Home NIV treatment quality in patients with chronic respiratory failure having participated to the French nationwide telemonitoring experimental program (The TELVENT study).

BACKGROUND: The ETAPES program is a national telemedicine experiment conducted in France between 2018 and 2023 to investigate whether home non-invasive ventilation (NIV) telemonitoring improves healthcare pathways in patients with chronic respiratory failure (CRF) and impacts healthcare organization. The program provides a combination of therapeutic education and NIV telemonitoring with data processed by an algorithm generating alerts. The TELVENT study objective was to analyze the evolution of ventilation quality in patients included in the ETAPES program. METHODS: Multicentric cohort study on patients undergoing long-term NIV included in the ETAPES program between September 2018 and December 2020 and who did not refuse the use of their data for this research. Data were obtained from homecare provider databases. The primary endpoint was to attain successful NIV treatment, which was determined by a combination of daily NIV usage for > 4 h per day, low leaks, and a low apnea-hypopnea index (AHI) identified by the NIV device. Respiratory disability was assessed using the DIRECT questionnaire. RESULTS: 329 patients were included in the study of which 145 had COPD and 83 had started NIV and ETAPES within one-month delay. Approximately 25% of patients did not achieve the criteria for successful NIV at ETAPES entry. The proportion of patients with successful NIV treatment increased to 86.8% at six months (p = 0.003, Cochran-Armitage trend test) regardless of NIV history and continued to increase at 12 months in newly equipped NIV patients (93.8%, at month 12, p = 0.0026 for trend test). Over time, a significant increase in NIV use and compliance was observed, while AHI significantly decreased in the overall population. No significant decrease was observed for non-intentional leaks. Approximately 4.9 alerts were generated per patient per 6 months. Their number and type (low NIV use, high AHI or leaks) differed among patients based on their NIV history. Respiratory disability score decreased over time compared with baseline. CONCLUSION: The TELVENT study highlights the importance of remote NIV monitoring to rapidly identify patients with unsuccessful ventilation. The combination of remote monitoring and therapeutic education may improve the quality of home NIV, especially in the first months of treatment.

Respiratory acidosis induced ST-segment elevation.

Acidosis has been reported to cause ST-segment elevation. We presented a woman with a history of rectal adenocarcinoma experienced cardiac arrest during the contrast-enhanced computed tomography examination. When spontaneous circulation returned, arterial blood gas revealed she had severe respiratory acidosis, and bedside electrocardiogram showed ST-segment elevation in anterior precordial leads. Emergent coronary angiography was normal. Echocardiography revealed no abnormality of cardiac cavity size, segmental wall motion, or pericardial echo. Carcinoma metastasis in the peritoneal cavity and lungs was detected on the contrast-enhanced computed tomography scan while the heart was not involved. The ST-segment regressed and the respiratory acidosis was corrected after she received mechanical ventilation which strongly suggested the association between acidosis and the electrocardiogram changes.

How do I wean a patient with acute hypercapnic respiratory failure from noninvasive ventilation?

Noninvasive ventilation (NIV) has been increasingly used for the management of different etiologies of acute hypercapnic respiratory failure (AHRF). Although NIV implementation has been framed well by the guidelines, limited number of studies evaluated the NIV weaning strategies, including a gradual decrease in the level of ventilator support and/or duration of NIV as well as abrupt discontinuation, once respiratory acidosis and distress have resolved. None of the methods have yet been established to be superior to the other in terms of the success rate of weaning and duration of NIV; as well as mortality, length of stay (LOS) in hospital, respiratory ICU (RICU), and ICU.  Patient-derived factors, such as etiology of AHRF, disease severity, history of prior NIV use, and clinical status can help to predict NIV weaning outcome and eventually choose the best method for each individual. In this paper, we have described the strategies for weaning a patient with AHRF from NIV and provided a quick guide for implementation of these data into daily practice based on our experience in and the current scientific evidence.

Acute and long-term management of severe bronchiectasis with high flow nasal therapy: A case report.

Bronchiectasis (BE) is a long-term, chronic lung condition featured by widened and scarred airways. These can alter the physiological mucociliary clearance, making it difficult to clear mucus and microorganisms, leading to frequent exacerbations. High flow nasal therapy (HFNT) is a noninvasive respiratory support that delivers heated and humidified gas eventually enriched with oxygen, through a nasal cannula.  Humidification is crucial for adequate airways mucociliary clearance, improving ciliary function and consequently reducing airways inflammation and recurrent infections. HFNT has been mostly used in patients with acute hypoxemic respiratory failure and in selected patients with chronic respiratory failure due to COPD. Still, evidence about its use in acute and long-term home setting in patients with clinically relevant BE are lacking. We report a case of severe widespread BE, already on top medical therapy and pulmonary rehabilitation, still suffering from difficult mucus expectoration and recurrent exacerbations, who has been additionally treated with HFNT, both in hospital and domiciliary, reporting significant improvements on relevant clinical and patient-centered outcomes. Thus, HFNT may confer additional benefits as an add-on treatment of patients with severe BE and respiratory failure.

Detection of Chronic Hypoventilation Among Infants With Robin Sequence Using Capillary Blood Gas Sampling.

OBJECTIVES/HYPOTHESIS: To describe the use of capillary blood gas (CBG) sampling to detect and quantify hypoventilation in infants with Robin sequence (RS). METHODS: Case series with chart review at two institutions. Infants with RS presenting over a 10-year period were identified using departmental databases. CBG values obtained during infancy or until airway intervention (AI) were reviewed. RESULTS: From 2008 to 2018, 111 infants with RS were identified as having had been assessed and managed from birth or transfer until discharge home and having CBG data available. In most cases, CBG sampling was obtained every other day until intervention or discharge. A total of 81 (73%) infants required AI: 72 (89%) underwent mandibular distraction osteogenesis, five (6%) underwent tracheotomy, and four (5%) were discharged home with a nasopharyngeal airway. The mean PCO2 at day of life (DOL) 7-30 for the AI group was 52.7 mmHg (95% confidence interval: 51.7-53.7) and for the no AI group was 45.9 mmHg (44.8-47.0; P < .0001). The mean HCO3 at DOL 7-30 for the AI group was 29.8 mEq/L (29.4-30.1) and for the no AI group was 27.0 mEq/L (26.5-27.4; P < .0001). Receiver operating characteristic curves were created for maximum PCO2 and HCO3 values and cutoffs were established by optimizing a balance of sensitivity and specificity. Infants requiring AI surpassed the PCO2 and HCO3 cutoff at a median of DOL 9. CONCLUSIONS: Among infants with RS and hypoventilation, objective measures of respiratory acidosis may be apparent by DOL 9. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2789-2794, 2021.

Sodium bicarbonate therapy for acute respiratory acidosis.

PURPOSE OF REVIEW: Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial. RECENT FINDINGS: There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained. SUMMARY: There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it.

Dead in the air- The need to adapt to CoVID adaptations.

During the recent CoVID-19 pandemic, airway management recommendations have been provided to decrease aerosolization and risk of viral spread to healthcare providers. High efficiency particulate air (HEPA) viral filters and adaptors are one way to decrease the risk of aerosolization during intubation. When placed proximal to the ventilator circuit, these viral filters and adaptors can create a significant amount of dead space, which in our smallest patients can significantly impact effective ventilation. We report a case of hypoventilation in a pediatric patient due to lack of provider team appreciation or ventilator sensing of additional dead space due to HEPA viral filter and adaptor.

Comparison of volume-controlled, pressure-controlled, and pressure-controlled volume-guaranteed ventilation during robot-assisted laparoscopic gynecologic surgery in the Trendelenburg position.

Background: Pressure-controlled ventilation volume-guaranteed (PCV-VG) is being increasingly used for ventilation during general anesthesia. Carbon dioxide (CO2) pneumoperitoneum in the Trendelenburg position is routinely used during robot-assisted laparoscopic gynecologic surgery. Here, we hypothesized that PCV-VG would reduce peak inspiratory pressure (Ppeak), compared to volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV). Methods: In total, 60 patients were enrolled in this study and randomly assigned to receive VCV, PCV, or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 minutes after the induction of anesthesia (T0), 30 and 60 minutes after CO2 pneumoperitoneum and Trendelenburg positioning (T1 and T2, respectively), and 15 minutes after placement in the supine position at the end of anesthesia (T3). Results: The Ppeak was higher in the VCV group than in the PCV and PCV-VG groups (p=0.011). Mean inspiratory pressure (Pmean) was higher in the PCV and PCV-VG groups than in the VCV group (p<0.001). Dynamic lung compliance (Cdyn) was lower in the VCV group than in the PCV and PCV-VG groups (p=0.001). Conclusion: Compared to VCV, PCV and PCV-VG provided lower Ppeak, higher Pmean, and improved Cdyn, without significant differences in hemodynamic variables or arterial blood gas results during robot-assisted laparoscopic gynecologic surgery with Trendelenburg position.

The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function.

Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts. This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

High flow nasal cannula in acute hypercapnic exacerbation of chronic obstructive pulmonary disease: an emerging utility.

High flow nasal cannula (HFNC) provides warmed and humidified air with flow rates up to 60 liters/min with relatively fixed oxygen content (FiO2). It has been extensively evaluated for hypoxemic respiratory failure and has been used in mild acute respiratory distress syndrome, pre-intubation, bronchoscopy and pediatric obstructive sleep apnea. Recent data has suggested a role in stable hypercapnic chronic obstructive pulmonary disease (COPD) and even in acute exacerbations, though, the use has not been advocated by any guidelines yet. We present a case of acute hypercapnic exacerbation of COPD, intolerant to non-invasive ventilation, showing response and improvement on use of HFNC. This case highlights this potential mechanisms and prospects for the same.

Hypoxia with acidosis in extremely preterm born infants was not associated with an increased risk of death or impaired neurodevelopmental outcome at 6.5 years.

AIM: It is not clear whether perinatal acidosis can predict poor outcomes in extremely preterm infants and we investigated associations between intrapartum hypoxia and mortality and neurodevelopmental outcomes. METHODS: We used nationwide data on 705 infants from the Extremely Preterm Infants in Sweden Study, delivered at 22-26 weeks of gestation during 2004-2007. Comprehensive neurodevelopmental assessments were performed on survivors at 2.5 (n = 456) and 6.5 (n = 441) years of corrected age. Gestational age-related changes in umbilical cord arterial pH were compared with reference values for term newborn infants, and base excess was also calculated. Associations between low blood gas values (<10th percentile) and mortality and neurodevelopmental outcome were estimated. RESULTS: Cord blood determination was more common in surviving infants (P < .001), with pH determined in 322/705 (46%) and base excess in 311/705 (44%). Extremely preterm infants had higher pH values than term infants (P < .0001), with no change from 22 to 26 weeks of gestation (P = .61, r2  = .001). Multiple logistic regression showed no association between low blood gas values and risk of death or neurodevelopmental impairment at 6.5 years (P ≥ .17). CONCLUSION: Hypoxia with acidosis at birth was not associated with an increased risk of death or impaired neurodevelopmental in extremely preterm born children at 6.5 years.

The evolutionary hypothesis of benign paroxysmal positional vertigo.

Human otoliths, primarily formed from salts of calcium and carbonate, are different from bones of the skeleton, which are composed of calcium phosphate. The echinoderms, which share the earliest common ancestor with us, began to protect the body by making an endoskeleton out of calcium and carbon dioxide dissolved in the sea. In subsequent vertebrates, aerobic respiration supported strong muscle activity, but an occasional shortage of oxygen led to low pH due to the accumulation of lactate produced by anaerobic respiration, increasing the risk of melting bones composed of calcium carbonate. So, all vertebrates used calcium phosphate to increase bone strength, having a stronger ionic bonding than calcium carbonate. But otoliths, which are in the inner ear and thereby not connected to muscles, still use calcium carbonate. Benign paroxysmal positional vertigo (BPPV) is a disorder in which otoliths detached from the utricle enter the semicircular canals and cause a sense of rotation. Otoliths, the calcium carbonate ear bones retaining a long evolutionary history, can be easily broken at low pH. During sleep, shallow breathing produces mild respiratory acidosis and low pH in the blood. Since otoliths are corroded at low pH during nighttime, BPPV occurs frequently in the morning. In addition, diabetes mellitus or gout often decreases pH in the blood and increases the occurrence of BPPV.

Noninvasive ventilation during weaning from prolonged mechanical ventilation.

BACKGROUND AND OBJECTIVE: Non invasive ventilation (NIV) is currently employed for weaning from invasive ventilation (IMV) in the acute setting but its use for weaning from prolonged ventilation is still occasional and not standardized. We wanted to evaluate whether a combined protocol of NIV and decannulation in tracheostomized patients needing prolonged mechanical ventilation was feasible and what would be the one-year outcome. METHODS: We studied patients still dependent from invasive mechanical ventilation with the following inclusion criteria: a) tolerance of at least 8h of unsupported breathing, b) progressive hypercapnia/acidosis after invasive ventilation discontinuation, c) good adaptation to NIV, d) favorable criteria for decannulation. These patients were switched from IMV to NIV and decannulated; then they were discharged on home NIV and followed-up for one year in order to evaluate survival and complications rate. RESULTS: Data from patients consecutively admitted to a weaning unit were prospectively collected between 2005 and 2018. Out of 587 patients admitted over that period, 341 were liberated from prolonged mechanical ventilation. Fifty-one out of 147 unweaned patients (35%) were eligible for the protocol but only 46 were enrolled. After a mean length of stay of 35 days they were decannulated and discharged on domiciliary NIV. After one year, 38 patients were still alive (survival rate 82%) and 37 were using NIV with good adherence (only one patient was switched again to invasive ventilation). CONCLUSIONS: NIV applied to patients with failed weaning from prolonged IMV is feasible and can facilitate the decannulation process. Patients successfully completing this process show good survival rates and few complications.

Respiratory acidosis during bronchoscopy-guided percutaneous dilatational tracheostomy: impact of ventilator settings and endotracheal tube size.

BACKGROUND: The current study investigates the effect of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) on the evolution of respiratory acidosis depending on endotracheal tube (ET) sizes. In addition, the impact of increasing tidal volumes during the intervention was investigated. METHODS: Two groups of ICU-patients undergoing bronchoscopy-guided PDT with varying tidal volumes and tube sizes were consecutively investigated: 6 ml/kg (N = 29, mean age 57.4 ± 14.5 years) and 12 ml/kg predicted body weight (N = 34, mean age 59.5 ± 12.8 years). RESULTS: The mean intervention time during all procedures was 10 ± 3 min. The combination of low tidal volumes and ETs of 7.5 mm internal diameter resulted in the most profound increase in PaCO2 (32.2 ± 11.6 mmHg) and decrease in pH-value (- 0.18 ± 0.05). In contrast, the combination of high tidal volumes and ETs of 8.5 mm internal diameter resulted in the least profound increase in PaCO2 (8.8 ± 9.0 mmHg) and decrease of pH (- 0.05 ± 0.04). The intervention-related increase in PaCO2 was significantly lower when using higher tidal volumes for larger ET: internal diameter 7.5, 8.0 and 8.5: P > 0.05, =0.006 and = 0.002, respectively. Transcutaneous PCO2 monitoring revealed steadily worsening hypercapnia during the intervention with a high correlation of 0.87 and a low bias of 0.7 ± 9.4 mmHg according to the Bland-Altman analysis when compared to PaCO2 measurements. CONCLUSIONS: Profound respiratory acidosis following bronchoscopy-guided PDT evolves in a rapid and dynamic process. Increasing the tidal volume from 6 to 12 ml/kg PBW was capable of attenuating the evolution of respiratory acidosis, but this effect was only evident when using larger ETs. TRIAL REGISTRATION: DRKS00011004 . Registered 20th September 2016.

Effects of chronic hypercapnia on ammonium transport in the mouse kidney.

Hypercapnia and subsequent respiratory acidosis are serious complications in many patients with respiratory disorders. The acute response to hypercapnia is buffering of H+ by hemoglobin and cellular proteins but this effect is limited. The chronic response is renal compensation that increases HCO3- reabsorption, and stimulates urinary excretion of titratable acids (TA) and NH4+ . However, the main effective pathway is the excretion of NH4+ in the collecting duct. Our hypothesis is that, the renal NH3 /NH4+ transporters, Rhbg and Rhcg, in the collecting duct mediate this response. The effect of hypercapnia on these transporters is unknown. We conducted in vivo experiments on mice subjected to chronic hypercapnia. One group breathed 8% CO2 and the other breathed normal air as control (0.04% CO2 ). After 3 days, the mice were euthanized and kidneys, blood, and urine samples were collected. We used immunohistochemistry and Western blot analysis to determine the effects of high CO2 on localization and expression of the Rh proteins, carbonic anhydrase IV, and pendrin. In hypercapnic animals, there was a significant increase in urinary NH4+ excretion but no change in TA. Western blot analysis showed a significant increase in cortical expression of Rhbg (43%) but not of Rhcg. Expression of CA-IV was increased but pendrin was reduced. These data suggest that hypercapnia leads to compensatory upregulation of Rhbg that contributes to excretion of NH3 /NH4+ in the kidney. These studies are the first to show a link among hypercapnia, NH4+ excretion, and Rh expression.

The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pH.

KEY POINTS: Normal pH is crucial for proper functioning of the brain, and disorders increasing the level of CO2 in the blood lead to a decrease in brain pH. CO2 can easily cross the barriers of the brain and will activate chemoreceptors leading to an increased exhalation of CO2 . The low pH, however, is harmful and bases such as HCO3- are imported across the brain barriers in order to normalize brain pH. We show that the HCO3- transporter NBCe2 in the choroid plexus of the blood-cerebrospinal fluid barrier is absolutely necessary for normalizing CSF pH during high levels of CO2 . This discovery represents a significant step in understanding the molecular mechanisms behind regulation of CSF pH during acid-base disturbances, such as chronic lung disease. ABSTRACT: The choroid plexus epithelium (CPE) is located in the brain ventricles where it produces the majority of the cerebrospinal fluid (CSF). The hypothesis that normal brain function is sustained by CPE-mediated CSF pH regulation by extrusion of acid-base equivalents was tested by determining the contribution of the electrogenic Na+ -HCO3- cotransporter NBCe2 to CSF pH regulation. A novel strain of NBCe2 (Slc4a5) knockout (KO) mice was generated and validated. The base extrusion rate after intracellular alkalization was reduced by 77% in NBCe2 KO mouse CPE cells compared to control mice. NBCe2 KO mice and mice with CPE-targeted NBCe2 siRNA knockdown displayed a reduction in CSF pH recovery during hypercapnia-induced acidosis of approximately 85% and 90%, respectively, compared to control mice. NBCe2 KO did not affect baseline respiration rate or tidal volume, and the NBCe2 KO and wild-type (WT) mice displayed similar ventilatory responses to 5% CO2 exposure. NBCe2 KO mice were not protected against pharmacological or heating-induced seizure development. In conclusion, we establish the concept that the CPE is involved in the regulation of CSF pH by demonstrating that NBCe2 is necessary for proper CSF pH recovery after hypercapnia-induced acidosis.