MODS can affect any organ or system (Table 74-2). Dysfunction may be mild or total. The lungs and circulatory system are most often involved.2 Trauma patients often exhibit a biphasic pattern of organ failure.26,41 Early organ failure (within 3 d of trauma) results from the initial shock, resuscitation, and tissue injury, whereas later organ failure (defined as >3 d after trauma) frequently results from infection.41
Table 74-2 Organs and Systems Affected by Multiple Organ Dysfunction Syndrome ||Download (.pdf)
Table 74-2 Organs and Systems Affected by Multiple Organ Dysfunction Syndrome
|Organ or System||Manifestations|
|Lung||Acute lung injury, acute respiratory distress syndrome, ventilator dependence|
|Cardiovascular||Arterial hypotension, hyperdynamic physiology, vasodilatation, myocardial dysfunction, pulmonary hypertension, shunting|
|Kidneys||Oliguria, anuria, renal failure, acute tubular necrosis, renal tubular acidoses, acid-base abnormalities, electrolyte abnormalities|
|Neurologic||Confusion, lethargy, agitation, coma|
|Liver||Elevated liver enzymes, hyperbilirubinemia, coagulopathy, hepatic encephalopathy|
|Hematologic||Anemia, thrombocytopenia, coagulation abnormalities, disseminated intravascular coagulopathy|
|Endocrine||Hyperglycemia, inappropriate adrenal response to stress ("relative adrenal insufficiency")|
|Metabolic||Electrolyte and glucose abnormalities, hyper- and hypokalemia, hyper- and hyponatremia, hypomagnesemia, hyper- and hypophosphatemia, hypocalcemia|
|Gastrointestinal (GI) tract||Hypomotility, inability to tolerate enteral nutrition, GI hemorrhage, stress ulcers|
Acute Respiratory Failure
Respiratory failure occurs in approximately 70% of patients with MODS.42 Risk factors for ARDS include pneumonia, sepsis, aspiration, trauma, and pancreatitis. MODS patients with respiratory failure have a high mortality rate.2 ALI and ARDS occur most frequently in patients with sepsis, particularly when the source of the sepsis is pulmonary.43-45 Moreover, mortality is highest when ARDS is caused by sepsis.46 A large study reported a 99% incidence of respiratory failure in trauma patients with MODS.47 However, they also found that the presence of respiratory failure did not correlate with mortality.
CV dysfunction occurs in approximately 87% of MODS cases and carries a high in-hospital mortality rate.2 Patients may manifest CV instability secondary to hypovolemia, vasodilatation, and/or myocardial dysfunction. Septic patients who have been volume resuscitated are often described as "hyperdynamic"; that is, they have an elevated cardiac output associated with decreased systemic vascular tone. These classic CV manifestations of sepsis also occur in patients with MODS caused by other systemic inflammatory processes. Septic patients can also develop myocardial dysfunction, manifested as a decreased left ventricular ejection fraction, ventricular dilation, and an impaired contractile response to volume loading.
Patients with MODS may develop dysrhythmias on the basis of metabolic abnormalities, intravascular volume disturbances, hypoxemia, or myocardial ischemia. Atrial dysrhythmias are common. Although immediate interventions, such as cardioversion, may be required for hemodynamically unstable dysrhythmias, correction of the underlying stimulus is usually required to prevent further occurrences.
Renal disturbances are common in MODS patients and range from mild renal dysfunction with an elevated blood urea nitrogen (BUN) and creatinine (Cr), to frank anuric renal failure.48 The introduction of the RIFLE classification, which stands for "risk of renal failure: injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal failure," has greatly aided both in defining the severity of acute kidney injury and in the risk stratification and prognosis of ICU patients with kidney injury.49,50 Based on stringent criteria for serum Cr levels and urine output, this classification system also allows early recognition of kidney injury and thus earlier institution of renal protective measures.
Renal dysfunction usually results from acute tubular necrosis (ATN). The urine sediment in ATN contains granular or "muddy" casts. Other causes of acute kidney injury include endogenous toxins such as myoglobin in patients with rhabdomyolysis, nephrotoxic drugs such as aminoglycosides or amphotericin B, intravenous (IV) contrast agents for imaging procedures, and cholesterol emboli caused by manipulation of the diseased aorta. The mortality in MODS patients with renal failure is high, particularly in the context of CV or respiratory failure.2,28
A variety of hepatic disturbances may occur in noncirrhotic patients with MODS. These include elevation of liver enzymes, hyperbilirubinemia, hypoglycemia, and impaired synthesis of proteins, including clotting factors. Preexisting hepatic dysfunction may complicate MODS in several ways. First, patients with cirrhosis fare poorly when they develop MODS. Mortality rates in excess of 80% have been reported in cirrhotic patients with either coma, renal failure, CV instability, or acute respiratory failure.51 Second, liver failure can further worsen in critically ill patients. Third, a coagulopathy and a propensity for bleeding may result from DIC and/or from decreased liver synthesis of clotting factors. Lastly, new acute liver failure can cause MODS, a situation that carries a particularly poor prognosis.52
Multiple hematologic abnormalities occur in MODS patients. Patients commonly exhibit either leukocytosis or leukopenia. Coagulation problems may arise from impaired synthesis and/or from increased coagulation factor consumption. Thrombocytopenia occurs in DIC but may also result from decreased production or increased destruction from other causes.
Anemia results from acute blood loss from trauma, GI bleeding, surgery, and frequent phlebotomy. Cytokines may contribute by decreasing endogenous erythropoietin production, by directly hindering bone marrow production of red blood cells (RBCs), and by altering iron metabolism. These observations have led to development of the term anemia of critical illness.
Coagulopathy is evaluated by measuring coagulation times (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) and fibrinogen levels. A prolonged PT or aPTT can be caused by either an absence of coagulation factors or the presence of factor inhibitors. Transfusion with normal plasma should correct a factor deficiency. Factor inhibitors should be suspected when the prolonged PT or aPTT does not correct with administration of normal plasma. Antiphospholipid antibodies such as lupus anticoagulant can also produce a prolonged aPTT. Paradoxically, lupus anticoagulants and the antiphospholipid antibody syndrome are associated with thrombosis, not bleeding.
Platelets are vital in hemostasis. Three basic mechanisms are responsible for thrombocytopenia in ICU patients: decreased platelet production, increased platelet destruction or sequestration, or dilution. Transfusion of blood for massive blood loss causes dilutional thrombocytopenia. Thrombocytopenia also results from sequestration of platelets in the liver, spleen, and, in patients with acute respiratory failure, lungs.53
Drug-induced thrombocytopenias may be hard to diagnose because many drugs can impair platelet production rates. Heparin-induced thrombocytopenia (HIT) is often considered as the cause of thrombocytopenia in critically ill patients.54 Treatment of HIT involves discontinuation of heparin administration, including both unfractionated heparin and low molecular weight heparins, and the use of alternative anticoagulants. Anticoagulant alternatives for patients with HIT include lepirudin, argatroban, and fondaparinux.55 Lepirudin is cleared by the kidneys, whereas argatroban is cleared by the liver. Thus the choice of one agent over another depends on the patient's renal and hepatic function. Both agents have short plasma half-lives (80 min for lepirudin and 40 min for argatroban) allowing rapid reversal of anticoagulation after administration is stopped. Platelets should never be given to patients with type 2 HIT because of an increased risk of thrombosis after platelet transfusions.
Disseminated Intravascular Coagulation
DIC is common in sepsis, occurring in up to 70% of patients with septic shock.56 In DIC, there is simultaneous activation of both the coagulation and fibrinolytic systems. Activation of the fibrinolytic portion of the clotting system can lead to hemorrhage including widespread oozing of blood, and bleeding from wounds and procedure site. The activation of coagulation can result in thrombosis. One dramatic manifestation of thrombosis is digital necrosis, which can be severe enough to require amputation. It is believed that microvascular thrombosis causes impaired oxygen delivery to tissues and resultant ischemia and organ dysfunction. The diagnosis of DIC is suggested by prolongation of the PT and/or the aPTT, and a reduction in the platelet concentration. Elevated D-dimer and reduced plasma fibrinogen levels provide useful supplemental diagnostic tests but are not diagnostic of DIC and may be abnormal in other disorders.
CNS manifestations range in severity from mild confusion and lethargy or agitation to frank coma. It is estimated that CNS disturbances occur in 70% of patients with sepsis.57 The presence of severe neurologic impairment, as manifested by a Glasgow Coma Scale score higher than 6 in the context of MODS, is associated with a high mortality rate (≥70%).2
Patients with MODS may also develop profound neuromuscular weakness from deconditioning and/or critical illness polyneuropathy. This can be exacerbated by the use of corticosteroids and neuromuscular blocking agents.58 Complications of weakness include difficulty weaning from mechanical ventilation and a prolonged rehabilitation period.59
Critically ill patients frequently require sedative = hypnotic agents and analgesics to treat anxiety and pain. Unfortunately, these very agents can significantly increase morbidity and mortality. Sedative-hypnotics are routinely titrated based on protocols that incorporate regular reassessment of the patient's level of pain and sedation, and daily interruptions of sedation. Both measures have been shown to reduce the complications of oversedation, including delirium and prolonged mechanical ventilation.60,61 Typical regimens include analgesic agents such as opioids and ketamine, and hypnotic agents such as benzodiazepines and propofol.62 Dexmedetomidine is also commonly used to facilitate sedation based on studies that suggest that as compared with benzodiazepines, this newer sedative allows patients to be more interactive with less delirium and to spend less time on mechanical ventilation.63-65 Further studies are necessary to assess the merits dexmedetomidine in comparison with agents such as propofol. Agents commonly used to treat delirium in the ICU include haloperidol, and atypical antipsychotic agents such as olanzapine, risperidone, and quetiapine.
Patients with MODS may have electrolyte abnormalities, including hyperkalemia, hypokalemia, hypernatremia, hyponatremia, hypocalcemia, hypomagnesemia, hyperphosphatemia, and/or hypophosphatemia. Glucose disturbances are common. Current evidence suggests that a moderate level of glycemic control using insulin infusions is sufficient to improve outcome in critically ill patients while avoiding the complication of hypoglycemia associated with tight glycemic control.66
Adrenal dysfunction is believed to complicate the course of many patients with septic shock. Although frank adrenal insufficiency is uncommon, there is evidence that critically ill patients experience a state of "relative adrenal insufficiency."67 Although controversy exists over whether or not to use corticosteroids to treat septic shock, corticosteroids should still be considered in patients with refractory septic shock despite volume resuscitation and maximal inotropic support.68,69 However the current data do not support using cosyntropin stimulation tests to identify patients to treat with corticosteroids.69
Common gastrointestinal disturbances in MODS patients include GI hypomotility and GI bleeding. GI dysmotility may lead to gastric distension, which increases the chance of regurgitation and aspiration. Critically ill patients often require nasogastric decompression. GI dysmotility may lead to intolerance of enteral nutrition. GI hemorrhage may result from stress ulceration. Critically ill patients who are at risk of stress ulceration should be treated with prophylactic agents (H2 blockers, proton pump inhibitors, or sucralfate). Patients may also develop low-grade GI bleeding from mucosal breakdown from nasogastric tubes.
MODS and Predisposition to Infections
Patients with MODS have a propensity to develop infections,4 which is believed to result from a state of immunosuppression.
Prevention of MODS is a major goal in managing critically ill patients. Preventive strategies include prompt therapy targeting the underlying source of inflammation, optimizing oxygen delivery to balance the increased demands that accompany SIRS, maintaining adequate tissue perfusion, and providing physiologic support to maintain homeostasis when required. Other strategies include prevention of the loss of gut integrity and ICU-related complications such as ventilator-associated pneumonia and catheter-related bloodstream infections. GI tract integrity may be supported with early enteral nutrition,4,70,71 VAP may be reduced by diligent head-of-bed elevation and oral hygiene,72 and central line infections may be reduced by improved sterile insertion techniques and careful line maintenance.73