From the Guidelines
Gangrene in septic shock develops through a complex process involving microcirculation failure, tissue hypoxia, and direct tissue damage, ultimately resulting in tissue necrosis and potentially requiring surgical debridement or amputation. During septic shock, widespread vasodilation and increased vascular permeability lead to decreased effective blood volume and hypotension, as noted in the Surviving Sepsis Campaign guidelines 1. Simultaneously, inflammatory mediators trigger microvascular thrombosis and endothelial dysfunction, severely compromising blood flow to peripheral tissues. The combination of hypoperfusion and microvascular occlusion results in tissue ischemia, particularly in distal extremities and areas with limited collateral circulation.
As tissues become oxygen-deprived, cellular metabolism shifts to anaerobic pathways, causing lactic acid accumulation and local acidosis that further damages tissues. In many cases, the infectious organisms themselves contribute directly to tissue destruction through toxin production and enzymatic activity. Neutrophil activation leads to release of reactive oxygen species and proteolytic enzymes, causing additional tissue damage. Without adequate blood supply, tissues cannot receive antibiotics or immune cells needed to fight infection, allowing bacterial proliferation. This creates a vicious cycle where tissue necrosis progresses, ultimately resulting in gangrene, characterized by black, mummified tissue.
The management of gangrene in septic shock involves early and aggressive infection source control, including surgical debridement, as recommended by the Surviving Sepsis Campaign guidelines 1 and the 2018 WSES/SIS-E consensus conference 1. Prompt and appropriate antibiotic therapy, as well as hemodynamic support, are also crucial in the treatment of Fournier’s gangrene, a severe type of necrotizing soft-tissue infection. Early and extensive initial surgical debridement can improve survival, and consideration for fecal diversion, such as colostomy or fecal tube system with negative pressure therapy, may be necessary in cases with fecal contamination.
Key factors to consider in the management of sepsis and septic shock include the anatomic site of infection, prevalent pathogens, resistance patterns, and the presence of specific immune defects, as outlined in the Surviving Sepsis Campaign guidelines 1. The choice of empiric antimicrobial therapy depends on complex issues related to the patient’s history, clinical status, and local epidemiologic factors. The initial empiric regimen should be broad enough to cover most pathogens isolated in healthcare-associated infections, and multidrug therapy may be required to ensure a sufficiently broad spectrum of empiric coverage.
In summary, the pathophysiology of gangrene in septic shock involves a complex interplay of microcirculation failure, tissue hypoxia, and direct tissue damage, and its management requires early and aggressive infection source control, prompt and appropriate antibiotic therapy, and hemodynamic support.
From the Research
Pathophysiology of Gangrene in Septic Shock
The pathophysiology of gangrene in septic shock is complex and involves multiple factors.
- Sepsis is a dysregulated host response to infection, leading to organ dysfunction 2, 3, 4.
- The inflammatory response to pathogenic microorganisms implies a dynamic, complex chain of events leading to endothelial and immune system activation 5.
- Endothelial cells undergo multiple phenotypic and functional modifications during sepsis, leading to microvascular dysfunction and multiorgan failure 6.
- Oxidative stress alters multiple endothelial cell functions, promoting a proinflammatory, procoagulant, and proadhesive phenotype, which can lead to gangrene 6.
- The host response activates or suppresses multiple downstream pathways, leading to multiple organ dysfunction, including gangrene 3.
Key Factors Contributing to Gangrene
- Dysregulated immune response to infection 5, 2, 3, 4
- Endothelial dysfunction and microvascular dysfunction 6
- Oxidative stress and altered antioxidant systems 6
- Activation or suppression of multiple downstream pathways leading to organ dysfunction 3
Understanding the Pathophysiology
- Sepsis represents a dysregulated host response to infection, leading to organ dysfunction, including gangrene 2, 3, 4.
- The pathogen triggers an initial exaggerated inflammatory-immune response that leads to activation or suppression of multiple endothelial, hormonal, bioenergetic, metabolic, immune, and other pathways 3.
- These processes, whereas superficially viewed as dysfunctional, may actually be adaptive/protective in the first instance, though spilling over into maladaptation/harm depending on the magnitude of the host response 3.