Gastric pressure monitoring unveils abnormal patient-ventilator interaction related to active expiration: a retrospective observational study.

BACKGROUND: Patient-ventilator dyssynchrony is frequently observed during assisted mechanical ventilation (MV). However, the effects of expiratory muscle contraction on patient-ventilator interaction are underexplored. We hypothesized that active expiration would affect patient-ventilator interaction and we tested our hypothesis in a mixed cohort of invasively ventilated patients with spontaneous breathing activity. METHODS: This is a retrospective observational study involving patients on assisted MV who had their esophageal (Pes) and gastric (Pgas) pressures monitored for clinical purposes. Active expiration was defined as Pgas rise (ΔPgas) ≥1.0 cmH2O during expiratory flow without a corresponding change in diaphragmatic pressure (Pdi). Waveforms of Pes, Pgas, Pdi, flow, and airway pressure (Paw) were analyzed to identify and characterize abnormal patient-ventilator interaction. RESULTS: We identified 76 patients with Pes and Pgas recordings, of whom 58 demonstrated active expiration with a median ΔPgas of 3.4 cmH2O (IQR=2.4-5.3) observed in this subgroup. Among these 58 patients, 23 presented the following events associated with expiratory muscle activity: (1) distortions in Paw and flow that resembled ineffective efforts, (2) distortions similar to autotriggering, (3) multiple triggering, (4) prolonged ventilatory cycles with biphasic inspiratory flow, with a median % (IQR) increase in mechanical inflation time and tidal volume of 54% (44-70%) and 25% (8-35%), respectively and (5) breathing exclusively by expiratory muscle relaxation. Gastric pressure monitoring was required to identify the association of active expiration with these events. Respiratory drive, assessed by the rate of inspiratory Pes decrease, was significantly higher in patients with active expiration (median [IQR] dPes/dt: 12.7 [9.0-18.5] vs 9.2 [6.8-14.2] cmH2O/sec; p<0.05). CONCLUSIONS: Active expiration can impair patient-ventilator interaction in critically ill patients. Without documenting Pgas, abnormal patient-ventilator interaction associated with expiratory muscle contraction may be mistakenly attributed to a mismatch between the patient´s inspiratory effort and mechanical inflation. This misinterpretation could potentially influence decisions regarding clinical management.

Chronic obstructive pulmonary disease (COPD) and COPD-like phenotypes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Historically, two COPD phenotypes have been described: chronic bronchitis and emphysema. Although these phenotypes may provide additional characterization of the pathophysiology of the disease, they are not extensive enough to reflect the heterogeneity of COPD and do not provide granular categorization that indicates specific treatment, perhaps with the exception of adding inhaled glucocorticoids (ICS) in patients with chronic bronchitis. In this review, we describe COPD phenotypes that provide prognostication and/or indicate specific treatment. We also describe COPD-like phenotypes that do not necessarily meet the current diagnostic criteria for COPD but provide additional prognostication and may be the targets for future clinical trials.

Sleep Architecture Patterns in Critically Ill Patients and Survivors of Critical Illness: A Retrospective Study.

Rationale: Sleep abnormalities are very frequent in critically ill patients during and after intensive care unit (ICU) stays. Their mechanisms are poorly understood. The odds ratio product (ORP) is a continuous metric (range, 0.0-2.5) of sleep depth measured in 3-second intervals and derived from the relationship of powers of different electroencephalographic frequencies to one another. When expressed as the percentage of epochs within 10 ORP deciles covering the entire ORP range, it provides information about the mechanism(s) of abnormal sleep. Objectives: To determine ORP architecture types in critically ill patients and survivors of critical illness who had previously undergone sleep studies. Methods: Nocturnal polysomnograms from 47 unsedated critically ill patients and 23 survivors of critical illness at hospital discharge were analyzed. Twelve critically ill patients were monitored also during the day, and 15 survivors underwent subsequent polysomnography 6 months after hospital discharge. In all polysomnograms, each 30-second epoch was characterized by the mean ORP of the 10 3-second epochs. The number of 30-second epochs with mean ORP within each of 10 ORP deciles covering the entire ORP range (0.0-2.5) was calculated and expressed as a percentage of total recording time. Thereafter, each polysomnogram was characterized using a two-digit ORP type, with the first digit (range, 1-3) reflecting increasing degrees of deep sleep (ORP < 0.5, deciles 1 and 2) and the second digit (range, 1-3) reflecting increasing degrees of full wakefulness (ORP > 2.25, decile 10). Results from patients were compared with those from 831 age- and gender-matched community dwellers free of sleep disorders. Results: In critically ill patients, types 1,1 and 1,2 (little deep sleep and little or average full wakefulness) dominated (46% of patients). In the community, these types are uncommon (<15%) and seen primarily in disorders that preclude progression to deep sleep (e.g., very severe obstructive sleep apnea). Next in frequency (22%) was type 1,3, consistent with hyperarousal. Day ORP sleep architecture was similar to night results. Survivors had similar patterns, with little improvement after 6 months. Conclusions: Sleep abnormalities in critically ill patients and survivors of critical illness result primarily from stimuli that preclude progression to deep sleep or from the presence of a hyperarousal state.

Prevalence and factors associated with compassion fatigue, compassion satisfaction, burnout in health professionals.

BACKGROUND: Constant exposure of health professionals to the pain and suffering of patients can adversely affect their emotional wellbeing. AIM: The study aimed to investigate the prevalence and the factors affecting the levels of secondary traumatic stress/compassion fatigue (STS/CF), burnout (BO) and compassion satisfaction (CS) of health professionals working in adult and paediatric Intensive Care Units (ICU) as well as in departments treating patients with serious illness in five hospitals in Crete. STUDY DESIGN: A descriptive cross-sectional survey with the use of the Professional Quality of Life Scale (ProQOL-CSF-R-IV) questionnaire. METHODS: We enrolled medical, nursing and support staff working in the adult and paediatric ICU, emergency, oncology, haematology and neurosurgical departments, haemodialysis unit and operating theatre. RESULTS: 598 health professionals completed the questionnaire (response rate 73.2%). Significantly increased levels of STS/CF were observed in non - ICU as compared to ICU staff (p = .009) females compared to males (p < .001), those who have previously experienced a traumatic event (p < .004), nurses and support staff compared to doctors (p = .007 and p = .028 respectively), and people not working in a department by choice (p < .001). CS was higher for older professionals, personnel subjected to stress reduction techniques (p < .019) and professionals working with children or mixed adults and children population (p = .009). Rolling schedule and bad working conditions negatively affected CS (p = .02, p = .001). Increased BO levels were associated with younger age (p = .029) and showed a positive correlation with STS/CF (r = .356, p < .001). CONCLUSIONS: STS/CF is common in health professionals regardless of their profession, working department or hospital level. Non-ICU staff displayed higher STS/CF levels. Working in a department by choice ameliorates CS, BO and STS/CF. RELEVANCE TO CLINICAL PRACTICE: Health professionals need to be informed about the risks of projecting patients' suffering on themselves. Hospital managers and department heads are responsible to provide appropriate support.

Respiratory system as the main determinant of dyspnea in patients with pulmonary hypertension.

Dyspnea on exertion is a devastating symptom, commonly observed in patients with pulmonary hypertension (PH). The pathophysiology of dyspnea in these patients has been mainly attributed to cardiovascular determinants and isolated abnormalities of the respiratory system during exercise, neglecting the contribution of the control of the breathing system. The aim of this review is to provide a novel approach to the interpretation of dyspnea in patients with PH, focused on the impact of the control of the breathing system during exercise. Exercise through multiple mechanisms affects the (1) ventilatory demands, as dictated by respiratory center activity, (2) actual ventilation, and (3) metabolic hyperbola. In patients with PH, exertional dyspnea can be explained by exercise-induced alterations in these variables. Compared to healthy subjects, at a given CO2 production during exercise, ventilatory demands in patients with PH are higher due to metabolic acidosis (early reaching the anaerobic threshold), hypoxemia, and excessive upward movement of metabolic hyperbola owing to abnormal exercise response of dead space to tidal volume ratio. Simultaneously, dynamic hyperinflation and respiratory muscles weakness decreases the actual ventilation for a given respiratory center activity, creating a dissociation between demands and ventilation. Consequently, a progressive increase in ventilatory demands and respiratory center activity occurs during exercise. The forebrain projection of high respiratory center activity causes exertional dyspnea despite the relatively low ventilation and significant ventilatory reserve. This type of analysis suggests that the respiratory system is the main determinant of exertional dyspnea in patients with PH, with the cardiovascular system being an indirect contributor.

Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study.

BACKGROUND: Before the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15-24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19. METHODS: We included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO2:FiO2 of equal to or less than 100 on the second day following intubation. RESULTS: A total of 280 intubated patients met criteria of ARDS with a median PaO2:FiO2 of 125.0 (interquartile range 93.0-161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%. CONCLUSIONS: Rapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

Effects of Sedatives on Sleep Architecture Measured With Odds Ratio Product in Critically Ill Patients.

Evaluation of sleep quality in critically ill patients is difficult using conventional scoring criteria. The aim of this study was to examine sleep in critically ill patients with and without light sedation using the odds ratio product, a validated continuous metric of sleep depth (0 = deep sleep; 2.5 = full wakefulness) that does not rely on the features needed for conventional staging. DESIGN: Retrospective study. SETTINGS: A 16-bed medical-surgical ICU. PATIENTS: Twenty-three mechanically ventilated patients who had previously undergone two nocturnal sleep studies, one without and one with sedation (propofol, n = 12; dexmedetomidine, n = 11). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sleep architecture was evaluated with odds ratio product analysis by the distribution of 30-second epochs with different odds ratio product values. Electroencephalogram spectral patterns and frequency of wake intrusions (3-s odds ratio product > 1.75) were measured at different odds ratio product levels. Thirty-seven normal sleepers were used as controls. Compared with normal sleepers, unsedated critically ill patients spent little time in stable sleep (percent odds ratio product < 1.0: 31% vs 63%; p < 0.001), whereas most of the time were either in stage wake (odds ratio product > 1.75) or in a transitional state (odds ratio product 1.0-1.75), characterized by frequent wake intrusions. Propofol and dexmedetomidine had comparable effects on sleep. Sedation resulted in significant shift in odds ratio product distribution toward normal; percent odds ratio product less than 1.0 increased by 54% (p = 0.006), and percent odds ratio product greater than 1.75 decreased by 48% (p = 0.013). In six patients (26%), sedation failed to improve sleep. CONCLUSIONS: In stable critically ill unsedated patients, sleep quality is poor with frequent wake intrusions and little stable sleep. Light sedation with propofol or dexmedetomidine resulted in a shift in sleep architecture toward normal in most, but not all, patients.

The central nervous system during lung injury and mechanical ventilation: a narrative review.

Mechanical ventilation induces a number of systemic responses for which the brain plays an essential role. During the last decade, substantial evidence has emerged showing that the brain modifies pulmonary responses to physical and biological stimuli by various mechanisms, including the modulation of neuroinflammatory reflexes and the onset of abnormal breathing patterns. Afferent signals and circulating factors from injured peripheral tissues, including the lung, can induce neuronal reprogramming, potentially contributing to neurocognitive dysfunction and psychological alterations seen in critically ill patients. These impairments are ubiquitous in the presence of positive pressure ventilation. This narrative review summarises current evidence of lung-brain crosstalk in patients receiving mechanical ventilation and describes the clinical implications of this crosstalk. Further, it proposes directions for future research ranging from identifying mechanisms of multiorgan failure to mitigating long-term sequelae after critical illness.

A rational approach on the use of extracorporeal membrane oxygenation in severe hypoxemia: advanced technology is not a panacea.

Veno-venous extracorporeal membrane oxygenation (ECMO) is a helpful intervention in patients with severe refractory hypoxemia either because mechanical ventilation cannot ensure adequate oxygenation or because lung protective ventilation is not feasible. Since ECMO is a highly invasive procedure with several, potentially devastating complications and its implementation is complex and expensive, simpler and less invasive therapeutic options should be first exploited. Low tidal volume and driving pressure ventilation, prone position, neuromuscular blocking agents and individualized ventilation based on transpulmonary pressure measurements have been demonstrated to successfully treat the vast majority of mechanically ventilated patients with severe hypoxemia. Veno-venous ECMO has a place in the small portion of severely hypoxemic patients in whom these strategies fail. A combined analysis of recent ARDS trials revealed that ECMO was used in only 2.15% of patients (n = 145/6736). Nevertheless, ECMO use has sharply increased in the last decade, raising questions regarding its thoughtful use. Such a policy could be harmful both for patients as well as for the ECMO technique itself. This narrative review attempts to describe together the practical approaches that can be offered to the sickest patients before going to ECMO, as well as the rationale and the limitations of ECMO. The benefit and the drawbacks associated with ECMO use along with a direct comparison with less invasive therapeutic strategies will be analyzed.

Esophageal and transdiaphragmatic pressure swings as indices of inspiratory effort.

AIM: To describe the correlation between the inspiratory esophageal and transdiaphragmatic pressure swings (ΔPes and ΔPdi), easily measured indices of inspiratory effort, with the gold-standard, the transdiaphragmatic pressure time product (PTPPdi/min), and assess the accuracy of swing pressures in predicting very high or low effort. METHOD: Retrospective analysis of data from patients enrolled in four previous studies. ROC curves of ΔPes and ΔPdi values for specific PTPPdi/min thresholds (50, 150, 200 cmH2O × sec/min) were constructed, and the diagnostic accuracy of different thresholds of swing values were computed. RESULTS: A threshold of inspiratory ΔP<7cmH2O can be used to identify most patients with low effort, as lower ΔP thresholds have low sensitivity. Thresholds of inspiratory ΔP>14-18cmH2O can be used to identify patients with very high inspiratory effort (PTPPdi/min> 200 cmH2O × sec/min). CONCLUSIONS: The results of this study can help clinicians better select and interpret thresholds of ΔP to evaluate inspiratory effort.

Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation.

BACKGROUND: The driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined. METHODS: Retrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a "passive-like" decrease followed by plateau, a pattern with "clear plateau," and an "irregular rise" pattern, which included all cases of late or continuous increase, with or without plateau. RESULTS: Data from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively. CONCLUSIONS: The pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.

Respiratory Drive in Critically Ill Patients. Pathophysiology and Clinical Implications.

Respiratory drive, the intensity of the respiratory center's output, determines the effort exerted in each breath. The increasing awareness of the adverse effects of both strong and weak respiratory efforts during mechanical ventilation on patient outcome brings attention to the respiratory drive of the critically ill patient. Critical illness can affect patients' respiratory drive through multiple pathways, mainly operating through three feedback systems: cortical, metabolic, and chemical. The chemical feedback system, defined as the response of the respiratory center's output to changes in arterial blood gases and pH, is one of the most important determinants of respiratory drive. The purpose of this state-of-the-art review is to describe the determinants of respiratory drive in critically ill patients, review the tools available to assess respiratory drive at the bedside, and discuss the implications of altered respiratory drive during mechanical ventilation. An analysis that relates arterial carbon dioxide levels with brain's response to this stimulus will be presented, contrasting the brain's responses to the patient's ability to generate effective alveolar ventilation, both during unassisted breathing and with different modes of ventilatory assist. This analysis may facilitate comprehension of the pathophysiology of respiratory drive in critically ill patients. As we aim to avoid both over- and under-assistance with mechanical ventilation, considering the patients' respiratory drive at the bedside may improve clinical assessment and management of the patient and the ventilator.

Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV1) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV1 or FVC; 2) FEV1-BDR, BDR in FEV1 but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV1; and 4) Combined-BDR, BDR in both FEV1 and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV1 over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV1-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV1 decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, -1.67; 95% confidence interval [CI], -2.68 to -0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03-1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05-1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58-0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV1 and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

Driving pressure during proportional assist ventilation: an observational study.

BACKGROUND: During passive mechanical ventilation, the driving pressure of the respiratory system is an important mediator of ventilator-induced lung injury. Monitoring of driving pressure during assisted ventilation, similar to controlled ventilation, could be a tool to identify patients at risk of ventilator-induced lung injury. The aim of this study was to describe driving pressure over time and to identify whether and when high driving pressure occurs in critically ill patients during assisted ventilation. METHODS: Sixty-two patients fulfilling criteria for assisted ventilation were prospectively studied. Patients were included when the treating physician selected proportional assist ventilation (PAV+), a mode that estimates respiratory system compliance. In these patients, continuous recordings of all ventilator parameters were obtained for up to 72 h. Driving pressure was calculated as tidal volume-to-respiratory system compliance ratio. The distribution of driving pressure and tidal volume values over time was examined, and periods of sustained high driving pressure (≥ 15 cmH2O) and of stable compliance were identified and analyzed. RESULTS: The analysis included 3200 h of ventilation, consisting of 8.8 million samples. For most (95%) of the time, driving pressure was < 15 cmH2O and tidal volume < 11 mL/kg (of ideal body weight). In most patients, high driving pressure was observed for short periods of time (median 2.5 min). Prolonged periods of high driving pressure were observed in five patients (8%). During the 661 periods of stable compliance, high driving pressure combined with a tidal volume ≥ 8 mL/kg was observed only in 11 cases (1.6%) pertaining to four patients. High driving pressure occurred almost exclusively when respiratory system compliance was low, and compliance above 30 mL/cmH2O excluded the presence of high driving pressure with 90% sensitivity and specificity. CONCLUSIONS: In critically ill patients fulfilling criteria for assisted ventilation, and ventilated in PAV+ mode, sustained high driving pressure occurred in a small, yet not negligible number of patients. The presence of sustained high driving pressure was not associated with high tidal volume, but occurred almost exclusively when compliance was below 30 mL/cmH2O.

The Injurious Effects of Elevated or Nonelevated Respiratory Rate during Mechanical Ventilation.

Respiratory rate is one of the key variables that is set and monitored during mechanical ventilation. As part of increasing efforts to optimize mechanical ventilation, it is prudent to expand understanding of the potential harmful effects of not only volume and pressures but also respiratory rate. The mechanisms by which respiratory rate may become injurious during mechanical ventilation can be distinguished in two broad categories. In the first, well-recognized category, concerning both controlled and assisted ventilation, the respiratory rate per se may promote ventilator-induced lung injury, dynamic hyperinflation, ineffective efforts, and respiratory alkalosis. It may also be misinterpreted as distress delaying the weaning process. In the second category, which concerns only assisted ventilation, the respiratory rate may induce injury in a less apparent way by remaining relatively quiescent while being challenged by chemical feedback. By responding minimally to chemical feedback, respiratory rate leaves the control of V. e almost exclusively to inspiratory effort. In such cases, when assist is high, weak inspiratory efforts promote ineffective triggering, periodic breathing, and diaphragmatic atrophy. Conversely, when assist is low, diaphragmatic efforts are intense and increase the risk for respiratory distress, asynchronies, ventilator-induced lung injury, diaphragmatic injury, and cardiovascular complications. This review thoroughly presents the multiple mechanisms by which respiratory rate may induce injury during mechanical ventilation, drawing the attention of critical care physicians to the potential injurious effects of respiratory rate insensitivity to chemical feedback during assisted ventilation.