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Initiation of home mechanical ventilation at home: A randomised controlled trial of efficacy, feasibility and costs

  • A. Hazenberg
    Correspondence
    Corresponding author. University Medical Center Groningen, Department of Pulmonology and Tuberculosis, Department of Home Mechanical Ventilation, Internal Postal Code AA62, Hanzeplein 1, 9700 RB Groningen, The Netherlands. Tel.: +31 50 3613200; fax: +31 50 3613900.
    Affiliations
    University of Groningen, University Medical Center Groningen, Department of Pulmonology and Tuberculosis, Department of Home Mechanical Ventilation, Groningen, The Netherlands

    University of Groningen, University Medical Center Groningen, GRIAC Research Institute, The Netherlands
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  • H.A.M. Kerstjens
    Affiliations
    University of Groningen, University Medical Center Groningen, Department of Pulmonology and Tuberculosis, Department of Home Mechanical Ventilation, Groningen, The Netherlands

    University of Groningen, University Medical Center Groningen, GRIAC Research Institute, The Netherlands
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  • S.C.L. Prins
    Affiliations
    TNO – The Netherlands Organization for Applied Scientific Research, The Netherlands
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  • K.M. Vermeulen
    Affiliations
    University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands
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  • P.J. Wijkstra
    Affiliations
    University of Groningen, University Medical Center Groningen, Department of Pulmonology and Tuberculosis, Department of Home Mechanical Ventilation, Groningen, The Netherlands

    University of Groningen, University Medical Center Groningen, GRIAC Research Institute, The Netherlands
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Open ArchivePublished:July 21, 2014DOI:https://doi.org/10.1016/j.rmed.2014.07.008

      Summary

      Introduction

      Home mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting.

      Methods

      Seventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months.

      Results

      PaCO2, improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group, both improvements being significant and the latter clearly not inferior.
      There were also significant improvements in quality of life in both groups, again not being inferior with home treatment.

      Conclusion

      This study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than € 3000 per patient can be saved compared to our standard care.

      Keywords

      Introduction

      Home mechanical ventilation (HMV) in the Netherlands routinely starts in a clinical setting as recommended in the national guideline and typically requires several days, up to a week of hospitalisation []. Nocturnal arterial blood gas analysis while on HMV complete the initiation period and are performed at the intensive care. It is intuitive that the costs of starting HMV in a hospital setting are substantial higher than at home which is the topic of our study. In addition being admitted to a hospital for patients is not only an emotional burden, it also increases the risk of developing a nosocomial infection [
      • van der Kooi T.I.
      • Mannien J.
      • Wille J.C.
      • van Benthem B.H.
      Prevalence of nosocomial infections in The Netherlands, 2007–2008: results of the first four national studies.
      ]. Patients on HMV are mostly severely disabled and it is often, perhaps paradoxically, challenging to provide the same high level of individually tailored care in hospital as compared to home. These are all very important reasons to investigate whether the initiation of HMV cannot be carried out in the home setting.
      A problem of the initiation of HMV at home so far has been the lack of professional supervision in the home environment and night time observation during sleep. A probable solution for this problem is the use of telemonitoring to transmit digital data and provide clinical health care outside the hospital [
      • Inglis S.C.
      • Clark R.A.
      • McAlister F.A.
      • Stewart S.
      • Cleland J.G.
      Which components of heart failure programmes are effective? A systematic review and meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of chronic heart failure management in 8323 patients: abridged cochrane review.
      ,
      • de Almeida J.P.
      • Pinto A.C.
      • Pereira J.
      • Pinto S.
      • de Carvalho M.
      Implementation of a wireless device for real-time telemedical assistance of home-ventilated amyotrophic lateral sclerosis patients: a feasibility study.
      ]. The data in patients with HMV comprises of ventilator settings and physiological data, for example carbon dioxide and oxygen saturation levels. It has been shown that telemonitoring can be cost-effective and in certain settings is able to transfer the burden of care from health-care professionals to family and home-care personnel [
      • Vitacca M.
      • Bianchi L.
      • Guerra A.
      • Fracchia C.
      • Spanevello A.
      • Balbi B.
      • et al.
      Tele-assistance in chronic respiratory failure patients: a randomised clinical trial.
      ]. In the latter study patients with chronic obstructive pulmonary disease (COPD) on oxygen or HMV were monitored by tele-assistance which reduced both hospitalisations and urgent calls compared to the control group that received standard care.
      As we do not know if the initiation of HMV at home is effective, technically feasible and cost-effective we set up a randomised controlled trail.
      Our hypothesis was that initiation of HMV at home, by using telemonitoring, in a selective group of patients with chronic respiratory failure due to neuromuscular disease (NMD) or thoracic cage disorder is not inferior compared to initiation in a hospital. The primary outcome measure was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcome measurements.

      Methods

      Subjects

      The study design was single-centre, prospective, randomised and controlled. Patients diagnosed with chronic respiratory failure due to a NMD or thoracic cage disorder being referred to our outpatient clinic were screened for participation in this study. Chronic respiratory failure was defined as daytime PaCO2 >6.0 kPa (>45 mmHg) [
      Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation–a consensus conference report.
      ,
      • Robert D.
      • Willig T.N.
      • Leger P.
      • Paulus J.
      Long-term nasal ventilation in neuromuscular disorders: report of a consensus conference.
      ] with complaints of respiratory failure (pulmonary infections, headache, daytime sleepiness, concentration problems) as stated in our national guideline. [] Patients with orthopnea due to diaphragm paralysis and daytime normocapnia were also included. Patients younger than 18 years, those who needed invasive ventilation and the ones that lived in a nursing home were excluded. We excluded patients with strictly COPD as HMV is not a standard therapy in the Netherlands in those patients. Patients not naïve to a mask, for example failure after CPAP therapy and patients with an acute episode of respiratory failure were also excluded. The study was approved by the Medical Ethics Committee of the University of Groningen, University Medical Center of Groningen and written informed consent was obtained from all patients. The trial was registered with the Netherlands Trial Registry (NTR number 1476).

      Randomisation and intervention

      Patients started HMV at home or in the hospital in random order. Stratification was done for patients with Amyotrophic Lateral Sclerosis (ALS) to prevent a possible imbalance between the two groups. Randomisation was done by an independent statistician using a stratified block randomisation with a block size of 6.

      Measurements

      Daytime arterial blood gasses were taken from the radial artery, in sitting position and without oxygen supplementation or HMV at baseline and 6 months after the initiation of HMV at the outpatient clinic.
      Patients completed the following questionnaires: Severe Respiratory Insufficiency (SRI) [
      • Windisch W.
      • Freidel K.
      • Schucher B.
      • Baumann H.
      • Wiebel M.
      • Matthys H.
      • et al.
      The severe respiratory insufficiency (SRI) questionnaire: a specific measure of health-related quality of life in patients receiving home mechanical ventilation.
      ], Maugeri Respiratory Failure (MRF-28) [
      • Carone M.
      • Bertolotti G.
      • Anchisi F.
      • Zotti A.M.
      • Donner C.F.
      • Jones P.W.
      Analysis of factors that characterize health impairment in patients with chronic respiratory failure. Quality of life in chronic respiratory failure group.
      ], Hospital Anxiety and Depression Scale (HADS) [
      • Zigmond A.S.
      • Snaith R.P.
      The hospital anxiety and depression scale.
      ] and the Short-Form Health Survey (SF-36) [
      • Aaronson N.K.
      • Muller M.
      • Cohen P.D.
      • Essink-Bot M.L.
      • Fekkes M.
      • Sanderman R.
      • et al.
      Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations.
      ]. The SRI contains seven domains; respiratory complaints, physical functioning, attendant symptoms and sleep, social relationships, anxiety, psychological well-being and social functioning. The MRF contains three domains; daily activity, cognitive function and invalidity. The HADS contains the anxiety and depression domain. The SF-36 contains eight domains; physical functioning; role physical; bodily pain; general health; vitality; social functioning; role emotional and mental health.
      Forced vital capacity was measured by spirometry (Masterscreen® Viasys, Bodystat Ltd, Isle of Man, UK.).
      Carbon dioxide and oxygen saturation were assessed through the skin of the earlobe, by Tosca® (Linde Medical Sensors AG. Basel. Switzerland) [
      • Hazenberg A.
      • Zijlstra J.G.
      • Kerstjens H.A.
      • Wijkstra P.J.
      Validation of a transcutaneous CO(2) monitor in adult patients with chronic respiratory failure.
      ].
      A standard procedure describing the technical setup of HMV was used both at home and in the hospital. All patients started with the Elisée 150® ventilator (ResMed Paris, Fr.). The choice of the interface could be a nasal, full-face, mouth or total-face mask. The ventilator in the pressure mode was set up at the start with an inspiratory pressure of 10 cm H2O; a positive end expiratory pressure (PEEP) of 4 cm H2O; a target volume of 8–10 ml/kg and a ventilatory rate close to the patients breathing frequency. The set up in the volume mode started at a volume of 8–10 ml/kg; a PEEP of 4 cm H2O and a ventilatory rate close to the patients breathing frequency. The standard procedure described which actions should be taken to change the ventilator settings during the initiation of HMV. For example, if the patient needed more air, the inspiratory pressure was increased and if the patient snored during the PEEP was increased. During the initiation of HMV adjustments to the ventilator and or interface were done to improve the blood gasses and the patients comfort resulting in a good night sleep.

      Initiation of home mechanical ventilation in the hospital

      Standard care during the initiation of HMV in our hospital entails admission on a regular respiratory ward with specifically trained personnel. The first day of admission the patient started HMV with the intention to get used to the interface and to adjust to the ventilator settings. Patients were instructed to use the ventilator as long as possible during the first night. They were allowed to stop the HMV during the night and if applicable start again early in the morning for another session. Every day the necessary actions including, adjusting ventilator settings or interface were performed. The patient had to sleep at least 6 h with the ventilator, before he was transferred to the intensive care unit (ICU) to assess arterial blood gasses, through a radialis catheter, during the night while using the HMV. The latter being the standard routine in the Netherlands. If normalisation of carbon dioxide and oxygen saturation levels while on the ventilator were reached, the patient was discharged. The ventilator was installed at home by a nurse of the department of HMV. After two months the patient was admitted again to the ICU for nocturnal arterial blood gas assessment while on HMV. The patient had to bring their own home ventilator to the hospital.
      Follow-up was six months after starting HMV at the outpatient clinic to assess an arterial blood gas analysis and lung function.

      Initiation of home mechanical ventilation at home

      Initiation of HMV at home started during the first visit at the patient's home by the nurse practitioner (NP). The ventilator, humidifier and transcutaneous monitor were installed in the patient's bedroom (Fig. 1). This installation also included the laptop, mobile connection and the software program that was used to send digital data of the devices to the hospital. The first time the patient was ventilated the NP was present. After instruction was given to the patient and if necessary to the caregivers they practiced the HMV themselves at daytime. If in the first night, when trying to sleep with the HMV, the patient woke up and could not continue because of discomfort they were allowed to stop. The following days and nights they tried to extend the number of hours on HMV. Patients were instructed to call the department of HMV 24/7 if problems occurred. If sputum mobilisation was a problem patients were instructed to use air stacking and one ventilator mode was adjusted for mouthpiece ventilation. Every day the ventilator information (e.g. volume, frequency, pressure levels, hours ventilator was used) was sent to the hospital and evaluated by the NP. The NP informed the patient about the results over the telephone and if necessary the ventilator settings were adjusted by the patient or the care giver. Changing the ventilator settings while on the phone with the NP is part of the instruction at the start of HMV. The transcutaneous monitor was attached the moment the patient could sleep for six hours while being on HMV. The next day the measurements of the transcutaneous monitor and the ventilator were evaluated, by using telemonitoring. When the results showed a normalisation of the carbon dioxide and oxygen saturation, the initiation period was ended during a house call by the NP. The transcutaneous monitor and the telemonitoring equipment were returned to the hospital. Two months after the initiation of HMV, transcutaneous monitoring at home was performed again.
      Figure thumbnail gr1
      Figure 1Setup of the telemonitoring equipment at home. Ventilator Elisée 150®, humidifier Fisher and Paykel HC 150®, transcutaneous monitor Tosca®, laptop with mobile connection.
      Follow-up was six months after starting HMV at the outpatient clinic to assess an arterial blood gas analysis and lung function.

      Telemonitoring

      Every morning during the initiation period of HMV at home, the data of the ventilator and if applicable of the transcutaneous monitor was sent to the hospital. The data comprised of ventilator settings, respiratory rate and carbon dioxide and oxygen saturation levels. The NP received the anonymised digital data by email and phoned with the patient to evaluate the results. A laptop was used to transfer the information collected by the ventilator and transcutaneous monitor to the hospital. A software program especially developed for this study started the data collection of the ventilator and transcutaneous monitor automatically.

      Cost analysis

      Units of health care consumption that were registered included admission days to the general ward and ICU, time spent by the nurse practitioner (including house calls) and travelling expenses. Volumes of health care consumption were multiplied with their cost prices according to the Dutch guideline for cost studies [
      • Hakkaart-van Roijne L.
      • Tan S.S.
      • Bouwmans C.A.M.
      Manual for costs research. Methods and standard prices for economic evaluations in health care.
      ]. The 2012 price level was used. Costs are displayed in Euro's (€). The time horizon of the cost study was equal to that of the clinical study and was 6 months. Mean total costs per patient were calculated for both interventions separately. Confidence intervals (95%CI's) were computed based on bootstrap re-sampling with 5000 replications of the trial dataset.

      Statistical analysis

      The primary outcome analysis was PaCO2 which was based on intention-to-treat (ITT) analysis. The power analysis was based on a non-inferiority test of the difference of two means. With an alpha of 0.05, a beta of 0.2, a standard deviation off 0.71 and a maximum difference in PaCO2 of 0.5 kPa, it was necessary to have two groups off 26 patients. A paired-sample T-test was performed to determine the difference within groups and an independent-sample T-test for the difference (Δ) between groups. The level of statistical significance was set at p < 0.05. Statistical analyses were performed using IBM SPSS Statistics 20 (IBM, New York, USA).

      Results

      380 patients started non-invasive HMV in the University Medical Center of Groningen (UMCG) during the inclusion period which lasted from October 2008 till October 2012 (Fig. 2). Of the 84 patients that were eligible, 77 were randomised (Table 1). Eight in each group withdrew during follow-up. Additional information in the Supplementary files Table 1. The largest group in this study was diagnosed with ALS (4 with bulbar involvement); 10 patients in the hospital group had diaphragm paralysis and 4 in the home group. Two patients crossed from intervention, one in the hospital group and the other in the home group. They remained in the initial group for all ITT analysis. Both analysis per protocol and ITT did not resulted in different outcomes. We also evaluated the variety in diagnoses and did not find a significant difference between both groups.
      Figure thumbnail gr2
      Figure 2Flow diagram. Home group: initiation of home mechanical ventilation at home. Hospital group: initiation of home mechanical ventilation in the hospital. COPD: chronic obstructive pulmonary disease. BIPAP: bi-level positive airway pressure. CPAP: continuous positive airway pressure.
      Table 1Baseline characteristics.
      Home group (n = 38)Hospital group (n = 39)
      Male2025
      Age in years59.9 ± 12.656.9 ± 13.9
      Neuromuscular disease3335
      Thoracic cage disorder54
      Body mass Index kg-m227 ± 6.327 ± 6.8
      Blood gas analysis room air
       Ph7.40 ± 0.37.40 ± 0.3
      PaCO2 kPa6.6 ± 0.96.6 ± 1.1
       PaO2 kPa10.0 ± 1.79.5 ± 1.3
       SaO2 %95 ± 2.994 ± 2.7
       HCO3 mmol/l30.2 ± 3.830.4 ± 3.8
      VC % predicted50.3 ± 20.951.6 ± 18.1
      FEV1/VC79.3 ± 12.281.2 ± 15.7
      Pack years14.3 ± 11.229.5 ± 17.8
      Current smokers23
      Wheelchair-bound1612
      Data are presented as n or mean ± SD.
      kPa: kilopascal. Ph: acidity level. PaCO2: partial pressure of arterial carbon dioxide. PaO2: partial pressure of arterial oxygen. SaO2: arterial oxygen saturation. HCO3: bicarbonate. VC: vital capacity. FEV1: forced expiratory volume in one second.
      One patient with limb girdle dystrophy in the home group and 1 patient with ALS in the hospital group used HMV when their blood gasses were assessed during 6 months follow-up due to the progression of their illness.
      In the home group 5 patients died versus 2 in the hospital group. In no case was this due to technical problems in the home settings. Patients died varying from one week up to almost 6 months after starting HMV, all experiencing a non-acute progression of their disease (ALS).
      Twenty-five patients in the home group and 28 patients in the hospital group were not able to perform physical activities regarding the maintenance of HMV. The care givers were instructed during the initiation of HMV at home while this was done after being discharged in the hospital group.

      Blood gas analysis and ventilator settings

      Daytime PaCO2, the primary endpoint, improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group being not significantly different between both groups (Table 2). Nocturnal transcutaneous registration showed an improvement in both groups, both after initiation and after two months (Table 3).
      Table 2Changes in daytime arterial blood gasses and lung function pre home mechanical ventilation to 6 months after the start.
      Home group (n = 30)Hospital group (n = 31)Between groups
      BaselineFollow-upP-Value
      P-value refers to paired t test analysis form starting ventilatory support to six months follow-up within each group.
      BaselineFollow-upP-Value
      P-value refers to paired t test analysis form starting ventilatory support to six months follow-up within each group.
      P-value
      P-value for difference in change Δ from baseline between groups.
      Ph7.40 ± 0.37.40 ± 0.30.2617.40 ± 0.37.40 ± 0.30.9130.423
      PaCO2 (kPa)6.6 ± 0.95.7 ± 0.80.0006.6 ± 1.15.9 ± 0.80.0000.631
      PaO2 (kPa)10.0 ± 1.711.3 ± 2.20.0029.5 ± 1.310.3 ± 1.70.0150.579
      SaO2 %95 ± 2.996 ± 1.90.02094 ± 2.795 ± 3.60.3480.598
      HCO3 (mmol/l)30.2 ± 3.826.6 ± 3.10.00030.4 ± 3.826.9 ± 2.50.0000.996
      aBE4.9 ± 2.62.6 ± 1.70.0004.8 ± 2.82.2 ± 1.80.0000.283
      FVC (% pred)51.6 ± 22.853.4 ± 21.80.52852.4 ± 18.549.8 ± 19.00.3010.428
      Data are presented as n or mean ± SD.
      kPa: kilopascal. Ph: acidity level. PaCO2: partial pressure of arterial carbon dioxide. PaO2: partial pressure of arterial oxygen. SaO2: arterial oxygen saturation. HCO3: bicarbonate. VC: vital capacity. Follow-up: six months after the initiation of home mechanical ventilation.
      Bold: p < 0.05 significant change.
      a P-value refers to paired t test analysis form starting ventilatory support to six months follow-up within each group.
      b P-value for difference in change Δ from baseline between groups.
      Table 3Changes in nocturnal transcutaneous carbon dioxide and oxygen saturation.
      Home group (n = 30)Hospital group (n = 31)
      BaselineAfter initiating HMV2 months follow-upBaselineAfter initiating HMV2 months follow-up
      tcpCO2 (kPa)7.6 ± 1.06.5 ± 0.95.8 ± 0.77.4 ± 1.36.4 ± 0.85.7 ± 0.7
      Maximal tcpCO2 (kPa)8.7 ± 1.47.3 ± 0.96.7 ± 0.88.4 ± 1.87.3 ± 0.96.6 ± 0.2
      Oxygen saturation (%)91.3 ± 5.195.2 ± 1.896.2 ± 1.891.8 ± 4.995.7 ± 1.795.9 ± 1.7
      Lowest oxygen saturation (%)74.6 ± 15.286.6 ± 8.284.7 ± 12.874.4 ± 14.684.1 ± 9.285.7 ± 7.2
      Data are presented mean ± SD.
      tcpCO2: transcutaneous carbon dioxide. kPa: kilo pascal.
      Both groups started with the same ventilator settings and only minor adjustments were needed during the follow-up of six months (Fig. 3). Three patients were ventilated in the volume mode and the other 74 in the pressure controlled mode. In the home group a mean of 11 (±1.86) days was needed to initiate HMV and in the hospital group 8 (±0.54) days. Follow-up after 6 months showed that patients at home slept a mean of 10.0 (±0.83) hours with HMV and the hospital group 8.5 (±0.67) hours.
      Figure thumbnail gr3
      Figure 3Ventilator settings from initiation to six months follow-up. Insp. pres: inspiratory pressure in cm H2O above peep. PEEP: positive end expiratory pressure in cm H2O. Frequency: ventilator frequency. Initiation: after the initiation of home mechanical ventilation. Follow-up: 6 months follow-up after starting home mechanical ventilation.

      Health related quality of life

      The hospital and home group improved significantly on two of seven SRI subscales. The improvements in SRI score form baseline to six months follow-up were not inferior (or significantly better) in the home group compared to the hospital group.
      The MRF-28 showed a significant improvement in the hospital group on the total score but not in the home group, however not being significantly different between both groups. The other MRF-28 domain scores were both within and between groups not significantly different. The HADS showed no significant changes both within and between groups. The SF-36 showed a significant improvement in the domain vitality in both groups. The other SF-36 domains showed no significant changes between groups (Table 4).
      Table 4Changes in health related quality of life measurements pre home mechanical ventilation to 6 months after the start.
      Home group (n = 30)Hospital group (n = 35)Between groups
      BaselineFollow-upP-value
      P-value refers to paired t test analysis form starting ventilatory support to six months follow-up within each group.
      BaselineFollow-upP-value
      P-value refers to paired t test analysis form starting ventilatory support to six months follow-up within each group.
      P-value
      P-value for difference in change Δ from baseline between groups.
      SRI
      RC47.6 ± 19.555.5 ± 17.30.02348.6 ± 18.551.9 ± 17.60.1140.462
      PF28.8 ± 21.431.9 ± 21.50.99436.6 ± 20.532.9 ± 20.50.4520.585
      AS55.1 ± 18.669.6 ± 18.00.00048.5 ± 19.160.9 ± 16.70.0000.904
      SR68.5 ± 12.369.5 ± 12.70.72371.2 ± 12.866.9 ± 11.80.2040.247
      AX55.0 ± 21.157.8 ± 24.20.47454.7 ± 16.860.9 ± 16.70.1590.628
      WB57.1 ± 19.857.3 ± 24.01.00060.3 ± 15.759.7 ± 18.30.9460.963
      SF52.7 ± 19.151.9 ± 22.30.29857.2 ± 17.555.1 ± 18.50.7330.603
      SS52.1 ± 14.456.2 ± 16.40.15353.9 ± 12.355.4 ± 12.00.2480.762
      MRF-28
      Daily activities58.1 ± 27.959.7 ± 27.60.74160.3 ± 29.053.2 ± 28.10.1820.706
      Cognition35.0 ± 32.629.4 ± 33.50.37237.1 ± 35.430.0 ± 34.70.1430.836
      Invalidity53.3 ± 38.561.3 ± 37.10.24157.1 ± 34.757.1 ± 34.71.0000.333
      Total score52.1 ± 21.149.2 ± 23.10.46658.2 ± 19.745.2 ± 20.90.0000.038
      HADS
      Depression6.6 ± 4.26.0 ± 4.50.3197.1 ± 3.56.4 ± 4.20.1390.985
      Anxiety6.4 ± 4.76.1 ± 4.90.1936.8 ± 3.86.1 ± 3.40.1950.589
      Total score13.0 ± 8.012.1 ± 8.70.66013.9 ± 6.812.5 ± 7.10.1750.760
      SF-36
      PF13.2 ± 18.515.6 ± 19.10.83217.1 ± 22.118.8 ± 23.60.7840.983
      RP15.7 ± 33.625.0 ± 35.90.56513.1 ± 24.425.7 ± 35.00.0130.337
      BP66.8 ± 30.766.1 ± 29.60.85364.2 ± 29.260.5 ± 24.50.6120.863
      GH30.7 ± 24.835.2 ± 27.20.80530.2 ± 17.336.0 ± 19.60.0580.205
      VT39.0 ± 21.452.1 ± 22.60.00436.5 ± 18.945.2 ± 18.90.0040.967
      SF52.6 ± 32.958.7 ± 32.80.88155.0 ± 21.760.3 ± 27.30.3380.602
      RE54.3 ± 52.857.4 ± 47.00.50848.2 ± 46.357.1 ± 45.40.2090.864
      MH66.3 ± 21.872.2 ± 22.00.04064.7 ± 17.569.7 ± 17.00.0550.993
      Data are presented as n or mean ± SD.
      SRI: Severe Respiratory Insufficiency (0 = worst possible health 100 = best possible health) respiratory complaints (RC), physical functioning (PF), attendant symptoms and sleep (AS), social relationship (SR), anxiety (AX), psychological well-being (WB), social functioning (SF), summary score (SS).
      MRF-28: Maugeri Respiratory Failure (0 = worst possible health 100 = best possible health).
      HADS: Hospital Anxiety Depression Scale (total score: 0 = best possible health 42 is worst possible health; separate score 0–21).
      SF-36: Short-Form Health Status Survey (0 = worst possible health 100 = best possible health) PF = physical functioning, RP = role physical; BP = bodily pain; GH = general health; VT = vitality; SF = social functioning; RE = role emotional; MH = mental health.
      Bold: p < 0.05 significant change.
      a P-value refers to paired t test analysis form starting ventilatory support to six months follow-up within each group.
      b P-value for difference in change Δ from baseline between groups.

      Costs

      Due to the travel time in the home group the total invested time by NP per patient was 91 min longer compared to the hospital group. In contrast the contact time per patient in the hospital group was higher (Fig. 4). The NP visited the patient the first day and if necessary the following days. This was not specified in the standard procedure and resulted in a mean of 3 visited during the initiation period of HMV.
      Figure thumbnail gr4
      Figure 4Time spent during initiation of home mechanical ventilation and 6 months follow-up. Contact: direct contact between the patient and the care giver of the department of home mechanical ventilation from initiation to 6 months follow-up. Travel time: driving time between hospital and patient during house calls. Total: is all time added up.
      Total mean costs per patient amounted to € 726 per patient in the home group and to € 3913 in the hospital group (difference – € 3187; 95% CI -€3643 to–€ 2694). Mean costs in the hospital group amounted to € 3618 for admission to the ICU and the ward, €198 for contact with the NP and € 97 for travelling expenses. Mean costs in the home group included € 192 of travelling expenses, € 266 of house calls and consult by telephone by the nurse practitioner, and € 268 for hospital admissions. As the other costs; masks, ventilator, disposables supply and transcutaneous measurement were similar in both groups this was not accounted for.

      Telemonitoring

      Since the procedure of initiation of HMV at a distance, i.e. at home, is new and the software program for telemonitoring was specifically developed for this study, patients were instructed to contact the 24/7 call service of the HMV department if necessary. The use of telemonitoring did not result in problems or calls during the night. Adjusting ventilator settings, while interacting with the patient or caregivers, went well after good instructions during the initiation process.
      Technical problems did occur initially in 11 out of the 38 patients who started HMV at home. In 3 patients the wireless connection was not successful because of insufficient mobile connection facilities as our part of the country is not very densely populated. Another reason was that patients with ALS sometimes live in an iron surfaced mobile unit, with bedroom and washroom facilities on the ground floor. The iron surface disturbs the mobile connection. In these 11 cases the evaluation of the patients' condition was done on individual clinical parameters; sleeping time with HMV, sleep quality and improvement of quality of life during the day.

      Discussion

      This is the first study showing that initiation of home mechanical ventilation at home, in a selective group of patients with a stable respiratory problem, resulted in improvements in blood gasses and quality of life being not inferior to in hospital initiation. In addition it showed that the start of HMV at home, by using telemonitoring, was safe, feasible and cheaper.
      Publications concerning the initiation of HMV outside the hospital by using telemonitoring are scarce. One study showed a reduction in health care utilization in patients with ALS after using home telemonitoring [
      • Pinto A.
      • Almeida J.P.
      • Pinto S.
      • Pereira J.
      • Oliveira A.G.
      • de Carvalho M.
      Home telemonitoring of non-invasive ventilation decreases healthcare utilisation in a prospective controlled trial of patients with amyotrophic lateral sclerosis.
      ]. Initiation of HMV was done in the hospital and the follow-up was carried out at home by using telemonitoring. They used a fixed telephone line with limited speed of data transferral. In our study we started HMV at home and we used a mobile connection allowing us to move the equipment from one patient to the other without technical workout delays. Another study showed that telemonitoring can be more effective in patients who are more compliant to the therapy [
      • Bertini S.
      • Picariello M.
      • Gorini M.
      • Renda T.
      • Augustynen A.
      • Villella G.
      • et al.
      Telemonitoring in chronic ventilatory failure: a new model of survellaince, a pilot study.
      ]. The installation of the telemonitoring system at the patient's home in our study was self-supporting meaning that the data transfer was not dependent on the technical skills or actions to be taken by the patient or compliance to therapy. A third study compared the initiation of HMV between inpatient and outpatient titration but did not use telemonitoring [
      • Chatwin M.
      • Nickol A.H.
      • Morrell M.J.
      • Polkey M.I.
      • Simonds A.K.
      Randomised trial of inpatient versus outpatient initiation of home mechanical ventilation in patients with nocturnal hypoventilation.
      ]. The improvement of blood gasses was equivalent between the two groups which is comparable to our study. However patients included in our study had a mean PaCO2 of 6.6 kPa while in the study of Chatwin patients had near normal daytime PaCO2.
      Our data provides a good example in the field of implementation of telemonitoring while not all studies have been successful so far. We believe that the results of this study contribute to the fact that the use of modern technologies in patients with a chronic disease can lower the burden to the health care system.
      Earlier studies showed an improvement in blood gasses after the initiation of HMV [
      • Janssens J.P.
      • Derivaz S.
      • Breitenstein E.
      • De Muralt B.
      • Fitting J.W.
      • Chevrolet J.C.
      • et al.
      Changing patterns in long-term noninvasive ventilation: a 7-year prospective study in the Geneva Lake area.
      ,
      • Windisch W.
      Impact of home mechanical ventilation on health-related quality of life.
      ]. We found a comparable improvement in blood gasses in both groups indicating that the initiation of HMV can be performed effectively at home in a selective group of patients with chronic respiratory failure due to a neuromuscular disease of thoracic cage disorder. Nevertheless it is obvious that a thorough scan of the home environment must be performed before starting HMV.
      This study also showed that it is possible to initiate HMV at home in patients with an age varying from 19 to 80 years of age. The youngest and the oldest started HMV at home and we did not notice any age related problems. In some cases the absence of a partner or family member resulted in recruiting home care professionals to support the patient during the first steps of HMV at home. In the home group patients started HMV one week after being included and in the hospital group this was 3 weeks. This delay in the hospital group was due to limited number of beds in the hospital.
      As in our center the initiation of HMV is done in a hospital based setting and therefore expensive, the present study was performed to search for an alternative. The medical ethics committee agreed to initiate HMV outside the hospital directly instead of starting in an outpatient clinic or on a ward without ICU admission first. This was done to save time and to facilitate patients to stay at home. Initiating HMV at home was not only effective and safe, it was also cost-effective. This study showed a mean reduction of € 3187 per patient when HMV started at home. Mobile data communication costs were negligible and variable and therefore not included in the total costs analysis. Since we initiate HMV in the Netherlands in approximately 600 patients per year [
      • Hazenberg A.
      • Cobben N.A.
      • Kampelmacher M.J.
      • Rischen J.
      • Wijkstra P.J.
      Home mechanical ventilation in the Netherlands.
      ], full implementation nationwide would save over € 1.8 million annually. Despite this enormous cost reduction we should stress the point that the inpatient initiation is very expensive being primarily due to the ICU admission. When the initiation is done on a non-ICU ward the benefit in costs would be lower compared to our situation.
      Despite these positive results this study has some limitations.
      Above all, there was a large group of patients with chronic respiratory failure that did not participate in this study for various reasons (Fig. 1). We excluded all patients with COPD as providing HMV to this group is still not current practice in our country. A recent meta-analysis showed that HMV in stable patients with COPD did not improve gas-exchange, lung function or QOL [
      • Struik F.M.
      • Lacasse Y.
      • Goldstein R.S.
      • Kerstjens H.A.
      • Wijkstra P.J.
      Nocturnal noninvasive positive pressure ventilation in stable COPD: a systematic review and individual patient data meta-analysis.
      ]. In this study only 2 patients with OHS were enrolled which is remarkable considering the growth of patients with OHS that start HMV [
      • Gaytant M.A.
      • Westermann E.J.
      • Zelissen P.M.
      • Kampelmacher M.J.
      Obesity hypoventilation syndrome–serious but reversible providing weight is lost.
      ]. The reason was that 27 patients with OHS had to start with HMV in hospital immediately due to an acute respiratory failure.
      Secondly, the effect of HMV with regard to quality of life (QOL) in our total group compared to previous studies seems to be less positive. Probably this is due to the large number of ALS patients included in our study, which was over the 35%. Although Bourke concluded that HMV in ALS does improve QOL, this was based on the increased duration of time (compared to control group) that the QOL was maintained above 75% of their baseline value [
      • Bourke S.C.
      • Tomlinson M.
      • Williams T.L.
      • Bullock R.E.
      • Shaw P.J.
      • Gibson G.J.
      Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.
      ]. As we assessed absolute values of QOL it is difficult to compare both studies. If we excluded the ALS group we did find a significant improvement in several domains being comparable with the previous studies.
      Another limitation of this study was that the initiation of HMV was done by just one NP in the home group. As we cannot conclude, based on this single study, that it can be duplicated in all other situations, we recommend an additional study were the implementation of this concept on a broader scale i.e. other regions, settings and with more people involved should be examined. Improvements in the technical and digital opportunities, during the last couple of years, will facilitate the development of future telemonitoring studies. Especially the use of polysomnography and microchip cards with detailed ventilator information, can be of great importance in future studies to better evaluate the patient-ventilator interaction.

      Conclusion

      In summary we showed that initiation of HMV at home in a selective group of patients with chronic respiratory failure due to neuromuscular disease or thoracic cage disorder is effective for gas exchange and quality of life and is not less effective than initiation in the hospital. In addition we found that it is safe and that more than € 3000 per patient can be saved. From a patients' perspective it is an ideal treatment as they do not have to be admitted to the hospital and their highly individualised care can be maintained during the initiation of HMV.

      Statement of interest

      This study was financially supported by the Health Care Insurance Board in the Netherlands, the University Medical Center Groningen, Vivisol Area UK & Benelux and ResMed.

      Acknowlegdements

      We are very grateful to all the patients, their family members and the homecare professionals who kindly agreed to participate in this study and to everyone who worked on this project. We would also like to thank the members of the Data Safety Monitoring Board; Prof. Dr. J.G. Zijlstra, Prof. Dr. E.R. van den Heuvel (University Medical Center Groningen) and Mw. Drs. A.F. Meinesz for their contribution.

      Appendix A. Supplementary data

      The following is the supplementary data related to this article:

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