Using Laboratory Models to Test Treatment

Banzett, Robert B.; Adams, Lewis; O’Donnell, Carl R.; Gilman, Sean; Lansing, Robert; Schwartzstein, Richard M.

doi:10.1164/rccm.201101-0005oc

Cited by 82 publications

(37 citation statements)

References 56 publications

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“…Of clinical relevance is the experimental finding that an effective way to induce air hunger is to increase ventilatory demand via mild hypercapnia while hindering the normal ventilatory response [29, 30]. Likewise, therapeutic interventions can have different effects on the sensory and the affective component of dyspnea [31]. …”

Section: Simplified Physiological Basis Of Dyspneic Sensationsmentioning

confidence: 99%

Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients

et al. 2013

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Background Intensive care unit (ICU) patients are exposed to many sources of discomfort. Although growing attention has been given to the detection and treatment of pain, very little has been given to the detection and treatment of dyspnea (defined as ‘breathing discomfort’). Discussion In this article, we review the published information on prevalence, mechanisms and potential negative impacts of dyspnea in mechanically ventilated patients. In addition, we review the most appropriate tools to detect and quantify dyspnea in ICU patients. Conclusions Growing evidence suggests that dyspnea is a frequent issue in mechanically ventilated ICU patients, is highly associated with anxiety and pain, and is improved in many patients by altering ventilator settings. Future studies are needed to better delineate the impact of dyspnea in the ICU, and to define diagnostic, monitoring and therapeutic protocols.

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Section: Simplified Physiological Basis Of Dyspneic Sensationsmentioning

confidence: 99%

Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients

et al. 2013

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“…Neither treatment produced worsening of dyspnea, thus results are unlikely to be due to random measurement noise. The frequent occurrence of a substantial positive treatment effect following saline puzzled us, as it had not been seen in prior studies of laboratory dyspnea in which the placebo arm was aerosol saline [2,3] or injected saline, [10]. Our recent study differed from earlier studies in that aerosol delivery was controlled by a mechanical ventilator, and in that subject expectations may have been heightened by our blinding procedures.…”

Section: Introductionmentioning

confidence: 87%

“…We used the same laboratory model to evoke dyspnea as was used in our recent study of furosemide; this model has been used several times in prior studies [13,10,14]. In brief, we induced dyspnea in healthy subjects before and after drug administration by varying inspired Pco 2 while restricting minute ventilation to 0.13 liters•min −1 •kg −1 by limiting the flow into an anesthetic bag.…”

Section: Methodsmentioning

confidence: 99%

“…To obtain a single metric for statistical testing of response to treatment, we used the same analysis approach established a priori for our earlier studies of IV morphine and aerosol furosemide [10]. In brief, using linear regression we found the Petco 2 at which BDVAS=60%Full Scale (%FS) prior to treatment (excluding points at Petco 2 exceeding 1.5 torr below resting).…”

Section: Methodsmentioning

confidence: 99%

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The Effect of Aerosol Saline on Laboratory-Induced Dyspnea

O’Donnell

Lansing

Schwartzstein

et al. 2016

Lung

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Purpose In the ‘placebo arm’ of a recent study we found that aerosol saline (sham treatment) produced substantial relief of laboratory-induced dyspnea (Breathing Discomfort – BD) in nearly half the subjects. The sham intervention included a physiological change, and instructions to subjects could have produced expectation of dyspnea relief. In the present study we attempted to discover whether the response to sham aerosol was driven by behavioral or physiological aspects of the intervention. Methods Dyspnea (air hunger) was evoked by constraining tidal volume during graded hypercapnia. We measured Petco2 vs BD relationship before and after aerosol saline. To minimize subjects’ expectations of dyspnea relief, participants in were clearly instructed that we would only deliver saline aerosol. In Protocol 1, we delivered aerosol saline with a ventilator (mimicking our prior study); in Protocol 2, we delivered aerosol without a ventilator. Results Administration of aerosol saline had little effect on BD in this group of subjects with one exception: one subject experienced appreciable reduction in BD in Protocol 1. This treatment effect was less in Protocol 2. The two most likely explanations are a) that procedures surrounding ventilator administration of aerosol produced a psychological placebo treatment effect even though the subject knew a drug was not given, b) there were behavioral changes in breathing undetected by our measurements of respiratory flow and volume that altered the subjects comfort. Conclusion When the expectation of treatment effect is minimized, a significant reduction in dyspnea in response to saline placebo is uncommon but not impossible.

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“…Importantly, standardised multidimensional measurement is essential to adequately capture treatment effects in clinical trials. For example, opioids have been found to have a stronger effect on the unpleasantness and associated anxiety than on the intensity of dyspnoea (11), and pulmonary rehabilitation improves the patient's coping and function in relation to dyspnoea whereas the symptom intensity may remain unchanged (12). …”

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confidence: 99%

Swedish translation and linguistic validation of the multidimensional dyspnoea profile

Ekström

Sundh

2016

European Clinical Respiratory Journal

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BackgroundDyspnoea, the feeling of breathing discomfort, consists of multiple dimensions that can vary in intensity, including the level of unpleasantness, qualities or descriptors of the sensation, emotional responses, and impact on function. No validated instrument for multidimensional measurement of dyspnoea is available in Swedish. The Multidimensional Dyspnea Profile (MDP) was recently developed to measure the unpleasantness, sensory qualities, and emotional responses of dyspnoea across diseases and settings. We aimed to take forward a Swedish version of the MDP.MethodsTranslation and linguistic validation of the MDP was conducted in collaboration with a specialised company in the field (Mapi, Lyon, France). The structured process involved forward and backward translations by two independent certified translators, input from an in-country linguistic consultant, the developers, and three respiratory physicians. Understandability and acceptability were evaluated through in-depth interviews with five patients with dyspnoea in accordance with international guidelines.Results and ConclusionA Swedish version of the MDP was obtained and linguistically validated. The MDP includes 11 rated items: the immediate unpleasantness of the sensation, the presence and intensity of five sensory qualities, and the intensity of five emotional responses to dyspnoea. The time period of measurement is specified by the user. The MDP is copyrighted by the developers but can be used free of charge in the context of non-funded academic research.ConclusionThe MDP is the first instrument for measuring multiple dimensions of dyspnoea available in Swedish and should be validated across diseases and settings. Multidimensional measurement is essential for improved assessment and management of dyspnoea in research and clinical care.

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Using Laboratory Models to Test Treatment

Cited by 82 publications

References 56 publications

Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients

Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients

The Effect of Aerosol Saline on Laboratory-Induced Dyspnea

Swedish translation and linguistic validation of the multidimensional dyspnoea profile

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