Can Biomarkers Predict Reintubation?

A groundbreaking study published in the April 2025 issue of Anesthesia & Analgesia reveals compelling evidence that acute systemic inflammation after elective cardiac surgery significantly increases the risk of postoperative pulmonary complications (PPCs). Conducted at Columbia University Irving Medical Center, this large-scale observational study offers new perspectives on how cytokine activity and lung epithelial injury biomarkers can predict respiratory outcomes after surgery.

Background

Postoperative pulmonary complications are a leading cause of morbidity following cardiac surgery. These include:

• Pneumonia
• Pleural effusions requiring drainage
• Reintubation or prolonged mechanical ventilation
• Use of noninvasive respiratory support (BiPAP, HFNC)

Despite their frequency, effective predictors and interventions remain elusive.

Key research question:

Can increases in inflammation-related biomarkers post-surgery predict the likelihood of PPCs, when accounting for preoperative conditions and surgical factors?

Methods in brief

Biomarkers measured:

• IL-6 (Interleukin-6)
• IL-8 (Interleukin-8)
• TNF-α (Tumor Necrosis Factor-alpha)
• sRAGE (Soluble Receptor for Advanced Glycation End-products)
  

Timing of measurements:

1. Baseline – After anesthesia induction, before surgery
2. POD 1 – Postoperative Day 1 (18–24 hours after surgery start)

Complication assessment:

• Used a graded PPC scale from 0 to 5
• Focused on moderate (Grade 3) and severe (Grade 4) complications

Major findings

1. Inflammatory cytokines and PPC risk

The study found that elevated levels of inflammatory cytokines on postoperative day 1 (POD 1), particularly IL-6 and IL-8, were significantly associated with an increased risk of moderate-to-severe PPCs. For every 50 pg/mL increase in IL-8, the odds of developing a PPC rose more than sevenfold. Similarly, a 50 pg/mL increase in IL-6 was linked to a 42% higher risk. In contrast, TNF-α and sRAGE levels were not significantly associated with PPC risk. These findings suggest that IL-6 and IL-8 are strong independent predictors of PPCs, even after controlling for patients’ baseline inflammatory status and perioperative variables.

2. sRAGE and ventilation duration

• Every 50 pg/mL increase in sRAGE was linked to a 25% increase in mechanical ventilation time.
• IL-6, IL-8, and TNF-α did not significantly correlate with ventilation time.

Clinical relevance

This study underscores that:

• Post-CPB inflammation, especially increases in IL-6 and IL-8, may directly contribute to PPCs.
• Alveolar epithelial damage, as indicated by sRAGE, prolongs the need for ventilation.
  

These biomarkers could guide early risk stratification and personalized interventions post-cardiac surgery.

Implications for future practice

• These findings open the door to targeted anti-inflammatory therapies post-surgery.
• IL-6 and IL-8 could become routine postoperative biomarkers in high-risk cardiac surgery patients.
• sRAGE may help forecast patients who will need prolonged ventilatory support.

Reference: Mittel A et al., Association of Acute Systemic Inflammation with Patient-Centric Postoperative Pulmonary Complications After Elective Cardiac Surgery, Anesthesia & Analgesia, 2025;140:947-956. 

For more information on inflammation and postoperative complications,  check out Anesthesia Updates on the NYSORA Anesthesia Assistant App. 

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