Use of High-Flow Nasal Cannula in Patients With Pneumonia and Hypoxemic Respiratory Failure at Altitudes Above 2600 m: What Is the Best Predictor of Success?

Introduction: The use of high-flow nasal cannulas (HFNC) in patients with hypoxemic ventilatory failure reduces the need for mechanical ventilation and does not increase mortality when intubation is promptly applied. The aim of the study is to describe the behavior of HFNC in patients who live at high altitudes, and the performance of predictors of success/failure of this strategy. Methods: Prospective multicenter cohort study, with patients aged over 18 years recruited for 12 months in 2020 to 21. All had a diagnosis of hypoxemic respiratory failure secondary to pneumonia, were admitted to intensive care units, and were receiving initial management with a high-flow nasal cannula. The variables assessed included need for intubation, mortality in ICU, and the validation of SaO2, respiratory rate (RR) and ROX index (IROX) as predictors of HFNC success / failure. Results: One hundred and six patients were recruited, with a mean age of 59 years and a success rate of 74.5%. Patients with treatment failure were more likely to be obese (BMI 27.2 vs 25.5; OR: 1.03; 95% CI: .95-1.1) and had higher severity scores at admission (APACHE II 12 vs 20; OR 1.15; 95% CI: 1.06-1.24). Respiratory rates after 12 (AUC .81 CI: .70-.92) and 18 h (AUC .85 CI: .72-0.90) of HFNC use were the best predictors of failure, performing better than those that included oxygenation. ICU mortality was higher in the failure group (6% vs 29%; OR 8.8; 95% CI:1.75-44.7). Conclusions: High-flow oxygen cannula therapy in patients with hypoxemic respiratory failure living at altitudes above 2600 m is associated with low rates of therapy failure and a reduced need for mechanical ventilation in the ICU. The geographical conditions and secondary physiological changes influence the performance of the traditionally validated predictors of therapy success. Respiratory rate <30 proved to be the best indicator of early success of the device at 12 h of use.

Adherence to long-term oxygen therapy in patients with chronic obstructive pulmonary disease.

Long-term oxygen therapy (LTOT) has beneficial effects on survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia at rest. Two landmark trials suggested that these benefits depend on the time of exposure to oxygen. Patients are usually prescribed LTOT for at least 15-18 hours/day. The primary objective of this study was to determine the average daily exposure to supplemental oxygen in patients with severely hypoxemic COPD who were newly prescribed LTOT and the proportion of patients who were adherent to their prescription. The secondary objective was to identify predictors of compliance to LTOT. We performed a retrospective observational study of patients newly registered in a regional home oxygen program in Quebec, Canada, between July 1, 2013, and December 31, 2014. Daily exposure to oxygen was objectively measured from the concentrator's counter clock. From 196 patients registered in the program during the study period, 115 contributed to the analysis. Most patients ( n = 84; 73%) were prescribed oxygen for ≥18 hours/day. Overall, the 115 patients were exposed to home oxygen for 17.8 hours/day; 60% of the patients were compliant according to our definition. Increasing age and ambulatory oxygen utilization predicted adherence to oxygen therapy. Adherence to home oxygen therapy is suboptimal. Behavioral and psychological interventions to improve compliance to LTOT should be investigated.

Regulation of lung maturation by prolyl hydroxylase domain inhibition in the lung of the normally grown and placentally restricted fetus in late gestation.

Intrauterine growth restriction induced by placental restriction (PR) in sheep leads to chronic hypoxemia and reduced surfactant maturation. The underlying molecular mechanism involves altered regulation of hypoxia signaling by increased prolyl hydroxylase domain (PHD) expression. Here, we evaluated the effect of intratracheal administration of the PHD inhibitor dimethyloxalylglycine (DMOG) on functional, molecular, and structural determinants of lung maturation in the control and PR sheep fetus. There was no effect of DMOG on fetal blood pressure or fetal breathing movements. DMOG reduced lung expression of genes regulating hypoxia signaling (HIF-3α, ACE1), antioxidant defense (CAT), lung liquid reabsorption (SCNN1-A, ATP1-A1, AQP-1, AQP-5), and surfactant maturation (SFTP-A, SFTP-B, SFTP-C, PCYT1A, LPCAT, ABCA3, LAMP3) in control fetuses. There were very few effects of DMOG on gene expression in the PR fetal lung (reduced lung expression of angiogenic factor ADM, water channel AQP-5, and increased expression of glucose transporter SLC2A1). DMOG administration in controls reduced total lung lavage phosphatidylcholine to the same degree as in PR fetuses. These changes appear to be regulated at the molecular level as there was no effect of DMOG on the percent tissue, air space, or numerical density of SFTP-B positive cells in the control and PR lung. Hence, DMOG administration mimics the effects of PR in reducing surfactant maturation in the lung of control fetuses. The limited responsiveness of the PR fetal lung suggests a potential biochemical limit or reduced plasticity to respond to changes in regulation of hypoxia signaling following exposure to chronic hypoxemia in utero.

Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients.

BACKGROUND: Fibroblast growth factor-23 (FGF23) levels are elevated in cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI); however, it is unknown how much of the circulating FGF23 is intact and bioactive. Hypoxia may induce FGF23 production, yet its impact in humans is unknown. Pediatric cardiac surgery patients have both a high incidence of CPB-associated AKI and a high prevalence of chronic hypoxemia. METHODS: We assessed the effects of hypoxemia and CPB-associated AKI on C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 32 pediatric cardiac surgery patients with normal estimated glomerular filtration rate (eGFR). Plasma cFGF23 and iFGF23 were measured preoperatively and serially postoperatively. RESULTS: Despite normal renal and ventricular function, preoperative cFGF23 levels were high and elevated out of proportion to iFGF23 levels. Preoperative oxygen saturation measurements correlated inversely with FGF23 levels. Preoperative cFGF23 and oxygen saturation both predicted postoperative AKI. Postoperatively, cFGF23 and iFGF23 increased by 2 h postreperfusion; iFGF23 then returned to baseline, but cFGF23 remained elevated through 24 h postreperfusion. Group status (AKI vs. non-AKI) modified the effect of time on changes in iFGF23 levels but not cFGF23 levels. CONCLUSIONS: Preoperative cFGF23 may predict CPB-associated kidney dysfunction. Changes over time in cFGF23 and iFGF23 levels post-CPB differ. Chronic hypoxemia may affect FGF23 production in humans.

Novel Insights into Cardiovascular Regulation in Patients with Chronic Mountain Sickness.

Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease in general. Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world affecting many millions of high-altitude dwellers. It is characterized by exaggerated chronic hypoxemia, erythrocytosis, and mild pulmonary hypertension. In later stages these patients often present with right heart failure and are predisposed to systemic cardiovascular disease, but the underlying mechanisms are poorly understood. Here, we present recent new data providing insight into underlying mechanisms that may cause these complications.

Tuberculosis Is Associated with Chronic Hypoxemia among Kenyan Adults (CHAKA): A Case-Control Study.

Rationale: Data on risk factors for chronic hypoxemia in low- and middle-income countries are lacking. Objectives: We aimed to quantify the association between potential risk factors and chronic hypoxemia among adults hospitalized in Kenya. Methods: A hospital-based, case-control study was conducted at Moi Teaching and Referral Hospital in Eldoret, Kenya. Adult inpatients were screened on admission and enrolled in a 1:2 case-to-control ratio. Cases were patients with chronic hypoxemia, defined as resting oxygen saturation as measured by pulse oximetry (SpO2) ⩽ 88% on admission and either 1-month postdischarge SpO2 ⩽ 88% or, if they died before follow-up, documented SpO2 ⩽ 88% in the 6 months before enrollment. Control subjects were randomly selected, stratified by sex, among nonhypoxemic inpatients. Data were collected using questionnaires and structured chart review. Regression was used to assess the associations between chronic hypoxemia and age, sex, smoking status, biomass fuel use, elevation, and self-reported history of tuberculosis and human immunodeficiency virus diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Results: We enrolled 108 chronically hypoxemic cases and 240 nonhypoxemic control subjects into our Chronic Hypoxemia among Kenyan Adults (CHAKA) cohort. In multivariable analysis, compared with control subjects, chronically hypoxemic cases had significantly higher odds of older age (OR, 1.2 per 5-year increase [95% CI, 1.1-1.3]), female sex (OR, 3.6 [95% CI, 1.8-7.2]), current or former tobacco use (OR, 4.7 [95% CI, 2.3-9.6]), and prior tuberculosis (OR, 11.8 [95% CI, 4.7-29.6]) but no increase in the odds of human immunodeficiency virus diagnosis and biomass fuel use. Conclusions: These findings highlight the potential impact of prior tuberculosis on chronic lung disease in Kenya and the need for further studies on posttuberculosis lung disease.

De novo progressive dural arteriovenous fistula with putamen hemorrhage associated with long-term Down syndrome: A case report and literature review.

Dural arteriovenous fistula (DAVF) is considered an acquired change in blood flow related to factors such as craniotomy, trauma, and infection. However, several factors related to its development remain unknown. Here, we present a case of a 48-year-old man with Down syndrome and Eisenmenger syndrome. He had a history of craniotomy for multiple brain abscesses, followed by the occurrence of a de novo straight sinus (StS) DAVF within the last 2 years. The patient presented with right putamen hemorrhage due to venous congestion by a StS DAVF. The shunt flow was occluded by transarterial embolization using Onyx. Several studies have reported on DAVF models induced by venous congestion and hypoxemia. In this case, local venous congestion due to craniotomy for multiple brain abscesses was considered as one of the causes of DAVF. Complication of venous thrombosis or chronic hypoxemia due to Eisenmenger syndrome might have led to its progression. Especially in DAVF cases with Down syndrome, concomitant symptoms such as hypoxemia due to congenital heart failure and coagulopathy could worsen the disease state progressively.

Conjunctival congestion: a novel clinical sign in older children with Tetralogy of Fallot.

Tetralogy of Fallot is the most common cyanotic heart disease in children. While doing echocardiographic examination of children with Tetralogy of Fallot, we observed that many older children with this condition had congestion in their bulbar conjunctiva, easily recognizable even from some distance. This observation led us to design and perform a research study in order to find out the presence of conjunctival congestion in children with Tetralogy of Fallot. 85% of children in the ≥ 5-years of age group had conjunctival congestion without any ocular symptom. This novel clinical finding can act as an adjunct clinical sign for recognizing Tetralogy of Fallot in older children.

Anesthesia of a high-altitude area inhabitant who underwent aortic dissection emergency surgery in a low-altitude area.

Heart surgery in patients from high-altitude areas is more challenging than usual. Few studies have been published on this issue, and none of them have discussed the effect of an altitude change (from high to low altitude) on a patient's physiology or its effects on a patient's perioperative management. Here, we present the case of a 46-year-old man who was a long-time resident of Tibetan area in Sichuan (altitude >3000 m) who underwent Stanford type A aortic dissection emergency surgery on the plain. Anesthetic management occurred through monitoring of the bispectral index (BIS) and transesophageal echocardiography (TEE), and we used a relatively loose fluid hydration strategy. The surgery was performed using cardiopulmonary bypass (CPB), deep hypothermia (DH), and selective antegrade cerebral perfusion. The most prominent anesthesia challenges for these patients are physiological changes due to habitation in an high-altitude environment (chronic hypoxemia), which can cause hyperhemoglobinemia, polycythemia, hypercoagulable blood, and even pulmonary hypertension, cor pulmonale, or congestive heart failure. Optimized perioperative management and close cooperation among the entire cardiac medical team were the key factors in the successful management of this rare case.

Predictors of Impaired Survival in Subjects With Long-Term Oxygen Therapy.

BACKGROUND: The need for long-term oxygen therapy (LTOT) is usually a sign of advanced disease, which could trigger advance care planning. However, LTOT is used in patients with different characteristics and multiple diagnoses beyond COPD. We studied the factors associated with survival in an unselected sample of subjects who started LTOT. METHODS: We conducted a retrospective study that included 195 subjects for whom LTOT was initiated in Tampere University Hospital from January 1, 2012, to December 31, 2015, and followed up until December 31, 2017. RESULTS: The most frequent diseases that caused the need for LTOT were COPD and interstitial lung diseases. Most of the subjects (69%) died during the study period; the median survival time was 2.2 y. The subjects with interstitial lung disease as a primary disease for LTOT had a shorter survival time (median 0.9 y) compared with those with COPD (median 2.4 y, P < .001). Survival was shorter in the subjects ages >75 y (median 1.4 y) compared with those who were ages ≤75 y (median 2.8 y, P = .001) and also in those who required help with daily activities (median 1.2 y) compared with those who did not (median 3.3 y, P < .001). In multivariate analysis, a diagnosis of interstitial lung disease (hazard ratio 2.1, 95% CI 1.4-3.2), Charlson comorbidity index (hazard ratio 1.26, 95% Cl 1.11-1.43), and required help in activities of daily living (hazard ratio 2.1, 95% CI 1.4-3.1) were associated with impaired survival. CONCLUSIONS: The survival of the subjects who started LTOT varied greatly. The subjects with interstitial lung disease and those who required assistance with activities of daily living were at risk of dying in ∼1 y, which suggested that advance care planning should be directed especially to these patients.

Resistance of subventricular neural stem cells to chronic hypoxemia despite structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival.

Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia.