Inspiratory Muscle Dysfunction Mediates and Predicts a Disease Continuum of Hypercapnic Failure in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Advanced chronic obstructive pulmonary disease (COPD) is associated with chronic hypercapnic failure. The present work aimed to comprehensively investigate inspiratory muscle function as a potential key determinant of hypercapnic respiratory failure in patients with COPD. METHODS: Prospective patient recruitment encompassed 61 stable subjects with COPD across different stages of respiratory failure, ranging from normocapnia to isolated nighttime hypercapnia and daytime hypercapnia. Arterialized blood gas analyses and overnight transcutaneous capnometry were used for patient stratification. Assessment of respiratory muscle function encompassed body plethysmography, maximum inspiratory pressure (MIP), diaphragm ultrasound, and transdiaphragmatic pressure recordings following cervical magnetic stimulation of the phrenic nerves (twPdi) and a maximum sniff manoeuvre (Sniff Pdi). RESULTS: Twenty patients showed no hypercapnia, 10 had isolated nocturnal hypercapnia, and 31 had daytime hypercapnia. Body plethysmography clearly distinguished patients with and without hypercapnia but did not discriminate patients with isolated nocturnal hypercapnia from those with daytime hypercapnia. In contrast to ultrasound parameters and transdiaphragmatic pressures, only MIP reflected the extent of hypercapnia across all three stages. MIP values below -48 cmH2O predicted nocturnal hypercapnia (area under the curve = 0.733, p = 0.052). CONCLUSION: In COPD, inspiratory muscle dysfunction contributes to progressive hypercapnic failure. In contrast to invasive tests of diaphragm strength only MIP fully reflects the pathophysiological continuum of hypercapnic failure and predicts isolated nocturnal hypercapnia.

Brain Oxygenation Response to Hypercapnia in Patients with Acute Brain Injury.

BACKGROUND: Cerebral hypoxia is a frequent cause of secondary brain damage in patients with acute brain injury. Although hypercapnia can increase intracranial pressure, it may have beneficial effects on tissue oxygenation. We aimed to assess the effects of hypercapnia on brain tissue oxygenation (PbtO2). METHODS: This single-center retrospective study (November 2014 to June 2022) included all patients admitted to the intensive care unit after acute brain injury who required multimodal monitoring, including PbtO2 monitoring, and who underwent induced moderate hypoventilation and hypercapnia according to the decision of the treating physician. Patients with imminent brain death were excluded. Responders to hypercapnia were defined as those with an increase of at least 20% in PbtO2 values when compared to their baseline levels. RESULTS: On a total of 163 eligible patients, we identified 23 (14%) patients who underwent moderate hypoventilation (arterial partial pressure of carbon dioxide [PaCO2] from 44 [42-45] to 50 [49-53] mm Hg; p < 0.001) during the study period at a median of 6 (4-10) days following intensive care unit admission; six patients had traumatic brain injury, and 17 had subarachnoid hemorrhage. A significant overall increase in median PbtO2 values from baseline (21 [19-26] to 24 [22-26] mm Hg; p = 0.02) was observed. Eight (35%) patients were considered as responders, with a median increase of 7 (from 4 to 11) mm Hg of PbtO2, whereas nonresponders showed no changes (from - 1 to 2 mm Hg of PbtO2). Because of the small sample size, no variable independently associated with PbtO2 response was identified. No correlation between changes in PaCO2 and in PbtO2 was observed. CONCLUSIONS: In this study, a heterogeneous response of PbtO2 to induced hypercapnia was observed but without any deleterious elevations of intracranial pressure.

Ultrastructural Changes in Hippocampal Region CA1 Neurons After Exposure to Permissive Hypercapnia and/or Normobaric Hypoxia.

Isolated exposure to intermittent hypoxia and permissive hypercapnia activates signaling mechanisms that induce ultrastructural changes in mitochondria and endoplasmic reticulum, accompanied by the development of maximal ischemic tolerance in neurons under the combined influence of these factors. However, there are a lack of data on the combined impact of these factors on the ultrastructure of neuronal organelles. The present study aims to comparatively assess the ultrastructural changes in neurons following isolated and combined exposure to hypoxia and hypercapnia, as well as to correlate these changes with the neuroprotective potential previously observed for these factors. Following a 15-session course of 30-min exposures to permissive hypercapnia (PCO2 ≈ 50 mmHg) and/or normobaric hypoxia (PO2 ≈ 150 mmHg), morphometric assessment was conducted to evaluate the extent of ultrastructural changes in hippocampal neurons (mitochondria, perinuclear space, and granular endoplasmic reticulum). It was found that in hippocampal neurons from the CA1 region, permissive hypercapnia resulted in increased mitochondrial size, expansion of membranous compartments of the granular endoplasmic reticulum, and perinuclear space. Normobaric hypoxia affected only mitochondrial size, while hypercapnic hypoxia specifically widened the perinuclear space. These ultrastructural changes objectively reflect varying degrees of the influence of hypoxia and hypercapnia on organelles responsible for energy metabolism, anti-apoptotic, and synthetic functions of neurons. This confirms the effect of potentiation of their neuroprotective effects under combined exposure and highlights the dominant role of the hypercapnic component in this mechanism.

Association between rate of change in PaCO2 and functional outcome for patients with hypercapnia after out-of-hospital cardiac arrest: Secondary analysis of a randomized clinical trial.

BACKGROUND: Normocapnia is suggested for post resuscitation care. For patients with hypercapnia after cardiac arrest, the relationship between rate of change in partial pressure of carbon dioxide (PaCO2) and functional outcome was unknown. METHODS: This was the secondary analysis of Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. Patients with at least 2 PaCO2 recorded and the first indicating hypercapnia (PaCO2 > 45 mmHg) after return of spontaneous circulation (ROSC) were included. The rate of change in PaCO2 was calculated as the ratio of the difference between the second and first PaCO2 to the time interval. The primary outcome was modified Rankin Score (mRS), dichotomized to good (mRS 0-3) and poor (mRS 4-6) outcomes at hospital discharge. The independent relationship between rate of change in PaCO2 and outcome was investigated with multivariable logistic regression model. RESULTS: A total of 746 patients with hypercapnia were included for analysis, of which 264 (35.4%) patients had good functional outcome. The median rate of change in PaCO2 was 4.7 (interquartile range [IQR] 1.7-12) mmHg per hour. After adjusting for confounders, the rate of change in PaCO2 (odds ratio [OR] 0.994, confidence interval [CI] 0.985-1.004, p = 0.230) was not associated the functional outcome. However, rate of change in PaCO2 (OR 1.010, CI 1.001-1.019, p = 0.029) was independently associated with hospital mortality. CONCLUSIONS: For OHCA patients with hypercapnia on admission, the rate of change in PaCO2 was not independently associated with functional outcome; however, there was a significant trend that higher decreased rate was associated with increased hospital mortality.

Hypercapnia in hospitalized children and adolescents with anorexia nervosa as a predictive marker for readmission: a prospective study.

PURPOSE: To determine whether hypercapnia is associated with risk of hospital readmission related to anorexia nervosa (AN) in children and adolescents. METHODS: We performed a prospective study of patients ≤ 18 years old admitted due to AN decompensation from November 2018 to October 2019. Both subtypes of AN, restricting subtype (AN-R) and binge-eating/purging subtype (AN-BP), were included. Study participants were evaluated upon admission, at discharge and six months after discharge. T-tests or Mann-Whitney U tests was used to compare means values. Pearson or Spearman correlations were used to measure the association between two variables. Logistic regression models were developed to evaluate the relationship between scoring methods and readmission. RESULTS: Of the 154 persons admitted during the study period, 131 met the inclusion criteria. Median age was 15.1 years. At admission, 71% of participants were malnourished and 33 (25%) had been previously admitted. We observed a marked decrease in venous pH and stable pCO2 elevation during follow-up period. Hypercapnia at discharge was associated with a twofold increased likelihood of readmission and the odds of readmission increased as discharge pCO2 rose. These findings did not depend on AN subtype or participant sex. Electrolytes persisted within the normal range. CONCLUSION: Hypercapnia and respiratory acidosis are common alterations in children and adolescents hospitalized due to AN decompensation. Hypercapnia persists for at least 6 months after discharge despite clinical improvement and is associated with higher odds of readmission. This is the first study to identify an abnormal laboratory finding as a potential predictor of readmission in AN. LEVEL OF EVIDENCE: IV: Multiple time series without intervention.

Hypercapnic respiratory failure - review.

This review summarizes the issue of acute hypercapnic respiratory failure. Acute respiratory failure is a condition in which the respiratory system is unable to fulfill its basic function, i.e. enriching the blood with oxygen and excreting carbon dioxide. Chronologically, we divide it into acute and chronic, and according to the manifestation into hypoxemic or hypoxemic with hypercapnia. Multiple factors, such as reduced ventilation and increased dead space, contribute to the development of hypoxemic-hypercapnic (global) respiratory failure. Both the patient's clinical presentation and laboratory examination of blood gases and acid-base balance (preferably from arterial blood) are used for diagnosis. In the absence of contraindications, non-invasive ventilation is used to establish normocapnia.

The difference in clinical features and prognosis of severe adenoviral pneumonia in children of different ages.

This study aims to analyze the difference in clinical features and prognosis of severe adenovirus pneumonia (SAP) in children of different ages and analyze the risk factors for poor prognosis in children with SAP. A retrospective observational study was performed to describe the clinical features and analyze the risk factors for death and postinfectious bronchiolitis obliterans (PIBO) in 303 children hospitalized with SAP from January 2015 through to January 2020. The participants were divided into four age groups: <6 months (n = 25, 8.3%); 6-12 months (n = 98, 32.3%); 12-36 months (n = 118, 38.9%); and >36 months (n = 62, 20.5%). Fever rate, peak, and duration were the lowest in the <6 months group, while no significant difference was found among other age groups. Serum levels of lactate dehydrogenase and a load of adenovirus were the lowest in the <6 months group, and the highest in the 6-12 and 12-36 months groups, respectively. A total of 80.9% of patients recovered, 3.3% of patients died, and 15.8% of patients were diagnosed with PIBO. The mortality rate showed no significance between age groups. The >36 months group had the highest recovery rate and the lowest incidence of PIBO, while the 6-12 months group had the lowest recovery rate and the highest incidence of PIBO. Independent risk factors for PIBO among all participants from the four groups were invasive mechanical ventilation, administration of intravenous steroids, duration of fever, and male gender. Independent risk factors for death among all participants from the four groups were hypercapnia, low albumin levels, and invasive mechanical ventilation. Risk factor analysis of different ages was not possible due to the limited sample size. The morbidity, clinical features, and prognosis of SAP are affected by children's ages. Pediatric patients with a longer duration of fever, hypercapnia, low serum albumin levels, invasive mechanical ventilation, and intravenous steroids use are more likely to develop a poor prognosis in SAP, especially if the patient is male.

A comparison between bronchial blockers and double-lumen tubes for patients undergoing lung resection: A propensity score-matched cohort study.

Objective: The aim of this study is to compare the effect of bronchial blockers (BB) and double-lumen tubes (DLT) on patients' postoperative recovery after lung resection. Method: 4,636 patients undergoing lung resection and receiving either BB or DLT intubation were reviewed and matched using the propensity score matching method. The primary outcome was the surgical duration. The secondary outcomes included diagnostic results of postoperative chest X-ray, postoperative oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, chest tube duration, incidence of ICU admission, length of hospital stay and incidence of the 30-day readmission. Results: After matching, 401 patients receiving BB were matched to 3,439 patients receiving DLT. There was no statistical difference on the surgical duration between the two groups (P>0.05). However, compared with the DLT group, patients in the BB group showed more infiltrate especially at the surgery side (14.96% versus 9.07%, P<0.001) based on the chest X-ray, together with higher incidence of ICU admission (5.23% versus 2.61%, P<0.05). Additionally, no statistical differences were found between the two groups about chest tube duration, oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, duration of surgery, hospital stays and 30-day readmission (P>0.05). Conclusions: Compared with the DLT, patients receiving BB technique tend to have increased pulmonary infiltrate (especially the surgery side) and higher incidence of ICU admission at the early post-operative stage, which may have an influence on the patients' recovery.

Optimal Targets of the First 24-h Partial Pressure of Carbon Dioxide in Patients with Cerebral Injury: Data from the MIMIC-III and IV Database.

BACKGROUND: It is generally believed that hypercapnia and hypocapnia will cause secondary injury to patients with craniocerebral diseases, but a small number of studies have shown that they may have potential benefits. We assessed the impact of partial pressure of arterial carbon dioxide (PaCO2) on in-hospital mortality of patients with craniocerebral diseases. The hypothesis of this research was that there is a nonlinear correlation between PaCO2 and in-hospital mortality in patients with craniocerebral diseases and that mortality rate is the lowest when PaCO2 is in a normal range. METHODS: We identified patients with craniocerebral diseases from Medical Information Mart for Intensive Care third and fourth edition databases. Cox regression analysis and restricted cubic splines were used to examine the association between PaCO2 and in-hospital mortality. RESULTS: Nine thousand six hundred and sixty patients were identified. A U-shaped association was found between the first 24-h PaCO2 and in-hospital mortality in all participants. The nadir for in-hospital mortality risk was estimated to be at 39.5 mm Hg (p for nonlinearity < 0.001). In the subsequent subgroup analysis, similar results were found in patients with traumatic brain injury, metabolic or toxic encephalopathy, subarachnoid hemorrhage, cerebral infarction, and other encephalopathies. Besides, the mortality risk reached a nadir at PaCO2 in the range of 35-45 mm Hg. The restricted cubic splines showed a U-shaped association between the first 24-h PaCO2 and in-hospital mortality in patients with other intracerebral hemorrhage and cerebral tumor. Nonetheless, nonlinearity tests were not statistically significant. In addition, Cox regression analysis showed that PaCO2 ranging 35-45 mm Hg had the lowest death risk in most patients. For patients with hypoxic-ischemic encephalopathy and intracranial infections, the first 24-h PaCO2 and in-hospital mortality did not seem to be correlated. CONCLUSIONS: Both hypercapnia and hypocapnia are harmful to most patients with craniocerebral diseases. Keeping the first 24-h PaCO2 in the normal range (35-45 mm Hg) is associated with lower death risk.

A Study of Cardiac Troponin T Levels in Acute Exacerbation of Copd and its Correlation with Severity.

Chronic obstructive pulmonary disease (COPD) is a significant health burden and is one of the leading causes of death having rising mortality rate in developed and developing countries. Cardiac troponin t (cTnT) is an established myocardial injury marker and not only increases in flow- limiting coronary artery stenosis or occlusion of coronary arteries but also in pulmonary embolism, septic shock, heart failure and stroke. The positive association between elevation of cTnT and neutrophils due to exaggerated inflammatory response leading to myocardial injury and increased cTnT can have prognostic value in acute exacerbation of COPD. Material: The present study was conducted with the aim of predicting the severity of COPD exacerbation based on level of cardiac TnT. 85 patients with a diagnosis of COPD age more than 20 years admitted in general medicine wards in SMS medical college during 2020 were enrolled in this study. Spirometry and Chest Xray were used in diagnosing COPD. Troponin T level was measured within 1 hour of admission. Severity of the exacerbation was estimated by PaO2 & PaCO2 levels and need for assisted ventilation. Observation: Here, in our study 43.53% cases has troponin-T elevated. And amongst those with Trop T elevated 82.4% needed assisted ventilation compared to 24.6 % patients with normal Trop T needing assisted ventilation indicating significant positive correlation of Trop t level with need for assisted ventilation in acute exacerbation of COPD. Amongst those with elevated Trop T, mean oxygen saturation was77.97 % and mean pco2 was 73%. Whilst those with normal troponin T level they had mean oxygen saturation of 86% and mean co2 level of 42% indicating that those with elevated cardiac Trop T has more severe hypoxia and more severe hypercapnia compared to those with normal cardiac Trop T level implying significant positive association of elevated Trop T level with severity of COPD exacerbation Conclusion: This observation implies there is a positive correlation of elevated trop T level and severity of acute exacerbation of COPD in terms of need for assisted ventilation, severity of hypoxia and hypercapnia .So assessment of Trop T level in acute exacerbation of COPD will be having prognostic benefit and can be used for assessing course of the disease along with better management of the patients.

Chronic psychic stress can cause metabolic syndrome through mild hypercapnia.

The author presents a new psychosomatic stress model. All the elements of the hypothesis are well known but, in this context, are published first. The following are the most critical aspects of the recommended chronic stress model. 1/ Stress contains both sympathetic and parasympathetic elements, but the latter predominate. 2/ The mediator of stress is carbon dioxide, the substance that can turn the psyche into soma. 3/ In humans, chronic stress is mainly social; people cause it to each other. Chronic social stress is created frequently due to deviations in civilisation, education and tolerance. 4/ The freeze response (or freezing behaviour) plays a subordinate role in the animal world; it lasts mainly for a maximum of minutes, while in humans, it dominates and can continue for decades. 5/ The decisive step of freeze is apnea, hypopnea, which occurs due to aversive psychological eff ects. After a more extended existence, mild chronic respiratory acidosis develops and most often appears in the clinical form of obstructive sleep apnea. 6/ Chronic hypercapnia can shape the metabolism into metabolic syndrome. 7/ After that, various cardiovascular and metabolic complications (hypertension, atherosclerosis, type 2 diabetes, depression) may develop - partly due to genetic and lifestyle reasons. (Neuropsychopharmacol Hung 2022; 24(3): 126-133).

Breath-holding as a novel approach to risk stratification in COVID-19.

BACKGROUND: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). METHODS: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. RESULTS: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. CONCLUSIONS: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.

Long-Term Noninvasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.

The effect of mild hypercapnia on hospital mortality after cardiac arrest may be modified by chronic obstructive pulmonary disease.

BACKGROUND: The main objective was to evaluate the effect of carbon dioxide on hospital mortality in chronic obstructive pulmonary disease (COPD) and non-COPD patients with out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a retrospective observational study in OHCA patients from the eICU database (eicu-crd.mit.edu). The main exposure was the partial pressure of arterial carbon dioxide (PaCO2). The proportion of time spent (PTS) within four predefined PaCO2 ranges (hypocapnia: <35 mmHg, normocapnia: 35-45 mmHg, mild hypercapnia: 46-55 mmHg, and severe hypercapnia: >55 mmHg) were calculated respectively. The primary outcome was hospital mortality. Multivariable logistic regression models were performed to assess the independent relationship between PTS within PaCO2 range and hospital mortality, and the interaction between PTS within PaCO2 range and COPD was explored. RESULTS: A total of 1721 OHCA patients were included, of which 272 (15.8%) had COPD. After adjusted for the confounders, the PTS within mild hypercapnia was associated with lower odds ratio for hospital mortality in COPD patients (OR 0.923; 95% CI 0.857-0.992; P = 0.036); however, it was associated with higher odds ratio for hospital mortality in non-COPD patients (OR 1.053; 95% CI 1.012-1.097; P = 0.012; Pinteraction = 0.008). The PTS within normocapnia was not associated with hospital mortality in COPD patients (OR 0.987; 95% CI 0.914-1.067; P = 0.739); however, it was associated with lower odds ratio for hospital mortality in non-COPD patients (OR 0.944; 95% CI 0.916-0.973; P < 0.001; Pinteraction = 0.113). CONCLUSIONS: The effect of carbon dioxide on hospital mortality differed between COPD and non-COPD patients. Mild hypercapnia was associated with increased hospital mortality for non-COPD patients but reduced hospital mortality for COPD patients. It would be reasonable to adjust PaCO2 targets in OHCA patients with COPD.

Coagulation dysfunction in patients with AECOPD and its relation to infection and hypercapnia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have coagulation abnormalities. However, the factors that lead to coagulation dysfunction in acute exacerbation of COPD (AECOPD) remain insufficiently explored. This study aimed to investigate the factors affecting coagulation status in patients with COPD and their influence on thrombosis. METHODS: Data of COPD patients, including 135 cases in acute exacerbation stage and 44 cases in stable stage from Nov 2016 to Nov 2019 in our hospital, were collected. Healthy people (n = 135) were enrolled as the controls. The coagulation parameters, blood gas indexes and blood routine examination results were collected and analyzed. RESULTS: White blood count (WBC), neutrophil count, neutrophil percentage (N%), platelet (PLT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), and activated partial thromboplastin time (APTT) increased, plasma thrombin time (TT) decreased in AECOPD group compared with the control group. In AECOPD group, PT, APTT, and FIB were positively correlated with neutrophils and C-reaction protein levels. PT was positively correlated with PCO2 and negatively with pH. Thrombosis was observed in five acute exacerbation and three stable stage COPD patients. CONCLUSIONS: Patients with AECOPD presented abnormal coagulation status, which was correlated to infection and hypercapnia and might be potentially the risk factor of thrombosis.

One-Year Readmission Following Undifferentiated Acute Hypercapnic Respiratory Failure.

Patients with acute hypercapnic respiratory failure (AHRF) often require hospitalization and respiratory support. Early identification of patients at risk of readmission would be helpful. We evaluated 1-y readmission and mortality rates of patients admitted for undifferentiated AHRF and identified the impact of initial severity on clinically important outcomes. We retrospectively analyzed patients who presented with AHRF to the emergency department of St Michael's Hospital in 2017. We collected data about patients' characteristics, hospital admission, readmission and mortality one year after the index admission. We analyzed predictors of readmission and mortality and conducted a survival analysis comparing patients who did and did not receive ventilatory support. A cohort of 212 patients with AHRF who survived their hospital admission were analyzed. At one year, 150 patients (70.8%) were readmitted and 19 (9%) had died. Main diagnoses included chronic obstructive pulmonary disease (60%), congestive heart failure (36%), asthma (22%) and obesity (19%), and these categories of patients had similar 1 y readmission rates. One third had more than one coexisting chronic illness. Although comorbidities were more frequent in readmitted patients, only a history of previous hospital admissions remained associated with 1 y readmission and mortality in multivariate analysis. Need for ventilatory support at admission was not associated with higher 1 y probability of readmission or death. Undifferentiated AHRF is the presentation of multiple chronic illnesses. Patients who survive one episode of AHRF and with previous history of admission have the highest risk of readmission and death regardless of whether they receive ventilatory support during index admission.

Cerebral Blood Flow in Chronic Kidney Disease.

The prevalence of mild cognitive impairment increases with age and is further exacerbated by chronic kidney disease (CKD). CKD is associated with (1) mild cognitive impairment, (2) impaired endothelial function, (3) impaired blood-brain barrier, (4) increased cerebral microhemorrhage burden, (5) increased cerebral blood flow (CBF), (6) impaired cerebral autoregulation, (7) impaired cerebrovascular reactivity, and (8) increased arterial stiffness. We report preliminary findings from our group that demonstrate altered cerebrovascular reactivity in a mouse model of CKD-associated vascular calcification. The CBF of CKD mice increased more quickly in response to hypercapnia (p < 0.05) but then decreased prematurely during hypercapnia challenge (p < 0.05). Together, these results indicate that altered kidney function can lead to alterations in the cerebral microvasculature, and hence brain health.

Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study.

BACKGROUND: Tidal expiratory flow limitation (EFLT) promotes intrinsic PEEP (PEEPi) in patients with chronic obstructive pulmonary disease (COPD). Applying non-invasive ventilation (NIV) with an expiratory positive airway pressure (EPAP) matching PEEPi improves gas exchange, reduces work of breathing and ineffective efforts. We aimed to evaluate the effects of a novel NIV mode that continuously adjusts EPAP to the minimum level that abolishes EFLT. METHODS: This prospective, cross-over, open-label study randomized patients to one night of fixed-EPAP and one night of EFLT-abolishing-EPAP. The primary outcome was transcutaneous carbon dioxide pressure (PtcCO2). Secondary outcomes were: peripheral oxygen saturation (SpO2), frequency of ineffective efforts, breathing patterns and oscillatory mechanics. RESULTS: We screened 36 patients and included 12 in the analysis (age 72 ± 8 years, FEV1 38 ± 14%Pred). The median EPAP did not differ between the EFLT-abolishing-EPAP and the fixed-EPAP night (median (IQR) = 7.0 (6.0, 8.8) cmH2O during night vs 7.5 (6.5, 10.5) cmH2O, p = 0.365). We found no differences in mean PtcCO2 (44.9 (41.6, 57.2) mmHg vs 54.5 (51.1, 59.0), p = 0.365), the percentage of night time with PtcCO2 > 45 mm Hg was lower (62(8,100)% vs 98(94,100)%, p = 0.031) and ineffective efforts were fewer (126(93,205) vs 261(205,351) events/hour, p = 0.003) during the EFLT-abolishing-EPAP than during the fixed-EPAP night. We found no differences in oxygen saturation and lung mechanics between nights. CONCLUSION: An adaptive ventilation mode targeted to abolish EFLT has the potential to reduce hypercapnia and ineffective efforts in stable COPD patients receiving nocturnal NIV. TRIAL REGISTRATION: ClicalTrials.gov, NCT04497090. Registered 29 July 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04497090 .

Fossorial giant Zambian mole-rats have blunted ventilatory responses to environmental hypoxia and hypercapnia.

Fossorial giant Zambian mole-rats are believed to live in a hypoxic and hypercapnic subterranean environment but their physiological responses to these challenges are entirely unknown. To investigate this, we exposed awake and freely-behaving animals to i) 6 h of normoxia, ii) acute graded normocapnic hypoxia (21, 18, 15, 12, 8, and 5% O2, 0% CO2, balance N2; 1 h each), or iii) acute graded normoxic hypercapnia (0, 2, 5, 7, 9, and 10% CO2, 21% O2, balance N2; 1 h each), followed by a 1 h normoxic normocapnic recovery period, while non-invasively measuring ventilation, metabolic rate, and body temperature (Tb). We found that these mole-rats had a blunted hypoxic ventilatory response that manifested at 12% inhaled O2, a robust hypoxic metabolic response (up to a 68% decrease, starting at 15% O2), and decreased Tb (at or below 8% O2). Upon reoxygenation, metabolic rate increased 52% above normoxic levels, suggesting the paying off of an O2 debt. Ventilation was less sensitive to environmental hypercapnia than to environmental hypoxia and animals also exhibited a blunted hypercapnic ventilatory response that did not manifest below 9% inhaled CO2. Conversely, metabolism and Tb were not affected by hypercapnia. Taken together, these results indicate that, like most other fossorial rodents, giant Zambian mole-rats have blunted hypoxic and hypercapnic ventilatory responses and employ metabolic suppression to tolerate acute hypoxia. Blunted physiological responses to hypoxia and hypercapnia likely reflect the subterranean lifestyle of this mammal, wherein intermittent but severe hypoxia and/or hypercapnia may be common challenges.

Predictors of NIV Treatment in Patients with COPD Exacerbation Complicated by Respiratory Acidaemia.

Non-invasive ventilation (NIV) treatment decisions are poorly understood for patients with COPD exacerbation complicated by acute hypercapnic respiratory failure and respiratory acidaemia (ECOPD-RA). We identified 420 NIV-eligible patients from the DECAF study cohorts admitted with an ECOPD-RA. Using bivariate and multivariate analyses, we examined which indices were associated with clinicians' decisions to start NIV, including whether the presence of pneumonia was a deterrent. Admitting hospital, admission from institutional care, partial pressure of oxygen, cerebrovascular disease, pH, systolic blood pressure and white cell count were all associated with the provision of NIV. Of these indices, only pH was also a predictor of inpatient death. Those not treated with NIV included those with milder acidaemia and higher (and sometimes excessive) oxygen levels, and a frailer population with higher Extended Medical Research Council Dyspnoea scores, presumably deemed not suitable for NIV. Pneumonia was not associated with NIV treatment; 34 of 111 (30.6%) NIV-untreated patients had pneumonia, whilst 107 of 309 (34.6%) NIV-treated patients had pneumonia (p = 0.483). In our study, one in four NIV-eligible patients were not treated with NIV. Clinicians' NIV treatment decisions are not based on those indices most strongly associated with mortality risk. One of the strongest predictors of whether a patient received a life-saving treatment is which hospital they attended. Further research is required to aid in the risk stratification of this patient group which may help standardise and improve care.