Sepsis and Septic Shock

Introduction/Definitions

• Sepsis refers to a life-threatening condition in which an abnormal and uncontrolled host response to infection leads to acute organ dysfunction. This organ injury is often recognized clinically by a rise in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points, indicating an increased risk of death.¹
• Septic shock is the most severe form of sepsis and is characterized by profound disturbances in circulation, cellular function, and metabolism. It is identified by persistent hypotension requiring vasopressor support to maintain a mean arterial pressure (MAP) ≥65 mmHg along with serum lactate >2 mmol/L despite sufficient fluid resuscitation, and is associated with a substantially higher mortality rate.¹
• Systemic Inflammatory Response Syndrome (SIRS) is the presence of ≥2 of the following: abnormal temperature, heart rate, respiratory rate, or white blood cell count.¹ Although historically used to identify sepsis, SIRS criteria lack specificity and are no longer required for diagnosis.²
• Anesthesiologists have a crucial role in managing septic patients in the operating room, where perioperative sepsis is highly lethal; however, early recognition and treatment improve mortality.
• A significant proportion of perioperative cardiac arrests are associated with sepsis, highlighting the importance of early anesthetic recognition and aggressive hemodynamic management.²

Pathophysiology

• The most common sources of sepsis are infection from the lungs (40-60%), abdomen (15-30%), genitourinary tract (15-30%), bloodstream, and skin or soft tissue. It is most commonly caused by gram-positive or gram-negative bacteria, but viral causes of sepsis have been increasing.³
• Sepsis results from a dysregulated immune response characterized by hyperinflammation, leading to widespread microvascular injury.² Activated neutrophils, macrophages, and cytotoxic T cells release inflammatory mediators and antimicrobial peptides and form neutrophil extracellular traps, which help contain pathogens but also damage the endothelium. The bone marrow then shifts toward emergency myelopoiesis, increasing granulocyte production at the expense of lymphocytes, thereby impairing immune function. This leads to increased vascular permeability, a prothrombotic state, and impaired fibrinolysis. In addition to inflammatory injury, sepsis is characterized by cellular metabolic and energy failure, in which tissues are unable to effectively utilize delivered oxygen despite adequate macrocirculatory flow. These processes result in tissue hypoperfusion, organ dysfunction, and frequently multiorgan failure.³

Clinical Presentation

• Patients with sepsis present with marked clinical heterogeneity due to variations in infection source, pathogen, degree of organ dysfunction, and underlying patient health. Patients commonly exhibit general signs and symptoms related to the site of infection, and manifestations of acute organ dysfunction such as altered mental status, oliguria, or dyspnea. Common laboratory abnormalities include leukocytosis or leukopenia, increased immature granulocytes, hyperglycemia, elevated creatinine, and elevated lactate.³
• Early recognition can be difficult because signs and symptoms are nonspecific, evolve over time, and may be subtle in the early stages. At times, clinical deterioration under anesthesia may be the first manifestation of sepsis. Clinical features may also be masked by medications such as beta-blockers or antipyretics. Sepsis should be suspected in any patient with infection accompanied by acute organ dysfunction or in patients with unexplained organ failure where infection is a possible cause. Importantly, it should be considered even in the absence of fever or focal signs of infection, especially in patients with an acute decompensation of a chronic disease.³
• Evaluation focuses on identifying the source of infection and assessing organ function and tissue perfusion. This typically includes imaging, microbiologic cultures, antigen testing, and pathogen-specific molecular assays when appropriate. Serum lactate measurement is recommended in all patients to detect occult hypoperfusion.³ Under general anesthesia, classic signs such as fever or tachypnea may be masked, requiring vigilance for unexplained hypotension, the need for vasopressors, or metabolic derangements.²

Anesthetic Management Principles

Preoperative Management

• Patients with sepsis or septic shock frequently require urgent or emergent surgery for source control. Preoperative assessment should be focused on identifying acute organ dysfunction using the SOFA score rather than a comprehensive evaluation. Cardiac dysfunction, including sepsis-induced cardiomyopathy, is common and should be assessed when possible, ideally with bedside echocardiography. Oxygenation, renal function, hemoglobin (target 7-9 g/dL), and coagulation status should be evaluated, recognizing that standard coagulation tests may underestimate clinically significant coagulopathy. When available, viscoelastic testing (TEG/ROTEM) may help identify hypocoagulability and guide transfusion decisions. Broad-spectrum antibiotics should be administered within 1 hour of the onset of suspected sepsis.⁴
• Hemodynamic optimization is critical before anesthesia induction. Balanced crystalloids are first-line for volume resuscitation (up to 30 mL/kg in the first 3 hours).⁵ Dynamic assessments of fluid responsiveness (e.g., passive leg raise, stroke volume variation, pulse pressure variation, echocardiography) are preferred over static targets such as central venous pressure. Fluid responsiveness should be assessed when feasible using dynamic parameters or echocardiography, recognizing that static measures such as blood pressure alone are unreliable.⁴ Vasopressors should be initiated early if hypotension persists despite fluid resuscitation, even while volume status is still being optimized. Norepinephrine is first-line and may be safely initiated via a peripheral vein while central access is being established.⁵ Point-of-care ultrasound-guided fluid management has been associated with lower positive fluid balance and reduced need for renal replacement therapy and invasive ventilation, although mortality benefit has not been demonstrated.⁵
• Blood cultures should be obtained before antibiotic administration when feasible, but this should not delay treatment. Broad-spectrum antibiotics must be administered as early as possible, ideally within 1 hour of sepsis recognition, with selection guided by infection source, local resistance patterns, and patient-specific risk factors. If the likelihood of infection is low and shock is absent, rapid evaluation within 3 hours with selective antibiotic use is reasonable.⁶
• Goal-Directed Therapy: Although early goal-directed therapy protocols with strict numeric targets have yielded mixed results, structured resuscitation bundles incorporating early recognition, prompt antibiotics, fluid resuscitation, and physiologic targets such as MAP and lactate clearance improve outcomes.⁶
• Current Surviving Sepsis Campaign guidelines recommend an initial MAP target of ≥65 mmHg.⁷ Higher MAP targets have not demonstrated a mortality benefit and are associated with increased risk of atrial fibrillation. Emerging evidence suggests that a permissive hypotension strategy (MAP 45-70 mmHg) with monitoring of end-organ perfusion may be safe in selected patients and may reduce vasopressor exposure, arrhythmias, transfusion requirements, and fluid overload.⁵

Intraoperative Management

• Rapid sequence induction is usually indicated due to urgency and the risk of aspiration. Patients with sepsis are highly sensitive to anesthetic agents and are at high risk for severe hypotension during induction because of vasodilation, relative hypovolemia, and myocardial depression. Anesthetic doses should be reduced, and hemodynamics optimized prior to induction with invasive arterial monitoring and vasopressors immediately available or already running.⁴ Ketamine or etomidate are preferred induction agents due to their relatively favorable hemodynamic profiles; clinicians should be aware of adrenal suppression when using etomidate, as well as the potential for myocardial depression as a side effect of ketamine due to depletion of catecholamines in shock states.⁵ Propofol should be avoided or carefully titrated due to its vasodilatory and myocardial depressant effects.⁵
• There is no definitive evidence favoring volatile versus intravenous anesthesia for maintenance. Sepsis reduces the minimum alveolar concentration of volatile anesthetics, and impaired pulmonary function may make delivery less predictable. Depth-of-anesthesia monitoring may help avoid overdose and reduce the risk of awareness. Advanced hemodynamic monitoring is recommended to guide fluid, vasopressor, and inotrope therapy, recognizing that uncalibrated cardiac output devices may be less reliable in profound vasoplegia.⁴
• Norepinephrine remains first-line for hypotension. Early vasopressin administration may provide catecholamine-sparing effects and has been associated with reduced incidence of atrial fibrillation and reduced need for renal replacement therapy. Angiotensin II is an emerging non-catecholamine vasopressor that increases MAP and reduces vasopressor requirements, with potential mortality benefit in patients with high disease severity, renal failure, or elevated renin levels. Dobutamine should be considered for low cardiac output with ongoing hypoperfusion despite adequate preload and afterload optimization. Methylene blue and hydroxocobalamin, which inhibit nitric oxide-mediated vasodilation, may be considered in refractory vasoplegic septic shock, with recent evidence suggesting improved MAP and possible reductions in mortality.⁵
• After adequate volume resuscitation and hemodynamic stabilization, ultrashort-acting beta-blockers (e.g., esmolol or landiolol) have been shown to reduce 28-day mortality without compromising cardiac output or MAP.⁵
• Low-dose hydrocortisone may be considered in vasopressor-dependent septic shock. Recent evidence suggests that combined hydrocortisone and fludrocortisone therapy may reduce mortality and increase vasopressor-free days, particularly in patients with community-acquired pneumonia or acute respiratory distress syndrome.⁵
• Lung-protective ventilation with low tidal volumes and cautious positive end-expiratory pressure is recommended, with careful attention to the hemodynamic effects of recruitment maneuvers, patient positioning, pneumoperitoneum, and surgical blood loss. Avoidance of iatrogenic injury, including ventilator-induced lung injury and excessive fluid administration, is a core principle of anesthetic management in sepsis. Antibiotic redosing may be required due to increased volume of distribution and altered pharmacokinetics, particularly for hydrophilic drugs.⁴

Postoperative Management

• Most patients with sepsis or septic shock require postoperative ICU admission, typically within 6 hours post-operation. Ongoing hemodynamic instability, tissue hypoperfusion, and evolving organ dysfunction are common and may necessitate continued vasopressor support, mechanical ventilation, renal replacement therapy, and close metabolic monitoring. Re-evaluation for persistent or recurrent infection is essential, as additional surgical or procedural interventions may be required to achieve definitive source control.⁴