• Sepsis describes a documented infection (culture or Gram stain of a normally sterile body fluid for pathogenic organism or focus of infection identified by visual inspection) and two or more manifestations of the systemic inflammatory response syndrome:
  • Temperature >38°C or <36°C
  • Heart rate >90 beats/min
  • Respiratory rate >20 breaths/min or paCO₂ <32 mm Hg
  • WBC >12,000/µL, <4,000/µL, or >10 immature (band) forms.
• Septic shock is a severe form of sepsis and involves hypotension despite adequate resuscitation, end-organ hypoperfusion (e.g., lactate >2 mmol/L), and organ dysfunction (e.g., urine output <0.5 mL/kg). It has features of high output cardiac failure and distributive shock.

• Gram-positive bacteria (30–50%): Staphylococcus pyrogenase, S. pneumonia, S. aureus
• Gram-negative bacteria (25%): Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenza
• Fungal: Candida albicans
• Anaerobes: Clostridium perfringens
• Older individuals (>65 years) have increased comorbidities, impaired immunological response to infections, and increased exposure to potentially resistant organisms in nursing homes, all contributing to increased mortality. They account for ~60% of severe sepsis cases.
• Immunocompromised patients (neoplasms, AIDS, hepatic or renal failure).
• Compared to community-acquired infection, nosocomial infections have a higher mortality rate (10% versus 15%).
• Community acquired pneumonia (CAP) patients will develop severe sepsis in 48% and septic shock in 5% of cases.
• Source of sepsis also determines outcomes, with urosepsis having a 30% mortality rate compared to 55% if the source was pulmonary, GI or unknown.

• The aim of normal inflammation is to locally contain the spread of infection. However, in certain cases, the inflammatory process spreads across the locally infected area, invades the bloodstream, and causes a generalized response, known as sepsis.
• Sepsis is a complex, malignant intravascular inflammation. The lipopolysaccharide of Gram-negative bacteria and the peptidoglycan of Gram-positive bacteria bind to cell receptors (CD 14, TLR-2,4) and induce production of pro-inflammatory cytokines (tumor necrosis factor [TNF ], interleukin-1 [IL-1]), chemokines (ICAM-1, VCAM-1), and nitric oxide. The endothelium cells express adherence molecules that attract leukocytes and macrophages that in turn release more cytokines (TNF and ILs). TNF further stimulates production of other secondary inflammatory mediators, besides being self-stimulating (autocrine). Activation of the complement system, release of IL-1, 2, 6, 8, 10, platelet-activating factor, interferons, and eicosanoids result in recruiting more leukocytes and macrophages. These inflammatory mediators cause local vasodilation, hyperemia, and increased permeability resulting in protein rich edema. They also contribute to cellular injury. Other proposed mechanisms of cellular injury are apoptosis (programmed cell death) and ischemic damage.
• Pattern recognition receptors (PRRs) recognize specific structures of microorganisms. In sepsis response, PRR such as toll-like receptors (TLR) are capable of sensing a wide range of organisms (bacteria, fungi, viruses and protozoa). Their activation leads to cellular activation and inflammatory response initiation.
• Some cytokines (IL-6, IL-10) have an anti-inflammatory effect by inhibiting production of TNF and IL-1. In a normal effective response to an infectious insult, the pro- and anti-inflammatory responses balance each other out and the initial infectious insult is overcome. In certain cases, the initial infectious assault may be so severe and sufficient to produce sepsis. In another scenario, after the initial insult, the balance between pro- and anti-inflammatory forces may not be established leading to a massive systemic inflammatory response, or a period of immune suppression.

• Initiate therapy early. Intubation and mechanical ventilation, invasive monitoring, laboratory work, antibiotics, and treatment of hypoperfusion.
• Intensive care unit (ICU) bundles may be carried out by the anesthesiologist in the ICU or continued into the perioperative period. They include
  • Identifying a specific anatomic site of infection within the first 6 hours. If intravascular devices are believed to be the source, they should be removed.
  • Broad-spectrum antibiotics should begin within 3 hours of ED admission and within 1 h of non-ED admission. However, blood cultures should be obtained prior to antibiotic administration.
  • Measure serum lactate
  • Hypotension and/or elevated lactate should be treated with IV fluids. If unresponsive, vasopressors should be implemented to maintain a MAP >65 mm Hg. Achieve a CVP of >8 mm Hg, central venous oxygen saturation (ScvO₂) >70%, or mixed venous oxygen saturation (SvO₂) >65%. This may require pRBC transfusion or inotropy.
  • Steroids (hydrocortisone 200–300 mg/day for 7 days) may be used in vasopressor-dependent shock.
  • Consider recombinant human activated protein C (rhAPC). Activated protein C normally regulates blood clotting, inflammation, cell death, and endothelial integrity. In sepsis the levels are reduced, and randomized controlled trials suggest that it can decrease mortality, especially in the first 24 hours in patients with APACHE score >25.

• Fever, rigors, chills
• Abdominal pain (if the source of sepsis is abdominal)
• Mental status changes and confusion (especially if patient febrile or hypoxic)

Intubation and mechanical ventilation. There is an increased work of breathing secondary to increased minute ventilation and airway resistance, and decreased lung compliance. Additionally, patients may have developed ALI/ARDS.

• Vasopressors: Norepinephrine, dopamine, phenylephrine, vasopressin. No definitive evidence of superiority has been demonstrated.
• Antibiotics: Broad-spectrums include vancomycin in combination with a 3^rd-generation cephalosporin or carbapenem. If pseudomonas is suspected, vancomycin with two antipseudomonal agents (e.g., ceftazidime, meropenem, ciprofloxacin, and meropenem) are used.

Underlying sources; see above

• Procedures should be limited to those absolutely necessary (source control) and that can potentially improve survival.
• Prior to the OR, proper resuscitation with IV fluids, vasopressors, and early goal directed therapy should be done (MAP >65 mm Hg, CVP 8–12 mm Hg, adequate urine output, correction of acid base abnormality and lactic acidosis, and achieving a mixed venous oxygen (MVO₂%) or ScvO₂% >70%).
• Patients in renal failure may need preoperative dialysis catheter placement followed by dialyses; intraoperative continuous veno-venous hemodialysis (CVVH) may be necessary.

ICU care for monitoring of vital signs, narrowing of antimicrobial therapy as guided by the culture results, supportive care such as continuation of mechanical ventilation, vasopressors, dialysis, and early initiation of enteral nutrition.

Infectious disease, nephrology as needed

• Acute Respiratory Distress Syndrome (Ards)

785.52 Septic shock

R65.21 Severe sepsis with septic shock

Anahat Dhillon , MD

Sumit Singh , MD