Association of Noninvasive Respiratory Support with Extubation Outcomes in Brain-injured Patients Receiving Mechanical Ventilation: A Secondary Analysis of the ENIO Prospective Observational Study.

Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). The primary endpoint was reintubation during ICU admission. We used mixed-effects logistic regression models with patient-level covariates and random intercepts for hospital and country to evaluate the association between prophylactic (i.e., planned) HFNC or NIPPV and reintubation. Measurements and Main Results: 1,115 patients were included from 62 hospitals and 19 countries, of whom 267 received HFNC or NIPPV following extubation (23.9%). Compared with conventional oxygen therapy, neither prophylactic HFNC nor NIPPV was associated with decreased odds of reintubation (respectively, odds ratios of 0.97 [95% confidence interval, 0.54-1.73] and 0.63 [0.30-1.32]). Findings remained consistent in sensitivity analyses accounting for alternate adjustment procedures, missing data, shorter time frames of the primary endpoint, and competing risks precluding reintubation. In a Bayesian analysis using skeptical and data-driven priors, the probabilities of reduced reintubation ranged from 17% to 34% for HFNC and from 46% to 74% for NIPPV. Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).

Repetitive postoperative extubation failure due to dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy.

BACKGROUND: This report describes a case of dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy that led to repeated post-operative extubation failure. CASE PRESENTATION: A 43-year-old woman who had undergone tracheostomy 25 years previously was admitted to our intensive-care unit (ICU) after coronary artery bypass graft surgery. On postoperative day (POD) 0, she was extubated, but stridor was observed. We suspected upper airway obstruction and she was therefore reintubated. Before reintubation, urgent laryngotracheoscopy revealed dynamic inspiratory airway collapse and obstruction concomitant with subglottic stenosis. Preoperative computed tomography showed mild subglottic stenosis. Although intravenous corticosteroids were administered to prevent tracheal mucosal edema and a cuff leak test was confirmed to be negative, she developed extubation failure on POD6. On POD12, we performed tracheostomy to reduce mechanical irritation from the endotracheal tube. Mechanical ventilation was withdrawn and she discharged from the ICU. On POD33, her tracheostomy tube was removed and she remained clinically asymptomatic. CONCLUSIONS: We should be aware of the history of tracheostomy, especially at high tracheostomy sites, even in the absence of respiratory symptoms as risk factors for dynamic inspiratory airway collapse concomitant with subglottic stenosis contributing to repeated respiratory failure after extubation. J. Med. Invest. 70 : 301-305, February, 2023.

The quality and quantity of sleep on dexmedetomidine during high-flow nasal cannula oxygen therapy in critically ill patients.

Purpose : High-flow nasal cannula oxygen therapy (HFNC) is a new type of non-invasive respiratory support for acute respiratory failure patients. However, patients receiving HFNC often develop sleep disturbances. We therefore examined whether dexmedetomidine could preserve the sleep characteristics in patients who underwent HFNC. Patients and Methods : This was a pilot, randomized controlled study. We assigned critically ill patients treated with HFNC to receive dexmedetomidine (0.2 to 0.7 µg / kg / h, DEX group) or not (non-DEX group) at night (9:00 p.m. to 6:00 a.m.). Polysomnograms were monitored during the study period. The primary outcomes were total sleep time (TST), sleep efficiency and duration of stage 2 non-rapid eye movement (stage N2) sleep. Results : Of the 28 patients who underwent randomization, 24 were included in the final analysis (12 patients per group). Dexmedetomidine increased the TST (369 min vs. 119 min, p = 0.024) and sleep efficiency (68% vs. 22%, P = 0.024). The duration of stage N2 was increased in the DEX group compared with the non-DEX group, but this finding did not reach statistical significance. The incidences of respiratory depression and hemodynamic instability were similar between the two groups. Conclusions : In critically ill patients who underwent HFNC, dexmedetomidine may optimize the sleep quantity without any adverse events. J. Med. Invest. 69 : 266-272, August, 2022.

Acquired laryngomalacia as a cause of post-extubation respiratory failure in patient with postoperative seizure and central pontine myelinolysis after craniotomy.

Background : Laryngomalacia is a congenital abnormality of the larynx that commonly occurs in children and rarely in adults. We report the first case of acquired laryngomalacia mainly due to postoperative seizure and central pontine myelinolysis after scheduled craniotomy. Case presentation : A 69-year-old man was admitted to the hospital for elective craniotomy for craniopharyngioma. After the surgery, he developed refractory seizure and required intubation and mechanical ventilation in the intensive-care unit (ICU). After treatment for the seizure, he was extubated. However, immediately after extubation, he developed stridor and respiratory retraction. We performed fiberoptic laryngoscopy and confirmed that the epiglottis had collapsed into the posterior wall of the pharynx during inspiration, which was suspected to be laryngomalacia. He received invasive mechanical ventilation for two days following re-extubation. After the second extubation, he developed stridor again due to acquired laryngomalacia. Six days later, his respiratory condition had worsened, and he received re-intubation and tracheostomy. After ICU discharge, central pontine myelinolysis was diagnosed by magnetic resonance imaging. Conclusions : Adult-onset laryngomalacia is a rare cause of upper airway obstruction but should be considered as a cause of postoperative extubation failure. We should not delay performing fiberoptic laryngoscopy to evaluate this pathology and provide optimal treatment. J. Med. Invest. 69 : 316-319, August, 2022.

Independent lung ventilation for the management of acute allograft rejection after single-lung transplantation for end-stage emphysema.

Background : We herein report the use of independent lung ventilation (ILV) for managing acute allograft rejection after single-lung transplantation (SLT) for end-stage emphysema. Case presentation : A 54-year-old woman was transferred to our hospital with severe hypoxemia and respiratory distress due to unilateral lung disease with diffuse alveolar damage in the right donor lung associated with acute allograft rejection and with hyperinflation of the left native lung due to emphysema. She was unresponsive to immunosuppressive medications and conventional ventilation strategies, so different ventilator settings for each lung were required. A double-lumen endotracheal tube (DLT) was inserted, and ILV was initiated. The right lung was ventilated with high positive end-expiratory pressure (PEEP), intended for lung recruitment, and the left lung was ventilated with lung protective strategies using a low tidal volume and low levels of PEEP to avoid hyperinflation. Two days later, her lung function was dramatically improved, and the DLT was replaced with a single-lumen endotracheal tube. Gas exchange was maintained, and she was successfully weaned from mechanical ventilation on intensive-care unit day 15. Conclusions : ILV appears to be effective and safe for managing acute allograft rejection after SLT for emphysema. J. Med. Invest. 69 : 323-327, August, 2022.

Relationships between double cycling and inspiratory effort with diaphragm thickness during the early phase of mechanical ventilation: A prospective observational study.

BACKGROUND: Increased and decreased diaphragm thickness during mechanical ventilation is associated with poor outcomes. Some types of patient-ventilator asynchrony theoretically cause myotrauma of the diaphragm. However, the effects of double cycling on structural changes in the diaphragm have not been previously evaluated. Hence, this study aimed to investigate the relationship between double cycling during the early phase of mechanical ventilation and changes in diaphragm thickness, and the involvement of inspiratory effort in the occurrence of double cycling. METHODS: We evaluated adult patients receiving invasive mechanical ventilation for more than 48 h. The end-expiratory diaphragm thickness (Tdiee) was assessed via ultrasonography on days 1, 2, 3, 5 and 7 after the initiation of mechanical ventilation. Then, the maximum rate of change from day 1 (ΔTdiee%) was evaluated. Concurrently, we recorded esophageal pressure and airway pressure on days 1, 2 and 3 for 1 h during spontaneous breathing. Then, the waveforms were retrospectively analyzed to calculate the incidence of double cycling (double cycling index) and inspiratory esophageal pressure swing (ΔPes). Finally, the correlation between double cycling index as well as ΔPes and ΔTdiee% was investigated using linear regression models. RESULTS: In total, 19 patients with a median age of 69 (interquartile range: 65-78) years were enrolled in this study, and all received pressure assist-control ventilation. The Tdiee increased by more than 10% from baseline in nine patients, decreased by more than 10% in nine and remained unchanged in one. The double cycling indexes on days 1, 2 and 3 were 2.2%, 1.3% and 4.5%, respectively. There was a linear correlation between the double cycling index on day 3 and ΔTdiee% (R2 = 0.446, p = 0.002). The double cycling index was correlated with the ΔPes on days 2 (R2 = 0.319, p = 0.004) and 3 (R2 = 0.635, p < 0.001). CONCLUSIONS: Double cycling on the third day of mechanical ventilation was associated with strong inspiratory efforts and, possibly, changes in diaphragm thickness.

Extubation in neurocritical care patients: the ENIO international prospective study.

PURPOSE: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. METHODS: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. RESULTS: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). CONCLUSIONS: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

Effect of controlled ventilation during assist-control ventilation on diaphragm thickness†:†a post hoc analysis of an observational study.

Background : Since diaphragm passivity induces oxidative stress that leads to rapid atrophy of diaphragm, we investigated the effect of controlled ventilation on diaphragm thickness during assist-control ventilation (ACV). Methods : Previously, we measured end-expiratory diaphragm thickness (Tdiee) of patients mechanically ventilated for more than 48 hours on days 1, 3, 5 and 7 after the start of ventilation. We retrospectively investigated the proportion of controlled ventilation during the initial 48-hour ACV (CV48%). Patients were classified according to CV48% : Low group, less than 25% ; High group, higher than 25%. Results : Of 56 patients under pressure-control ACV, Tdiee increased more than 10% in 6 patients (11%), unchanged in 8 patients (14%) and decreased more than 10% in 42 patients (75%). During the first week of ventilation, Tdiee decreased in both groups : Low (difference, -7.4% ; 95% confidence interval [CI], -10.1% to -4.6% ; p < 0.001) and High group (difference, -5.2% ; 95% CI, -8.5% to -2.0% ; p = 0.049). Maximum Tdiee variation from baseline did not differ between Low (-15.8% ; interquartile range [IQR], -22.3 to -1.5) and High group (-16.7% ; IQR, -22.6 to -11.1, p = 0.676). Conclusions : During ACV, maximum variation in Tdiee was not associated with proportion of controlled ventilation higher than 25%. J. Med. Invest. 67 : 332-337, August, 2020.

Effect of Electrical Muscle Stimulation on Upper and Lower Limb Muscles in Critically Ill Patients: A Two-Center Randomized Controlled Trial.

OBJECTIVES: Electrical muscle stimulation is widely used to enhance lower limb mobilization. Although upper limb muscle atrophy is common in critically ill patients, electrical muscle stimulation application for the upper limbs has been rarely reported. The purpose of this study was to investigate whether electrical muscle stimulation prevents upper and lower limb muscle atrophy and improves physical function. DESIGN: Randomized controlled trial. SETTING: Two-center, mixed medical/surgical ICU. PATIENTS: Adult patients who were expected to be mechanically ventilated for greater than 48 hours and stay in the ICU for greater than 5 days. INTERVENTIONS: Forty-two patients were randomly assigned to the electrical muscle stimulation (n = 17) or control group (n = 19). MEASUREMENTS AND MAIN RESULTS: Primary outcomes were change in muscle thickness and cross-sectional area of the biceps brachii and rectus femoris from day 1 to 5. Secondary outcomes included occurrence of ICU-acquired weakness, ICU mobility scale, length of hospitalization, and amino acid levels. The change in biceps brachii muscle thickness was -1.9% versus -11.2% in the electrical muscle stimulation and control (p = 0.007) groups, and the change in cross-sectional area was -2.7% versus -10.0% (p = 0.03). The change in rectus femoris muscle thickness was -0.9% versus -14.7% (p = 0.003) and cross-sectional area was -1.7% versus -10.4% (p = 0.04). No significant difference was found in ICU-acquired weakness (13% vs 40%; p = 0.20) and ICU mobility scale (3 vs 2; p = 0.42) between the groups. The length of hospitalization was shorter in the electrical muscle stimulation group (23 d [19-34 d] vs 40 d [26-64 d]) (p = 0.04). On day 3, the change in the branched-chain amino acid level was lower in the electrical muscle stimulation group (40.5% vs 71.5%; p = 0.04). CONCLUSIONS: In critically ill patients, electrical muscle stimulation prevented upper and lower limb muscle atrophy and attenuated proteolysis and decreased the length of hospitalization.

Effect of High-Flow Nasal Cannula on Sleep-disordered Breathing and Sleep Quality in Patients With Acute Stroke.

Introduction Sleep-disordered breathing (SDB) is common after stroke. Although the standard treatment of SDB is continuous positive airway pressure (CPAP) ventilation, the patient's intolerance and discomfort result in low adherence rates. Alternatively, high-flow nasal cannula (HFNC) may be useful as it reduces upper airway collapse with low level of positive pressure and well tolerability. The aim of this study was to investigate whether HFNC therapy reduces SDB and improves sleep quality with higher compliance rate. Methods We included acute stroke patients with SDB for the assessment of apnea-hypopnea index (AHI) >5/h using WatchPAT 200 (Itamar Medical Ltd, Caesarea, Israel). Patients who met inclusion criteria received HFNC therapy (40 L/min) with monitoring by WatchPAT. AHI, oxygen desaturation index (ODI), sleep efficiency, and rapid eye movement (REM) sleep were compared in patients with and without HFNC therapy. We also evaluated the patient's comfort of HFNC therapy (discomfort or not). Results Among 17 patients assessed for AHI, 12 received HFNC therapy. HFNC therapy was not adhered in two patients due to intolerance. Eight patients remained for final analysis. There were no differences in SDB and sleep quality with and without HFNC therapy as follows: HFNC therapy vs control; AHI 24.9 ± 20.1 vs 21.3 ± 15.0/h (p = 0.63), ODI 16.2 ± 16.5 vs 12.9 ± 12.3/h (p = 0.54), sleep efficiency 80.4 ± 12.9 vs 87.1 ± 6.2 (p = 0.28), percentage of REM sleep 19.4% ± 9.6% vs 27.6% ± 8.9% (p = 0.07). Two patients (17%) complained of discomfort among eight patients. Conclusion HFNC therapy did not improve SDB and sleep quality. Nonadherence and discomfort were observed in HFNC therapy. We need a large trial to confirm this result.

Change in diaphragm and intercostal muscle thickness in mechanically ventilated patients: a prospective observational ultrasonography study.

BACKGROUND: Diaphragm atrophy is observed in mechanically ventilated patients. However, the atrophy is not investigated in other respiratory muscles. Therefore, we conducted a two-center prospective observational study to evaluate changes in diaphragm and intercostal muscle thickness in mechanically ventilated patients. METHODS: Consecutive adult patients who were expected to be mechanically ventilated longer than 48 h in the ICU were enrolled. Diaphragm and intercostal muscle thickness were measured on days 1, 3, 5, and 7 with ultrasonography. The primary outcome was the direction of change in muscle thickness, and the secondary outcomes were the relationship of changes in muscle thickness with patient characteristics. RESULTS: Eighty patients (54 males and 26 females; mean age, 68 ± 14 years) were enrolled. Diaphragm muscle thickness decreased, increased, and remained unchanged in 50 (63%), 15 (19%), and 15 (19%) patients, respectively. Intercostal muscle thickness decreased, increased, and remained unchanged in 48 (60%), 15 (19%), and 17 (21%) patients, respectively. Decreased diaphragm or intercostal muscle thickness was associated with prolonged mechanical ventilation (median difference (MD), 3 days; 95% CI (confidence interval), 1-7 and MD, 3 days; 95% CI, 1-7, respectively) and length of ICU stay (MD, 3 days; 95% CI, 1-7 and MD, 3 days; 95% CI, 1-7, respectively) compared with the unchanged group. After adjusting for sex, age, and APACHE II score, they were still associated with prolonged mechanical ventilation (hazard ratio (HR), 4.19; 95% CI, 2.14-7.93 and HR, 2.87; 95% CI, 1.53-5.21, respectively) and length of ICU stay (HR, 3.44; 95% CI, 1.77-6.45 and HR, 2.58; 95% CI, 1.39-4.63, respectively) compared with the unchanged group. CONCLUSIONS: Decreased diaphragm and intercostal muscle thickness were frequently seen in patients under mechanical ventilation. They were associated with prolonged mechanical ventilation and length of ICU stay. TRIAL REGISTRATION: UMIN000031316. Registered on 15 February 2018.

Monitoring of muscle mass in critically ill patients: comparison of ultrasound and two bioelectrical impedance analysis devices.

BACKGROUND: Skeletal muscle atrophy commonly occurs in critically ill patients, and decreased muscle mass is associated with worse clinical outcomes. Muscle mass can be assessed using various tools, including ultrasound and bioelectrical impedance analysis (BIA). However, the effectiveness of muscle mass monitoring is unclear in critically ill patients. This study was conducted to compare ultrasound and BIA for the monitoring of muscle mass in critically ill patients. METHODS: We recruited adult patients who were expected to undergo mechanical ventilation for > 48 h and to remain in the intensive care unit (ICU) for > 5 days. On days 1, 3, 5, 7, and 10, muscle mass was evaluated using an ultrasound and two BIA devices (Bioscan: Malton International, England; Physion: Nippon Shooter, Japan). The influence of fluid balance was also evaluated between each measurement day. RESULTS: We analyzed 93 images in 21 patients. The age of the patients was 69 (interquartile range, IQR, 59-74) years, with 16 men and 5 women. The length of ICU stay was 11 days (IQR, 9-25 days). The muscle mass, monitored by ultrasound, decreased progressively by 9.2% (95% confidence interval (CI), 5.9-12.5%), 12.7% (95% CI, 9.3-16.1%), 18.2% (95% CI, 14.7-21.6%), and 21.8% (95% CI, 17.9-25.7%) on days 3, 5, 7, and 10 (p <  0.01), respectively, with no influence of fluid balance (r = 0.04, p = 0.74). The muscle mass did not decrease significantly in both the BIA devices (Bioscan, p = 0.14; Physion, p = 0.60), and an influence of fluid balance was observed (Bioscan, r = 0.37, p <  0.01; Physion, r = 0.51, p <  0.01). The muscle mass assessment at one point between ultrasound and BIA was moderately correlated (Bioscan, r = 0.51, p <  0.01; Physion, r = 0.37, p <  0.01), but the change of muscle mass in the same patient did not correlate between these two devices (Bioscan, r = - 0.05, p = 0.69; Physion, r = 0.23, p = 0.07). CONCLUSIONS: Ultrasound is suitable for sequential monitoring of muscle atrophy in critically ill patients. Monitoring by BIA should be carefully interpreted owing to the influence of fluid change. TRIAL REGISTRATION: UMIN000031316. Retrospectively registered on 15 February 2018.

Reverse triggering induced by endotracheal tube leak in lightly sedated ARDS patient.

Reverse triggering is respiratory entrainment triggered by the ventilator especially seen among heavily sedated patients. We confirmed reverse triggering induced by auto-triggering in lightly sedated patient through an esophageal pressure monitoring. The reverse triggering frequently caused breath stacking with increased tidal volume. Physicians should be aware, even at an optimal level of sedation, that reverse triggering can develop, possibly caused by auto-triggering.

Change in Ratio of Observed-to-Expected Deaths in Pediatric Patients after Implementing a Closed Policy in an Adult ICU That Admits Children.

Backgrounds. We examined the effect on the prognosis of critically ill pediatric patients after a closed ICU policy was implemented into an adult ICU that admitted children. Materials and Methods. We assessed the Pediatric Index of Mortality 2 (PIM2) score of pediatric patients (≤15 y.o.) admitted to the ICU from 2001 to 2009. In our teaching hospital, the department for intensive care was established in January 2004. Since then, for critical care patients, we have followed a closed ICU policy with full-time intensivists. We subsequently compared PIM2 scores and the ratio of observed-to-expected deaths (O/E ratio) for three three-year periods: 2001-2003 (before closed policy), 2004-2006, and 2007-2009. Results. Data was collected from 532 pediatric patients. While the PIM2 score statistically significantly increased from 0.066 ± 0.130 for 2001-2003 to 0.114 ± 0.239 for 2004-2006 and 0.086 ± 0.147 for 2007-2009, the O/E ratio decreased from 1.49 for 2001-2003 to 0.82 for 2004-2006 and remained at 0.82 for 2007-2009. Conclusion. The O/E ratio for critically ill pediatric patients improved after the establishment of a closed policy in an adult ICU that admitted children.

A bench study of the effects of leak on ventilator performance during noninvasive ventilation.

BACKGROUND: During noninvasive ventilation (NIV), leak around the mask may cause inadequate ventilatory support or patient-ventilator asynchrony such as auto-triggering. Some NIV ventilators may be better than others at compensating for leak. METHODS: We bench studied 3 NIV ventilators (Vision, Carina, and Trilogy100) and 2 ICU ventilators (Puritan Bennett 840 and Evita XL) to assess how they coped with 2 leak levels and zero leak during NIV. With a 2-bellows-in-a-box lung model we simulated spontaneous breathing with tidal volumes of 300 mL and 500 mL, at pressure support of 0 and 10 cm H(2)O and PEEP of 5 and 10 cm H(2)O. We affixed the airway opening of the lung model to the mouth of a mannequin head and secured a mask on the mannequin face. We created a medium leak and a large leak with different size holes, and measured PEEP in the presence of leak. We also measured the actual pressure-support values and calculated the deviations from the set pressure-support value and the pressure-time product (PTP) of the airway opening pressure below and above baseline. RESULTS: With the medium leak only the Vision and Carina maintained the set PEEP and pressure support. With the large leak the pressure support was decreased with all the tested ventilators. With the larger leak and pressure support of 10 cm H(2)O the PTP below baseline for triggering increased with 2 ventilators, and the PTP above baseline for supporting the patient's inspiratory effort decreased with all 5 ventilators. The larger tidal volume increased the PTP below baseline with all 5 ventilators and at all leak sizes. CONCLUSIONS: Some of the ventilators compensated for leak better than others. With the larger leak none of the ventilators maintained the set PEEP or pressure support.