Noninvasive Ventilation in Obese Patients After Acute Respiratory Failure: Big Questions Remain

Obesity is a global health epidemic,¹ and obesity-hypoventilation syndrome is increasingly common; the prevalence of obesity-hypoventilation syndrome in patients attending sleep laboratories or admitted to hospitals is estimated to be 11–38%,^2–4 while estimates of the prevalence in the general population range from 0.3% to 0.4%⁵ In many countries, obesity-hypoventilation syndrome is the most common indication for domiciliary noninvasive ventilation (NIV).^6,7

The term obesity-hypoventilation syndrome is used to define individuals with obesity (body mass index [BMI] > 30 kg/m²) and diurnal hypoventilation (daytime P_aCO2 > 45 mm Hg) in the absence of any other cause of hypoventilation.⁸ Although not included in the definition, these individuals usually (but not always) have sleep-disordered breathing, consisting of rapid eye movement, sleep hypoventilation, obstructive sleep apnea (in 90% of patients with obesity-hypoventilation syndrome^9,10), or both.¹¹

Most patients are diagnosed with obesity-hypoventilation syndrome because of an increase in daytime and/or sleep-related symptoms, but about one third are not diagnosed until an episode of acute respiratory failure.^12–14 Of all the complications related to obesity, the development of respiratory failure is probably the most significant because it is associated with a 4-fold increase in mortality if left untreated.³ Without treatment, individuals with obesity-hypoventilation syndrome are at risk of pulmonary hypertension, cor pulmonale, and acute respiratory failure. Compared with obese patients without daytime hypercapnia, individuals with obesity-hypoventilation syndrome have higher rates of hospital admission, increased use of intensive-care resources, worse health-related quality of life scores, and reduced functional capacity and physical activity levels.^15,16

Although weight loss is the ideal treatment for obesity-hypoventilation syndrome,¹⁷ in practice it is difficult to achieve and maintain in this group. Bariatric surgery is also often not an alternative for this group because of the significant morbidity and mortality.¹⁸

Positive airway pressure (PAP) is effective in managing both acute and chronic respiratory failure due to obesity-hypoventilation syndrome.^9,19–23 Despite this, there are no established guidelines for the use of NIV or CPAP in subjects with obesity-hypoventilation syndrome, and to date only a few randomized controlled trials have been published. Nevertheless, there is a strong physiologic rationale for the use of PAP in obesity-hypoventilation syndrome, and evidence supporting its use in this area is growing.

Although the mechanisms by which obesity-hypoventilation syndrome results in diurnal respiratory failure are not entirely understood, there appear to be 3 main mechanisms at play²⁴: abnormal respiratory mechanics, including respiratory muscle dysfunction;²⁵ central hypoventilation due to leptin resistance;^26–29 and sleep-disordered breathing, both sleep hypoventilation and obstructive apneas.^5,30 PAP, either in the form of CPAP or NIV, is able to influence all 3 of these areas, although the exact mechanism(s) by which these treatments are able to improve respiratory failure in obesity-hypoventilation syndrome are complex and remain to be fully explained.

In acute hypercapnic respiratory failure due to obesity-hypoventilation syndrome, although no randomized clinical trial has been conducted to test the effectiveness of NIV for this indication, NIV is the preferred mode of ventilatory support, unless the patient is severely unwell or there is other organ dysfunction, in which case endotracheal intubation and mechanical ventilation in the ICU is mandatory.³¹ NIV in this cohort results in improvements in pH and P_aCO2,^{9,20,22,32,33} with lower mortality in patients treated with NIV compared with those who refused it (3% mortality with NIV and 57% without⁹). Lemyze and co-workers,³¹ in a study exploring the determinants of NIV success in acute respiratory failure in the morbidly obese, found that pneumonia and high symptom-severity scores at admission were associated with NIV failure in this group, while high P_aCO2 and HCO₃ levels at admission and idiopathic hypercapnic decompensation of obesity-hypoventilation syndrome were associated with successful NIV application.

The benefits of positive airway pressure (CPAP or NIV) in chronic respiratory failure due to obesity-hypoventilation syndrome have been demonstrated in randomized controlled trials.^34,35 Both therapies result in significant reductions in daytime P_aCO2 and bicarbonate, as well as improvements in apnea-hypopnea index, with restoration of sleep architecture and improvements in daytime sleepiness.^34–37 Some health-related quality of life measures improve to a greater extent with NIV compared to CPAP.³⁴

In the chronic setting, there are 3 distinct patterns of sleep-disordered breathing, which can be determined on the basis of respiratory sleep studies: isolated severe obstructive sleep apnea; isolated sleep hypoventilation; and combined obstructive sleep apnea and hypoventilation. Each of these merits a different management strategy.

In patients with a predominance of obstructive events during sleep, and high sleep time in apnea, in whom daytime P_aCO2 is < 55 mm Hg, CPAP is clinically and cost-effective³⁷ and has been shown to be equivalent to NIV, at least in the medium term, in newly diagnosed patients with both mild and severe obesity-hypoventilation syndrome.^34,36,37 In those patients with persistent nocturnal hypoventilation on CPAP, or with a predominance of hypoventilation over obstructive events on initial sleep study, NIV is preferred, and should be established with the aim of normalizing daytime P_aCO2. Following adequate treatment, demonstrated by normalization of daytime blood gas tensions, it may be possible to step these patients down to CPAP therapy.^9,36,38 Importantly, clinical outcomes are closely related to adherence with therapy: an average use of 4 h per night is recommended in order to achieve a reduction in daytime P_aCO2 levels, and it is this latter which is associated with improvements in health related quality of life measures and daytime sleepiness.^34,36,37

In this edition of Respiratory Care, Bry and co-workers³⁹ present data on the predictors of long-term NIV use in a cohort of obese subjects (mean BMI 42 ± 11 kg/m²) admitted to their respiratory ICU with acute hypercapnic respiratory failure. In this retrospective study, the authors identified 53 subjects over a 2-year period, in which 70% of subjects were presenting for the first time in respiratory failure; 8 subjects had previously been prescribed home NIV, but only one was using the device on a regular basis by the time of the study, while 9 subjects had previously been prescribed CPAP. Unfortunately, no previous sleep study data were presented, and it is not possible to determine whether these 17 subjects had sleep hypoventilation, sleep apnea, or a combination of both. Subjects were followed for up to 1 y after discharge from the ICU.

In the study by Bry et al,³⁹ 30% of the subjects were current smokers and 41% had obstructive spirometry. A high proportion of the subjects had other non-respiratory pathologies, including hypertension (60%), diabetes (38%), and ischemic cardiomyopathy (19%). Most subjects (62%) were admitted with idiopathic acute respiratory failure. Mean pH at admission was 7.32 and mean P_aCO2 was 61 mm Hg. Forty subjects received NIV as first-line therapy, while 4 were initially invasively ventilated and subsequently received NIV. The recorded NIV failure rate was 10%, which compares favorably to the published literature,^20,31,32 although mean BMI was lower in this study and respiratory failure was less severe.

After initial acute management in the ICU, 34 subjects received some form of PAP on discharge, and in half of those this was a new prescription. NIV was more frequently prescribed than CPAP, which was selected on the basis of positive overnight oximetry and when P_aCO2 was < 45 mm Hg, and 9 subjects (26%) required supplementary oxygen therapy. Eight subjects were considered to have no ongoing requirement for home ventilatory support.³⁹

The authors found that subjects who required some form of PAP on discharge generally had a higher BMI than those who did not, and they required higher inspiratory PAP levels within the first 48 h of admission. There was no significant difference at admission in blood gas tensions, cause of respiratory failure, or prior use of home ventilatory support between those who were discharged with PAP and those who were not. Mean duration of NIV after discharge was 6 ± 4.2 months (no follow-up data were available for subjects discharged on CPAP). Adherence with NIV was surprisingly good, with mean adherence at 1 month being 5.7 ± 2.9 h per day, and 7.1 ± 2.1 h per day at 12 months. Poor adherence at 1 month was strongly associated with poor adherence at 6 months. Mean BMI was significantly lower at 12 months compared with baseline. Bicarbonate and P_aCO2 levels were also significantly lower at 12 months when compared with baseline (26 vs 27 mmol/L and 42 ± 7 vs 44 ± 8 mm Hg, respectively, P = .006 and P = .01, respectively). There was a trend toward lower readmission rates in those individuals who received NIV at home (10% readmission rate) compared with those who did not (36% readmission rate, P = .07).

So what have we learned from this study? Although this was a retrospective study, with all the limitations such a trial design entails, and the numbers included were small, which necessarily limits some of the conclusions that can be drawn, the study concurs with the findings of other, larger studies demonstrating that NIV is an effective strategy for the management of acute hypercapnic respiratory failure in subjects with obesity-hypoventilation syndrome, particularly in subjects presenting with an idiopathic decompensation of obesity-hypoventilation syndrome.³¹

Those subjects requiring domiciliary NIV or CPAP after admission had a higher BMI than those who did not, and they required higher inspiratory PAP levels at initiation of NIV. This matches with observational data confirming that the incidence of obesity-hypoventilation syndrome increases significantly as weight increases.^3,5 A higher driving pressure is likely to be required to overcome the respiratory muscle load in more obese patients.

Finally, this study confirms findings from other studies that NIV in this group of subjects improves chronic respiratory failure^34,36,37 and supports weight loss⁴⁰ in adherent individuals. There was also a trend toward lower admission rates in those receiving domiciliary NIV, confirming data from longer-term observational studies.^15,41

Despite the fact that obesity-hypoventilation syndrome is now a common indication for domiciliary NIV, significant questions remain. In particular, in relation to whether NIV is superior to CPAP with respect to longer-term outcomes such as cardiovascular events, length of hospitalization, and mortality, and whether either is superior to surgical and new non-surgical approaches to weight loss. It also remains to be demonstrated whether early initiation of NIV for nocturnal hypoventilation without daytime hypercapnia might be able to prevent progression to diurnal respiratory failure. Finally, the optimal NIV settings and modes for the management of respiratory failure in obesity-hypoventilation syndrome are not well established, and the role of newer modalities, including auto-titrating volume-targeted modes, is yet to be clarified.

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