Positive role of continuous positive airway pressure for intensive care unit patients with severe hypoxaemic respiratory failure due to COVID-19 pneumonia: A single centre experience.

OBJECTIVES: Continuous positive airway pressure (CPAP) may be a useful treatment strategy for patients with severe COVID-19 pneumonia but its effectiveness in preventing mechanical ventilation is unknown. We aimed to evaluate the outcomes of COVID-19 patients treated with CPAP and determine predictors of CPAP response. DESIGN: This was a retrospective observational cohort study. SETTING: The study took place in the intensive care unit (ICU) at Royal Papworth Hospital (RPH) in Cambridge, UK. PATIENTS: We included all consecutive patients with confirmed COVID-19 pneumonia who were transferred from neighbouring hospitals between 14th March and 6th May, 2020 for consideration of ventilatory support. INTERVENTION: We instituted the use of CPAP for all patients who arrived in RPH not intubated and were not making satisfactory progress on supplemental oxygen alone. MEASUREMENTS AND MAIN RESULTS: Of 33 self-ventilating patients included in this study, 22 (66.7%) were male and the mean age was 54 ± 13.23 patients received CPAP. They were more hypoxaemic than those treated with oxygen alone (PaO2/FiO2 ratio; 84.3 ± 19.0 vs 170.0 ± 46.0 mmHg, p = 0.001). There was a significant improvement in PaO2/FiO2 ratio 1-2 hours after CPAP initiation (167.4 ± 49.0 from 84.3 ± 19.0 mmHg, p = 0.001). 14 (61%) patients responded to CPAP and 9 required intubation. There was no difference between these two groups in terms of the severity of baseline hypoxaemia (PaO2/FiO2 ratio; 84.5 ± 16.0 vs 83.9 ± 23.0 mmHg, p = 0.94) but CPAP responders had significantly lower C-reactive protein (CRP) (176 ± 83 vs 274 ± 63 mg/L, p = 0.007), interleukin-6 (IL-6) (30 ± 47 vs 139 ± 148 pg/mL, p = 0.037), and D-dimer (321 ± 267 vs 941 + 1990 ng/mL, p = 0.003). CT pulmonary angiogram was performed in 6 out of 9 intubated patients and demonstrated pulmonary emboli in 5 of them. All patients were discharged from ICU and there were no fatalities. CONCLUSIONS: In this cohort, CPAP was an effective treatment modality to improve hypoxaemia and prevent invasive ventilation in a substantial proportion of patients with severe respiratory failure. Accepting the small sample size, we also found raised biomarkers of inflammation (CRP and IL-6) and coagulopathy (D-Dimer) to be more useful predictors of CPAP responsiveness than the severity of hypoxaemia, and could help to guide intubation decisions in this clinical setting.

Effects of Patent Foramen Ovale Closure on Obstructive Sleep Apnea Syndrome: PCOSA Study.

BACKGROUND: Previous studies have shown a higher prevalence of patent foramen ovale (PFO) in patients with obstructive sleep apnea syndrome (OSAS). Right to left shunting through a PFO may be encouraged by the respiratory physiology of OSAS, contributing to the disease pathophysiology. We assessed whether PFO closure would improve respiratory polygraphy parameters compared with baseline measurements in patients with OSAS. METHODS: Twenty-six patients with newly diagnosed OSAS and a moderate-large PFO (prevalence, 18% of 143 patients screened) were referred for PFO closure. The oxygen desaturation index (ODI), apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), 6-minute walk test (6MWT), and Sleep Apnea Quality of Life Index (SAQLI) results were compared in these patients at baseline (before continuous positive pressure ventilation [CPAP]) and at 6-month follow-up (after interrupting CPAP for 1 week). RESULTS: All PFOs were safely sealed at 6 months, as confirmed by repeated transthoracic echocardiography. The ODI (44.8 [interquartile range (IQR), 31.2-63.5) vs 42.3 [IQR, 34.0-60.8]; P = 0.89) and AHI (47.9 [IQR, 31.5-65.2] vs 42.3 [IQR, 32.1-63]; P = 0.99) did not change after PFO closure nor did the 6MWT, although the ESS (13.0 [IQR, 12.0-16.8] vs 6.0 [IQR, 4.0-8.8]; P < 0.001) and the SAQLI (3.4 [IQR, 2.8-4.3] vs 4.4 [IQR, 3.9-5.3]; P < 0.001) did improve. CONCLUSIONS: The prevalence of PFO in OSAS appears to be no higher than that in the general population. Although PFO closure is safe and effective, it did not improve respiratory polygraphy measures of OSAS severity. The improvement in the ESS and SAQLI likely reflect residual benefits from CPAP.

The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery.

BACKGROUND: Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. METHODS: We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). RESULTS: In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); p<0.05) and both the P/F ratio and oxygenation index (OI: kPa/cm H2O=PaO2/mean airway pressure×FiO2) demonstrated sustained improvement to day 5 (P/F day 5: 39.85 (12.8); OI day 0: 2.88 (1.10) vs day 5: 4.06 (1.73); both p<0.01). The drain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). CONCLUSIONS: Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation.

Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD.

BACKGROUND: The addition of domiciliary non-invasive ventilation (NIV) to standard therapy in chronic obstructive pulmonary disease (COPD) patients with compensated ventilatory failure (CVF) is reported to have beneficial effects. Compliance with NIV is an important factor. Volume assured NIV (va-NIV) may improve compliance and ventilation during sleep by automatically titrating ventilatory pressures. METHODS: A prospective single centre, randomised, parallel group trial comparing va-NIV and pressure preset NIV (pp-NIV) in COPD patients with CVF naïve to domiciliary NIV was performed (ISCRTN91892415). The primary outcomes were arterial blood gases, mean overnight oximetry (mSpO2) and compliance after three months. Secondary outcomes included pulmonary function, exercise capacity and health-related quality of life assessment. RESULTS: Forty patients were randomised in a 1:1 ratio. The va-NIV median target minute ventilation was 8.4 L/min and pp-NIV median inspiratory pressure was 28 cmH2O. There were no significant differences between groups in primary or secondary outcomes after three months. Mean (SD) PaO2 8.7 (1.7) versus 7.9 (1.7) kPa (p = 0.19), PaCO2 6.7 (0.5) versus 7.3 (1.1) kPa (p = 0.1), mSpO2 89.7 (4.2) versus 89.8 (3.9) % (p = 0.95), compliance 5.0 (3.1) versus 4.7 (3.2) hours (p = 0.8) in va-NIV versus pp-NIV respectively. Patients allocated va-NIV spent fewer days in hospital initiating therapy 3.3 (1.6) versus 5.2 (2.8) (p = 0.02). Both groups showed significant improvements in PaCO2 and mSpO2 after three months treatment. CONCLUSIONS: Domiciliary va-NIV and pp-NIV have similar effects on physiological outcomes in COPD patients with CVF and both are well tolerated.

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO).

RATIONALE: Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. OBJECTIVES: To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. MEASUREMENTS AND METHODS: This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5-<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. MAIN RESULTS: 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20,000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39,800/QALY. CONCLUSIONS: Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice. TRIAL REGISTRATION NUMBER: ISRCTN02309506.

An open study to assess the efficacy clinically and immunologically of M. vaccae vaccine in patients with atopic dermatitis.

OBJECTIVE: To assess clinical and immunological changes in a group of atopic dermatitis patients treated with Mycobacterium vaccae (M. vaccae). METHODS: In an open, randomized, placebo-controlled, clinical observer-blinded trial, 20 patients with moderately severe to severe atopic dermatitis were treated with two subcutaneous M. vaccae injections 3 months apart. Clinical scoring and total serum IgE estimation were performed at the start, during and 3 months after the end of the study. RESULTS: Modest clinical improvement was seen in the patients after M. vaccae immunotherapy. There was no significant change in patients' total serum IgE levels. CONCLUSIONS: This study has shown limited improvement clinically in a group of patients with atopic dermatitis treated with two M. vaccae injections. It is suggested that further trials using four to six injections would produce much greater benefit.

The effect of varying tonicity on nasal epithelial ion transport in cystic fibrosis.

There is reasonable evidence that the fluid layer of the airway epithelium is exposed to changes in tonicity. The inspiration of cool, dry air causes an increased tonicity, whereas this tonicity may be decreased by glandular secretions. We hypothesized that the cystic fibrosis transmembrane conductance regulator (CFTR) is involved in the responses to changes in tonicity and that these may be altered in cystic fibrosis (CF). Using nasal potential difference (PD) protocols in 8 subjects with CF and 10 subjects without CF, we investigated the effects of hyper- and hypotonicity on ion transport processes. We found significant differences between the two groups. In response to a hypertonic challenge (mannitol 500 mM), there was a decreased PD in both groups, suggesting decreased sodium absorption. However, after the prior inhibition of sodium transport using amiloride, there was an increased PD in the non-CF group alone, suggesting CFTR-mediated chloride secretion in response to luminal hypertonicity. For the hypotonic solution, we found that hypotonicity inhibited CFTR-mediated chloride secretion in the non-CF group. These data suggest that CFTR plays a role in the recognition and regulation of airway fluid tonicity.