Correction to: The effect of corticosteroids on the mortality of patients with influenza pneumonia: a systematic review and meta-analysis.

An amendment to this paper has been published and can be accessed via the original article.

The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis.

BACKGROUND: The effect of corticosteroids on clinical outcomes in patients with influenza pneumonia remains controversial. We aimed to further evaluate the influence of corticosteroids on mortality in adult patients with influenza pneumonia by comparing corticosteroid-treated and placebo-treated patients. METHODS: The PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Information Sciences Institute (ISI) Web of Science databases were searched for all controlled studies that compared the effects of corticosteroids and placebo in adult patients with influenza pneumonia. The primary outcome was mortality, and the secondary outcomes were mechanical ventilation (MV) days, length of stay in the intensive care unit (ICU LOS), and the rate of secondary infection. RESULTS: Ten trials involving 6548 patients were pooled in our final analysis. Significant heterogeneity was found in all outcome measures except for ICU LOS (I2 = 38%, P = 0.21). Compared with placebo, corticosteroids were associated with higher mortality (risk ratio [RR] 1.75, 95% confidence interval [CI] 1.30 ~ 2.36, Z = 3.71, P = 0.0002), longer ICU LOS (mean difference [MD] 2.14, 95% CI 1.17 ~ 3.10, Z = 4.35, P < 0.0001), and a higher rate of secondary infection (RR 1.98, 95% CI 1.04 ~ 3.78, Z = 2.08, P = 0.04) but not MV days (MD 0.81, 95% CI - 1.23 ~ 2.84, Z = 0.78, P = 0.44) in patients with influenza pneumonia. CONCLUSIONS: In patients with influenza pneumonia, corticosteroid use is associated with higher mortality. TRIAL REGISTRATION: PROSPERO (ID: CRD42018112384 ).

Can corticosteroids reduce the mortality of patients with severe sepsis? A systematic review and meta-analysis.

BACKGROUND: The effects of corticosteroids on clinical outcomes of patients with sepsis remains controversial. We aimed to further determine the effectiveness of corticosteroids in reducing mortality in adult patients with severe sepsis by comparison with placebo. METHODS: Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all controlled studies that compared corticosteroids and placebo in adult patients with severe sepsis. The primary outcome was the mortality 28-day mortality and the secondary outcomes were mortality at longest follow up, occurrence, and reoccurrence of septic shock. RESULTS: A total of 19 trials involving 7035 patients were pooled in our final analyses. No significant heterogeneity was found in any of the outcome measures. Compared with placebo, corticosteroids were associated with a lower 28-day mortality (RR 0.91, 95% CI 0.85-0.98, Z = 2.57, P = 0.01) both in patients having sepsis and in those who developed septic shock (RR 0.92, 95% CI 0.85-0.99, Z = 2.19, P = 0.03), while no significant difference was found in mortality with the longest follow up in patients either having sepsis (RR 0.94, 95% CI 0.89-1.00, Z = 1.93, P = 0.05), or occurrence (RR 0.83, 95% CI 0.56-1.24, Z = 0.90, P = 0.37) or reoccurrence of septic shock (RR 1.08, 95% CI 1.00-1.16, Z = 1.89, P = 0.06). CONCLUSIONS: Corticosteroids were effective in reducing the 28-day mortality in patients with severe sepsis and in those with septic shock.

The effect of hyperoxia on mortality in critically ill patients: a systematic review and meta analysis.

BACKGROUND: Studies investigating the role of hyperoxia in critically ill patients have reported conflicting results. We did this analysis to reveal the effect of hyperoxia in the patients admitted to the intensive care unit (ICU). METHODS: Electronic databases were searched for all the studies exploring the role of hyperoxia in adult patients admitted to ICU. The primary outcome was mortality. Random-effect model was used for quantitative synthesis of the adjusted odds ratio (aOR). RESULTS: We identified 24 trials in our final analysis. Statistical heterogeneity was found between hyperoxia and normoxia groups in patients with mechanical ventilation (I2 = 92%, P < 0.01), cardiac arrest(I2 = 63%, P = 0.01), traumatic brain injury (I2 = 85%, P < 0.01) and post cardiac surgery (I2 = 80%, P = 0.03). Compared with normoxia, hyperoxia was associated with higher mortality in overall patients (OR 1.22, 95% CI 1.12~1.33), as well as in the subgroups of cardiac arrest (OR 1.30, 95% CI 1.08~1.57) and extracorporeal life support (ELS) (OR 1.44, 95% CI 1.03~2.02). CONCLUSIONS: Hyperoxia would lead to higher mortality in critically ill patients especially in the patients with cardiac arrest and ELS.

The effect of aspirin in preventing the acute respiratory distress syndrome/acute lung injury: A meta-analysis.

BACKGROUND: The effects of aspirin in preventing the occurrence of acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) among adult patients are controversial. We aimed to further determine the effectiveness of aspirin in reducing the rate of ARDS/ALI. METHODS: The Pubmed, Embase, Medline, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all controlled studies that research the role of aspirin in adult patients who have the risk of ARDS/ALI. The outcomes were the ARDS/ALI rate and the mortality. Cochrane systematic review software, Review Manager (RevMan), the R software for statistical computing version 3.2.0, and the metafor package were used to test the hypothesis by Mann-Whitney U test. The heterogeneity test and sensitivity analyses were conducted, and random-effects or fixed-effects model was applied to calculate odds ratio (OR) and mean difference (MD) for dichotomous and continuous data, respectively. RESULTS: Six trials involving 6562 patients were pooled in our final study. No significant heterogeneity was found in outcome measures. Aspirin could reduce the rate of ARDS/ALI (OR 0.71, 95% confidence interval (CI) 0.58-0.86) but not the mortality (OR 0.87, 95% CI 0.71-1.07). CONCLUSIONS: In patients with risk of ARDS/ALI, aspirin could provide protective effect on the rate of ARDS/ALI, but it could not reduce the mortality.

The effect of high-flow nasal cannula in reducing the mortality and the rate of endotracheal intubation when used before mechanical ventilation compared with conventional oxygen therapy and noninvasive positive pressure ventilation. A systematic review and meta-analysis.

BACKGROUND: The effects of high flow nasal cannula (HFNC) on adult patients when used before mechanical ventilation (MV) are unclear. We aimed to determine the effectiveness of HFNC when used before MV by comparison to conventional oxygen therapy (COT) and noninvasive positive pressure ventilation (NIPPV). METHODS: The Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all the controlled studies that compared HFNC with NIPPV and COT when used before MV in adult patients. The primary outcome was the rate of endotracheal intubation and the secondary outcomes were intensive care unit (ICU) mortality and length of ICU stay (ICU LOS). RESULTS: Eight trials with a total of 1084 patients were pooled in our final studies. No significant heterogeneity was found in outcome measures. Compared both with COT and NIPPV, HFNC could reduce both of the rate of endotracheal intubation (OR 0.62, 95% CI 0.38-0.99, P=0.05; OR 0.48, 95% CI 0.31-0.73, P=0.0006) and ICU mortality (OR 0.47, 95% CI 0.24-0.93, P=0.03; OR 0.36, 95% CI 0.20-0.63, P=0.0004). As for the ICU LOS, we did not find any advantage of HFNC over COT or NIPPV. CONCLUSIONS: When used before MV, HFNC can improve the prognosis of patients compared both with the COT and NIPPV.

Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome? A meta-analysis.

BACKGROUND: The effects of body mass index (BMI) on the prognosis of acute respiratory distress syndrome (ARDS) are controversial. We aimed to further determine the relationship between BMI and the acute outcomes of patients with ARDS. METHODS: We searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and ISI Web of Science for trials published between 1946 and July 2016, using "BMI" or "body mass index" or "overweight" or "obese" and "ARDS" or "ALI" or "acute respiratory distress syndrome" or "acute lung injury", without limitations on publication type or language. Heterogeneity and sensitivity analyses were conducted, and a random-effects model was applied to calculate the odds ratio (OR) or mean difference (MD). Review Manager (RevMan) was used to test the hypothesis using the Mann-Whitney U test. The primary outcome was unadjusted mortality, and secondary outcomes included mechanical ventilation (MV)-free days and length of stay (LOS) in the intensive care unit (ICU) and in hospital. RESULTS: Five trials with a total of 6268 patients were pooled in our final analysis. There was statistical heterogeneity between normal-weight and overweight patients in LOS in the ICU (I 2 = 71%, χ 2 = 10.27, P = 0.02) and in MV-free days (I 2 = 89%, χ 2 = 18.45, P < 0.0001). Compared with normal weight, being underweight was associated with higher mortality (OR 1.59, 95% confidence interval (CI) 1.22, 2.08, P = 0.0006), while obesity and morbid obesity were more likely to result in lower mortality (OR 0.68, 95% CI 0.57, 0.80, P < 0.00001; OR 0.72, 95% CI 0.56, 0.93, P = 0.01). MV-free days were much longer in patients with morbid obesity (MD 2.64, 95% CI 0.60, 4.67, P = 0.01), but ICU and hospital LOS were not influenced by BMI. An important limitation of our analysis is the lack of adjustment for age, sex, illness severity, comorbid illness, and interaction of outcome parameters. CONCLUSIONS: Obesity and morbid obesity are associated with lower mortality in patients with ARDS.

The effect of sedation and/or analgesia as rescue treatment during noninvasive positive pressure ventilation in the patients with Interface intolerance after Extubation.

BACKGROUND: Sedation and/or analgesia can relieve the patient-ventilator asynchrony. However, whether sedation and/or analgesia can benefit the clinical outcome of the patients with interface intolerance is still unclear. METHODS: A retrospective study was performed on patients with interface intolerance who received noninvasive positive pressure ventilation (NIPPV) after extubation in seven intensive care units (ICU) of West China Hospital, Sichuan University. The primary outcome was rate of NIPPV failure (defined as need for reintubation and mechanical ventilation); Secondary outcomes were hospital mortality rate and length of ICU stay after extubation. RESULTS: A total of 80 patients with oral-nasal mask (90%) and facial mask (10%) were included in the analysis. 41 out of 80 patients received sedation and/or analgesia treatment (17 used analgesia, 11 used sedation and 13 used both) at some time during NIPPV. They showed a decrease of NIPPV failure rate, (15% vs. 38%, P = 0.015; adjusted odd ratio [OR] 0.29, 95% confidence interval [CI] 0.10-0.86, P = 0.025), mortality rate (7% vs. 33%, P = 0.004; adjusted OR 0.14, 95% CI 0.03-0.60, P = 0.008), and the length of ICU stay after extubation. CONCLUSION: This clinical study suggests that sedation and/or analgesia treatment can decrease the rate of NIPPV failure, hospital mortality rate and ICU LOS in patients with interface intolerance after extubution during NIPPV.

Can high-flow nasal cannula reduce the rate of reintubation in adult patients after extubation? A meta-analysis.

BACKGROUND: The effects of high flow nasal cannula (HFNC) on adult patients after extubation remain controversial. We aimed to further determine the effectiveness of HFNC in comparison to noninvasive positive pressure ventilation (NIPPV) and conventional oxygen therapy (COT). METHODS: The Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trails (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all the controlled study comparing HFNC with NIPPV and COT in adult patients after extubation. The primary outcome was rate of reintubation and the secondary outcomes were intensive care unit (ICU) mortality and length of ICU stay (ICU LOS). RESULTS: Eight trials with a total of 2936 patients were pooled in our final studies. No significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with lower rate of reintubation (Z = 2.97, P = 0.003), and the same result was found in the comparison between HFNC and NIPPV (Z = 0.87, P = 0.38). As for the ICU mortality and ICU LOS, we did not find any advantage of HFNC over COT or NIPPV. CONCLUSIONS: In patients after extubation, HFNC is a reliable alternative of NIPPV to reduce rate of reintubation compared with COT.

The association between the effective apnea-hypopnea index and blood pressure reduction efficacy following CPAP/oxygen treatment.

BACKGROUND: The effect of sleep apnea treatment on reducing cardiovascular disease risk remains inconclusive. This study aims to assess if the effective apnea hypopnea index (eAHI), a measure of residual sleep apnea burden post-treatment, is a factor in determining blood pressure (BP) response to continuous positive airway pressure therapy. The eAHI integrates time on therapy, residual apnea, and % of sleep time untreated. METHODS: A secondary analysis of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a randomized, controlled, parallel group assessment of continuous positive airway pressure (CPAP), oxygen and sleep hygiene. The Delta-AHI (▲AHI) was defined as the difference between baseline AHI and effective AHI at 12 weeks. Logistic and linear regression models estimated the predictors for nocturnal systolic BP change following sleep apnea therapy. RESULTS: One hundred and sixty-nine subjects with a mean age of 62.82 ± 6.99 years were included in the final analysis. Fifty subjects had ▲AHI ≤8/hour of sleep and 119 subjects were higher. After adjustment, baseline mean nighttime systolic blood pressure (OR 1.036, 95% CI 1.015-1.058, p: 0.001) and ▲AHI ≥8/hour (OR 2.406, 95% CI 1.116-5.185, p:0.025) were independent predictors for mean nighttime systolic blood pressure change >3 mm Hg. The higher effective AHI was negatively related with BNP (ß: -2.564, SE: 1.167, p: 0.029) and positively related with troponin change (ß: 0.703, SE: 0.256, p: 0.007). CONCLUSION: The ▲AHI was an independent predictor of the blood pressure response to sleep apnea treatment. REGISTER NUMBER: NCT01086800.

Sleep apnea-related hypoxic burden as a predictor of pregnancy and neonatal outcome.

STUDY OBJECTIVES: To determine the clinical impact of sleep apnea-related hypoxic burden in pregnant women and neonates. METHODS: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) study. Hypoxia burden was calculated from the home sleep apnea test (HSAT) and defined as the total area under respiratory events. Logistic regression analysis assessed the relationship between hypoxia burden and pregnancy/neonatal outcomes. RESULTS: A total of 3006 subjects in the early term, and 2326 subjects in the middle term of pregnancy, had HSAT. A hypoxic burden greater than 6.8%min was present in 1740 at early term and associated with a higher risk of preeclampsia (odds ratio 1.297, 95 % confidence interval 1.032-1.630, p: 0.026) after adjusted by obstructive sleep apnea (OSA) severity. In the middle term, 1058 subjects had a hypoxia burden more than 11.8%min, which was a predictor for higher incidence of gestational diabetes (OR 1.795, 95 % CI 1.097-2.938, p: 0.020) and an Apgar <7 at 1 min (OR 1.446, 95 % CI 1.079-1.939, p: 0.012) after adjusted by obstructive sleep apnea (OSA) severity. After adjusted by oxygenation disturbance index, HB was not related with Apgar <7 at 1 min (p:0.565). CONCLUSIONS: The hypoxic burden is an independent predictor for preeclampsia and gestational diabetes and an Apgar <7 at 1 min.

Cardiopulmonary coupling predictors of blood pressure response to positive airway pressure therapy.

RATIONALE: The effect of continuous positive airway pressure (CPAP) treatment on reducing cardiovascular disease risk in sleep apnea subjects remains inconclusive. It is plausible that pathological respiratory chemoreflex activation (high loop gain) is a predictive signal biomarker. OBJECTIVE: To determine whether narrow band (e-LFCNB%) metric derived from cardiopulmonary coupling analysis is related with blood pressure reduction after CPAP. METHODS: A secondary analysis of the Apnea Positive Pressure Long-term Efficacy Study (APPLES). The elevated low frequency coupling - narrow band (e-LFCNB %) metric derived from cardiopulmonary coupling analysis detects periodic breathing (as a surrogate for high loop gain), and was estimated in baseline polysomnogram. Linear regression analysis was performed to identify the potential association between e-LFCNB% of total sleep time and the observed reduction in blood pressure following the specified treatment. RESULTS: A total of 388 subjects received CPAP and had e-LFCNB % measurements. At 2 months, 90/322 subjects had e-LFCNB ≥ 4 % at baseline. At 6 months 137/313 subjects had e-LFCNB higher than 2 % at baseline. For morning systolic blood pressure, e-LFCNB ≥ 4 % [ß: 2.534, standard error (SE): 1.198, p: 0.035] was positively related with the extent of systolic blood pressure reductions after 2 months CPAP treatment and e-LFCNB ≥ 2 % was marginally related with systolic blood pressure decrement after 6 months (ß: 2.162, SE: 1.173, p: 0.066). For the morning diastolic blood pressure, e-LFCNB ≥ 2 % predicted reductions at 6 months of treatment (ß: 1.883, SE: 0.888, p: 0.035). CONCLUSION: e-LFCNB % (probable high loop gain) was positively related to systolic blood pressure reduction (short-term) and diastolic blood pressure reduction (longer-term), following CPAP.

Predictors and consequences of residual apnea during positive airway pressure therapy.

STUDY OBJECTIVES: Determine the risk factors for, and consequences of, residual apnea during long-term positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA). METHODS: A prospective cohort study of 195 subjects after a split-night polysomnogram. Estimation of residual respiratory events on PAP were done by both automated and manual scoring of data in EncoreAnywhere™. Clinical and polysomnographic predictors of residual apnea were estimated. RESULTS: There were 166 and 101 patients still on PAP at the 3 and 12 months, respectively. Seventy four (44.6%) and 46 (45.5%) had a residual scored respiratory event index-flow (sREIFLOW) ≥ 15/hour of use and 46 (45.5%) at the 3rd and 12th month, respectively. Treatment phase central apnea hypopnea index (TCAHI), a surrogate of high loop gain, was the main predictor for residual sREIFLOW (ß = 0.345, p: 0.025) at the 3rd and 12th month (ß = 0.147, p: 0.020). TCAHI also predicted unstable breathing (U) %. The body mass index (hazard ratio [HR] 1.034, 95% CI 1.008-1.062, p: 0.012) and effective sREIFLOW>15/hour in the first month (HR 2.477, 95% CI 1.510-4.065, p < 0.001) were the key predictors for drop out of PAP use at the 12th month. Effective sREIFLOW>15/hour in the first month was also a predictor for median usage duration >4 h for 70% of the night at both the 3rd month (odds ratio [OR] 0.947, 95% CI 0.909-0.986, p: 0.008) and 12th month (OR 0.973, 95% CI 0.951-0.994, p: 0.014). CONCLUSIONS: Treatment-phase CAHI predicts long-term residual apnea on PAP. High residual disease adversely impacts adherence.

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea.

BACKGROUND: The acute effect during positive pressure titration and long term efficacy of acetazolamide (AZT) in high loop gain sleep apnea (HLGSA) is inadequately assessed. We predicted that AZT may improve HLGSA in both conditions. METHODS: A retrospective analysis of polysomnograms from patients with presumed HLGSA and residual respiratory instability administered AZT (125 or 250 mg) about 3 h into an initially drug-free positive pressure titration. A responder was defined as ≥ 50% reduction of the apnea hypopnea index(AHI 3% or arousal) before and after AZT. A multivariable logistic regression model estimated responder predictors. Long term efficacy of AZT was assessed by comparing both auto-machine (aREIFLOW) and manually scored respiratory events (sREIFLOW) extracted from the ventilator, prior to and after 3 months of AZT, in a subset. RESULTS: Of the 231 participants (median age of 61[51-68] years) and 184 (80%) males in the acute effect testing: 77 and 154 patients were given 125 mg and 250 mg AZT. Compared to PAP alone, PAP plus AZT was associated with a lower breathing related arousal index (8 [3-16] vs. 5 [2-10], p < 0.001), and AHI3% (19 [7-37] vs. 11 [5-21], p < 0.001); 98 patients were responders. The non-rapid eye movement sleep (NREM) AHI3% (OR 1.031, 95%CI [1.016-1.046], p < 0.001) was a strong predictor for responder status with AZT exposure. In the 109 participants with 3-month data, both aREIFLOW and sREIFLOWwere significantly reduced after AZT. CONCLUSIONS: AZT acutely and chronically reduced residual sleep apnea in presumed HLGSA; NREM AHI3% is a response predictor. AZT was well tolerated and beneficial for at least 3 months.

Association between ventilatory ratio and ICU mortality in interstitial lung disease patients on mechanical ventilation: A retrospective study.

BACKGROUND: Ventilatory ratio (VR) is a simple bedside index of ventilatory efficiency. Interstitial lung disease (ILD) is a diverse group of diseases that causes fibrosis or inflammation of the pulmonary parenchyma, and the main clinical manifestation is hypoxemia. To date, no study has explored ventilation efficiency in patients with ILD. OBJECTIVES: This study aimed to explore the features of VR in mechanically ventilated patients with ILD and their relationship with intensive care unit (ICU) mortality. METHODS: In this retrospective analysis, we included mechanically ventilated patients with ILD in the ICU of West China Hospital, Sichuan University, from 2013 to 2021. Demographic data and mechanical ventilation (MV) parameters within 24 h of intubation were collected. The characteristics of VR and their relationships with ICU mortality were also analyzed. RESULTS: 224 patients were included in the final analysis. There were 146 males (53.9%), and the median age was 65 years (interquartile range [IQR]54∼74). The mean value of VR was 2.22, and VR was significantly higher in nonsurvivors than in survivors (1.79 vs 2.32, P < 0.001). A high VR value was an independent risk factor for ICU mortality (odds ratio=1.602, P = 0.038) after adjustment. A high value of VR was associated with a shorter survival time after admission to ICU (hazard ratio=1.485, P = 0.006) CONCLUSIONS: VR in patients with ILD on MV was increased, and the VR of nonsurvivors within 24 h of intubation was higher than that of survivors. The high VR value within 24 h of intubation was an independent risk factor for ICU mortality after adjusting for other factors.

A longitudinal study of the accuracy of positive airway pressure therapy machine-detected apnea-hypopnea events.

STUDY OBJECTIVES: During positive airway pressure (PAP) therapy for sleep apnea syndromes, the machine-detected respiratory event index (REIFLOW) is an important method for clinicians to evaluate the beneficial effects of PAP. There are concerns about the accuracy of this detection, which also confounds a related question, How common and severe are residual events on PAP? METHODS: Patients with obstructive sleep apnea who underwent a split-night polysomnography were recruited prospectively. Those treated with PAP and tracked by the EncoreAnywhere system (Philips Respironics, Murrysville, PA) were analyzed. Those who stopped PAP within 1 month were excluded from this analysis. Compliance, therapy data, and waveform data were analyzed. Machine-detected vs manually scored events were compared at the first, third, sixth, and 12th month from PAP initiation. Logistic regression was used to determine factors associated with a high REIFLOW difference. RESULTS: One hundred and seventy-nine patients with a mean age 59.06 ± 13.97 years, median body mass index of 33.60 (29.75-38.75) kg/m2, and median baseline apnea-hypopnea index of 46.30 (31.50-65.90) events/h were included. The difference between the machine-detected REIFLOW and manually scored REIFLOW was 10.72 ± 8.43 events/h in the first month and remained stable for up to 12 months. Male sex and large leak ≥ 1.5% were more frequent in patients who had an REIFLOW difference of ≥ 5 events/h of use. A titration arousal index ≥ 15 events/h of sleep, and higher ratio of unstable to stable breathing were also associated with an REIFLOW difference ≥ 5 events/h of use. CONCLUSIONS: There is a substantial and sustained difference between manual and automated event estimates during PAP therapy, and some associated factors were identified. CITATION: Ni Y-N, Thomas RJ. A longitudinal study of the accuracy of positive airway pressure therapy machine-detected apnea-hypopnea events. J Clin Sleep Med. 2022;18(4):1121-1134.

The role of acetazolamide in sleep apnea at sea level: a systematic review and meta-analysis.

STUDY OBJECTIVES: The recognition of specific endotypes as drivers of sleep apnea suggests the need of therapies targeting individual mechanisms. Acetazolamide is known to stabilize respiration at high altitude but benefits at sea level are less well understood. METHODS: All controlled studies of acetazolamide in obstructive sleep apnea and/or central sleep apnea (CSA) were evaluated. The primary outcome was the apnea-hypopnea index. RESULTS: Fifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall apnea-hypopnea index (mean difference [MD] -15.82, 95% CI: -21.91 to -9.74, P < .00001) in central sleep apnea (MD -22.60, 95% CI: -29.11 to -16.09, P < .00001), but not in obstructive sleep apnea (MD -10.29, 95% CI: -33.34 to 12.77, P = .38). Acetazolamide reduced the respiratory related arousal index (MD -0.82, 95% CI: -1.56 to -0.08, P = .03), improved partial arterial of oxygen (MD 11.62, 95% CI: 9.13-14.11, P < .00001), mean oxygen saturation (MD 1.78, 95% CI: 0.53-3.04, P = .005), total sleep time (MD 25.74, 95% CI: 4.10-47.38, P = .02), N2 sleep (MD 3.34, 95% CI: 0.12-6.56, P = .04) and sleep efficiency (MD 4.83, 95% CI: 0.53-9.13, P = .03). CONCLUSIONS: Acetazolamide improves the apnea-hypopnea index and several sleep metrics in central sleep apnea. The drug may be of clinical benefit in patients with high loop gain apnea of various etiologies and patterns. The existence of high heterogeneity is an important limitation in applicability of our analysis. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; Name: The effect of acetazolamide in patients with sleep apnea at sea level: a systematic review and meta analysis; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316; Identifier: CRD42020163316.

The Effect of Conservative Oxygen Therapy in Reducing Mortality in Critical Care Patients: A Meta-Analysis and Trial Sequential Analysis.

Background: Conservative oxygen therapy can prevent both hypoxemia and hyperoxemia, but the effect on the prognosis of patients admitted to the intensive care unit (ICU) remains controversial. Methods: All controlled studies comparing conservative oxygen therapy and conventional oxygen therapy in adult patients admitted to the ICU were searched. The primary outcome was mortality, and the secondary outcomes were length of ICU stay (ICU LOS), length of hospital stay (hospital LOS), length of mechanical ventilation (MV) hours, new organ failure during ICU stay, and new infections during ICU stay. Results: Nine trials with a total of 5,759 patients were pooled in our final studies. Compared with conventional oxygen therapy, conservative oxygen therapy did not reduce overall mortality (Z = 0.31, p = 0.75) or ICU LOS (Z = 0.17, p = 0.86), with firm evidence from trial sequential analysis, or hospital LOS (Z = 1.98, p = 0.05) or new infections during the ICU stay (Z = 1.45, p = 0.15). However, conservative oxygen therapy was associated with a shorter MV time (Z = 5.05, p < 0.00001), reduction of new organ failure during the ICU stay (Z = 2.15, p = 0.03) and lower risk of renal replacement therapy (RRT) (Z = 2.18, p = 0.03). Conclusion: Conservative oxygen therapy did not reduce mortality but did decrease MV time, new organ failure and risk of RRT in critically ill patients. Systematic Review Registration: identifier [CRD42020171055].

The independent factors associated with oxygen therapy in COVID-19 patients under 65 years old.

BACKGROUND: The number of hospitalized young coronavirus disease 2019 (COVID-19) patients has increased significantly. However, specific data about COVID-19 patients under 65 years old who are admitted to the hospital are scarce. METHODS: The COVID-19 patients under 65 years old who were admitted to the hospital in Sichuan Province, Renmin Hospital of Wuhan University, and Wuhan Red Cross Hospital were included in this study. Demographic information, laboratory data and clinical treatment courses were extracted from electronic medical records. Risk factors associated with oxygen therapy were explored. RESULTS: Eight hundred thirty-three COVID-19 patients under 65 years old were included. Of the included patients, 29.4% had one or more comorbidities. Oxygen therapy was required in 63.1% of these patients, and the mortality was 2.9% among the oxygen therapy patients. Fever (odds ratio [OR] 2.072, 95% confidence interval [CI] 1.312-3.271, p = 0.002), dyspnea (OR 2.522, 95% CI 1.213-5.243, p = 0.013), chest distress (OR 2.278, 95% CI 1.160-4.473, p = 0.017), elevated respiratory rate (OR 1.114, 95% CI 1.010-1.228, p = 0.031), and decreased albumin (OR 0.932, 95% CI 0.880-0.987, p = 0.016) and globulin levels (OR 0.929, 95% 0.881-0.980, p = 0.007) were independent factors related to oxygen therapy. CONCLUSIONS: Oxygen therapy is highly required in COVID-19 patients under 65 years old who are admitted to the hospital, but the success rate is high. Respiratory failure-related symptoms, elevated respiratory rate, low albumin and globulin levels, and fever at admission are independent risk factors related to the requirement of oxygen.

Could the loss of diaphragm thickness measured by computer tomography predict the rate of reintubation?

BACKGROUND: Diaphragm function loss is very common in the intensive care unit (ICU) and can predict the success of weaning. However, whether diaphragm thickness loss during mechanical ventilation (MV) as measured by computed tomography (CT) can predict the rate of reintubation remains unclear. Therefore, we hypothesized that a loss of diaphragm thickness would impact the outcome of weaning. METHODS: A retrospective study was performed on patients who received MV in the ICU of West China Hospital, Sichuan University. The diaphragm thickness of each patient on the CT scans within 48 hours after MV and 24 hours before weaning were measured by at least two independent investigators. The primary outcome was the rate of reintubation, and the second outcomes included hospital mortality and the length of ICU stay (ICU LOS) after extubation. RESULTS: A total of 145 patients were included in the analysis. According to the receiver operating characteristic curve, all patients were divided into two groups (less or more than 1.55 mm diaphragm thickness loss in reintubation). As a result, less loss of diaphragm thickness was a protective factor for the rate of reintubation [33% vs. 12%; adjusted odds ratio (aOR) 0.001; 95% confidence interval (CI), 0.001-0.271; P=0.018] and hospital mortality (18% vs. 4%; aOR 0.001; 95% CI, 0.001-0.035; P=0.007). However, no significant difference was found in the ICU LOS after extubation between the two groups. CONCLUSIONS: Less diaphragm thickness loss was related to a lower rate of reintubation and hospital mortality.