What is the significance of the oxygenation index (OI) in assessing respiratory failure and what are the management strategies for patients with a high oxygenation index?

Oxygenation Index in Respiratory Failure

Definition and Calculation

The oxygenation index (OI) is calculated as (mean airway pressure × FiO₂ × 100) / PaO₂ and serves as a critical gauge for judging the severity of respiratory failure, particularly in determining the need for escalation of care including ECMO. 1

Clinical Significance by Population

Neonatal Respiratory Failure

• An OI >40 is an indication to consider referral to an ECMO center for neonates with persistent pulmonary hypertension of the newborn (PPHN) or severe respiratory failure. 1

• Inhaled nitric oxide (iNO) is indicated to reduce the need for ECMO support in term and near-term infants with PPHN or hypoxemic respiratory failure who have an OI exceeding 25. 1, 2

• In clinical trials, infants with mean OI of 43-44 cm H₂O/mm Hg who received iNO had significantly reduced ECMO requirements (39% vs 55%, p=0.014 in NINOS study; 31% vs 57%, p<0.001 in CINRGI study). 2

• Delaying iNO initiation until OI reaches >40 may increase the length of time on oxygen, suggesting earlier intervention at OI >25 is preferable. 1

• ECMO support is indicated for term and near-term neonates with severe pulmonary hypertension or hypoxemia that is refractory to iNO and optimization of respiratory and cardiac function. 1

Adult Respiratory Failure

• In adults with ARDS, failure to improve OI by at least 1.71 over the first 7 days predicts mortality, and failure to decrease OI by at least 2.34 predicts ventilator-free days <14. 3

• Day 3 OI is an independent predictor of hospital mortality in adults with severe acute respiratory failure (multivariate analysis, p=0.004). 4

• Higher day 3 OI is associated with shorter survival time in severe acute respiratory failure. 4

• Age-adjusted OI (AOI) correlates positively with 28-day mortality in adult ARDS with area under ROC curve of 0.70-0.78, demonstrating equivalent or better performance than other mortality prediction systems. 5

Post-Lung Transplantation

• OI elevation ≥30 following lung transplantation is an early predictor of severe respiratory failure requiring acute intervention (ECMO or reoperation). 6

• Early intervention (≤2 hours) after OI elevation above 30 significantly improves survival compared to no or late intervention (80% vs 15% survival, p=0.02). 6

• Patients undergoing transplantation for fibrotic lung diseases are more likely to develop severe reperfusion injury with OI ≥30 compared to obstructive lung diseases (21% vs 5%, p=0.005). 6

Management Strategies Based on OI Thresholds

OI 15-25 (Mild-Moderate Respiratory Failure)

• In neonates, iNO at this OI range did not decrease the incidence of ECMO or death or improve outcomes including chronic lung disease or neurodevelopmental impairment. 1

• Continue standard respiratory support with high-flow nasal oxygen or non-invasive ventilation as appropriate. 1

OI 25-40 (Severe Respiratory Failure)

• For neonates with PPHN, initiate iNO at 20 ppm (doses >20 ppm do not enhance oxygenation and increase methemoglobinemia risk). 1

• Implement lung recruitment strategies to improve iNO efficacy, especially in patients with parenchymal lung disease. 1

• For adults with COVID-19 or other causes, if OI corresponds to PaO₂/FiO₂ ≤150 mmHg and no improvement occurs within 1-2 hours with high-flow nasal oxygen or non-invasive ventilation, perform endotracheal intubation and invasive mechanical ventilation promptly. 1

• Sildenafil is a reasonable adjunctive therapy for infants with PPHN refractory to iNO, especially with OI exceeding 25. 1

OI >40 (Critical Respiratory Failure)

• Refer neonates to an ECMO center immediately. 1

• For adults with ARDS and optimized mechanical ventilation, consider ECMO when PaO₂/FiO₂ <100 mmHg despite neuromuscular blockade and prone ventilation. 1

• In post-lung transplant patients, intervene within 2 hours of OI reaching ≥30 to optimize survival. 6

Mechanical Ventilation Strategies for High OI

• Use lung protective ventilation with low tidal volume (4-6 mL/kg predicted body weight) and plateau pressure <30 cmH₂O. 1

• Apply appropriate PEEP levels; for moderate ARDS (PaO₂/FiO₂ 200-300 mmHg), use low PEEP strategy (<10 cmH₂O) to avoid impeding venous return. 1

• For severe ARDS (PaO₂/FiO₂ <150 mmHg), use higher PEEP and perform prone ventilation for >12 hours daily with deep sedation in the first 48 hours. 1

Monitoring and Reassessment

• Serial OI measurements within the first 3 days of mechanical ventilation predict outcomes better than single measurements. 4

• Recheck arterial blood gases after 30-60 minutes of oxygen therapy or sooner if clinical deterioration occurs in patients at risk of hypercapnic respiratory failure. 7, 8

• Monitor for improvement in OI over 7 days; failure to improve suggests therapy is unlikely to succeed and alternative strategies should be considered. 3

Critical Pitfalls to Avoid

• Do not delay ECMO referral in neonates once OI exceeds 40, as mortality increases significantly with delayed intervention. 1

• Avoid using iNO doses >20 ppm, as they provide no additional benefit and increase toxicity risk. 1

• Do not abruptly discontinue iNO even if no oxygenation improvement was observed, as rebound pulmonary hypertension can be life-threatening; wean to 1 ppm before discontinuation. 1

• In adults, recognize that OI is a poor predictor of individual patient outcome but useful for identifying therapies unlikely to succeed at the population level. 3

• For patients with chronic hypercapnia, maintain target oxygen saturation at 88-92% rather than 94-98% to avoid worsening respiratory acidosis. 7, 8