Septic Shock: Comprehensive Overview
Definition
Septic shock is a subset of sepsis characterized by profound circulatory, cellular, and metabolic abnormalities requiring vasopressor therapy to maintain mean arterial pressure ≥65 mmHg AND serum lactate >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation, with hospital mortality rates exceeding 40%. 1, 2, 3
- Septic shock represents the most severe manifestation on the sepsis spectrum, distinguished from sepsis alone by the presence of persistent hypotension requiring vasopressors and elevated lactate despite volume resuscitation 1, 4
- The operational criteria specifically require BOTH vasopressor dependence AND metabolic dysfunction (lactate elevation) to differentiate from other forms of shock 2, 3
Anatomy and Pathophysiology
Circulatory Dysfunction
- Profound vasodilation and increased vascular permeability lead to distributive shock with inadequate tissue perfusion despite normal or elevated cardiac output 1, 2
- Microcirculatory dysfunction causes tissue hypoperfusion at the cellular level, even when macrocirculatory parameters appear adequate 1, 2
- Peripheral vasoconstriction affects multiple vascular beds including renal, splanchnic, mucosal, and skin circulation 5
Cellular and Metabolic Abnormalities
- Altered cellular metabolism results from mitochondrial dysfunction and impaired oxygen utilization, leading to lactate accumulation independent of tissue hypoxia 1, 2
- Dysregulated host response to infection triggers excessive inflammatory signaling through pathogen-associated molecular patterns (PAMPs) recognition 4
- Metabolic derangements include hyperglycemia from increased glycogenolysis, reduced glucose uptake, and inhibited insulin release 5
Organ Dysfunction Cascade
- Life-threatening organ dysfunction is defined by an increase in Sequential Organ Failure Assessment (SOFA) score ≥2 points, associated with >10% in-hospital mortality 4, 3
- Multi-organ failure results from the combination of hypoperfusion, cellular metabolic dysfunction, and dysregulated inflammation 4, 6
Etiology
Microbiological Causes
- Bacteria cause >90% of septic shock cases, with Gram-negative and Gram-positive organisms occurring with approximately equal frequency 4
- Fungi, particularly Candida species, account for a significant minority of cases 4
- The causative pathogen significantly influences the inflammatory response pattern and clinical course 4
Host Factors
- Age and comorbidities significantly affect sepsis progression and outcomes 4
- Immunocompromised patients (HIV-positive, transplant recipients) have increased susceptibility due to pre-existing immune system dysfunction and exhaustion 4
- Genetic characteristics and co-existing illnesses modulate the host inflammatory response 4
Signs and Symptoms
Early Recognition Criteria (qSOFA)
For rapid identification outside the ICU, presence of ≥2 of the following suggests higher risk:
- Respiratory rate ≥22 breaths/min 4, 3
- Altered mental status (Glasgow Coma Scale ≤13) 4, 3
- Systolic blood pressure ≤100 mmHg 4, 3
Clinical Presentation
- Fever and hyperventilation represent the earliest recognizable clinical presentation 7
- Persistent hypotension despite adequate fluid resuscitation requiring vasopressor support 1, 2
- Signs of tissue hypoperfusion: altered mentation, decreased urine output, mottled skin 8
Special Population Considerations
- Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection 1, 4
- Immunocompromised patients may lack typical fever response 4
Diagnosis and Evaluation
Diagnostic Criteria
Septic shock diagnosis requires ALL of the following:
- Documented or suspected infection 3
- Vasopressor requirement to maintain MAP ≥65 mmHg 1, 2, 3
- Serum lactate >2 mmol/L (>18 mg/dL) 1, 2, 3
- Absence of hypovolemia (adequate fluid resuscitation completed) 1, 2, 3
Essential Laboratory Evaluation
- Blood cultures before antibiotic administration are the cornerstone of microbiological diagnosis 4
- Serial lactate measurements to assess metabolic dysfunction and response to therapy 1, 2
- SOFA score calculation to quantify organ dysfunction 4, 3
- Complete blood count, comprehensive metabolic panel, coagulation studies 8
Monitoring Parameters
- Mean arterial pressure (target ≥65 mmHg) 1, 2
- Lactate clearance as marker of resuscitation adequacy 1
- Urine output, mental status, and other perfusion indicators 8
Diagnostic Pitfalls to Avoid
- Not measuring lactate levels, which are essential for diagnosis according to current definitions 2
- Failing to recognize perfusion abnormalities despite normal blood pressure in patients receiving vasopressors 1, 2
- Confusing septic shock with other forms of distributive shock (anaphylaxis, neurogenic) 2
- Interpreting negative cultures as ruling out infection when prior antibiotics were administered 4
Interventions and Treatments
Immediate Resuscitation Priorities
Hour-One Bundle (based on Surviving Sepsis Campaign):
Fluid Resuscitation
- Initiate with 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L 9
- Use balanced crystalloids rather than normal saline when possible 6
- Avoid excessive fluid administration which may worsen outcomes and cause pulmonary edema 1, 5
- Transition to restrictive fluid strategy after initial resuscitation 6
Vasopressor Therapy
- Norepinephrine is the first-line vasopressor for septic shock 9, 1
- Target MAP 65-70 mmHg (not higher unless specific indications) 1
- Initiate vasopressors early rather than delaying with excessive fluid administration 1, 2
- Peripheral vasopressor administration is safe and increasingly utilized 6
- Epinephrine acts on alpha and beta-adrenergic receptors, increasing myocardial contractility, heart rate, and peripheral vasoconstriction, with onset <5 minutes and duration ~20 minutes 5
Antimicrobial Therapy
Source Control
Advanced Management
Hemodynamic Optimization:
- Avoid routine central venous pressure and mixed venous oxygen saturation monitoring 6
- Minimize use of inotropes unless specific cardiac dysfunction identified 6
- Adopt restrictive red blood cell transfusion strategy 6
Metabolic Support:
- Monitor for and correct hyperglycemia (target <180 mg/dL) 9
- Address electrolyte abnormalities, particularly hypokalemia potentiated by epinephrine 5
Organ Support:
- Lung-protective ventilation strategies for acute respiratory distress syndrome 9
- Renal replacement therapy for acute kidney injury when indicated 9
Monitoring and Reassessment
- Frequent reassessment (every 15-30 minutes initially) to optimize therapy and detect complications early 10
- Serial lactate measurements to guide resuscitation 1, 8
- Continuous hemodynamic monitoring during vasopressor therapy 1
Potential Complications
Cardiovascular Complications
- Cardiac arrhythmias and myocardial ischemia from vasopressor therapy and underlying metabolic derangements 5
- Hypertension from excessive vasopressor dosing 5
- Pulmonary edema from fluid overload or cardiac dysfunction 5
Organ Failure
- Acute kidney injury requiring renal replacement therapy 9
- Acute respiratory distress syndrome requiring mechanical ventilation 9
- Hepatic dysfunction and coagulopathy 8
- Encephalopathy and critical illness neuropathy 8
Treatment-Related Complications
- Extravasation and tissue necrosis with peripheral or central vasopressor infusion 5
- Renal impairment from vasopressor-induced vasoconstriction 5
- Allergic reactions associated with sulfite preservatives in epinephrine formulations 5
- Complications from excessive fluid resuscitation including abdominal compartment syndrome 1, 6
Drug Interactions
- Beta-blockers and alpha-blockers antagonize pressor effects of vasopressors 5
- Tricyclic antidepressants and MAO inhibitors potentiate pressor effects 5
- Cardiac glycosides, general anesthetics, and antiarrhythmics potentiate arrhythmogenic effects 5
Relevant Red Flags and CVICU Tips
Critical Recognition Pitfalls
- Failing to recognize that normal blood pressure on vasopressors does NOT equal adequate perfusion - continue monitoring lactate and end-organ function 1, 2
- Delaying vasopressor initiation while pursuing excessive fluid resuscitation - start vasopressors early if hypotension persists after initial 30 mL/kg bolus 1, 2
- Missing septic shock in elderly patients who may lack typical fever and tachycardia responses 1, 4
High-Risk Clinical Scenarios
- Lactate >4 mmol/L indicates severe metabolic dysfunction requiring aggressive intervention 3
- Rapidly rising vasopressor requirements suggest inadequate source control or progression to refractory shock 8
- Persistent altered mental status despite MAP >65 mmHg may indicate cerebral hypoperfusion requiring higher MAP targets 8
CVICU-Specific Considerations
- Avoid routine pulmonary artery catheter placement - not shown to improve outcomes and carries risks 6
- Peripheral vasopressor infusion is safe for initial management while obtaining central access 6
- Balanced crystalloids preferred over normal saline to reduce hyperchloremic acidosis 6
- Restrictive transfusion strategy (hemoglobin >7 g/dL) unless active bleeding or severe coronary disease 6
Prognostic Indicators
- Hospital mortality >40% when both vasopressor requirement and lactate >2 mmol/L present 3
- SOFA score increase ≥2 points associated with >10% mortality 4, 3
- Failure of lactate clearance within 6 hours predicts worse outcomes 8