Abstract
Sepsis, systemic inflammatory response syndrome (SIRS), and multiple organ dysfunction syndrome (MODS) are clinical syndromes that may present during the perioperative period. Their clinical manifestations may affect virtually all organ systems and range from mild to life threatening. A thorough understanding of the pathophysiology of these conditions is critical to provide optimal perioperative care.
Keywords
multiple organ dysfunction syndrome, sepsis, systemic inflammatory response syndrome
Case Synopsis
A 35-year-old man sustains a gunshot wound to the abdomen. He is taken emergently to the operating room where he is found to have a perforated colon with stool and pus in the abdomen. He undergoes a partial colectomy and colostomy. Throughout the surgery he becomes progressively more tachycardic and hypotensive requiring large-volume resuscitation and the initiation of vasopressors and invasive hemodynamic monitoring. At the completion of the surgery he is transported to the intensive care unit for further management.
Problem Analysis
Definition and Recognition
The systemic inflammatory response syndrome (SIRS), sepsis, and multiple organ dysfunction syndrome (MODS) are conditions that may arise in patients throughout the perioperative period. They are defined by the presence of specific signs and symptoms ( Boxes 24.1 and 24.2 ). Advances in medical care and improved therapies for patients suffering from complex medical and surgical conditions, along with a desire to facilitate categorization and comparison of patients with multiple medical morbidities, have helped the definitions of SIRS, sepsis, and MODS evolve to their current states.
Fever or hypothermia (core temperature >38° C or <36° C)
White blood cell count >12,000 or <4000, or >10% bands
Heart rate >90 beats/min or >2 standard deviations above normal for age
Tachypnea (respiratory rate >20 breaths/min)
Sepsis: SIRS in the presence of infection
Severe sepsis: Sepsis with the presence of dysfunction in at least one organ system
Septic shock: Sepsis with persistent hypotension despite administration of intravenous fluids
SIRS, Systemic inflammatory response syndrome.
SIRS criteria are general enough that some anxious preoperative patients, and virtually all postoperative patients, may meet the criteria. Its development may therefore fail to trigger a heightened level of concern for the clinician in the perioperative period. However, SIRS criteria often herald the development of the more troublesome condition of sepsis, and the considerable morbidity and mortality that it carries. As the difference between SIRS and sepsis hinges merely on the presence of infection, many patients presenting for surgery meet the criteria for sepsis. The proinflammatory nature of surgery has the potential to further progress a patient into the category of septic shock.
MODS is a dynamic process characterized by the progressive failure of multiple organ systems and may be precipitated by sepsis, trauma, or other processes. MODS is commonly observed in patients in the intensive care unit (ICU) and may be encountered in the perioperative setting when an ICU patient requires surgical intervention.
Risk Assessment and Implications
Although the physiologic parameters that define SIRS are common and may represent a heightened stress response, sepsis is a highly pathologic condition. Surgery and acute illness have a profound effect on metabolic and immunologic function and may increase a patient’s risk for developing sepsis and MODS. The body’s ability to extract and utilize oxygen is impaired in sepsis, and lactate production is increased. Endocrine abnormalities become prominent, including a reduction in vasopressin production and resistance to other hormones, including insulin and catecholamines.
Each year millions of patients experience surgical site infections, and surgical patients account for 30% of patients with sepsis. Risk factors for perioperative sepsis include the elderly population, male sex, and African American race. Early identification of patients at risk for developing sepsis and MODS may facilitate early intervention and proper triage of patients to an intensive care environment. Early and aggressive treatment of sepsis has been shown to reduce morbidity and improve survival. Anesthesiologists are in a unique and favorable position to initiate therapy for patients with SIRS and sepsis, including securing central venous access and invasive monitors, providing volume resuscitation, and administering antibiotics. For patients with MODS, diagnostic interventions such as echocardiography may be performed in the operating room or ICU, and supportive treatment initiated or continued under an anesthesiologist’s care.
Management and Prevention
There is no simple cure for SIRS, sepsis, or MODS. They are complex physiologic processes that require a multimodal approach to manage and limit their progression. Without one specific target to focus on, management is based on a combination of source control, supportive care, and prevention of further complications. The Surviving Sepsis Campaign is an international organization dedicated to advancing the care of patients with sepsis and septic shock, and novel therapies for sepsis remain a strong area of research.
Source Control
The inflammatory process that defines SIRS may be initiated by any number of insults to the body—infection, trauma, metabolic abnormality, or disease process. The patient’s history, physical examination, and laboratory or diagnostic studies are useful to identify infectious causes of continuing inflammation. Source control is a hallmark of management. Early identification and treatment of the underlying condition may prevent progression of inflammation and/or the development of sepsis or MODS. In some situations, such as surgical debridement of an infection, achieving source control may transiently worsen a patient’s clinical condition as the patient’s body reacts to the additional stress of surgery.
Supportive Care
Supportive care may be divided into different categories.
1
Fluid and Blood Product Administration
SIRS and sepsis are characterized by systemic capillary leak, and volume resuscitation is a cornerstone of management. The benchmark study “Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock” by Rivers and colleagues aimed to achieve a central venous pressure of 8 to 12 mm Hg as part of an effort to optimize the patient’s central venous oxygen saturation and hemodynamics. The Surviving Sepsis Campaign recommends administration of 30 mL/kg of crystalloid for hypotension or an elevated lactate. Patient responsiveness to volume administration may be assessed by improvements in hemodynamics, monitoring pulse pressure variation, and metabolic markers such as trends in lactate levels. Restoration of adequate blood pressure is usually defined as a mean arterial pressure of 60 to 65 mm Hg.
Although studies of crystalloid versus colloid administration are difficult to compare because of a heterogeneous patient mix, duration of fluid administration, and bias risks, resuscitation with balanced crystalloids or albumin, compared with other fluids, may be associated with reduced mortality. Red blood cell transfusion triggers have been widely studied in numerous patient populations, and most studies suggest that a hemoglobin of 7.0 g/dL is sufficient for critically ill patients who are not actively bleeding. The Surviving Sepsis Campaign recommends a transfusion trigger of 7.0 g/dL with a target hemoglobin of 7.0 to 9.0 g/dL in adults, assuming there is no active myocardial ischemia, severe hypoxemia, or active hemorrhage.
2
Vasopressors and Inotropic Support
In patients with sepsis or septic shock, fluid resuscitation may be inadequate to restore organ perfusion. Hypotension in the setting of sepsis is often multifactorial—hypovolemia, vasodilation, and myocardial dysfunction may all contribute. Although sepsis-induced myocardial dysfunction may occur in up to 40% of cases of sepsis, vasodilation is a hallmark of sepsis physiology and often necessitates the use of vasopressors. Dopamine has historically been used for patients with hypotension and sepsis, but current recommendations call for norepinephrine as the first-line drug. Norepinephrine, with both α- and β-receptor activity, reduces vasodilation and enhances cardiac contractility.
If a second agent is needed, the Surviving Sepsis Guidelines recommend epinephrine. Endogenous vasopressin levels in septic shock may be reduced relative to a patient’s increased needs, a condition known as a “relative vasopressin deficiency,” and low-dose vasopressin infusion may be added to norepinephrine if needed. In settings of severely reduced cardiac contractility, inotropic agents such as dobutamine may be used, although their β-receptor activity may worsen vasodilation.
3
Mechanical Ventilation
Sepsis-induced respiratory failure is common. Increased metabolic demands from the respiratory muscles combined with limited energy supplies and production create an imbalance and may precipitate respiratory failure and the need for mechanical ventilation. Acute lung injury and acute respiratory distress syndrome (ARDS) are common in patients with sepsis, and respiratory failure is often part of MODS. Respiratory support in patients with sepsis-induced respiratory failure parallel the guidelines for patients with ARDS. The Surviving Sepsis Campaign recommends that clinicians use a tidal volume of 6 mL/kg of predicted body weight and that plateau pressures be maintained less than 30 cm H 2 O. Such a lung protective strategy of ventilation has been shown to improve outcomes. The use of positive end-expiratory pressure (PEEP) is encouraged to maintain alveolar recruitment, with the supplemental use of recruitment maneuvers in patients with refractory hypoxemia. The head of the bed should be maintained between 30 and 45 degrees (a strategy that may not be possible intraoperatively) to reduce the risk of pulmonary aspiration.
4
Antibiotics
SIRS often progresses to sepsis when active infection is identified. Early administration of antibiotics is a cornerstone of treating sepsis. Mortality risk increases with delay in antibiotic administration, and the Surviving Sepsis Guidelines recommend that antibiotics be started within 1 hour of the diagnosis of severe sepsis or septic shock. Although antibiotics are usually administered at the beginning of surgery, the choice of antibiotic should be carefully considered in a patient with SIRS or sepsis. A detailed history and physical examination can suggest the source of infection, and antibiotics can be tailored appropriately. In many cases patients will already be receiving appropriate antibiotics before they undergo surgery.
5
Endocrine Support
Sepsis may be characterized by suboptimal cortisol production and relative adrenal insufficiency. In the past, adrenal responsiveness was assessed via the ACTH stimulation test; however, this is no longer recommended. Numerous studies have investigated the use of steroid administration for patients with sepsis and septic shock, with often conflicting results. Based on the available data, most sources agree that patients with sepsis in the absence of shock should not receive steroid supplementation. In patients with refractory septic shock (hypotension failing to respond to fluid resuscitation and vasopressor support), stress steroids are indicated. Hydrocortisone is usually administered in divided doses for a total of 200 to 300 mg per day. There is no consensus on the duration of steroids or whether a taper is necessary.
As discussed, a relative vasopressin deficiency exists in the pituitary gland during sepsis. Vasopressin is most active in controlling tone in the splanchnic circulation, and a major component of sepsis-associated vasodilation arises in this bed. Infusion of replacement vasopressin (0.01–0.04 U/min) restores normotension and may help wean the patient from other vasoactive substances.
6
Renal Replacement and Acid-Base Support
Acidemia is common in patients with sepsis and MODS and is often multifactorial in etiology. Sepsis-induced renal failure may contribute to acidosis, and organ hypoperfusion may cause lactic acidosis that may only improve with correction of the underlying process. Renal replacement therapy (RRT) may be indicated for a variety of reasons in patients with sepsis and MODS, including acidosis, electrolyte abnormalities, volume overload, and uremia. Both continuous RRT and intermittent hemodialysis are reasonable, although continuous RRT may be better tolerated in patients with unstable hemodynamics. Acidosis may be transiently corrected with the administration of sodium bicarbonate, although this is not recommended except in cases of severe acidemia that is refractory to vasopressors.
7
Glucose Control
The systemic inflammatory and stress response from SIRS and sepsis causes hyperglycemia. Although it is generally accepted that hyperglycemia in sepsis should be treated, the target glucose level is less well defined. Tight glucose control (80–100 mg/dL) leads to an increased risk of hypoglycemia, and many practitioners and protocols target a serum glucose less than 150 mg/dL. The Surviving Sepsis Campaign recommends a target of less than 180 mg/dL. Given the rapid changes in patients’ metabolic status, frequent glucose monitoring is prudent, and insulin administered by infusion allows for easier adjustment of doses.
Prevention of Further Complications
The myriad complications that stem from sepsis and MODS span across virtually every organ system ( Table 24.1 ). The classic teaching that “an ounce of prevention is worth a pound of cure” strongly applies to our management of patients with SIRS and developing sepsis. Early source control, aggressive volume resuscitation, initiation of antibiotics, and hemodynamic support can decrease morbidity and mortality. When early intervention and source control involve operative intervention, anesthesiologists are well positioned to ensure optimal care for patients with SIRS, sepsis, or MODS.
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