Outcomes and clinical practice in patients with COVID-19 admitted to the intensive care unit in Montréal, Canada: a descriptive analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is responsible for millions of infections worldwide, and a substantial number of these patients will be admitted to the intensive care unit (ICU). Our objective was to describe the characteristics, outcomes and management of critically ill patients with COVID-19 pneumonia at a single designated pandemic centre in Montréal, Canada. METHODS: A descriptive analysis was performed on consecutive critically ill patients with COVID-19 pneumonia admitted to the ICU at the Jewish General Hospital, a designated pandemic centre in Montréal, between Mar. 5 and May 21, 2020. Complete follow-up data corresponding to death or discharge from hospital health records were included to Aug. 4, 2020. We summarized baseline characteristics, management and outcomes, including mortality. RESULTS: A total of 106 patients were included in this study. Twenty-one patients (19.8%) died during their hospital stay, and the ICU mortality was 17.0% (18/106); all patients were discharged home or died, except for 4 patients (2 awaiting a rehabilitation bed and 2 awaiting long-term care). Twelve of 65 patients (18.5%) requiring mechanical ventilation died. Prone positioning was used in 29 patients (27.4%), including in 10 patients who were spontaneously breathing; no patient was placed on extracorporeal membrane oxygenation. High-flow nasal cannula was used in 51 patients (48.1%). Acute kidney injury was the most common complication, seen in 20 patients (18.9%), and 12 patients (11.3%) required renal replacement therapy. A total of 53 patients (50.0%) received corticosteroids. INTERPRETATION: Our cohort of critically ill patients with COVID-19 had lower mortality than that previously described in other jurisdictions. These findings may help guide critical care decision-making in similar health care systems in further COVID-19 surges.

Intensive care unit clinicians identify many barriers to, and facilitators of, early mobilisation: a qualitative study using the Theoretical Domains Framework.

QUESTION: From the perspective of intensive care unit (ICU) clinicians, what are the barriers to and facilitators of implementing early mobilisation? DESIGN: A qualitative study using focus groups, with analysis using the Theoretical Domains Framework. PARTICIPANTS: Physicians, nurses, respiratory therapists and physiotherapists from the ICUs of three university-affiliated hospitals in Montreal, Canada. METHODS: Four focus group meetings were conducted with 33 participating ICU clinicians. Two researchers independently performed thematic content analysis on verbatim transcriptions of the audio recordings using the Theoretical Domains Framework. RESULTS: Data saturation was reached after the third focus group. Thirty-six barriers were categorised in 13 domains of the Theoretical Domains Framework. The key barriers to early mobilisation were: lack of conviction and knowledge regarding the available evidence about early mobilisation; lack of attention to the provision of optimal care; poor communication; the unpredictable nature of the ICU; and limited staffing, equipment, time and clinical knowledge. Twenty-five facilitators categorised in ten TDF domains were also identified. These included individual-level facilitators (intrinsic motivation, positive outcome expectations, conscious effort to mobilise early, good planning/coordination, the presence of ICU champions, and expert support by a physiotherapist) and organisational-level facilitators (reminder system, pro-early mobilisation culture, implementation of an early mobilisation protocol, and improved ICU organisation). CONCLUSIONS: A broad array of barriers to and facilitators of early mobilisation in the ICU were identified in this study. Clinicians can consider whether these barriers and facilitators are operating in their ICU. These may inform the design of tailored knowledge translation interventions to promote early mobilisation in the ICU.

Interprofessional Survey of Perceived Barriers and Facilitators to Early Mobilization of Critically Ill Patients in Montreal, Canada.

OBJECTIVE: Early mobilization is safe, feasible, and associated with better outcomes in patients with critical illness. However, barriers to mobilization in clinical practice still exist. The objective of this study was to assess the knowledge and practice patterns of intensive care unit (ICU) clinicians, as well as the barriers and facilitators to early mobilization. DESIGN: Cross-sectional survey. SETTING: Intensive care units of 3 university-affiliated hospitals in Montreal, Canada. PARTICIPANTS: One hundred and thirty-eight ICU clinicians, including nurses, physicians, respiratory therapists, and physiotherapists. INTERVENTIONS: None. MEASUREMENTS: Perceived barriers, facilitators, knowledge, and practice patterns of early mobilization were assessed using a previously validated mobility survey tool. MAIN RESULTS: The overall response rate was 50.0% (138 of 274). Early mobilization was not perceived as a top priority in 49% of respondents. Results showed that clinicians were not fully aware of the benefits of early mobilization as per the current literature. About 58% of clinicians did not feel well trained and informed to mobilize mechanically ventilated patients. Perceptions on patient-level barriers varied with clinicians' professional training, but there was a high degree of interprofessional and intraprofessional disagreement on the permissible maximal level activity in different scenarios of critically ill patients. CONCLUSIONS: Our survey shows limited awareness, among our respondents, of the clinical benefits of early mobilization and high level of disagreement on the permissible maximal level of activity in the critically ill patients. Future studies should evaluate the role of knowledge translation in modifying these barriers and improving early mobilization.

Mechanical ventilation modulates pro-inflammatory cytokine expression in spinal cord tissue after injury in rats.

RATIONALE: Spinal cord injury (SCI) may induce significant respiratory muscle weakness and paralysis, which in turn may cause a patient to require ventilator support. Central nervous system alterations can also exacerbate local inflammatory responses with immune cell infiltration leading to additional risk of inflammation at the injury site. Although mechanical ventilation is the traditional treatment for respiratory insufficiency, evidence has shown that it may directly affect distant organs through systemic inflammation. OBJECTIVES: This study aimed to better understand the impact of invasive mechanical ventilation on local spinal cord inflammatory responses following cervical or thoracic SCI. METHODS: Five groups of female Sprague-Dawley rats were anesthetised for 24 h. Three groups received mechanical ventilation: seven rats without SCI, seven rats with cervical injury (C4-C5), and seven rats with thoracic injury (T10); whereas, two groups were non-ventilated: six rats without SCI; and six rats with thoracic injury (T10). Changes in inflammatory responses were determined in the spinal cord tissues collected at the local site of injury. Cytokines were measured using ELISA. MAIN RESULTS: SCI induced local pro-inflammatory cytokine IL-6 expression for all groups. Mechanical ventilation also had effects on pro-inflammatory cytokines and independently increased TNF-α and decreased IL-1ß levels in the spinal cords of anesthetized rats. CONCLUSION: These data provide the first evidence that mechanical ventilation contributes to local inflammation after SCI and in the absence of direct tissue injury.

Effects of Pressure Support Ventilation May Be Lost at High Exercise Intensities in People with COPD.

Pressure support ventilation (PSV) may be used for exercise training in chronic obstructive pulmonary disease (COPD), but its acute effect on maximum exercise capacity is not fully known. The objective of this study was to evaluate the effect of 10 cm H2O PSV and a fixed PSV level titrated to patient comfort at rest on maximum exercise workload (WLmax), breathing pattern and metabolic parameters during a symptom-limited incremental bicycle test in individuals with COPD. Eleven individuals with COPD (forced expiratory volume in one second: 49 ± 16%; age: 64 ± 7 years) performed three exercise tests: without a ventilator, with 10 cm H2O of PSV and with a fixed level titrated to comfort at rest, using a SERVO-i ventilator. Tests were performed in randomized order and at least 48 hours apart. The WLmax, breathing pattern, metabolic parameters, and mouth pressure (Pmo) were compared using repeated measures analysis of variance. Mean PSV during titration was 8.2 ± 4.5 cm H2O. There was no difference in the WLmax achieved during the three tests. At rest, PSV increased the tidal volume, minute ventilation, and mean inspiratory flow with a lower end-tidal CO2; this was not sustained at peak exercise. Pmo decreased progressively (decreased unloading) with PSV at workloads close to peak, suggesting the ventilator was unable to keep up with the increased ventilatory demand at high workloads. In conclusion, with a Servo-i ventilator, 10 cm H2O of PSV and a fixed level of PSV established by titration to comfort at rest, is ineffective for the purpose of achieving higher exercise workloads as the acute physiological effects may not be sustained at peak exercise.

Spinal cord injury modulates the lung inflammatory response in mechanically ventilated rats: a comparative animal study.

Mechanical ventilation (MV) is widely used in spinal injury patients to compensate for respiratory muscle failure. MV is known to induce lung inflammation, while spinal cord injury (SCI) is known to contribute to local inflammatory response. Interaction between MV and SCI was evaluated in order to assess the impact it may have on the pulmonary inflammatory profile. Sprague Dawley rats were anesthetized for 24 h and randomized to receive either MV or not. The MV group included C4-C5 SCI, T10 SCI and uninjured animals. The nonventilated (NV) group included T10 SCI and uninjured animals. Inflammatory cytokine profile, inflammation related to the SCI level, and oxidative stress mediators were measured in the bronchoalveolar lavage (BAL). The cytokine profile in BAL of MV animals showed increased levels of TNF-α, IL-1ß, IL-6 and a decrease in IL-10 (P = 0.007) compared to the NV group. SCI did not modify IL-6 and IL-10 levels either in the MV or the NV groups, but cervical injury induced a decrease in IL-1ß levels in MV animals. Cervical injury also reduced MV-induced pulmonary oxidative stress responses by decreasing isoprostane levels while increasing heme oxygenase-1 level. The thoracic SCI in NV animals increased M-CSF expression and promoted antioxidant pulmonary responses with low isoprostane and high heme oxygenase-1 levels. SCI shows a positive impact on MV-induced pulmonary inflammation, modulating specific lung immune and oxidative stress responses. Inflammation induced by MV and SCI interact closely and may have strong clinical implications since effective treatment of ventilated SCI patients may amplify pulmonary biotrauma.

Bi-level Positive Airway Pressure (BiPAP) with standard exhalation valve does not improve maximum exercise capacity in patients with COPD.

BACKGROUND: Although BiPAP has been used as an adjunct to exercise, little is know about its effect on exercise in COPD. We aimed to evaluate the acute effect of BiPAP delivered with a standard valve (Vision, Respironics), compared to no assist, on exercise capacity in individuals with COPD. METHODS: Peak exercise workload (WLpeak), dyspnea (Borg), end-expiratory lung volume (EELV), tidal volume (VT), minute ventilation (VE), O2 uptake (VO2), and CO2 production (VCO2) were assessed in 10 COPD patients (FEV1 53 ± 22% pred) during three symptom-limited bicycle exercise tests while breathing i) without a ventilator (noPS), ii) with a pressure support (PS) of 0 cm H2O (PS0; IPAP & EPAP 4 cm H2O) and iii) PS of 10 cm H2O (PS10; IPAP 14 & EPAP 4 cm H2O) on separate days using a randomized crossover design. RESULTS: WLpeak was significantly lower with PS10 (33 ± 16) and PS0 (30.5 ± 13) than noPS (43 ± 19) (p < 0.001). Dyspnea at peak exercise was similar with noPS, PS0 and PS10; at isoload it was lower with noPS compared to PS10 and PS0 (p < 0.01). VT and VE were highest with PS10 and lowest with noPS both at peak exercise and isoload (p < 0.001). EELV was similar at peak exercise with all three conditions. VO2 and VCO2 were greater with PS10 and PS0 than noPS (p < 0.001), both at peak exercise and isoload. CONCLUSION: Use of BiPAP with a standard exhalation valve during exercise increases VT and VE at the expense of augmenting VCO2 and dyspnea, which in turns reduces WLpeak in COPD patients.

Patient-ventilator interaction during pressure support ventilation and neurally adjusted ventilatory assist.

OBJECTIVE: To compare the effect of pressure support ventilation and neurally adjusted ventilatory assist on breathing pattern, patient-ventilator synchrony, diaphragm unloading, and gas exchange. Increasing the level of pressure support ventilation can increase tidal volume, reduce respiratory rate, and lead to delayed ventilator triggering and cycling. Neurally adjusted ventilatory assist uses diaphragm electrical activity to control the timing and pressure of assist delivery and is expected to enhance patient-ventilator synchrony. DESIGN: Prospective, comparative, crossover study. SETTING: Adult critical care unit in a tertiary university hospital. PATIENTS: Fourteen nonsedated mechanically ventilated patients (n = 12 with chronic obstructive pulmonary disease). INTERVENTIONS: Patients were ventilated for 10-min periods, using two pressure support ventilation levels (lowest tolerable and +7 cm H2O higher) and two neurally adjusted ventilatory assist levels (same peak pressures and external positive end-expiratory pressure as with pressure support ventilation), delivered in a randomized order. MEASUREMENTS AND MAIN RESULTS: Diaphragm electrical activity, respiratory pressures, air flow, volume, neural and ventilator respiratory rates, and arterial blood gases were measured. Peak pressures were 17 +/- 6 cm H2O and 24 +/- 6 cm H2O and 19 +/- 5 cm H2O and 24 +/- 6 cm H2O with high and low pressure support ventilation and neurally adjusted ventilatory assist, respectively. The breathing pattern was comparable with pressure support ventilation and neurally adjusted ventilatory assist during low assist; during higher assist, larger tidal volumes (p = .003) and lower breathing frequencies (p = .008) were observed with pressure support ventilation. Increasing the assist increased cycling delays only with pressure support ventilation (p = .003). Compared with pressure support ventilation, neurally adjusted ventilatory assist reduced delays of ventilator triggering (p < .001 for low and high assist) and cycling (high assist: p = .004; low assist: p = .04), and abolished wasted inspiratory efforts observed with pressure support ventilation in six subjects. The diaphragm electrical activity and pressure-time product for ventilator triggering were lower with neurally adjusted ventilatory assist (p = .005 and p = .02, respectively; analysis of variance). Arterial blood gases were similar with both modes. CONCLUSIONS: Neurally adjusted ventilatory assist can improve patient-ventilator synchrony by reducing the triggering and cycling delays, especially at higher levels of assist, at the same time preserving breathing and maintaining blood gases.

Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.

Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at rest and during exercise in COPD.

STUDY OBJECTIVES: To investigate the effect of volitional pursed-lips breathing (PLB) on breathing pattern, respiratory mechanics, operational lung volumes, and dyspnea in patients with COPD. SUBJECTS: Eight COPD patients (6 male and 2 female) with a mean (+/-SD) age of 58 +/- 11 years and a mean FEV1 of 1.34 +/- 0.44 L (50 +/- 21% predicted). METHODS: Wearing a tight-fitting transparent facemask, patients breathed for 8 min each, with and without PLB at rest and during constant-work-rate bicycle exercise (60% of maximum). RESULTS: PLB promoted a slower and deeper breathing pattern both at rest and during exercise. Whereas patients had no dyspnea with or without PLB at rest, during exercise dyspnea was variably affected by PLB across patients. Changes in the individual dyspnea scores with PLB during exercise were significantly correlated with changes in the end-expiratory lung volume (EELV) values estimated from inspiratory capacity maneuvers (as a percentage of total lung capacity; r2 = 0.82, p = 0.002) and with changes in the mean inspiratory ratio of pleural pressure to the maximal static inspiratory pressure-generating capacity (PcapI) [r2 = 0.84; p = 0.001], measured using an esophageal balloon, where PcapI was determined over the range of inspiratory lung volumes and adjusted for flow. CONCLUSION: PLB can have a variable effect on dyspnea when performed volitionally during exercise by patients with COPD. The effect of PLB on dyspnea is related to the combined change that it promotes in the tidal volume and EELV and their impact on the available capacity of the respiratory muscles to meet the demands placed on them in terms of pressure generation.

Effect of increased diaphragm activation on diaphragm power spectrum center frequency.

Increased transdiaphragmatic pressure, reduced muscle blood flow, and increased duty cycle have all been associated with a reduction in the center frequency (CFdi) of the diaphragm's electrical activity (EAdi). However, the specific influence of diaphragm activation on CFdi is unknown. We evaluated whether increased diaphragm activation would result in a greater decline in the CFdi when pressure-time product (PTPdi) was kept constant. Five healthy subjects performed periods of intermittent quasi-static diaphragmatic contractions with a fixed duty cycle. In separate runs, subjects targeted transdiaphragmatic pressures (Pdi) by performing end-inspiratory holds with the glottis open and expulsive maneuvers at end-expiratory lung volume (EELV). Diaphragm activation and pressures were measured with an electrode array and balloons mounted on an esophago-gastric catheter, respectively. The EAdi, which was 25+/-8%(S.D.) of maximum at EELV, increased to 61+/-8% (P<0.001) when an identical Pdi (averaging 31+/-13 cmH2O) was generated at a higher lung volume (77% of inspiratory capacity). The latter was associated with a 17% greater decline in CFdi (P=0.012). In order to reproduce at EELV, the decrease in CFdi observed at the increased lung volume, a two-fold increase in PTPdi was required. We conclude that CFdi responds specifically to increased diaphragm activation when pressure-time product remains constant.

Closed-loop control of respiratory drive using pressure-support ventilation: target drive ventilation.

By using diaphragm electrical activity (multiple-array esophageal electrode) as an index of respiratory drive, and allowing such activity above or below a preset target range to indicate an increased or reduced demand for ventilatory assistance (target drive ventilation), we evaluated whether the level of pressure-support ventilation can be automatically adjusted in response to exercise-induced changes in ventilatory demand. Eleven healthy individuals breathed through a circuit (18 cm H2O/L/second inspiratory resistance at 1 L/second flow; 0.5-1.0 L/second expiratory flow limitation) connected to a modified ventilator. Subjects breathed for 6-minute periods at rest and during 20 and 40 W of bicycle exercise, with and without target drive ventilation (the target was set to 60% of the increase in diaphragm electrical activity observed between rest and 20 W of unassisted exercise). With target drive ventilation during exercise, the level of pressure-support ventilation was automatically increased, reaching 13.3 +/- 4.0 and 20.3 +/- 2.8 cm H2O during 20- and 40-W exercise, respectively, whereas diaphragm electrical activity was reduced to a level within the target range. Both diaphragmatic pressure-time product and end-tidal CO2 were significantly reduced with target drive ventilation at the end of the 20- (p < 0.01) and 40-W (p < 0.001) exercise periods. Minute ventilation was not altered. These results demonstrate that target drive ventilation can automatically adjust pressure-support ventilation, maintaining a constant neural drive and compensating for changes in respiratory demand.