Postoperative Sepsis

Postoperative sepsis is life threatening organ dysfunction caused by a dysregulated host response to infection arising within 30 days of surgery. Dysfunction is identified by an acute rise of 2 or more in the Sequential Organ Failure Assessment score. Septic shock is sepsis needing vasopressors to hold mean arterial pressure at 65 mmHg or more, with lactate over 2 mmol/L despite adequate fluid.

Epidemiology. Sepsis affects about 1% to 2% of elective noncardiac surgery and over 10% of emergency laparotomy. Mortality is about 10% to 20% for sepsis and 30% to 50% for septic shock. Figures are approximate.

Sources and organisms. Intra-abdominal infection and anastomotic leak (enteric Gram negative bacilli, anaerobes, enterococci), surgical site infection (Staphylococcus aureus, streptococci), pneumonia, urinary and line infection, and Clostridioides difficile colitis. Candida is relevant after repeated laparotomy or perforation.

Risk factors. Emergency or contaminated surgery, long operations, age over 65, diabetes, malnutrition, immunosuppression, obesity, transfusion, prosthetic material and delayed source control.

Pathophysiology.

Pathogen products activate innate immunity, releasing cytokines that cause vasodilation, capillary leak, endothelial injury and microvascular thrombosis. Distributive shock, myocardial depression and tissue hypoxia follow.

Surgical injury primes the same response and impairs host defence for several days.

Fever or hypothermia, tachycardia, tachypnoea, hypotension, confusion, oliguria, mottled or flushed skin, raised respiratory rate, ileus, and signs at the source (wound, abdomen, chest, urine, line site). Older adults may present with delirium or falls alone.

Red flags.

• Lactate over 4 mmol/L or mean arterial pressure under 65 mmHg after fluid.
• Mottling, purpura or reduced consciousness.
• Pain out of proportion, blistering or crepitus (necrotising infection).
• Peritonism or rising drain output with enteric contents.
• Oxygen need over 40% or urine output under 0.5 mL/kg/h for 2 hours.

Combine clinical assessment with the Sequential Organ Failure Assessment score. A bedside screen (respiratory rate 22/min or more, altered mentation, systolic pressure 100 mmHg or under) flags patients for assessment.

Investigations. Lactate, two sets of blood cultures before antibiotics, full blood count, C-reactive protein, procalcitonin as an adjunct, urea, creatinine, bilirubin, coagulation screen, blood gas, glucose. Culture urine, sputum, wound and drain fluid. Chest radiograph. Contrast CT of abdomen and pelvis for suspected leak or collection. Echocardiography if endocarditis or myocardial depression is suspected.

Differential diagnosis.

• Non-infectious inflammatory response.
• Haemorrhage.
• Pulmonary embolism.
• Myocardial infarction.
• Anaphylaxis.
• Adrenal insufficiency.
• Pancreatitis.
• Drug or transfusion reaction.

First hour. Give oxygen, obtain access, send lactate and cultures, start antibiotics, begin fluid, and call critical care. Repeat lactate within 2 to 4 hours if over 2 mmol/L. Aim for lactate clearance and urine output of at least 0.5 mL/kg/h.

Fluid. Balanced crystalloid 30 mL/kg within the first 3 hours for hypotension or lactate of 4 mmol/L or more, in boluses of 250 to 500 mL with reassessment after each. Use smaller volumes in heart failure, renal failure or when the operation has already involved large volumes.

Source control. Drain, debride, repair, remove infected devices or re-operate as early as possible, within 6 to 12 hours when feasible.

Antibiotics. Start within 1 hour for shock or probable sepsis. Narrow at 48 to 72 hours from cultures. Usual duration is 7 days, and 4 to 7 days after adequate source control for intra-abdominal infection.

• Piperacillin-tazobactam: 4.5 g IV every 6 hours (extended infusion over 4 hours is acceptable); duration 7 days (4 to 7 days after adequate source control for intra-abdominal infection); maximum 18 g daily; monitor creatinine, full blood count and sodium; for creatinine clearance 20 to 40 mL/min give 3.375 g every 6 hours, under 20 mL/min give 2.25 g every 6 hours.
• Meropenem (resistant Gram negatives or prior broad spectrum use): 1 g IV every 8 hours; duration 7 days (4 to 7 days after adequate source control for intra-abdominal infection); maximum 3 g daily; monitor creatinine and seizures; for creatinine clearance 26 to 50 mL/min give 1 g every 12 hours, 10 to 25 mL/min give 500 mg every 12 hours, under 10 mL/min give 500 mg every 24 hours.
• Vancomycin (suspected meticillin resistant Staphylococcus aureus or line source): 25 to 30 mg/kg IV loading dose, then 15 to 20 mg/kg every 8 to 12 hours; stop when not needed; monitor area under the curve (400 to 600) and creatinine; extend the interval in renal impairment.
• Severe immediate penicillin allergy: aztreonam 2 g IV every 8 hours plus vancomycin; duration 7 days; maximum 8 g daily; monitor creatinine; for creatinine clearance 10 to 30 mL/min halve the dose, under 10 mL/min give a quarter.

Vasopressors and steroid.

• Noradrenaline: 0.05 to 0.5 microgram/kg/min IV infusion titrated to mean arterial pressure 65 mmHg or more; continue until pressure is stable off support; reassess the diagnosis above 0.5 microgram/kg/min; arterial line and central access preferred; lower starting rate in older adults and after beta blockade; reduce for tachyarrhythmia.
• Vasopressin: 0.03 units/min IV infusion added when noradrenaline reaches 0.25 microgram/kg/min or more; stop before noradrenaline; maximum 0.04 units/min; monitor for digital, mesenteric and myocardial ischaemia and sodium; avoid in severe peripheral vascular disease.
• Hydrocortisone: 50 mg IV every 6 hours (200 mg daily) when noradrenaline of 0.25 microgram/kg/min or more is needed for 4 hours or longer; stop when vasopressors are no longer needed; maximum 200 mg daily; monitor glucose, sodium and potassium; caution in uncontrolled fungal infection.

Supportive. Lung protective ventilation, glucose 7.8 to 10 mmol/L (140 to 180 mg/dL), venous thromboembolism prophylaxis, stress ulcer prophylaxis if ventilated or coagulopathic, early enteral nutrition, and renal replacement therapy for usual indications such as refractory hyperkalaemia, acidosis or overload.

Monitoring. Continuous ECG, arterial pressure, lactate, urine output, white cell count, C-reactive protein and drug levels. Reassess source daily.

Referral and escalation. Critical care for lactate over 2 mmol/L after fluid, vasopressors or organ failure. Surgical and interventional radiology review for source control. Infectious diseases advice for resistant organisms, fungal infection or prosthetic material.

Special groups. In pregnancy use beta lactams and avoid tetracyclines and fluoroquinolones. In neutropenia start meropenem early and add antifungal cover when fever persists.