Automated Oxygen Administration -Rethinking Interventions Alleviating Dyspnea in Patients With COPD
Automated Oxygen Administration -Rethinking Interventions Alleviating Dyspnea in Patients With COPD
Chronic Obstructive Pulmonary Disease (COPD) is associated with high morbidity and mortality.
 The Danish Lung Association estimates that 320,000 Danes live with COPD, of which
 approximately 50,000 with severe COPD. In 2017, records showed that 23,979 admissions in
 Denmark were related to COPD; of these patients, about 20% were readmitted 2-30 days after
 discharge. The main symptom is dyspnea, which is often accompanied by anxiety. Primary
 treatment is; oxygen, bronchiolitis, prednisolone, morfica, NIV, and anxiolytics.

 Researchers at Hvidovre Hospital have developed an oxygen robot that continuously monitors
 the patient's SaO2 (oxygen saturation) and automatically administrates the oxygen depending
 on it. The preliminary results show that patients with robot-administrated oxygen were within
 defined SaO2 range in 85.7% of the time versus 46.6% when oxygen was nurse-administrated. The
 research was conducted as a multicentre Randomized Controlled Trial focusing on physiological
 end-points.

 There is a lack of knowledge about the patient perspective of treatment with the oxygen
 robot.

 The purpose of this study is:

 1. To examine the effect of robot-administered oxygen on patients' perception of dyspnoea,
 including the emotional response in the form of anxiety and depression

 The perspective is to be able to provide a holistic response to whether robot-administered
 oxygen can be a better method of treating and alleviating dyspnoea.
Chronic Obstructive Pulmonary Disease (COPD) is a high prevalence disease and is associated
 with high morbidity and mortality worldwide. In 2017, there were 23.979 COPD related
 admissions in Denmark, approximately 10% died during hospitalization, while 20% of survivors
 were readmitted between day 2-30 after discharge.

 Patients with COPD often experience long disease trajectories characterized by a substantial
 burden of symptoms, impaired functional status, multiple admissions and thereby reduced
 quality of life.

 The cardinal symptom dyspnea is associated with hypoxemia, anxiety and depression. Evidence
 shows that depression is a significant risk factor for disabling dyspnea, while risk of
 anxiety increases with the severity of Dyspnea. The prevalence of anxiety and depression is
 indicated to lie between 10%-55% and 10%-86% in patients hospitalized with COPD in
 exacerbation . Patients with COPD have an 85% increased risk of developing anxiety compared
 to a matching control group without COPD. The prevalence of anxiety is 10 times higher among
 patients with COPD than in the background population and are strongly associated with the
 risk of hospitalization, long admissions, readmissions and death. Anxiety and depression are
 often treated with benzodiazepines which have a respiratory suppressive effect. Consumption
 of benzodiazepines increases disease progression, and studies have shown that 31.7% of
 patients with COPD have a benzodiazepine consumption and that 9% initiate a new
 benzodiazepine ordination in conjunction with an exacerbation.

 The evidence that oxygen prevents disease progression and mortality is consistent, but there
 is a lack of knowledge about whether oxygen, can reduce the intensity of dyspnea in patients
 with COPD.

 In the acute phase of an exacerbation the oxygen flow is titrated to achieve a SaO2 between
 88-92%. Keeping patients with COPD within the given SaO2 range is essential because too low
 SaO2 can induce tissue damage, heart overload and difficulty concentrating, while
 hyperoxaemia can inhibit respiration and increase the risk of hypercapnia, acidosis and the
 need for ventilatory support in the form of Non-invasive Ventilation (NIV).

 In clinical practice, oxygen flow is administered and titrated, via aggregates, by nurses
 based on point observations, with the risk of patients being outside optimal SaO2 range,
 between observations.

 To improve practice, a group of researchers at Hvidovre Hospital has developed an oxygen
 robot, called O2matic, which continuously monitors the patient's SaO2 and automatically
 administrates oxygenflow according to it.

 O2Matic has been tested in a randomized controlled trial in 2018. Patients admitted with an
 exacerbation of COPD and hypoxemia (SaO2 ≤ 88%) was included (N = 19). The design was
 crossover and patients were allocated to either 4 hours of manual oxygen administration via
 nurse followed by 4 hours of oxygen administration via O2Matic, or vice versa. The study
 showed that patients with O2matic controlled oxygen administration were within defined SaO2
 range in 85.7% of the time versus 46,6% of the time when the oxygen was controlled and
 administrated by a nurse . These results are in consensus with a former Canadian study
 testing an alternative oxygen robot (FreeO2). The two RCT Studies provide evidence to
 investigate robot-administered oxygen therapy for inpatient patients with exacerbation of
 COPD in a larger multicenter RCT.

 Dyspnea is defined as; "A subjective experience of breathing discomfort that consist of
 qualitatively distinct sensations that vary in intensity". The experience of dyspnea is a
 product of a physical perception based on signals from the body to the brain followed by the
 cognitive processing of these into an emotional experience. Dyspnea is thus an emotional and
 sensational experience based on perceptual afferent feedback from various respiratory
 receptors. Up to 16 possible mechanisms are involved in the process . Given the above,
 dyspnea is a complex symptom, mainly induced by the body's attempts to obtain homeostasis,
 when subjected to hypoxemia. Despite this dyspnea is not the same as hypoxemia, as it has not
 been clearly demonstrated that reduced hypoxemia, by oxygen therapy also reduces Dyspnea.
 However, there are indications in the literature that oxygen therapy can reduce the
 experience of dyspnea. A significant barrier to the use of oxygen therapy as an intervention
 on fragmentary dyspnea in patients with COPD is the risk of hypercapnia and acidosis. Oxygen
 therapy administrated according to saturation in a closed-loop-feedback-system by a robot,
 could potentially be an intervention to relieve fragmentary dyspnea in patients with COPD.
 International guidelines show that dyspnea is not treated consistently nor effectively in the
 advanced stages of the disease.

 Opioids are one of the most widely used agents in the treatments of dyspnea. Opioids
 suppress' respiration and treatment should be balanced to avoid respiratory depression.

 Guidelines points out the importance of identifying and graduate the intensity of dyspnea in
 clinical practice, without indicating any superior instruments to achieve this. Majority of
 instruments developed, describe dyspnea in relation to activity. As COPD progress, dyspnea
 intensifies and patients will become more inactive and often live a sedentary life.

 Few questionnaires measure the sensory and emotional domains of dyspnea independently of
 activity and diagnose. One is the multidimensional Dyspnoea profile (MDP) that has currently
 been translated into Danish.

 In order to reduce symptom burden, length of hospital stay, number of re-admissions and
 mortality, new knowledge and more effective methods for treating and alleviating dyspnea and
 the associated anxiety and depression are needed in patients with COPD.

 Studies investigating the effect of oxygen therapy, including time with and degree of
 hypoxemia, in hypoxemic patients experiencing dyspnea, anxiety or depression during
 hospitalization with acute exacerbation, could not be identified.

 Because O2matic provides a new and unique opportunity to reduce and illuminate time with
 hypoxemia during hospitalization and patient's subjective experience of the sensory and
 emotional aspects of dyspnea can be reported on a validated questionnaire via MDP, the
 investigators now have an option to investigate if a robot intervention, that reduces time
 with hypoxemia, has an effect on dyspnea in patients admitted with a exacerbation of COPD.
 Furthermore, investigators want to examine whether this intervention alters the consumption
 of opioids and benzodiazepines.

 Primary hypothesis. Robot-administered oxygen reduces the perception of dyspnea measured at
 scale A1 on the multidimensional Dyspnea Profile (MDP), in patients with COPD and hypoxemia.

 Primary objective. To investigate if oxygen administration by O2matic has an effect on the
 perception of dyspnea in patients admitted with an exacerbation of COPD and hypoxemia, versus
 conventional oxygen administration by oxygen aggregate and a nurse Primary end points.

 -  Global dyspnea measured on scale A1 on multidimensional Dyspnea Profile (MDP) Secondary
 hypothesis. Oxygen administration by O2matic reduces the sensory and emotional dimension
 of dyspnea, respiratory symptoms, anxiety and depression, as well as consumption of
 anxiolytics in patients admitted with hypoxemia and exacerbation of COPD versus
 conventional Oxygen management by aggregate and nurse Secondary aim. To investigate if
 oxygen administration by O2matic has an effect on the sensory and emotional dimension of
 dyspnea, respiratory symptoms, anxiety and depression, as well as the consumption of
 anxiolytics in patients admitted with hypoxemia and exacerbation in COPD versus
 Conventional oxygen management by aggregate and nurse Secondary end-points.

 -  Sensory and emotional dimension of dyspnea described by The Sensory Quality scale (SQ)
 and the A2 scale of the MDP

 -  Current dyspnea measured on visual Analog scale (VAS)

 -  Accumulated dyspnea over 3 days measured on VAS

 -  Respiratory symptoms described by COPD Assessment Test

 -  Anxiety described by HADS A score

 -  Depression described by HADS D scores

 -  Consumption of anxiolytics reported in Mg and in number of administrations

 Following variables will be tested for confounding:

 Age, gender, BMI, smoking status, package year, Long-term Oxygen Therapy (LOT), FEV1, GOLD
 classification A-D and Prednisolone reported in Mg
Inclusion Criteria:

 -  COPD veryfied by Forced Expiratory Volume in 1 sec (Fev1) divided by forced Vital
 Capacity (FVC)< 0,70

 -  Admission due to exercabation in COPD

 -  COPD exacerbation and pneumonia can be included

 -  Expeted duration of admission >48 hours

 -  Need for oxygen supplementation (SpO2<= 88% in room air) Cognitive able to participate
 in the study

 -  Willing to participate and give informed consent

 Exclusion Criteria:

 -  Need or anticipated need for mechanical ventilation ( Intermittent continuous Positive
 Airway Pressure (CPAP) is allowed)

 -  Major comorbidities causing hypoxemia (cancer, heart disease, pulmonary embolia)

 -  Asthma or other respiratory conditions requiring higher SpO2 than normal for COPD
 Pregnancy

 -  Cognitive barrierers for participation