Preemptive Noninvasive Ventilation to Facilitate Weaning from Mechanical Ventilation in Obese Patients at High Risk of Reintubation.

Weaning from mechanical ventilation and extubation are critical procedures in mechanically ventilated patients, as weaning failure and reintubation occur in up to 10–30% of cases and are associated with increased mortality (1). Different tools have been proposed to prevent and treat postextubation respiratory failure, but there is a substantial lack of final evidence regarding the optimal tool for the management of patients undergoing scheduled extubation in the ICU.

Although the uncontrolled use of preemptive noninvasive ventilation (NIV) using pressure support ventilation with positive end-expiratory pressure (PEEP) in unselected cohorts of critically ill patients may lead to delayed reintubation and worsen mortality (1), it may be of benefit as a bridge to full spontaneous breathing in hypercapnic patients and in selected cohorts of hypoxemic subjects at high risk of weaning failure (2).

Heated and humidified high-flow nasal cannula (HFNC) appears as the optimal tool to administer oxygen to hypoxemic patients in the weaning phase (3, 4). HFNC allows accurate delivery of the set FiO, provides a low PEEP level (<5 cm H2O), and reduces work of breathing by favoring CO2 clearance from upper airways (5, 6). Preemptive HFNC has been shown to reduce the need for reintubation in a large randomized trial when compared with low-flow oxygen after the extubation of critically ill patients at low risk of weaning failure (7), and seemed as effective as NIV in patients at high risk of weaning failure (8).

These data indicate that, in patients who have high risk of extubation failure, both HFNC and NIV are promising techniques and may finally improve clinical outcomes (9). Further evidence regarding the best balance between these two techniques came from a recently published multicenter clinical trial, in which 641 critically ill patients showing at least one risk factor for extubation failure (i.e., age >65 yr, underlying chronic cardiac or lung disease, 50% of patients were recovering from respiratory failure) were randomly assigned to receive NIV alternating with HFNC or HFNC alone as preemptive treatments after scheduled extubation in the ICU (8). NIV was delivered for sessions of at least 4 hours, with a minimal treatment duration of 12 hours per day in the initial 48 hours, and was applied through a face mask and specific settings: pressure support titrated to obtain an expiratory Vt between 6 and 8 ml/kg of predicted body weight and PEEP ranging between 5 and 10 cm H2O. Study results showed that the preemptive combined use of NIV and HFNC resulted in a lower rate of reintubation at 7 days and in a lower incidence of postextubation respiratory failure as compared with HFNC alone.

In this issue of the Journal, Thille and colleagues (pp. 440–449) report the results of a post hoc analysis of the trial, in which intergroup differences in study outcomes were analyzed after classifying patients according to whether they were obese (BMI ⩾ 30 kg/m2; 206 patients), overweight (25 kg/m2 ⩽ BMI < 30 kg/m2; 204 patients), or normal/underweight (BMI < 25 kg/m2; 213 patients) (10). The research question addressing the potential heterogeneity in NIV effects according to different BMI is sound, as obesity significantly interferes with the physiology of respiratory system; this may affect the effect of applied interventions (11, 12).

Study results showed that, in the subgroup of patients who are obese or overweight, the rate of reintubation rate at Day 7 was significantly lower in patients treated with NIV alternating with HFNC than in those who received HFNC alone (7% [15/204] vs. 20% [41/206], with an absolute risk reduction of 13% and a number needed-to-treat of 8). This result was accompanied by significantly lower time in the ICU and 90-day mortality in patients treated with NIV alternating with HFNC.

Conversely, no intergroup difference in study outcomes was found in patients who had BMI <25 kg/m2.

These results have a robust physiological rationale. Obesity is associated with increased absolute values of pleural pressure, which favors the development of atelectasis; atelectasis yields intrapulmonary shunt and consequent hypoxemia (11), which is the most frequent cause of extubation failure. Atelectasis may also cause reduction in lung and respiratory system compliance, which increases the muscle workload to generate an adequate Vt. PEEP, by counterbalancing pleural pressure, maintains positive transpulmonary pressure, prevents atelectasis due to alveolar collapse, and favors a more homogeneous ventilation (11). Also, airway closure and expiratory flow limitation are magnified in patients who are obese (13, 14). Application of PEEP may reduce work of breathing by preventing airway closure and limiting the isometric muscle workload needed to generate inspiratory flow. This, together with the inspiratory assistance provided by pressure support, may reduce the occurrence of muscle exhaustion, which is a frequent cause of weaning failure (15). From study results, it would be reasonable to suggest that, contrarily to pressure support ventilation, which delivers adequate sufficient positive insufflation pressure, HFNC generated a PEEP effect that was insufficient to reopen collapsed alveoli and relieve respiratory muscle workload.

Finally, patients who are obese may show a lower risk of alveolar overdistension due to high alveolar pressure (11), which is a major concern when NIV in the pressure support mode is applied in patients with hypoxemia (16). This may have mitigated the risk of self-inflicted lung injury during NIV.

The authors must be commended for their effort in better understanding the results of their trial. The results of this study indicate the clinical benefit of an approach including preemptive NIV alternating with HFNC over HFNC alone after extubation in critically ill patients with at least one risk factor for reintubation is magnified in and limited to patients who are overweight or obese.

Despite the nonprespecified post hoc nature of the analysis, which makes the results hypothesis-generating rather than conclusive, we believe these results provide novel and relevant insights on the management of weaning from mechanical ventilation and represent an important step ahead toward the individualization of care in patients receiving mechanical ventilation. Further randomized controlled studies are needed to confirm these promising findings.