Silent hypoxaemia in COVID-19 patients.

The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labelled with 'happy hypoxia', in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key respiratory and neurological components that could underlie variation in the presentation of silent hypoxaemia and define priorities for subsequent investigation.

Association of dyspnoea, mortality and resource use in hospitalised patients.

As many as one in 10 patients experience dyspnoea at hospital admission but the relationship between dyspnoea and patient outcomes is unknown. We sought to determine whether dyspnoea on admission predicts outcomes.We conducted a retrospective cohort study in a single, academic medical centre. We analysed 67 362 consecutive hospital admissions with available data on dyspnoea, pain and outcomes. As part of the Initial Patient Assessment by nurses, patients rated "breathing discomfort" using a 0 to 10 scale (10="unbearable"). Patients reported dyspnoea at the time of admission and recalled dyspnoea experienced in the 24 h prior to admission. Outcomes included in-hospital mortality, 2-year mortality, length of stay, need for rapid response system activation, transfer to the intensive care unit, discharge to extended care, and 7- and 30-day all-cause readmission to the same institution.Patients who reported any dyspnoea were at an increased risk of death during that hospital stay; the greater the dyspnoea, the greater the risk of death (dyspnoea 0: 0.8% in-hospital mortality; dyspnoea 1-3: 2.5% in-hospital mortality; dyspnoea ≥4: 3.7% in-hospital mortality; p<0.001). After adjustment for patient comorbidities, demographics and severity of illness, increasing dyspnoea remained associated with inpatient mortality (dyspnoea 1-3: adjusted OR 2.1, 95% CI 1.7-2.6; dyspnoea ≥4: adjusted OR 3.1, 95% CI 2.4-3.9). Pain did not predict increased mortality. Patients reporting dyspnoea also used more hospital resources, were more likely to be readmitted and were at increased risk of death within 2 years (dyspnoea 1-3: adjusted hazard ratio 1.5, 95% CI 1.3-1.6; dyspnoea ≥4: adjusted hazard ratio 1.7, 95% CI 1.5-1.8).We found that dyspnoea of any rating was associated with an increased risk of death. Dyspnoea ratings can be rapidly collected by nursing staff, which may allow for better monitoring or interventions that could reduce mortality and morbidity.

Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.

PURPOSE: Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS: Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS: Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS: High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.

Routine dyspnea assessment and documentation: Nurses' experience yields wide acceptance.

BACKGROUND: Dyspnea (breathing discomfort) is a common and distressing symptom. Routine assessment and documentation can improve management and relieve suffering. A major barrier to routine dyspnea documentation is the concern that it will have a deleterious effect on nursing workflow and that it will not be readily accepted by nurses. Nurses at our institution recently began to assess and document dyspnea on all medical-surgical patients upon admission and once per shift throughout their hospitalization. A year after dyspnea measurement was implemented we explored nurses' approach to dyspnea assessment, their perception of patient response, and their perception of the utility and burden of dyspnea measurement. METHODS: We obtained feedback from nurses using a three-part assessment of practice: 1) a series of recorded focus group interviews with nurses, 2) a time-motion observation of nurses performing routine dyspnea and pain assessment, and 3) a randomized, anonymous on-line survey based, in part, on issues raised in focus groups. RESULTS: Ninety-four percent of the nurses surveyed reported administering the dyspnea assessment is "easy" or "very easy". None of the nurses reported that assessing dyspnea negatively impacted workflow and many reported that it positively improved their practice by increasing their awareness. Our time-motion data showed dyspnea assessment and documentation takes well less than a minute. Nurses endorsed the importance of routine measurement and agreed that most patients were able to provide a meaningful rating of their dyspnea. Nurses found the patient report very useful, and used it in conjunction with observed signs to respond to changes in a patient's condition. CONCLUSIONS: In this study, we have demonstrated that routine dyspnea assessment and documentation was widely accepted by the nurses at our institution. Our nurses fully incorporated routine dyspnea assessment and documentation into their practice and felt that it improved patient-centered care.

Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research.

There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test-retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions.

An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea.

BACKGROUND: Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular diseases. Since the ATS published a consensus statement on dyspnea in 1999, there has been enormous growth in knowledge about the neurophysiology of dyspnea and increasing interest in dyspnea as a patient-reported outcome. PURPOSE: The purpose of this document is to update the 1999 ATS Consensus Statement on dyspnea. METHODS: An interdisciplinary committee of experts representing ATS assemblies on Nursing, Clinical Problems, Sleep and Respiratory Neurobiology, Pulmonary Rehabilitation, and Behavioral Science determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant expertise. The final content of this statement was agreed upon by all members. RESULTS: Progress has been made in clarifying mechanisms underlying several qualitatively and mechanistically distinct breathing sensations. Brain imaging studies have consistently shown dyspnea stimuli to be correlated with activation of cortico-limbic areas involved with interoception and nociception. Endogenous and exogenous opioids may modulate perception of dyspnea. Instruments for measuring dyspnea are often poorly characterized; a framework is proposed for more consistent identification of measurement domains. CONCLUSIONS: Progress in treatment of dyspnea has not matched progress in elucidating underlying mechanisms. There is a critical need for interdisciplinary translational research to connect dyspnea mechanisms with clinical treatment and to validate dyspnea measures as patient-reported outcomes for clinical trials.

Dyspnea affective response: comparing COPD patients with healthy volunteers and laboratory model with activities of daily living.

BACKGROUND: Laboratory-induced dyspnea (breathing discomfort) in healthy subjects is widely used to study perceptual mechanisms, yet the relationship between laboratory-induced dyspnea in healthy volunteers and spontaneous dyspnea in patients with chronic lung disease is not well established. We compared affective responses to dyspnea 1) in COPD patients vs. healthy volunteers (HV) undergoing the same laboratory stimulus; 2) in COPD during laboratory dyspnea vs. during activities of daily living (ADL). METHODS: We induced moderate and high dyspnea levels in 13 COPD patients and 12 HV by increasing end-tidal CO2 (PETCO2) during restricted ventilation, evoking air hunger. We used the multidimensional dyspnea profile (MDP) to measure intensity of sensory qualities (e.g., air hunger (AH) and work/effort (W/E)) as well as immediate discomfort (A1) and secondary emotions (A2). Ten of the COPD subjects also completed the MDP outside the laboratory following dyspnea evoked by ADL. RESULTS: COPD patients and HV reported similar levels of immediate discomfort relative to sensory intensity. COPD patients and HV reported anxiety and frustration during laboratory-induced dyspnea; variation among individuals far outweighed the small differences between subject groups. COPD patients reported similar intensities of sensory qualities, discomfort, and emotions during ADL vs. during moderate laboratory dyspnea. Patients with COPD described limiting ADL to avoid greater dyspnea. CONCLUSIONS: In this pilot study, we found no evidence that a history of COPD alters the affective response to laboratory-induced dyspnea, and no difference in affective response between dyspnea evoked by this laboratory model and dyspnea evoked by ADL.

Rating Dyspnea and Pain: "No" is Not Always "Zero".

Nurses routinely assess pain in hospitalized patients; similar assessment of dyspnea is increasing. Most nurses start with a yes-no question when assessing pain or dyspnea; many record "no" as a zero rating, skipping the rating scale. We tested the hypothesis that recording "no" answers as "zero" fails to detect the symptoms that would have been detected with a rating scale. Nurses asked 60 patients yes-no questions about the presence of dyspnea and pain, then asked patients to rate the symptoms using a 0-10 scale. All "yes" answers were followed by a concordant rating (i.e., greater than zero). More than 25% of "no" answers were followed by a discordant rating (> zero). Documenting "no" as "zero" missed information potentially useful in care planning; patients who rate dyspnea above zero are at greater risk of adverse outcomes. This information can also provide opportunity to start a discussion with patients who may benefit from symptom management.

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

RATIONALE: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely. OBJECTIVES: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions. METHODS: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO(2) stimulus: (1) perceptual response (breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (Pet(CO2)) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing. MEASUREMENTS AND MAIN RESULTS: We determined the Pet(CO2) that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting Pet(CO2)). At the same Pet(CO2) after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same Pet(CO2); P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect. CONCLUSIONS: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.

Air Hunger: A Primal Sensation and a Primary Element of Dyspnea.

The sensation that develops as a long breath hold continues is what this article is about. We term this sensation of an urge to breathe "air hunger." Air hunger, a primal sensation, alerts us to a failure to meet an urgent homeostatic need maintaining gas exchange. Anxiety, frustration, and fear evoked by air hunger motivate behavioral actions to address the failure. The unpleasantness and emotional consequences of air hunger make it the most debilitating component of clinical dyspnea, a symptom associated with respiratory, cardiovascular, and metabolic diseases. In most clinical populations studied, air hunger is the predominant form of dyspnea (colloquially, shortness of breath). Most experimental subjects can reliably quantify air hunger using rating scales, that is, there is a consistent relationship between stimulus and rating. Stimuli that increase air hunger include hypercapnia, hypoxia, exercise, and acidosis; tidal expansion of the lungs reduces air hunger. Thus, the defining experimental paradigm to evoke air hunger is to elevate the drive to breathe while mechanically restricting ventilation. Functional brain imaging studies have shown that air hunger activates the insular cortex (an integration center for perceptions related to homeostasis, including pain, food hunger, and thirst), as well as limbic structures involved with anxiety and fear. Although much has been learned about air hunger in the past few decades, much remains to be discovered, such as an accepted method to quantify air hunger in nonhuman animals, fundamental questions about neural mechanisms, and adequate and safe methods to mitigate air hunger in clinical situations. © 2021 American Physiological Society. Compr Physiol 11:1449-1483, 2021.

Dyspnea, Acute Respiratory Failure, Psychological Trauma, and Post-ICU Mental Health: A Caution and a Call for Research.

Dyspnea is an uncomfortable sensation with the potential to cause psychological trauma. Patients presenting with acute respiratory failure, particularly when tidal volume is restricted during mechanical ventilation, may experience the most distressing form of dyspnea known as air hunger. Air hunger activates brain pathways known to be involved in posttraumatic stress disorder (PTSD), anxiety, and depression. These conditions are considered part of the post-intensive care syndrome. These sequelae may be even more prevalent among patients with ARDS. Low tidal volume, a mainstay of modern therapy for ARDS, is difficult to avoid and is likely to cause air hunger despite sedation. Adjunctive neuromuscular blockade does not prevent or relieve air hunger, but it does prevent the patient from communicating discomfort to caregivers. Consequently, paralysis may also contribute to the development of PTSD. Although research has identified post-ARDS PTSD as a cause for concern, and investigators have taken steps to quantify the burden of disease, there is little information to guide mechanical ventilation strategies designed to reduce its occurrence. We suggest such efforts will be more successful if they are directed at the known mechanisms of air hunger. Investigation of the antidyspnea effects of sedative and analgesic drugs commonly used in the ICU and their impact on post-ARDS PTSD symptoms is a logical next step. Although in practice we often accept negative consequences of life-saving therapies as unavoidable, we must understand the negative sequelae of our therapies and work to minimize them under our primary directive to "first, do no harm" to patients.

Intensive Care Nurses' Perceptions of Routine Dyspnea Assessment.

BACKGROUND: Dyspnea (breathing discomfort) is commonly experienced by critically ill patients and at this time is not routinely assessed and documented. Intensive care unit nurses at the study institution recently instituted routine assessment and documentation of dyspnea in all patients able to report using a numeric scale ranging from 0 to 10. OBJECTIVE: To assess nurses' perceptions of the utility of routine dyspnea measurement, patients' comprehension of assessment questions, and the impact on nursing practice and to gather nurses' suggestions for improvement. METHODS: Data were obtained from interviews with intensive care unit nurses in small focus groups and an anonymous online survey randomly distributed to nurses representing all intensive care units. RESULTS: Intensive care unit nurses affirmed the importance of routine dyspnea assessment and documentation. Before implementing the measurement tool, nurses often assessed for breathing discomfort in patients by using observed signs. Most nurses agreed that routine assessment can be used to predict patients' outcomes and improve patient-centered care. Nurses found the assessment tool easy to use and reported that it did not interfere with workflow. Nurses felt that patients were able to provide meaningful ratings of dyspnea, similar to ratings of pain, and often used patients' ratings in conjunction with observed physical signs to optimize patient care. CONCLUSION: Our study shows that nurses understand the importance of routine dyspnea assessment and that the addition of a simple patient report scale can improve care delivery and does not add to the burden of work-flow.

'Scared to death' dyspnoea from the hospitalised patient's perspective.

Because dyspnoea is seldom experienced by healthy people, it can be hard for clinicians and researchers to comprehend the patient's experience. We collected patients' descriptions of dyspnoea in their own words during a parent study in which 156 hospitalised patients completed a quantitative multidimensional dyspnoea questionnaire. These volunteered comments describe the severity and wide range of experiences associated with dyspnoea and its impacts on a patients' life. They provide insights not conveyed by structured rating scales. We organised these comments into the most prominent themes, which included sensory experiences, emotional responses, self-blame and precipitating events. Patients often mentioned air hunger ('Not being able to get air is the worst thing that could ever happen to you.'), anxiety, and fear ('Scared. I thought the world was going to end, like in a box.'). Their value in patient care is suggested by one subject's comment: 'They should have doctors experience these symptoms, especially dyspnoea, so they understand what patients are going through.' Patients' own words can help to bridge this gap of understanding.

The affective dimension of laboratory dyspnea: air hunger is more unpleasant than work/effort.

RATIONALE: It is hypothesized that the affective dimension of dyspnea (unpleasantness, emotional response) is not strictly dependent on the intensity of dyspnea. OBJECTIVES: We tested the hypothesis that the ratio of immediate unpleasantness (A(1)) to sensory intensity (SI) varies depending on the type of dyspnea. METHODS: Twelve healthy subjects experienced three stimuli: stimulus 1: maximal eucapnic voluntary hyperpnea against inspiratory resistance, requiring 15 times the work of resting breathing; stimulus 2: Pet(CO(2)) 6.1 mm Hg above resting with ventilation restricted to less than spontaneous breathing; stimulus 3: Pet(CO(2)) 7.7 mm Hg above resting with ventilation further restricted. After each trial, subjects rated SI, A(1), and qualities of dyspnea on the Multidimensional Dyspnea Profile (MDP), a comprehensive instrument tested here for the first time. MEASUREMENTS AND MAIN RESULTS: Stimulus 1 was always limited by subjects failing to meet a higher ventilation target; none signaled severe discomfort. This evoked work and effort sensations, with relatively low unpleasantness (mean A(1)/SI = 0.64). Stimulus 2, titrated to produce dyspnea ratings similar to those subjects gave during stimulus 1, evoked air hunger and produced significantly greater unpleasantness (mean A(1)/SI = 0.95). Stimulus 3, increased until air hunger was intolerable, evoked the highest intensity and unpleasantness ratings and high unpleasantness ratio (mean A(1)/SI = 1.09). When asked which they would prefer to repeat, all subjects chose stimulus 1. CONCLUSIONS: (1) Maximal respiratory work is less unpleasant than moderately intense air hunger in this brief test; (2) unpleasantness of dyspnea can vary independently from perceived intensity, consistent with the prevailing model of pain; (3) separate dimensions of dyspnea can be measured with the MDP.

A Multidimensional Profile of Dyspnea in Hospitalized Patients.

BACKGROUND: Dyspnea is prevalent among hospitalized patients but little is known about the experience of dyspnea among inpatients. We sought to characterize the multiple sensations and associated emotions of dyspnea in patients admitted with dyspnea to a tertiary care hospital. METHODS: We selected patients who reported breathing discomfort of at least 4/10 on admission (10 = unbearable). Research staff recruited 156 patients within 24 hours of admission and evaluated daily patients' current and worst dyspnea with the Multidimensional Dyspnea Profile; patients participated in the study 2.6 days on average. The Multidimensional Dyspnea Profile assesses overall breathing discomfort (A1), intensity of five sensory qualities of dyspnea, and 5 negative emotional responses to dyspnea. Patients were also asked to rate whether current levels of dyspnea were "acceptable." RESULTS: At the time of the first research interview, patients reported slight to moderate dyspnea (A1 median 4); however, most patients reported experiencing severe dyspnea in the 24 hours before the interview (A1 mean 7.8). A total of 54% of patients with dyspnea ≥4 on day 1 found the symptom unacceptable. The worst dyspnea each day in the prior 24 hours usually occurred at rest. Dyspnea declined but persisted through hospitalization for most patients. "Air hunger" was the dominant sensation, especially when dyspnea was strong (>4). Anxiety and frustration were the dominant emotions associated with dyspnea. CONCLUSIONS: This first multidimensional portrait of dyspnea in a general inpatient population characterizes the sensations and emotions dyspneic patients endure. The finding that air hunger is the dominant sensation of severe dyspnea has implications for design of laboratory models of these sensations and may have implications for targets of palliation of symptoms.