Chapter 74. Evaluation of the Patient with Multiple Organ Dysfunction Syndrome

1. Multiple organ dysfunction syndrome (MODS) is common in critically ill patients and associated with a high mortality rate.

2. There are many underlying etiologies of MODS. In the overall intensive care unit (ICU) population, sepsis is the most common cause of MODS.

3. MODS is characterized by dysfunction of 2 or more organs or systems.

4. Inflammation and microvascular abnormalities are involved in the development of MODS.

5. Therapies for MODS should target the underlying cause, supporting the patient and correcting the physiologic and metabolic derangements caused by dysfunction of the organs and systems.

6. Patients with MODS often require surgery and other invasive procedures.

7. Whenever possible, optimize MODS patients preoperatively.

8. Methods of optimization are dictated by the affected organs and the severity of physiologic and metabolic derangements.

Progress in life support therapies has led to the recognition of pathophysiologic states that are unique to critically ill patients. Diverse disease states can cause progressive dysfunction and ultimately complete failure of various organs and systems. This condition is commonly referred to as the multiple organ dysfunction syndrome (MODS). High-grade organ failure that necessitates life-sustaining therapies is often referred to as multiorgan system failure. The development of MODS portends a poor outcome. In fact, MODS is one of the leading causes of death for ICU patients.1,2 This chapter reviews basic aspects of MODS, surgical and nonsurgical procedures that are commonly performed in patients with MODS, and the preoperative preparation and optimization of MODS patients for surgery.

The development of organ dysfunction as a separate disease process from the initial injury was first appreciated during World War II. Wounded soldiers were rapidly and aggressively resuscitated with blood products to normalize blood pressure, and they were more promptly evacuated to medical facilities than in previous wars. Although initial survival was improved, many soldiers who survived the initial trauma subsequently died of renal failure.3,4 This led to changes in fluid resuscitation practices in subsequent wars, including the rapid infusion of crystalloids and more aggressive resuscitation. During the Vietnam War, many soldiers who survived their initial trauma developed "shock lung" (acute respiratory failure). At the same time, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) were increasingly being described in civilian ICUs.5 During the 1970s, advances in critical care medicine led to improved initial survival from many injuries. However, many patients who survived initial resuscitation went on to develop progressive failure of various organs and systems.6,7

Various terms have been used to describe the spectrum of dysfunction of different organs and systems (reviewed in Bone et al8), including multiple organ failure,9 multiple-organ-failure-syndrome,1 multiple system organ failure,10 progressive or sequential organ failure,6 or MODS.8,11 The term MODS is most widely used and encompasses the spectrum from mild organ dysfunction to complete organ failure. In addition, scoring systems have been devised to assess patients and to predict outcome.4,12-16 In this chapter the term MODS is used as an inclusive definition for all the studies and articles that have used all of these terms over the past several decades.

Definitions

In 1992, recommendations for the definitions of sepsis, systemic inflammatory responses, and organ dysfunction were published based on a consensus conference of the American College of Chest Physicians and Society of Critical Care Medicine.8 The acronyms SIRS (the systemic inflammatory response syndrome) and MODS were coined at the consensus conference, and they are widely used in patient care and in clinical study design.

SIRS

The term SIRS describes a complex inflammatory process that is driven by many differing disease states. Underlying etiologies of SIRS include, but are not limited to, infection, trauma, burns, aspiration, pancreatitis, vascular compromise with resultant ischemia and/or necrosis, malignancy, and multiple blood transfusions. Table 74-1 lists the criteria for SIRS.

Sepsis

Sepsis was defined as the systemic inflammatory response to infection. Sepsis was further stratified based on its severity, with severe sepsis and septic shock representing the spectrum of progressively worsening status.

MODS

MODS was used to describe a pattern of progressive dysfunction of organs that is related pathogenically regardless of the inciting process and requires intervention to maintain homeostasis.

Etiologies

There are 2 broad categories of MODS.17 Primary MODS results from direct organ injury, such as from trauma, and occurs early after the injury. Secondary MODS occurs later and results from the systemic host response to an injury. For the remainder of the chapter, the term MODS is used to describe secondary MODS, which occurs far more frequently than primary MODS.

MODS is caused by inflammatory processes. Common etiologies are infection, trauma, aspiration pneumonitis, pancreatitis, surgery, blood product transfusions, ischemia-reperfusion, necrosis, and burns.18 Other etiologies include cardiac arrest, malignancy, and vasculitis.

Surgical and nonsurgical patients can develop MODS. In patients with nonoperative MODS, the most frequent ICU admission diagnoses are cardiac arrest, sepsis, pneumonia, congestive heart failure, upper gastrointestinal (GI) bleeding, and nonoperative head trauma.19 Postoperative MODS occurs most frequently following surgery for head trauma, elective abdominal aneurysm repairs, aortic dissection or rupture, GI perforation, GI inflammatory diseases, and GI malignancy. Other risk factors for the development of MODS include preexisting organ dysfunction, delayed or inadequate resuscitation, an ongoing infection or focus of inflammation, major hematoma, age 65 years or older, surgical complications, seriously deranged physiologic parameters on admission to the ICU, and chronic health problems.12,13,18-21

Sepsis is the most common cause of MODS. In septic shock, systemic inflammation triggers pathophysiologic processes that cause vasodilatation, relative or absolute hypovolemia, myocardial dysfunction, and an altered systemic blood flow distribution.22 About half of the patients who succumb to septic shock die of multiple organ failure.

Epidemiology

MODS occurs in approximately 15% of ICU admissions23 and is associated with up to 80% of ICU deaths.2,19,24 MODS occurs more frequently and has a higher mortality in patients admitted to the ICU with medical as compared with those admitted with surgical diagnoses.2,19,25 In addition, high Acute Physiology and Chronic Health Evaluation III scores on the first day of admission to the ICU are associated with MODS.19

For the general ICU population, the risk of MODS is related to age older than 65 years, severity of coexisting diseases, and a nonoperative ICU admission diagnosis.2,19 However, trauma patients who develop MODS do not seem to fit this profile. A prospective study of multiple organ failure (MOF) following major trauma showed that age, a large red blood cell transfusion requirement, a high Injury Severity Score, a large base deficit, and elevated lactate levels are risk factors for the subsequent development of MOF.26

MODS Scoring Systems

Many scoring systems have been devised to assist with the diagnosis and quantification of the severity of MODS. The sepsis-related or sequential organ failure assessment (SOFA) score14 and the MODS score15 are widely used systems that take into account the number of dysfunctional organs or systems and the degree of dysfunction of each organ.

The SOFA score was created to describe organ dysfunction in individual patients and groups of patients over time.14 It is calculated based on the degree of dysfunction of 6 organ systems (respiratory, renal, cardiovascular [CV], central nervous system [CNS], hepatic, and coagulation) and is commonly used to follow the progression of organ dysfunction rather than to predict outcome.

The MODS score was developed to provide a "reliable and meaningful index of the severity" of MODS in individual ICU patients and to quantify the association between the degree of dysfunction and the risk of mortality.15 The MODS score incorporates 6 organ system evaluations (respiratory, renal, cardiovascular, CNS, hepatic, and hematologic). Data are collected repeatedly during the ICU stay. The highest possible score is 24, which indicates the most severe MODS.

The Denver Multi Organ Failure (MOF) score is widely used in outcome studies of trauma patients.4 The revised Denver MOF score takes into account 4 organ systems: pulmonary, cardiac, renal, and hepatic. Each is assigned a grade based on the degree of dysfunction.

Prognosis of MODS

The mortality of MODS is in excess of 50%.4,16,26,27 Studies consistently show that across all ICU populations, mortality in MODS is proportional to the number of failing organs. Single-organ failure is associated with a low mortality, whereas 3 failing organs is associated with 80% to 90% mortality, and mortality approaches 100% with 4 failing organs.2,17,19,23 Mortality is higher in MODS patients older than 65 years.2,28 The prognosis of MODS differs depending on the inciting process. For example, the mortality associated with MODS due to trauma was reported to be lower than that associated with MODS due to sepsis or cardiac arrest (45% vs 75%-80%, respectively).19 Finally, the degree of physiologic derangement on the first day of failure of the organ is an important determinant of mortality.19

Pathogenesis

The combination of systemic inflammation (SIRS), microcirculatory abnormalities, and impaired oxygen delivery and/or use can all contribute to the development of MODS.18,29,30 SIRS is initiated by mediators that are released into the circulation by inflammatory cells in response to infection and other inflammatory stimuli. Leukocytes, platelets, and endothelial cells participate in SIRS. Endothelial cells help to maintain homeostasis in the coagulation system and participate in leukocyte recruitment to sites of infection and inflammation.31-34 Imbalances in the coagulation system can result in disseminated intravascular coagulopathy (DIC) and are believed to be important in the development of microvascular thrombosis.35,36

The GI tract has been postulated to contribute to MODS through the failure of mucosal integrity brought on by stresses such as trauma, burns, or septic shock. This is believed to result in translocation of bacteria and their products out of the GI tract lumen and/or to increased production of inflammatory mediators by the gut.29,37,38 Thus far clinical studies have neither proven nor disproven this hypothesis.29,39,40

Manifestations

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

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.

Cardiovascular

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.

Dysrhythmias

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

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

Hepatic

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

Hematologic

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

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

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.

Platelet Abnormalities

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.

Neurologic

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.

Metabolic/Endocrine

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

Gastrointestinal

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.

Preventive Strategies

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

The management of MODS involves a combination of locating and reversing the condition(s) that are driving the MODS, and supportive therapies that target specific organs and systems.

Supportive Therapies

Respiratory failure is managed with mechanical ventilation, the CV system is supported with volume, vasopressors, and inotropes, and renal failure is managed with renal replacement therapies. Management of specific organs and systems is discussed later in "Preoperative Preparation of Patients with MODS."

Adjunctive Therapies

Numerous studies have tested the effects of agents that interfere with inflammatory responses. Most of these studies focused on SIRS caused by sepsis.

Antimediator Therapies

Experimental therapies that have targeted specific inflammatory mediators including cytokines such as tumor necrosis factor or interleukin-1, have not improved patient outcomes in large clinical trials.74

Activated Protein C

Activated protein C (APC) is currently approved by the US Food and Drug Administration for the treatment of patients with severe sepsis in the appropriate clinical setting. APC is postulated to exert its effects by preventing microvascular thrombosis and by modulating inflammation. Although initial studies showed a significant mortality reduction in patients with severe sepsis,36 concerns about the efficacy and potential complications of APC have reduced its widespread use. Therefore, another large multicenter trial of APC is currently underway.

Insulin Therapy

Based on recent studies and concerns for deleterious hypoglycemia, tight glycemic control, targeting plasma glucose concentrations between 80 and 108 mg/dL has given way to moderate glycemic control targeting plasma glucose concentrations of more than 180 mg/dL.66 Protocols to regulate insulin infusions for effective glycemic control are commonly used.

Nutritional Support

Patients with MODS are often profoundly malnourished. The GI tract is the preferred route of nutrition, both for the benefits of maintaining GI mucosal integrity and for decreasing the infectious complications associated with parenteral nutrition. Studies suggest that early enteral nutrition may modulate the systemic stress and immune response to reduce infections in ICU patients.71 MODS patients often do not tolerate high-rate enteral feedings, but many practitioners advocate continuing tube feeds at a low rate for these patients to prevent mucosal atrophy. For those patients who cannot be fed enterally, total parenteral nutrition (TPN) can be used. Enteral or parenteral supplementation with arginine, glutamine, and ω-3 fatty acids are being studied for their immune-modulating properties in certain illnesses, such as ARDS, and may be useful in specific critically ill populations.71

Patients with MODS require a variety of procedures. Some may be necessary to correct the underlying cause of the MODS, whereas other procedures may be necessary to deal with the complications of MODS. The timing of procedures should be based on the urgency of the intervention balanced against the precariousness of the patient's physiologic status.

Common Surgical Procedures in Patients with MODS Based on Etiology

Infection

Infection is the most common cause of MODS. Although some infections may be treated with antibiotics alone, many require either surgical debridement or drainage. Immediate debridement for necrotizing fasciitis and infectious myonecrosis is of paramount importance. Similarly, exploratory laparotomies are performed immediately on patients with sepsis due to intestinal perforation. Other infections that may require surgery include toxic megacolon caused by Clostridium difficile colitis, empyema that has failed thoracostomy drainage as a result of a pleural peel or adhesions, and mediastinitis. Abscesses located in the thorax, abdomen, and pelvis may be treated with drainage, either with surgery or using percutaneous catheters.

Pancreatitis

Patients with pancreatitis may require surgery for pancreatic necrosis, pancreatic hemorrhage, or drainage of pancreatic abscesses or infected pseudocysts.75

Trauma

Often surgery is performed early in the trauma patient's course. However, in some situations, surgery may be delayed while the patient is stabilized. Some of these patients develop MODS before definitive procedures for their traumatic injuries, for instance, before pinning of hip fractures or before definitive procedures for spine stabilization.

Limb Ischemia-Necrosis

Patients with limb ischemia-necrosis may require fasciotomies, vessel exploration with revascularization (embolectomy or bypass procedures), or amputation.

Burns

Patients may require excision and grafting, and other treatments.

Surgical Procedures Stemming from MODS

Common procedures in MODS patients include tracheostomy tube placement for ventilator dependence or the inability to handle secretions, and placement of feeding tubes for nutritional support and drug administration. Other procedures that are sometimes required include amputations of digits or distal limbs and debridement of secondarily infected wounds.

Nonsurgical Procedures in Patients with MODS

Sometimes nonsurgical procedures are required to treat the underlying etiology of MODS, such as catheter drainage of intra-abdominal fluid collections. Other nonsurgical procedures include placement of central venous, peripheral arterial, and hemodialysis catheters, and bronchoscopy.

A thorough preoperative evaluation with prioritization of the importance of the various physiologic derangements is essential in anticipating the needs for every phase of the perioperative period (Table 74-3). Based on a comprehensive preoperative evaluation, the anesthesiologist should (1) determine whether or not additional therapies should be initiated preoperatively to optimize the patient's condition, (2) anticipate and arrange for appropriate transportation to the operating room, (3) prepare an anesthetic plan, (4) prepare the operating room in advance for the arrival of the patient, and (5) set up tentative plans for postoperative care. Several of these issues are discussed in more detail in other chapters.

The preoperative assessment should include a review of past and present medical problems, a targeted physical examination, a complete review of the medications and available laboratory and radiographic data, assessment of the ventilator settings, a review of in situ tubes and lines, and, in some cases, a clarification of the plans for resuscitation in the operating room.

Review of Past Medical History

The basic aspects of the past medical history that are important in planning any anesthetic should be reviewed. Preexisting vascular disease, cardiac dysfunction, dysrhythmias, the presence of pacemakers or an implantable cardioverter-defibrillator, preexisting respiratory disease, and cirrhosis may all profoundly impair the response of MODS patients to anesthesia and surgery.

Review of Recent History

A thorough knowledge of the inciting event(s) and all of the organs and systems that are involved is a crucial part of the preoperative assessment.

Respiratory

Information about the degree and nature of respiratory dysfunction and past responses to different ventilation strategies should be actively sought. The chart should be reviewed for information on the airway, including anatomic issues with intubation, difficulties with the endotracheal tube or cuff, quantity and frequency of suctioning of respiratory secretions, and any need for cervical spine immobilization.

Circulation

Critically ill patients have a myriad of cardiovascular problems. The patient's current hemodynamic status, including intravascular volume status, myocardial function, and peripheral vascular tone, should be ascertained. Bedside clinical assessment can provide useful information about global perfusion. Indications of decreased perfusion include oliguria, clouded sensorium, delayed capillary refill, and cool skin. However, organ dysfunction and regional hypoperfusion can occur in the absence of overt signs of global hypoperfusion.76 Elevated serum lactate may reflect anaerobic metabolism caused by hypoperfusion, and a rising lactate may be an indicator of septic shock. Arterial waveform analyses have been shown to be beneficial in predicting the patient's fluid responsiveness.77 The central venous pressure may reflect intravascular volume status in some patients but may be an unreliable estimate of the patient's volume status in the context of cardiac dysfunction, pulmonary hypertension, or elevated intra-abdominal or intrathoracic pressures. Patients with these problems may benefit from echocardiography or pulmonary artery catheterization to help estimate volume status, ventricular filling, myocardial function, and vasomotor tone.

In addition to perfusion and volume assessment, the preoperative evaluation should note the degree of hemodynamic instability, electrocardiographic evidence of dysrhythmias or ischemia, and the hemodynamic responses to vasopressors, inotropes, and fluids.

Renal

Renal dysfunction along with its consequent metabolic and intravascular volume disturbances should be identified. Evaluation should focus on volume status, electrolyte balance, and acid-base status. Physical examination may reveal the presence of a pericardial friction rub secondary to significant uremia or rales secondary to pulmonary edema. Patients can be hyper-, hypo-, or euvolemic. In fact, these patients are often total-body-volume overloaded but intravascularly depleted. Data such as BUN, Cr, plasma potassium, arterial blood pH, and urine output rate should be obtained.

In patients receiving renal replacement therapy (RRT), the type of therapy—continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis, or intermittent HD (hemodialysis)—should be noted. If the patient is on HD, the frequency and timing of the last dialysis should be noted. The ability of the patient to tolerate being without a continuous form of RRT should be assessed. In patients on RRT, electrolyte levels should be measured often. Either hyperkalemia from inadequate clearance or hypokalemia from aggressive preoperative dialysis can lead to life-threatening dysrhythmias. Profound hypophosphatemia from excessive clearance can lead to muscle weakness, increased susceptibility to muscle relaxants, and respiratory insufficiency. A compensated mild metabolic acidosis is common in patients with chronic renal failure. Profound acidemia can occur quickly in the context of shock because of a diminished serum buffering capacity. In this setting, hemofiltration may be performed with the explicit goal of bicarbonate repletion to increase the serum buffering capacity. Uremia can cause platelet dysfunction that improves with dialysis or with the infusion of cryoprecipitate, 1-deamino-8-D-arginine-vasopressin (DDAVP), or estrogen conjugates.

Hepatic

The presence of hepatic dysfunction can have important effects on a patient's response to surgery. Hepatic failure can cause hypoglycemia, coagulation disturbances, and impaired processing of drugs and toxins. Blood studies that should be considered preoperatively include coagulation profile (PT/PTT), platelet count, glucose, bilirubin, albumin, lactate, and transaminase levels to assess the degree of liver injury and synthetic dysfunction.

Hematologic

Anemia, thrombocytopenia, and coagulation dysfunction should be identified, and in some cases corrected, preoperatively. It may be necessary to assess the hemoglobin, platelet concentration, and coagulation studies immediately before surgery. The patient's medication record should be reviewed for anticoagulants such as heparin, Coumadin (warfarin), thrombolytic agents, and antiplatelet drugs.

Metabolic/Endocrine

Major metabolic and endocrine disturbances and recent use of steroids should be identified. The acid-base status should be analyzed. Appropriate preoperative chemical studies in MODS patients include measuring plasma potassium, sodium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose, and arterial blood gases (pH, Paco2, Pao2).

The insulin infusion rate should be noted as well as how frequently the rate requires adjustment.

Neurologic

Baseline neurologic function should be ascertained. Dosages and rates of infusions of sedative-hypnotic and analgesic agents should be noted, and a decision made whether or not these agents should be continued intraoperatively. Opioids, benzodiazepine, and hypnotic infusions used in the ICU may be titrated intraoperatively as part of the anesthetic or alternative agents can be given.

Infection

The sites and severity of infection should be noted. Patients who are actively infected often have more pronounced hemodynamic depression with anesthetic administration. In addition, if the purpose of the surgery is source control, manipulation of the infected site may precipitate or worsen existing instability, including producing hypotension, metabolic acidosis, DIC, and/or worsening respiratory dysfunction.

Physical Examination

The respiratory system should be evaluated by visual assessment of the airway and the respiratory pattern, and auscultation of breath sounds. Signs of respiratory distress such as tachypnea, labored breathing, accessory respiratory muscle use, and inability to clear respiratory secretions should be noted. In addition to assessing the patient's anatomy for the ease of direct laryngoscopy, the airway examination should note the position and fixation of a preexisting endotracheal tube, the presence of tracheal deviation, and the degree of airway edema. The chest should be auscultated and abnormalities noted. Positions of arterial, peripheral venous, and central venous catheters, and other drainage tubes should be noted. Pressure sores and areas of skin breakdown should be identified to plan for appropriate padding in the operating room.

Review of Monitors

A review of the monitors and lines already present and any technical issues associated with these monitors is crucial. Trends of hemodynamic parameters and peak airway pressures should be noted. In addition to standard ICU monitors, including pulse oximetry, electrocardiogram (ECG), and noninvasive blood pressure, monitors that are commonly used in patients with MODS include intra-arterial catheters, central venous catheters, and intracranial pressure monitors.

Review of Scheduled Medications and Infusions

All medications should be reviewed. There should be close attention to continuous drug infusions, including rates of infusions, the lines being used for infusions, and their compatibility with drugs that will be infused in the operating room. Because abrupt cessation of TPN can cause hypoglycemia, plans should be made to either continue the TPN infusion in the operating room or to provide another continuous source of sugar, such as 10% aqueous dextrose solution (D10W).

Laboratory and Radiographic Data

The basic laboratory data to review should include recent values of electrolytes (Na+, K+, Cl−, HCO3−, ionized Ca2+, Mg2+), BUN and Cr, hemoglobin or hematocrit, coagulation studies, and an ECG. Liver function studies, including transaminases and bilirubin levels, also may be useful. All pertinent radiographic data should be reviewed, and the chest radiograph should be visualized to assess endotracheal tube positioning and seek evidence of infiltrates, pulmonary edema, pneumothorax, and pleural fluid.

Ventilator Settings

Most patients with MODS require mechanical ventilation. The details of the ventilator settings should be noted, including the mode of ventilation (controlled vs spontaneous ventilation, pressure vs volume ventilation), the ventilator rate, the FiO2, the level of positive end-expiratory pressure (PEEP), tidal volume and airway pressures, and inspiratory-to-expiratory (I:E) ratios or inspiratory time. Often the standard operating room ventilators are inadequate for patients with low compliance and severe respiratory failure and an ICU ventilator may need to be used for transport and intraoperative management. Generally, patients receiving high levels of PEEP should travel with a PEEP valve. In patients with severe respiratory failure, it may be helpful to perform a trial of manual ventilation in the ICU before transporting to the operating room. In some critical situations it may be appropriate to perform the procedure in the ICU.

Consent for Anesthesia

Unless the surgery is emergent, informed consent must be obtained from either the patient or from a designated surrogate if the patient is unable to give consent.

Resuscitation Status

Occasionally, critically ill patients who have a do not resuscitate (DNR) order require surgical procedures. In some cases, based on the wishes of the patient or their surrogate decision maker, the DNR status is suspended for the intraoperative and immediate postoperative period. This is based on the notion that acute, but reversible intra- and postoperative events, as opposed to the underlying process, may precipitate a cardiac arrest during and immediately after surgery. It is important to clarify whether or not the ICU DNR status will remain in effect or will be suspended in the operating room.

Whenever possible, efforts should be made to correct physiologic derangements and optimize the patient's condition before surgery. Examples of situations that may require preoperative optimization include CV instability, respiratory failure, bronchospasm, renal failure, coagulopathy, thrombocytopenia, electrolyte imbalances, and hyperglycemia or hypoglycemia.

Immediate versus Delayed Surgery

The risk-to-benefit ratio of doing immediate surgery versus delaying surgery for optimization must be carefully assessed. The extremes are usually obvious: Totally elective surgery should not be performed until the patient's physiologic/metabolic situation has been fully optimized, whereas emergency surgery, such as for a ruptured aortic aneurysm or necrotizing fasciitis, needs to be performed before or during optimization. For urgent surgery, there may be sufficient time available to improve physiologic and metabolic parameters. Decisions about the timing of surgery are made by close communication between the anesthesiologist, the surgeon, and the intensivist.

Respiratory

Preoperative optimization of respiratory status may include treatment of bronchospasm with bronchodilators and steroids, pulmonary suctioning for copious secretions, and antibiotics if the clinical scenario is consistent with a respiratory infection. Patients with a tenuous respiratory status may need to be intubated before they are moved to the operating room. A chest tube should be placed if a pneumothorax is present and the patient is to receive positive pressure ventilation.

Mechanical ventilation with positive pressure can cause ventilator-associated lung injury78 and may play a role in causing or worsening MODS.79 A lung protective strategy of mechanical ventilation in ARDS has been shown to decrease mortality, improve respiratory function, and decrease MODS.80 The ARDS Network strategy of limiting tidal volumes and airway pressures has changed the approach to ARDS. The current standards for mechanical ventilation of patients with ARDS are reviewed in Table 74-4.81 With the ARDS network strategy, permissive hypercapnia is used as long as an acceptable arterial pH can be maintained. Recent studies suggest that permissive hypercapnia and acidosis may be protective in early ARDS and sepsis.82-84 However, the degree of hypercapnia should be limited in patients with preexisting metabolic acidosis, and hypercapnia is contraindicated in patients with increased intracranial pressure.

Several other therapies have been investigated in patients with refractory hypoxemia. Inhaled nitric oxide, prone positioning, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation have all been shown to improve hypoxemia in the short term, but thus far, none have demonstrated a long-term mortality benefit.15,85,86 The worldwide clinical experience with severe ARDS caused by the H1N1 influenza virus that emerged in 2009 has renewed interest in many of these rescue modalities.87 If these adjunctive therapies have been implemented in the ICU preoperatively, consideration should be given to the necessity and urgency of the planned surgical procedure, and efforts should be made to wean patients off these modalities before transport to the operating room.

Cardiovascular

Patients with MODS may have hemodynamic instability as a result of impaired myocardial function, decreased systemic vascular tone, hypovolemia, and/or restrictive and obstructive processes that impair ventricular filling. Anesthesia and surgery may further complicate the hemodynamic issues. Poor cardiac contractility and low vascular tone may be exacerbated by inhaled or IV anesthetics, and hemodynamic instability may be worsened by blood loss and third space fluid losses.

Before volume repletion, patients with septic shock may have a combination of low peripheral vascular tone, reduced cardiac filling pressures, and decreased stroke volume. A hyperdynamic picture can emerge after volume resuscitation. Hypovolemia should be corrected with balanced electrolyte solutions and/or blood products, depending on the etiology and associated issues (such as a coagulopathy). Fluid infusion alone will reverse the hypotension and restore hemodynamic stability in roughly half of the septic patients who present with hypotension.76 If fluid resuscitation fails to restore adequate systemic blood pressure and organ perfusion promptly, infusion of vasopressor agents should be initiated.76 The choice of vasopressors in sepsis has been the subject of debate. Norepinephrine and dopamine have both emerged as acceptable first-line agents, whereas phenylephrine and epinephrine are not currently recommended as first-line agents.69 In addition, recent evidence suggests there is a relative "vasopressin-depleted" state in sepsis,88 which has prompted an evaluation of the early addition of vasopressin for the treatment of septic shock.89 Most recently, dopamine and norepinephrine have been compared with each other in the treatment of shock.90 Although no difference was observed in 28-day mortality between the 2 groups, those receiving dopamine experienced more dysrhythmias, and the subgroup of patients with cardiogenic shock receiving dopamine had a higher mortality rate.90

In some patients pulmonary artery catheters (PACs) may be used to facilitate preoperative optimization and/or for intraoperative and postoperative care. In recent years, PAC use has fallen out of favor in ICU patients and in the intraoperative setting based on multiple studies that failed to show a survival benefit of the PAC.91 Transesophageal echocardiography has replaced the PAC for intraoperative monitoring in many surgical situations. However, the PAC may still be useful for patients undergoing major surgery who have significant myocardial dysfunction, pulmonary hypertension, or constrictive or restrictive cardiac processes.

Renal

Goals for renal optimization before surgery include correction of metabolic and physiologic derangements, and protecting the kidneys from further damage. Whenever possible metabolic disturbances should be corrected before surgery. Some patients with renal failure may require preoperative RRT to treat metabolic acidosis, electrolyte imbalances, uremic pericarditis, or volume overload. Hyperkalemia should be corrected, either with binding agents such as sodium polystyrene sulfonate or with RRT. Consideration should be given to infusing DDAVP to correct uremic platelet dysfunction.

Both CVVH and intermittent hemodialysis are used in critically ill patients who require RRT. However, CVVH is often preferred because it is better tolerated hemodynamically and allows continuous control of fluid balance and toxin removal. In hemofiltration, blood under pressure passes along one side of a highly permeable membrane that allows transfer of both water and substances below a molecular weight of approximately 20000 Da.92 Urea, Cr, and phosphate are cleared from the blood at similar rates. Larger molecules, such as heparin, insulin, and vancomycin, are also cleared. The filtrate is discarded and the patient receives a replacement fluid composed of physiologic levels of the major crystalloid components of plasma. Total-body-fluid balance is regulated by varying the volume of replacement fluid.

A variety of factors may have a negative impact on kidney function. Intravascular hypovolemia, systemic inflammation, and the infusion of nephrotoxins such as IV contrast agents can all contribute to perioperative renal failure. Preventive measures include optimization of intravascular volume and avoidance of nephrotoxins. In patients who are to receive an IV contrast agent, preemptive strategies should be considered, including volume loading, alkalinization using IV NaHCO3, and/or administration of N-acetylcysteine.93

Hepatic

Patients with liver dysfunction have a variety of issues. Hypoglycemia should be identified and plasma glucose levels should be maintained in a normal range using a dextrose infusion. Severe coagulopathy should be corrected. Hepatic encephalopathy should be treated with lactulose.

Hematologic

Critically ill patients often have anemia, coagulopathy, and thrombocytopenia. Their preoperative management will depend on the cause and severity of the disturbance, and the nature of the surgery. The anesthetic plan should take into account the anticipated blood loss for the procedure and the risks and benefits of stopping anticoagulant therapy preoperatively. If transfusion of blood products is anticipated, an adequate recipient sample should be available in the blood bank and the availability of sufficient supplies of blood products should be confirmed preoperatively. Patients who have had multiple transfusions may have developed circulating antibodies to non-ABO antigens. A consultation with a blood bank physician may be needed to select appropriate blood components for transfusion.

Anemia

RBC transfusions are given to augment oxygen delivery and to avoid the deleterious effects of oxygen debt. ICU patients are at increased risk for complications of transfusion therapy. Current recommendations are that in the absence of active coronary artery disease, RBC transfusions should only be given for hemoglobin levels of 7.0 g/dL or lower.94,95

Coagulopathy

Coagulopathy may result from consumptive processes such as DIC or from decreased factor production, as occurs in hepatic failure. Prophylactic administration of plasma products may be indicated to correct a coagulopathy before invasive procedures. If there is active bleeding, plasma products should be administered until the bleeding stops or the coagulopathy is reversed.94,96 Vitamin K administration is indicated if vitamin K deficiency is present to raise the levels of vitamin K-dependent clotting factors (II, VII, IX, and X).

In the absence of coagulation inhibitors (including heparin) and in the presence of adequate fibrinogen levels (>100 mg/dL), hemostasis can usually be achieved when the activity of coagulation factors is at least 25% to 30% of normal. Fresh-frozen plasma (FFP) contains all of the plasma clotting factors and is used to correct coagulopathies that result from a factor deficiency or from anticoagulation with warfarin. Cryoprecipitate is rich in von Willebrand factor, factor VIII, factor XIII, and fibrinogen, and it is used to treat deficiencies of fibrinogen and factor XIII, and to manage von Willebrand disease.

Some patients may be receiving anticoagulation therapy because of deep vein thrombosis, atrial fibrillation or atrial flutter, the presence of prosthetic valves, or HIT. If possible, time should be allowed for Coumadin anticoagulation to reverse before, which may require several days. For emergent or urgent procedures, the PT can be rapidly corrected with FFP. If vitamin K is used to reverse the effects of Coumadin, very low doses should be administered (about 1 mg) because larger doses may make it difficult to re-anticoagulate the patient after the procedure. Patients with severe vascular disease or with coronary artery stents may be receiving antiplatelet agents such as Plavix (clopidogrel) and aspirin. When possible, surgery should be delayed in patients who are on Plavix until 7 days after the last dose. Consideration should be given to continuing aspirin in patients who have drug-eluting stents because they may be at risk for perioperative stent thrombosis.

Thrombocytopenia

Platelet transfusions are used to manage patients who are bleeding or who are at risk of bleeding as a consequence of thrombocytopenia or impaired platelet function. Surgical bleeding solely caused by thrombocytopenia usually occurs when platelet concentrations are below 50000/μL, and spontaneous bleeding occurs when platelet levels drop below 10000/μL. However, additional factors, such as a concomitant coagulopathy, fever, renal failure, or treatment with nonsteroidal anti-inflammatory drugs, may increase the bleeding risk from severe thrombocytopenia. Consequently, the threshold platelet concentration for triggering a prophylactic platelet transfusion should take into account these clinical considerations.94,96

Metabolic/Endocrine

Acid-Base Status

Acid-base disturbances may complicate intraoperative management and/or be exacerbated by major surgery. For instance, metabolic acidosis may worsen during and after a surgery in which there is hemorrhage. Metabolic acidosis may also result from ischemia-reperfusion events, such as relief of vascular occlusion, opening an aortic cross clamp, or releasing a tourniquet on a limb at the conclusion of a peripheral orthopedic procedure.

In the preoperative period, acid-base disturbances should be identified, classified, corrected, if severe. Common causes of metabolic acidosis in MODS patients include impaired tissue perfusion from hypovolemia and/or hypotension, limb or GI vascular occlusion, renal failure, and administration of large volumes of normal saline.

Respiratory acidosis may be managed by increasing the minute ventilation. Some patients with severe hypercapnic respiratory failure do not augment carbon dioxide exchange with increased minute ventilation due to a very high dead space fraction.97 Moreover, currently used lung protective ventilation strategies often require patients to have a high PaCO2. Perioperatively, the acidosis of permissive hypercapnia may be more problematic because of the propensity to develop a superimposed metabolic acidosis.

Electrolytes

If time permits, electrolyte abnormalities should be corrected before surgery. CVVH or hemodialysis may be required to correct hyperkalemia. Hypokalemia and hypomagnesemia can generally be corrected using IV supplementation. If surgery is emergent, IV treatment with insulin and glucose, and rectal or oral administration of sodium polystyrene sulfonate may be required to treat hyperkalemia.

Glucose

Hyperglycemia and hypoglycemia should be corrected with insulin and glucose infusions, respectively. All patients who are receiving an insulin infusion should also receive an infusion of glucose to prevent hypoglycemia. Consideration should be given to continuing insulin infusions intraoperatively and measuring frequent blood sugar levels.

Adrenal Dysfunction

Adrenal insufficiency should be considered in patients with persistent vasopressor requirements despite adequate volume repletion and other appropriate therapies. In addition, patients who have been receiving steroids for sustained periods of time may have suppressed adrenal function, and they may require perioperative "stress-dose" steroids.

Planning the Anesthetic

As is the case for all procedures, the anesthetic should be carefully planned and tailored to the individual patient's constellation of problems/issues. Specifics of developing the anesthetic plan in critically ill patients with MODS is reviewed elsewhere in this text.

Decisions Regarding Continuation of Intensive Care Unit Therapies in the Operating Room

During the preoperative visit, the anesthesiologist will decide whether or not to continue various therapies that are ongoing in the ICU. Some therapies may be too cumbersome to implement in the operating room. For instance, because CVVH requires extra equipment and extensive education for proper use, if it is continued in the operating room, the presence of additional personnel with CVVH expertise will be necessary. The anesthesiologist will also assess the need to continue infusions such as TPN, sedative-hypnotics, opioids, vasoactive agents, and insulin. If the patient requires high levels of ventilatory support or a complicated mode of ventilation, arrangements should be made to use an ICU ventilator in the operating room and to have someone who is skilled in its use immediately available to assist with ventilatory changes in the operating room.

Preparing the Operating Room

The operating room should be completely ready to receive the patient before leaving the ICU. The operating room should be equipped with an ICU ventilator, if appropriate, and should be stocked with the same vasopressors and inotropic agents that the patient is receiving in the ICU.

Transportation to the operating room can be risky. This topic is reviewed in detail in Chapter 78. Briefly, the anesthetist should plan to personally accompany the patient from the ICU to the operating room. Arrangements should be made to continue monitoring appropriate parameters, such as systemic arterial, central venous, pulmonary arterial, and intracranial pressures. It may be necessary to transport the patient with severe respiratory failure with an ICU ventilator. Transport with a PEEP valve may be appropriate in patients who are PEEP dependent and who can tolerate short periods of manual ventilation. An early trial of manual ventilation in the ICU may be helpful in determining if a respiratory failure patient can tolerate traveling from the ICU to the operating room.

As technologies and therapies for basic diseases and acute processes such as shock and respiratory failure advance, a modern syndrome has evolved. MODS is an enigmatic process that is caused by generalized inflammation and microvascular circulatory abnormalities. The similarity of MODS resulting from either infectious or noninfectious diseases suggests that common pathways are involved.

Anesthesiologists are frequently involved in the care of patients with MODS, either in the ICU or in the operating room. MODS patients require surgery to treat the primary processes that have caused MODS or to deal with complications. The anesthesiologist will be involved in decisions regarding the timing of surgery and in optimizing the patient for surgery. Communication between the anesthesiologist, the ICU team, and the surgeon is crucial as part of preoperative preparation.

Before transport to the operating room, a comprehensive plan tailored to each patient's individual constellation of abnormalities should be in place. Preoperative planning should include making informed decisions regarding continuation of therapies such as CVVH, TPN, and insulin; arrangements for the patient's ventilator to accompany the patient to the operating room if appropriate; sedation and analgesia; availability of appropriate fluids, drugs, blood products and monitoring equipment; and a clear understanding of the plan regarding perioperative resuscitation for unexpected cardiac arrest or catastrophic events. Preoperative and intraoperative interventions will be dictated by the pattern and intensity of organ failure.

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