Search

Introduction Surgery is one of the most frequently used options in the treatment of head and neck squamous cell carcinoma. In surgical patients, the use of arterial lactate to assess hypoxemia and severe inflammatory states is well-founded. However, there are few studies on its use in patients with head and neck squamous cell carcinoma. The aim of this study was to investigate whether the serum arterial lactate level on the 1st postoperative day would be a predictor of postoperative complications in head and neck squamous cell carcinoma surgeries. Methods This is a prospective cohort, which evaluated 44 adult patients of both genders, with HNSCC, who underwent surgery associated with monobloc neck dissection as an initial treatment. Patients were divided into two groups, according to the presence or absence of postoperative complications: with complication (Clavien-Dindo II-V) and without complications (Clavien-Dindo 0-I). Student’s t-test and its variants were used to compare continuous data. Pearson’s or Spearman’s test was used to correlate the data and p values 1.7 mmoL/L was identified, with a sensitivity of 65.38% and specificity of 66.67%. Conclusion Arterial lactate measured on the first postoperative day is a good predictor of postoperative complications in patients with head and neck squamous cell carcinoma. Resumo Introdução A cirurgia é uma das opções mais usadas no tratamento do carcinoma epidermoide de cabeça e pescoço. Nos pacientes cirúrgicos, o uso do lactato arterial para avaliação de hipoxemia e de quadros inflamatórios graves é bem fundamentado. Entretanto, existem poucos estudos sobre o seu uso em pacientes com carcinoma epidermoide de cabeça e pescoço. O objetivo deste estudo foi investigar se o lactato arterial sérico no 1° dia de pós‐operatório seria um preditor de complicações pós‐operatórias nas cirurgias do carcinoma epidermoide de cabeça e pescoço. Método Trata‐se de uma coorte prospectiva, que avaliou 44 pacientes adultos, de ambos os gêneros, com carcinoma epidermoide de cabeça e pescoço, submetidos a cirurgia associada ao esvaziamento cervical em monobloco como tratamento inicial. Os pacientes foram divididos em dois grupos, segundo a presença ou não de complicações pós‐operatórias: complicados (Clavien‐Dindo II a V) e sem complicações (Clavien‐Dindo 0-I). Na comparação dos dados contínuos, foi usado o teste t de Student e as suas variantes. Na correlação dos dados, usou‐se o teste de Pearson ou Spearman. Valores de p inferiores a 0,05 (p < 0,05) foram considerados estatisticamente significativos. Resultados Dos pacientes, 59% (n = 26/44) desenvolveram complicações pós‐operatórias. O lactato sérico foi significantemente maior no grupo com complicações em relação aos pacientes sem complicações, respectivamente 2,15 mmoL/L (1,10-3,90) e 1,59 mmoL/L (0,70-3,44); p = 0,03. A acurácia prognóstica do lactato arterial foi de 69% (95% IC 54%-82%; p = 0,03), estimada pela curva ROC. Foi identificado um cut‐off> 1,7 mmoL/L, com sensibilidade de 65,38% e especificidade de 66,67%. Conclusão O lactato arterial do primeiro dia de pós‐operatório é um bom preditor de complicações pós‐operatórias nos pacientes com carcinoma epidermoide de cabeça e pescoço.

We report a clinically significant right-to-left intracardiac shunt through a patent foramen ovale, diagnosed during investigations for hypoxemia and left ventricular dilation on the late postoperative period of a HeartMate3 implantation. We discuss diagnostic pitfalls and haemodynamic influences in this scenario, as well as the possibility of successful percutaneous treatment.

STUDY OBJECTIVES: Biological models suggest that obstructive sleep apnea (OSA) is potentially carcinogenic. We aimed to clarify the inconsistent epidemiological literature by considering various traditional and novel OSA severity indices. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane Library for observational or randomized studies of associations of OSA, measured by diagnostic codes or any index, each with all-cancer incidence or mortality in adults, compared with participants with no/mild OSA. Two reviewers independently selected studies, extracted data, and evaluated study bias using the Newcastle-Ottawa scale and quality of evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). We performed inverse variance-weighted, random-effects meta-analyses and sensitivity analyses. RESULTS: We included 20 observational studies (5,340,965 participants), all with moderate/low bias, from 1,698 records. Based on T90 (sleep duration with oxygen saturation < 90%), patients with OSA who had moderate (T90 > 1.2%, hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.07–1.54) and severe nocturnal hypoxemia (T90 > 12%, HR = 1.43, 95% CI = 1.16–1.76) experienced 30%–40% higher pooled all-cancer risk than normoxemic patients, after multiple adjustment for covariates including obesity. Furthermore, severe nocturnal hypoxemia nearly tripled all-cancer mortality (HR = 2.66, 95% CI = 1.21–5.85). Patients with apnea-hypopnea index–defined severe OSA, but not moderate OSA, had higher all-cancer risk (HR = 1.18, 95% CI = 1.03–1.35) but similar all-cancer mortality as patients without OSA. An OSA diagnosis was not associated with all-cancer risk. Evidence quality ranged from low to moderate. Insufficient evidence was available on the oxygen desaturation index, lowest/median saturation, and arousal index. CONCLUSIONS: In patients with OSA, nocturnal hypoxemia is independently associated with all-cancer risk and mortality. Future studies should explore if risk differs by cancer type, and whether cancer screening and OSA treatment are beneficial. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220836; Identifier: CRD42021220836. CITATION: Tan BKJ, Teo YH, Tan NKW, et al. Association of obstructive sleep apnea and nocturnal hypoxemia with all-cancer incidence and mortality: a systematic review and meta-analysis. J Clin Sleep Med. 2022;18(5):1427–1440.

Noninvasive ventilation (NIV) provides respiratory support without the use of invasive ventilation with techniques that do not bypass the upper airway. NIV is particularly attractive given its associated reduced risk of complications associated with intubation. Available NIV modes include nasal cannula, simple mask, nonrebreather, high flow nasal cannula, continuous positive airway pressure (CPAP), and bilevel positive airway pressure. Acute exacerbation of COPD, cardiogenic pulmonary edema, and COVID-19 are conditions for which NIV has shown to be beneficial, whereas there is no consensus among the use of NIV in trauma patients and ARDS.

There has been strong evidence of myocardial injury in coronavirus disease 2019 (COVID-19) patients with significantly elevated serum cardiac troponin (cTn). While the exact mechanism of injury is unclear, possible suggested pathological mechanisms of injury are discussed. These include increased susceptibility of the myocardium and endothelium to viral invasion, underlying hyperinflammatory state and subsequent cytokine storm, a hypercoagulable and prothrombotic state, and indirect myocardial injury due to hypoxemia. As a result of these pathological mechanisms in COVID-19 patients, cTn may be elevated largely due to myocarditis, microangiopathy or myocardial infarction. The utility of cTn as a biomarker for measuring myocardial injury in these patients and assessing its ability as a prognostic factor for clinical outcome is also discussed.

Opioids are widely prescribed for pain management, and it is estimated that 40% of adults in the United States use prescription opioids every year. Opioid misuse leads to high mortality, with respiratory depression as the main cause of death. Animal and human studies indicate that opioid use may lead to sleep-disordered breathing. Opioids affect control of breathing and impair upper airway function, causing central apneas, upper airway obstruction, and hypoxemia during sleep. The presence of obstructive sleep apnea (OSA) increases the risk of opioid-induced respiratory depression. However, even if the relationship between opioids and central sleep apnea is firmly established, the question of whether opioids can aggravate OSA remains unanswered. While several reports have shown a high prevalence of OSA and nocturnal hypoxemia in patients receiving a high dose of opioids, other studies did not find a correlation between opioid use and obstructive events. These differences can be attributed to considerable interindividual variability, divergent effects of opioids on different phenotypic traits of OSA, and wide-ranging methodology. This review will discuss mechanistic insights into the effects of opioids on the upper airway and hypoglossal motor activity and the association of opioid use and obstructive sleep apnea. CITATION: Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647–652.

Pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) affects 5% to 10% of adults with CHD and is associated with significant morbidity and mortality. PAH-CHD develops as a consequence of intracardiac or extracardiac systemic-to-pulmonary shunts that lead to pulmonary vascular remodeling through a pathologic process that is similar to other causes of PAH. Eisenmenger syndrome is the most severe phenotype of PAH-CHD and is characterized by severe elevation in pulmonary vascular resistance, with shunt reversal causing hypoxemia and central cyanosis. The primary management strategy for most patients with PAH-CHD is medical therapy, although defect closure is considered in select cases.

Background: The effectiveness and side effects of dexmedetomidine (DEX) in combination with midazolam and propofol have not been comparatively studied in a single clinical trial as sedative agents to general anesthesia before. Objective: The objective of this study is to compare intra and post-operative sedation between DEX-Midazolam and DEX-Propofol in patients who underwent major abdominal surgery on the duration of general anesthesia, hemodynamic and sedation effect. Method: This prospective, randomized, double-blinded clinical trial included 50 patients who were 20 to 60 years of age and admitted for major abdominal surgery. The patients were randomly assigned by a computer-generated random numbers table to sedation with DEX plus midazolam (DM group) (n=25) or DEX plus propofol (DP group) (n=25). In the DM group, patients received a bolus dose of 0.1 mg/kg of midazolam and immediately initiated the intravenous (i.v.) infusion of DEX 1 μg/kg over a 10 min and 0.5 μg/kg/hr by continuous i.v. infusion within operation period. In the DP group, patients received pre-anesthetic i.v. DEX 1 μg/kg over 15 min before anesthesia induction and 0.2-1 μg/kg/hr by continuous i.v. infusion during the operative period. After preoxygenation for at least 2 min, during the surgery, patients received propofol infusion dose of 250 μg/kg/min for 15 min then a basal infusion dose of 50 μg/kg/min. The bispectral index (BIS) value, as well as mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), oxygen saturation (SaO2), percutaneous arterial oxygen saturation (SpO2) and end-tidal carbon dioxide tension (ETCO2) were recorded before anesthesia (T0), during anesthesia (at 15-min intervals throughout the surgical procedure), by a blinded observer. Evidence of apnea, hypotension, hypertension and hypoxemia were recorded during surgery. Results: The hemodynamic changes, including HR, MAP, BIS, VT, SaO2, and RR had a downward tendency with time, but no significant difference was observed between the groups (P>0.05). However, the two groups showed no significant differences in ETCO2 and SPO2 values in any of the assessed interval (P>0.05). In this study, the two groups showed no significant differences in the incidence of nausea, vomiting, coughing, apnea, hypotension, hypertension, bradycardia and hypoxemia (P>0.05). Respiratory depression and serious adverse events were not reported in either group. Extubation time after surgery was respectively 6.3 ± 1.7 and 5.8 ± 1.4 hr. in the DM and DP groups and the difference was not statistically significant (P= 0.46). Conclusion: Our study showed no significant differences between the groups in hemodynamic and respiratory changes in each of the time intervals. There were also no significant differences between the two groups in the incidence of complication intra and post-operative. Further investigations are required to specify the optimum doses of using drugs which provide safety in cardiovascular and respiratory system without adverse disturbance during surgery. Clinical Trial Registration Number: HTCY-MA2018-74.

Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days. Complement biomarkers in patient sera and healthy controls were quantified by enzyme-linked immunosorbent assays. Correlations with respiratory function and mortality were analyzed. Activation of complement via the classical/lectin pathways was variably increased. Strikingly, all patients had increased activation of the alternative pathway (AP) with elevated levels of activation fragments, Ba and Bb. This was associated with a reduction of the AP negative regulator, factor (F) H. Correspondingly, terminal pathway biomarkers of complement activation, C5a and sC5b-9, were significantly elevated in all COVID-19 patient sera. C5a and AP constituents Ba and Bb, were significantly associated with hypoxemia. Ba and FD at the time of ICU admission were strong independent predictors of mortality in the following 30 days. Levels of all complement activation markers were sustained throughout the patients’ ICU stays, contrasting with the varying serum levels of IL-6, C-reactive protein, and ferritin. Severely ill COVID-19 patients have increased and persistent activation of complement, mediated strongly via the AP. Complement activation biomarkers may be valuable measures of severity of lung disease and the risk of mortality. Large-scale studies will reveal the relevance of these findings to thrombo-inflammation in acute and post-acute COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s00430-021-00725-2.

Background Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with ‘pneumonia’ the year previously. Methods We conducted a medical record review of patients admitted with Covid-19 and a pulmonary infiltrate and compared them with patients diagnosed with pneumonia admitted in the prior year before the pandemic. Data abstracted included baseline demographics, comorbidities, signs and symptoms, laboratory and microbiological results, and imaging findings. Outcomes were bacterial infections and mortality. Patients presenting with and without Covid-19 were compared using univariable and multivariable analyses. Results There were 1398 and 1001 patients admitted through the emergency department (ED) with and without Covid-19 respectively. Compared with non-Covid-19 patients, those with Covid-19 were younger (61±18 vs. 65±25 years, P

Background It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. Design and methods The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. Discussion The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation—patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible—however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Trial registration ISRCTN ISRCTN11536318. Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Background/Aims: Hypoxemia in chronic obstructive pulmonary disease (COPD) leads to reduced ability to exercise, decreased quality of life, and, eventually, increased mortality. Home oxygen therapy in patients with severe COPD reduces distress symptoms and mortality rates. However, there have been few studies on physicians’ prescription behavior toward home oxygen therapy. Therefore, we investigated the respiratory specialists’ perspective on home oxygen therapy.Methods: In this cross-sectional, study, a questionnaire was completed by 30 pulmonary specialists who worked in tertiary hospitals and prescribed home oxygen therapy. The questionnaire consisted of 28 items, including 15 items on oxygen prescription for outpatients, four for inpatients, and nine on service improvement.Results: All physicians were prescribing less than 2 L/min of oxygen for either 24 (n = 10, 33.3%) or 15 hours (n = 9, 30.3%). All (n = 30) used pulse oximetry, 26 (86.7%) analyzed arterial blood gas. Thirteen physicians had imposed restrictions and recommended oxygen use only during exercise or sleep. Sixteen (53.3%) physicians were educating their patients about home oxygen therapy. Furthermore, physicians prescribed home oxygen to patients that did not fit the typical criteria for longterm oxygen therapy, with 30 prescribing it for acute relief and 17 for patients with borderline hypoxemia.Conclusions: This study identified the prescription pattern of home oxygen therapy in Korea. Respiratory physicians prescribe home oxygen therapy to hypoxemic COPD patients for at least 15 hours/day, and at a rate of less than 2 L/min. More research is needed to provide evidence for establishing policies on oxygen therapy in COPD patients.

STUDY OBJECTIVES: Although cognitive impairment in obstructive sleep apnea (OSA) is primarily attributed to intermittent hypoxemia and sleep fragmentation, hypercapnia may also play a role in patients whose OSA is complicated by hypoventilation. This study investigated the impact of hypercapnia on cognitive function in severe sleep-disordered breathing (OSA accompanied by hypoventilation). METHODS: Patients with severe OSA (apnea-hypopnea index >30 events/h; n = 246) underwent evaluation for accompanying hypoventilation with polysomnography that included continuous transcutaneous carbon dioxide (TcCO(2)) monitoring and awake arterial blood gas analysis. Patients were categorized as having no hypoventilation (n = 84), isolated sleep hypoventilation (n = 40), or awake hypoventilation (n = 122). Global cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), memory with the Rey Auditory Verbal Learning Test (RAVLT), and processing speed with the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV), Digit Symbol Coding subtest (DSC). RESULTS: Apnea-hypopnea index was similar across groups (P = .15), but the sleep and awake hypoventilation groups had greater nocturnal hypoxemia compared with the no-hypoventilation group (P < .01). Within all groups, mean MoCA scores were < 26, which is the validated threshold to indicate mild cognitive impairment; RAVLT scores were lower than age-matched norms only in the awake-hypoventilation group (P ≤ .01); and DSC scores were lower than age-matched norms within all groups (P < .01). In multivariable regression analyses, higher arterial partial pressure of carbon dioxide (PaCO(2)) and TcCO(2) during wakefulness were associated with lower MoCA and DSC scores (P ≤ .03), independent of confounders including overlap syndrome (OSA + chronic obstructive pulmonary disease). CONCLUSIONS: Awake hypoventilation is associated with greater deficits in cognitive function in patients with severe sleep-disordered breathing. CITATION: Beaudin AE, Raneri JK, Ayas NT, Skomro RP, Smith EE, Hanly PJ; on behalf of Canadian Sleep and Circadian Network. Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing. J Clin Sleep Med. 2022;18(1):245–254.

Background In patients receiving single lung transplantation for idiopathic pulmonary fibrosis, worsening of fibrosis of the native lung is usually progressive over time, with no significant effects on gas exchange. Case presentation Here, we describe the cases of two Caucasian male recipients of single lung transplants for idiopathic pulmonary fibrosis, 65 and 62 years of age, who exhibited acute worsening of lung fibrosis after an episode of serious viral infection (cytomegalovirus primo-infection in one case and COVID-19 in the other). In both cases, along with opacification of the native lung over several days, the patients presented acute respiratory failure that required the use of high-flow nasal oxygen therapy. Eventually, hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung. Conclusion We conclude that acute worsening of fibrosis on the native lung secondary to a severe viral infection should be added to the list of potential complications developing on the native lung after single lung transplantation for idiopathic pulmonary fibrosis.

Low tidal volume ventilation protects the lung in mechanically ventilated patients. The impact of the accompanying permissive hypoxemia and hypercapnia on endothelial cell recovery from injury is poorly understood. CA (carbonic anhydrase) IX is expressed in pulmonary microvascular endothelial cells (PMVECs), where it contributes to CO(2) and pH homeostasis, bioenergetics, and angiogenesis. We hypothesized that CA IX is important for PMVEC survival and that CA IX expression and release from PMVECs are increased during infection. Although the plasma concentration of CA IX was unchanged in human and rat pneumonia, there was a trend toward increasing CA IX in the bronchoalveolar fluid of mechanically ventilated critically ill patients with pneumonia and a significant increase in CA IX in the lung tissue lysates of pneumonia rats. To investigate the functional implications of the lung CA IX increase, we generated PMVEC cell lines harboring domain-specific CA IX mutations. By using these cells, we found that infection promotes intracellular (IC) expression, release, and MMP (metalloproteinase)-mediated extracellular cleavage of CA IX in PMVECs. IC domain deletion uniquely impaired CA IX membrane localization. Loss of the CA IX IC domain promoted cell death after infection, suggesting that the IC domain has an important role in PMVEC survival. We also found that hypoxia improves survival, whereas hypercapnia reverses the protective effect of hypoxia, during infection. Thus, we report 1) that CA IX increases in the lungs of pneumonia rats and 2) that the CA IX IC domain and hypoxia promote PMVEC survival during infection.

Sepsis is a clinical syndrome resulting from infection followed by inflammation and is one of the significant causes of mortality worldwide. The underlying reason is the host's uncontrolled inflammatory response due to an infection led to multiple organ dysfunction/failure. Neutrophils, an innate immune cell, are forerunners to reach the site of infection/inflammation for clearing the infection and resolute the inflammation during sepsis. A relatively new neutrophil effector function, neutrophil extracellular traps (NETs), have been demonstrated to kill the pathogens by releasing DNA decorated with histone and granular proteins. A growing number of pieces of shreds of evidence suggest that unregulated incidence of NETs have a significant influence on the pathogenesis of sepsis-induced multiple organ damage, including arterial hypotension, hypoxemia, coagulopathy, renal, neurological, and hepatic dysfunction. Thus, excessive production and improper resolution of NETs are of significant therapeutic value in combating sepsis-induced multiple organ failure. The purpose of this review is intended to highlight the role of NETs in sepsis-induced organ failure. Furthermore, the current status of therapeutic strategies to intersect the harmful effects of NETs to restore organ functions is discussed.

Human lives and nations’ economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.

Key points Vascular dysfunction has been demonstrated in lowlanders at high-altitude (>4,000 m), however the extent of impairment and the delineation of contributing mechanisms have remained unclear. Using the gold-standard isolated perfused forearm model, we determined the extent of vasodilatory dysfunction and oxidative stress as a contributing mechanism in healthy lowlanders before and 4-6 days after rapid ascent to 4,300 m. The total forearm blood flow response to acetylcholine at high-altitude was decreased by ∼30%. Co-infusion of acetylcholine with the antioxidant vitamin C partially restored the total forearm blood flow by ∼20%. The magnitude of forearm blood flow reduction, as well as the impact of oxidative stress, was positively associated with the individual severity of hypoxemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourn, with important implications for understanding the etiology of high-altitude related changes in endothelial-mediated vasodilatory function. Abstract High-altitude induced hypoxemia is often associated with peripheral vascular dysfunction; however, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high-altitude. Ten young healthy lowlanders were tested at sea-level (344 m) and following 4-6 days at high-altitude (4,300 m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain-gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP), and co-infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high-altitude compared to sea-level (P = 0.048). There was no difference in the response to SNP at high-altitude (P = 0.860). At sea-level, co-infusion of ACh+VitC had no influence on the FBF dose response (P = 0.268); however, at high-altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% (P = 0.019). At high-altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxemia (R2 = 0.60, P = 0.008 and R2 = 0.63, P = 0.006, respectively). Collectively, these data support the hypothesis that impairments in vascular endothelial function at high-altitude are in part attributable to oxidative stress, consequent of the magnitude of hypoxemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourn, with important implications for understanding the etiology of high-altitude related vascular dysfunction. This article is protected by copyright. All rights reserved.

Background: The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global crisis challenging the worldwide healthcare systems. Many patients present with a mismatch of profound hypoxemia and few signs of respiratory distress (i.e., silent hypoxemia). This particular clinical presentation is often cited, but data are limited. Main Body: We describe dyspnea sensation as assessed by using the BORG scale in pulmonary patients admitted to the emergency room during a 4-week period and transferred to the respiratory department of Siloah Hospital, Hannover, Germany. From October 1 to November 1, 2020, 82 patients with hypoxemia defined as oxygen demand to achieve an oxygen saturation (SpO2) ≥92% were included. In 45/82 (55%) patients, SARS-CoV-2 was detected by PCR on admission. Among non-COVID patients, exacerbation of COPD was the main diagnosis (15/37, 41%). All subjects rated their perceived dyspnea using the modified Borg CR10 scale. Patients in the non-COVID group suffered from more dyspnea on the modified Borg CR10 scale (median 1, IQR: 0–2 vs. median 5, IQR: 3–6, p < 0.001). In multivariate analysis, “silent hypoxemia” as defined by the dyspnea Borg CR10 scale ≥5 was independently associated with COVID-19 and presence of severe hypocapnia with an odds ratio of 0.221 (95% confidence interval 0.054, 0.907, p 0.036). Conclusion: Among pulmonary patients with acute hypoxemia defined as oxygen demand, patients suffering from COVID-19 experience less dyspnea compared to non-COVID patients. “Silent” hypoxemia was more common in COVID-19 patients.

With the advent of thoracoscopic surgery, the benefits of lung isolation in children have been increasingly recognized. However, because of the small airway dimensions, equipment limitations in size and maneuverability, and limited respiratory reserve, one-lung ventilation in children remains challenging. This article highlights some of the most common error traps in the management of pediatric lung isolation and focuses on practical solutions for their management. The error traps discussed are as follows: (1) the failure to take into consideration relevant aspects of tracheobronchial anatomy when selecting the size of the lung isolation device, (2) failure to execute correct placement of the device chosen for lung isolation, (3) failure to maintain lung isolation related to surgical manipulation and isolation device movement, (4) failure to select appropriate ventilator strategies during one-lung ventilation, and (5) failure to appropriately manage and treat hypoxemia in the setting of one-lung ventilation.

Background Whether dysregulated iron metabolism is associated with COVID‐19‐associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID‐19 subjects with and without mucormycosis. Methods We conducted a case–control study enrolling COVID‐19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron‐binding capacity [TIBC], unsaturated iron‐binding capacity and percentage transferrin saturation) between CAM cases and COVID‐19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. Results We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino‐orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID‐19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 μg/dl, p = .03) and TIBC (166.6 vs. 201.6 μg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95–0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21–22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non‐survivors. Conclusions The CAM is associated with lower TIBC levels than COVID‐19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla...

Congenital interstitial lung diseases can affect both adults and children. Pediatric congenital interstitial lung diseases generally carry high risk for morbidly and mortality and include congenital alveolar capillary dysplasia with misalignment of pulmonary veins, congenital alveolar dysplasia, acinar dysplasia, congenital pulmonary lymphangiectasis, diffuse pulmonary lymphangiomatosis, neuroendocrine cell hyperplasia of infancy, pulmonary hemosiderosis, pulmonary alveolar proteinosis, and pulmonary interstitial glycogenosis. Given their usual non-specific clinical presentation, they are frequently misdiagnosed and recognized late, particularly in children who have been apparently healthy for several years (eg, diffuse pulmonary lymphangiomatosis). Some diseases have a very poor prognosis, whereas others have a benign course with appropriate treatment. The current manuscript reviews congenital interstitial lung diseases that typically affect neonates and young children and may be encountered by the pediatric anesthesiologist.

SARS‐CoV‐2 infection can present either an asymptomatic or symptomatic; the spectrum of symptomatic infection ranges from mild to critical. A majority of patients have experienced mild symptoms with a good prognosis. But approximately 14% of them have severe infection presenting with hypoxemia and extensive lung involvement. The current mini‐review describes the dysregulation of immune response for SARS‐CoV‐2 viral pneumonia and virus‐induced lung injury. Also, many confounding factors can increase lung injury, in addition to virus‐induced lung injury. Especially in critically ill patients, confounding factors can cause the inflammatory cascade, acute respiratory distress syndrome (ARDS), and mortality.

Background Angioedema, a localized swelling of subcutaneous and submucosal tissues, may involve the upper airway. A subset of patients presenting for emergent evaluation of angioedema will require intubation. Little is known about airway management practices in patients with angioedema requiring intubation in the emergency department (ED). Objective To describe airway management practices in patients intubated for angioedema in the ED. Methods We analyzed data from the National Emergency Airway Registry. All patients with an intubation attempt for angioedema between January 1, 2016 and December 31, 2018 were included. We report univariate descriptive data as proportions with cluster-adjusted 95% confidence intervals. Results Of 19,071 patient encounters, intubation was performed for angioedema in 98 (0.5%). First-attempt success was achieved in 81%, with emergency physicians performing the procedure in 94% of encounters. The most common device used was a flexible endoscope (49%), and 42% of attempts were via a nasal route. Pharmacologic methods included sedation with paralysis (61%), topical anesthesia with or without sedation (13% and 13%, respectively), and sedation only (10%). Among 19 (19%) patients requiring additional attempts, intubation was achieved on second attempt in 10 (53%). The most common adverse events were hypotension (13%) and hypoxemia (12%). Cricothyrotomy occurred in 2 patients (2%). No deaths were observed. Conclusions Angioedema was a rare indication for intubation in the ED setting. Emergency physicians achieved first-attempt success in 81% of encounters and used a broad range of intubation devices and methods, including flexible endoscopic techniques. Cricothyrotomy was rare, and no ED deaths were reported. © 2021 Elsevier Inc.

Background The aim of this study was to retrospectively describe the evolution of symptoms, infections, and mortality at a nursing facility in France that had implemented a protocol for the prevention and treatment of COVID-19. Methods A database was created on 21 March 2020 to store all information related to residents, including co-morbidities, as well as COVID-19 symptoms, incidence, and mortality. Residents followed a COVID-19 protocol, consisting of preventive (administering vitamins and zinc, social distancing, and temperature checks) and active (antibiotics, anticoagulants, and corticosteroids) measures. RT-PCR and serology testing were performed on residents. A new coefficient, named the Zemgor coefficient, was calculated as the haemoglobin-to-albumin ratio at 2 time points 15 days apart, to monitor hypoxemia. Results In January 2020, the nursing facility housed 192 residents, 75 men and 117 women, aged 80±11. One or more co-morbidities were present in 94% of residents, with the most common being dementia. The COVID-19 protocol provided 61% of residents with anticoagulants, 51%with antibiotics, 21% with oxygen therapy, and 3% with corticosteroids. The COVID-19 incidence was 51% based on presence of COVID-19 symptoms, 35% based on positive RT-PCR (amongst residents tested for RT-PCR) and 41% based on positive serology (amongst residents tested for serology), and the COVID-19 mortality rate was 8%. The Zemgor coefficient was 0.049±0.053 for patients with hypoxemia compared to 0.011±0.041 for patients without hypoxemia (P=0.001). Conclusions The protocol for the prevention and treatment of COVID-19 implemented at this nursing facility resulted in a COVID-19 incidence and mortality at the lower end of that reported by other nursing facilities.

Background Extracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza. Methods We searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza. Results The study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P

Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02860-3.

BACKGROUND Oxygen therapy is required to prevent hypoxaemia during the endobronchial ultrasonography (EBUS) procedure. AIMS To compare the effectiveness of oxygen therapy delivered through high-flow nasal cannula (HFNC) and conventional nasal cannula (CNC) in patients undergoing EBUS. The primary outcome was the proportion of patients who desaturated. Patient compliance and satisfaction were also evaluated. METHODS This single-centre prospective interventional study was conducted in a tertiary hospital among patients who presented to the EBUS unit in 2018 and 2019. Patients were randomly assigned to the HFNC group or the CNC group. RESULTS The study included 170 patients (111 men and 59 women) with a mean age of 58 ± 14 years. The number of patients experiencing desaturation while receiving oxygen was statistically significantly lower (P

Factors causing atrial tachyarrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF) remain undetermined. This study aimed to investigate the effect of nocturnal hypoxemia on the recurrence of atrial tachyarrhythmia after CA of AF. Among 594 patients with AF who underwent an ambulatory sleep study at the National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (2014–2019), 365 underwent CA of AF; 290 patients who underwent CA were followed up for > 3 months. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) using clinical variables, to identify the independent predictors of atrial tachyarrhythmia recurrence after the final CA. Atrial tachyarrhythmia recurred in 45 of 290 (15.5%) patients during the median follow-up period of 479 days (interquartile range 225–1002). On the performing multivariate analysis of the data of patients who did not receive continuous positive airway pressure (CPAP), severe nocturnal hypoxemia [defined as the percentage of sleep time spent with SaO2 of

BACKGROUND: The delivery of a high and consistent [Formula: see text] is imperative to treat acute hypoxemia. The objective of this study was to analyze the effective inspired oxygen concentration delivered by different low-flow oxygen therapy systems challenged with different oxygen flows and respiratory patterns in an experimental lung model. METHODS: An adult lung model ventilated in volume control mode simulated different respiratory patterns to obtain mean inspiratory flow of 22.5, 30.0, 37.5, or 45.0 L/min. The oxygen concentration sampled inside the lung model by nasal cannula, simple face mask, non-rebreather mask, and double-trunk mask above nasal cannula tested at oxygen flows of 10, 12.5, and 15 L/min was quantified. The 3 masks were sealed tight onto the model’s airway opening. They were also tested with standardized leaks to determine their clinical performance. RESULTS: All oxygen delivery systems delivered higher oxygen concentration with increasing oxygen flows, regardless of the respiratory pattern. Within each device, the increase in inspiratory flow decreased oxygen concentration when using nasal cannula (P = .03), the simple face mask (P = .03), but not the non-rebreather mask (P = .051) nor the double-trunk mask (P = .13). In sealed condition, the double-trunk mask outperformed the non-rebreather mask and simple face mask (P < .001); mean oxygen concentration was 84.2%, 68.5%, and 60.8%, respectively. Leaks amplified oxygen concentration differences between the double-trunk mask and the other masks as the oxygen delivery decreased by 4.6% with simple face mask (95% CI 3.1–6.1%, P < .001), 7.8% with non-rebreather mask (95% CI 6.3–9.3%, P < .001), and 2.5% with double-trunk mask (95% CI 1–4%, P = .002). With leaks, the oxygen concentration provided by the simple face mask and the non-rebreather mask was similar (P = .15). CONCLUSIONS: Lung oxygen concentration values delivered by the double-trunk mask were higher than those obtained with other oxygen delivery systems, especially when leaks were present.

Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial collapse of the upper airway and reduction of airflow during sleep. It is associated with significantly increased daytime muscle sympathetic nerve activity thought to result from the repetitive intermittent periods of hypoxemia during sleep and brain alterations that are likely to result. Different brain regions are affected by subsequent hypoxia/anoxia. Neurodegenerative processes result in measurable atrophy of cortical gray matter in the temporal lobes and posterior cingulate cortex, as well as in subcortical structures such as the hippocampus, amygdala, and thalamus. This study involved a group of firstly diagnosed, therapy-naive, nonalcoholic fatty liver disease (NAFLD) patients, out of which 144 (96 males and 48 females), aged 34–57 (mean 47.88 ± 6.07), satisfied the recruiting criteria for the study and control groups. All the patients underwent MRI scanning, polysomnography testing, and cognitive evaluation. Cognitively, worse results were obtained in the group with OSA ( p < 0.05 ) and NAFLD ( p = 0.047 ). A significant decrease in volumes of cortical and subcortical structures was revealed ( p < 0.001 ). In conclusion, brain deterioration followed by cognitive impairment is, most likely, the result of intermittent hypoxia and anoxia episodes that initiate the domino process of deteriorating biochemical reactions in the brain.

An relevance of the topic was defined by the high occurrence, unfavorable prognosis, lack of diagnostic techniques for early stages of acute kidney injury (AKI) disclosed in patients with COVID-19 (Coronavirus Disease 2019). Screening of medical literature for selection of AKI preclinical biomarkers was considered as main aim of this review. More than 200 publications from Russian Science Citation Index (RSCI), Scopus, The Cochrane Library, and MEDLINE were reviewed. Such risk factors as hypoxemia, increased intrathoracic pressure associated with Acute Respiratory Distress Syndrome (ARDS), hypertension (HT) involving endothelial dysfunction, and Diabetes mellitus were considered to be associated with AKI. There were explicated cytopathic and immune-mediated (cytokine-induced) mechanisms of COVID-19 associated AKI pathogenesis. Multiple methodological approaches were defined for detection and identification of the biomarkers based on urine proteome and metabolome screening. Perspective ways in the preclinical diagnostics of AKI such as detection of the markers of injury of the hypoxia-sensitive proximal canaliculi and the ATP metabolites that reflect first stages of the energy metabolism disorder in the epithelium lining canaliculi were identified in this study. The instantaneous and non-invasive investigation of different markers was regarded as possible method of the prognostication. The accuracy of the diagnosis on the initial stages of AKI, substantiate for preventive start of therapy, and make projections on the disease`s outcome will be improved due to the identification of high-sensitive specific biomarkers.

Aims Non-invasive ventilation represents an established treatment for acute cardiogenic pulmonary oedema (ACPO) although no data regarding the best ventilatory strategy are available. We aimed to compare the effectiveness of helmet CPAP (hCPAP) and high flow nasal cannula (HFNC) in the early treatment of ACPO. Methods and results Single-centre randomized controlled trial of patients admitted to the emergency department due to ACPO with hypoxemia and dyspnoea on face mask oxygen therapy. Patients were randomly assigned with a 1:1 ratio to receive hCPAP or HFNC and FiO2 set to achieve an arterial oxygen saturation >94%. The primary outcome was a reduction in respiratory rate; secondary outcomes included changes in heart rate, PaO2/FiO2 ratio, Heart rate, Acidosis, Consciousness, Oxygenation, and Respiratory rate (HACOR) score, Dyspnoea Scale, and intubation rate. Data were collected before hCPAP/HFNC placement and after 1 h of treatment. Amongst 188 patients randomized, hCPAP was more effective than HFNC in reducing respiratory rate [−12 (95% CI; 11–13) vs. −9 (95% CI; 8–10), P Conclusion Amongst patients with ACPO, hCPAP resulted in a greater short-term improvement in respiratory and hemodynamic parameters as compared with HFNC. Trial registration Clinical trial submission: NMRR-17-1839-36966 (IIR). Registry name: Medical Research and Ethics Committee of Malaysia Ministry of Health. Clinicaltrials.gov identifier: NCT04005092. URL registry: https://clinicaltrials.gov/ct2/show/NCT04005092.

Objective Pulse oximetry is commonly used in Neonatology, however recent adult data suggest racial disparity in accuracy, with overestimation of oxygen saturation for Black patients. Study design Black and White infants 90% when SaO2