Residency · Residency · Anesthesiology

Sepsis and Septic Shock: Anesthetic and Critical Care Perspectives

Introduction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, as established by the Sepsis-3 consensus in 2016. Septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction associated with higher mortality. Anesthesiologists encounter sepsis both in the operating room during emergent source control surgery and in the ICU, where they frequently manage hemodynamics, ventilation, and organ support.

Definitions (Sepsis-3)

Sepsis is defined as suspected or documented infection with an acute increase in SOFA score of 2 or more points. Septic shock is sepsis with persistent hypotension requiring vasopressors to maintain a MAP of 65 mmHg or greater AND a serum lactate above 2 mmol/L despite adequate volume resuscitation. The qSOFA (quick SOFA) is a bedside screening tool that includes respiratory rate of 22 or greater, altered mentation, and systolic blood pressure of 100 mmHg or less; two or more criteria suggest sepsis, and it is used for screening outside the ICU. The terms SIRS, severe sepsis, and the SIRS criteria for defining sepsis have been retired in Sepsis-3.

Two or more criteria = positive screen (assess for sepsis).

Pathophysiology

Infection triggers activation of innate immune pathways through pattern recognition receptors and toll-like receptors. This leads to the release of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6) and anti-inflammatory mediators. Endothelial dysfunction results in increased permeability, glycocalyx degradation, and capillary leak. Nitric oxide-mediated vasodilation causes loss of vascular tone. Septic cardiomyopathy produces a reduced ejection fraction that is often reversible. Microcirculatory failure creates heterogeneous perfusion and impaired oxygen extraction. The coagulation cascade becomes activated, leading to microvascular thrombosis and DIC. Mitochondrial dysfunction impairs cellular oxygen utilization, a phenomenon termed "cytopathic hypoxia."

The Surviving Sepsis Campaign: Key Bundles

Hour-1 Bundle (2021 Update)

The Hour-1 Bundle requires measuring the lactate level and remeasuring if the initial lactate is above 2 mmol/L. Blood cultures should be obtained before antibiotics, but antibiotics must not be delayed. Broad-spectrum antibiotics are administered within 1 hour of recognition. Rapid fluid resuscitation with 30 mL/kg of crystalloid is initiated for hypotension or lactate of 4 mmol/L or greater. Vasopressors are applied if hypotension persists during or after fluid resuscitation to maintain a MAP of 65 mmHg or greater.

Fluid Resuscitation

The initial bolus is 30 mL/kg of isotonic crystalloid (lactated Ringer's or 0.9% NaCl) within the first 3 hours. Balanced crystalloid (LR, Plasmalyte) may be preferred over 0.9% NaCl, as the SMART trial showed a lower composite renal outcome.

After the initial bolus, fluid responsiveness should be reassessed using dynamic parameters. Pulse pressure variation or stroke volume variation greater than 12 to 13% in mechanically ventilated patients suggests responsiveness. The passive leg raise test, in which an increase in cardiac output greater than 10% predicts fluid responsiveness, is useful in spontaneously breathing patients. Point-of-care ultrasound can assess IVC collapsibility index and cardiac function.

Fluid overload must be avoided because beyond the initial resuscitation, a conservative fluid strategy improves outcomes. Albumin (4 to 5%) may be considered when patients require substantial crystalloid volumes.

Vasopressor and Inotrope Therapy

First-Line

Norepinephrine, an alpha-1 and beta-1 agonist, is the first-line vasopressor with a target MAP of 65 mmHg or greater. It can be started via peripheral IV if central access is delayed, as short-term peripheral infusion is safe.

Second-Line

Vasopressin at 0.03 to 0.04 units/min as a fixed dose is added to norepinephrine to reduce catecholamine requirements and acts via V1 receptors independent of adrenergic pathways. Epinephrine is added when cardiac output augmentation is needed; it increases heart rate and contractility but may worsen tachyarrhythmias and increase lactate.

Refractory Shock

Angiotensin II (Giapreza) at 20 to 40 ng/kg/min is used for vasodilatory shock refractory to catecholamines and was shown to reduce norepinephrine requirements in the ATHOS-3 trial. Stress-dose corticosteroids with hydrocortisone 200 mg/day IV (either 50 mg every 6 hours or as a continuous infusion) are given to patients on escalating vasopressors and reduce time to shock reversal, as demonstrated in the ADRENAL and APROCCHSS trials.

Inotropic Support

Dobutamine at 2 to 20 mcg/kg/min is used for sepsis-induced myocardial dysfunction with low cardiac output despite adequate volume and MAP. Tachycardia and hypotension from beta-2 vasodilation should be monitored.

Anesthetic Management for Emergent Source Control

Source control surgery (such as treatment of perforated viscus, abscess drainage, or necrotizing fasciitis debridement) should not be delayed. For induction, ketamine at 1 to 2 mg/kg or etomidate at 0.2 to 0.3 mg/kg provides hemodynamic stability; propofol should be markedly reduced or omitted. A vasopressor infusion should be running before induction. Push-dose epinephrine (10 to 20 mcg IV) or phenylephrine (100 to 200 mcg IV) should be immediately available.

Induction of anesthesia in septic shock removes sympathetic tone and can cause cardiovascular collapse. Volatile agent concentration should be reduced, and an opioid-based technique with low-dose volatile agent or TIVA may be considered. Aggressive fluid resuscitation and vasopressor support are maintained intraoperatively. An arterial line and central venous access are essential. Lactate clearance is monitored as a marker of resuscitation adequacy.

Organ Support in the ICU

Respiratory

Many septic patients develop ARDS, and lung-protective ventilation should be applied with tidal volumes of 6 to 8 mL/kg IBW, plateau pressure below 30 cmH2O, and PEEP per ARDSNet tables. Prone positioning for 16 or more hours per day is indicated if the PaO2/FiO2 ratio is below 150, as shown in the PROSEVA trial. Conservative oxygen targets of SpO2 92 to 96% are appropriate.

Renal

Acute kidney injury occurs in 40 to 50% of septic shock patients. Nephrotoxins should be avoided and renal perfusion pressure maintained. Continuous renal replacement therapy is used for refractory hyperkalemia, acidosis, fluid overload, or uremia. There is no benefit to early initiation of RRT in the absence of absolute indications, as shown in the STARRT-AKI trial.

Hematologic

Packed red blood cells are transfused for a hemoglobin below 7 g/dL in most patients, based on the TRICC and TRISS trials. Platelet transfusion is given for counts below 10,000 or below 20,000 with bleeding risk. DVT prophylaxis with LMWH is provided unless contraindicated.

Glucose and Nutrition

The glucose target is 140 to 180 mg/dL, avoiding tight glucose control due to hypoglycemia risk. Early enteral nutrition should be initiated within 24 to 48 hours.

Sedation

The target is light sedation with a Richmond Agitation-Sedation Scale of 0 to -2. Daily sedation interruption or protocol-based titration is employed. Benzodiazepines should be avoided when possible because they are associated with delirium; propofol or dexmedetomidine is preferred.

Monitoring Endpoints of Resuscitation

Lactate clearance is a key endpoint, with a target of at least 10 to 20% decrease per 2-hour interval; normalization of lactate is associated with improved survival. MAP should be maintained at 65 mmHg or greater, urine output at 0.5 mL/kg/hr or greater, and central venous oxygen saturation (ScvO2) at 70% or greater if monitored. Point-of-care echocardiography is used to assess cardiac function and filling and to guide fluid and vasopressor therapy.

Clinical Pearls

Induction of general anesthesia in the septic patient can be the most dangerous moment; vasopressors should be running, hemodynamically stable agents used, and the team prepared for cardiovascular collapse. Norepinephrine is the first-line vasopressor in septic shock, and dopamine is no longer recommended due to higher arrhythmia rates. Antibiotics within 1 hour of sepsis recognition reduce mortality, and each hour of delay is associated with a measurable increase in death. Fluid responsiveness must be assessed dynamically after the initial 30 mL/kg bolus because continued indiscriminate fluid loading worsens outcomes. Lactate is the single best biomarker for assessing the adequacy of resuscitation and predicting outcomes in sepsis.

References

1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810.
2. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.
3. Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults (SMART Trial). N Engl J Med. 2018;378(9):829-839.
4. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock (APROCCHSS). N Engl J Med. 2018;378(9):809-818.

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