- This prospective study followed plasma levels of soluble suppression of tumerogenicity-2 (sST2) and interleukin-6 (IL-6) in 200 patients with acute hypoxemic respiratory failure who required mechanical ventilation
- Elevated baseline sST2 levels were associated with death or continued mechanical ventilation at day 29
- Measured longitudinally, each log-unit elevation in sST2 was associated with a 20% decrease in the probability of liberation from mechanical ventilation
- Patients with elevated sST2 levels on the day of liberation were more likely to require reintubation, even after adjustment for standard physiological measures
- Concentrations of IL-6 did not provide prognostic information on ventilator dependence
Conventional assessment of extubation readiness for patients with acute hypoxemic respiratory failure (AHRF) still relies on cutoff values of the PaO2:FiO2 ratio, positive end-expiratory pressure and minute ventilation. However, 10%–20% of patients who have adequate values and pass spontaneous awakening and breathing trials require reintubation within 48 hours. Clearly, the physiologic parameters relied upon do not always reflect the degree of lung injury.
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Researchers at Massachusetts General Hospital wondered whether inflammatory biomarkers could be better tools for determining readiness for ventilator liberation. In a previous study, they showed in patients with acute respiratory distress syndrome (ARDS) that elevated plasma levels of soluble suppression of tumerogenicity-2 (sST2) and interleukin-6 (IL-6) are associated with increased mortality and decreased likelihood of being successfully extubated.
However, in that study, biomarkers were measured only at baseline and on day 3. Now, Mass General's Jehan W. Alladina, MD, physician in the Division of Pulmonary and Critical Care Medicine, and Ednan K. Bajwa, MD, MICU director, and colleagues have shown that measurements of sST2 over time can provide real-time prognostic information about the clinical trajectory of a patient with AHRF and readiness for ventilator liberation. Their report appears in the American Journal of Respiratory and Critical Care Medicine.
The study was prospective and enrolled 209 patients with AHRF within 24 hours of intubation between November 2015 and January 2017. 199 of the patients met Berlin criteria for ARDS.
The primary outcome was breathing without the need for mechanical ventilation on day 29. Nine patients were terminally extubated prior to day 29 and were excluded. Among the 200 remaining patients, 127 (64%) met the primary endpoint.
Baseline sST2 and IL-6
- Median baseline sST2 concentrations were higher in patients who were dead or mechanically ventilated at day 29 compared with those who were breathing unassisted (492 vs. 314 ng/mL; P=0.0003)
- Median baseline IL-6 values were similar between the two groups
sST2 Over Time
After adjustment for baseline covariates and accounting for the competing risk of death, higher sST2 values at any given timepoint during the first nine days after intubation were associated with decreased adjusted probability of ventilator liberation over time (HR, 0.80 per log-unit increase; 95% CI, 0.76–0.84; P=0.03).
sST2 on Day of Ventilator Liberation
- Patients with log-transformed sST2 ≥5.68 ng/mL on the day of liberation had significantly lower odds of liberation success than those with sST2 < 5.68 ng/mL (adjusted OR, 0.34; 95% CI, 0.12–0.89; P=0.03)
- Conventionally used physiologic measures were not associated with liberation success
Even after adjustment for important clinical factors such as age, modified Sequential Organ Failure Assessment score and PaO2:FiO2 ratio, only sST2 concentration was significantly associated with liberation success.
Support for a Different Strategy
Physiologic measures of global lung function are unlikely to reflect the degree of underlying lung injury accurately, particularly when the injury is heterogeneous. These data support the use of a biomarker-directed approach to ventilator management, as elevated sST2 concentrations could indicate the presence of ongoing lung injury that isn't evident from standard clinical measures.
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