What is liquefactive necrosis?

From the Guidelines

Liquefactive necrosis is a type of tissue death that requires prompt treatment, typically involving drainage of abscesses and administration of appropriate antimicrobial therapy, to prevent further tissue damage and improve patient outcomes. This type of necrosis occurs primarily in tissues with high water content and abundant neutrophils, such as the brain and in bacterial infections. The process begins when neutrophils release powerful hydrolytic enzymes that break down cellular components, including cell membranes and organelles. Common causes include bacterial infections (particularly those causing abscesses), fungal infections, and ischemic brain injuries like strokes. In the brain, liquefactive necrosis leads to the formation of fluid-filled cavities that eventually become cystic spaces. The clinical significance varies by location - in the brain, it can cause permanent neurological deficits, while in soft tissues, it often manifests as abscesses requiring drainage. Unlike coagulative necrosis (which preserves cellular outlines) or caseous necrosis (which creates cheese-like material), liquefactive necrosis completely dissolves the tissue architecture.

Key Considerations

• Early surgical debridement with complete removal of necrotic tissue is essential to decrease mortality and other complications in patients with necrotizing infections, as highlighted in a study by Sartelli et al. 1.
• The use of antimicrobial therapy is an adjuvant treatment and must be combined with early surgical debridement, with broad-spectrum coverage initially commenced and adjusted based on culture-specific results and sensitivities 1.
• Treatment depends on the underlying cause but typically involves addressing the primary condition, draining abscesses when present, and administering appropriate antimicrobial therapy for infectious causes.

Treatment Approach

• Prompt surgical intervention is crucial in cases of necrotizing fasciitis, with repeated operative procedures until no further need for debridement is found, as recommended by the Infectious Diseases Society of America 1.
• Antimicrobial therapy must be directed at the pathogens and used in appropriate doses until repeated operative procedures are no longer needed, the patient has demonstrated obvious clinical improvement, and fever has been absent for 48–72 h.
• The best choice of antibiotics for community-acquired mixed infections is a combination of ampicillin-sulbactam plus clindamycin plus ciprofloxacin, as suggested by the 2005 practice guidelines for the diagnosis and management of skin and soft-tissue infections 1.

From the Research

Definition and Process of Liquefactive Necrosis

• Liquefactive necrosis is a stage of infarct resolution that occurs after stroke, lasting for months, although the exact length of time is currently unknown 2.
• This process involves the damaged tissue undergoing necrosis, leading to the formation of a liquid mass 2.

Pathophysiology and Consequences

• The formation of a glial scar is a critical component of the healing response to stroke, as it compartmentalizes the area of liquefactive necrosis from the rest of the brain 2.
• However, the glial scar is permeable, allowing molecules present in the area of liquefactive necrosis to leak across and cause delayed atrophy, cytotoxic edema, and neuron loss in adjacent regions 2.
• Liquefactive necrosis is also associated with a second burst of inflammation, which shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs) 3.

Molecular Profile and Mediators

• The inflammatory response to ischemia in the brain is resolved between eight and 24 weeks, compared to one to four weeks in the heart 3.
• Osteopontin (OPN) plays a crucial role in the perpetuation of an inflammatory response in areas of liquefactive necrosis, leading to secondary neurodegeneration 3.
• The expression of pro-inflammatory proteins and MMPs is reduced in OPN-/- mice, resulting in faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area 3.

Clinical Implications and Treatment

• Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy, with a lower risk associated with tenecteplase compared to alteplase 4.
• Tenecteplase has emerged as a potential alternative thrombolytic agent, with an improved safety profile and increased efficacy, particularly in patients with large vessel occlusion 5.
• Ongoing research efforts are focused on developing new thrombolytic agents, adjunct therapies, and treatment strategies to reduce the risk of vessel reocclusion and improve tissue reperfusion 5.