstable patients.
5. Liver and coagulation: correct only when bleeding or for a procedure (fresh frozen plasma 15 mL/kg, platelets for counts under 10 × 10^9/L, or under 50 × 10^9/L with bleeding). Avoid hepatotoxic drugs.
6. Gut and nutrition: enteral feeding within 24 to 48 hours at 20 to 25 kcal/kg a day rising to 25 to 30 kcal/kg, with protein 1.3 to 2.0 g/kg a day. Parenteral nutrition only if enteral feeding fails after 7 days. Pantoprazole 40 mg IV daily for stress ulcer prophylaxis in ventilated patients with coagulopathy or shock.
7. Prevention of complications:
   • Enoxaparin 40 mg SC once daily (adjust in renal impairment).
   • Glucose 7.8 to 10 mmol/L with insulin infusion.
   • Red cell transfusion at a hemoglobin under 70 g/L.
   • Daily sedation interruption, early mobilization and delirium prevention.
8. Goals of care: review trajectory by day 3 to 5 with the family, and discuss limiting treatment when organ failure is progressing despite maximal support.

Follow-up in an intensive care recovery clinic at 1, 3, 6 and 12 months, with screening for weakness, cognitive impairment, depression and post-traumatic stress, and rehabilitation. Counsel the family candidly on prognosis.