Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06160687 |
| Other study ID # |
DM-1129 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2023 |
| Est. completion date |
January 31, 2025 |
Study information
| Verified date |
December 2023 |
| Source |
Postgraduate Institute of Medical Education and Research |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is defined acute worsening
of respiratory symptoms requiring additional therapy. COPD exacerbations affects the health
status and quality of life of affected patients. The inpatient mortality during exacerbation
is 3 to 4% while, intensive care unit (ICU) mortality approaches 43 to 46%. Each episode of
exacerbation increases the risk of mortality subsequently(1) Non-invasive ventilation (NIV)
therapy has established role in mild to moderate exacerbations of COPD. But the use of NIV
therapy outside of acute exacerbation is uncertain(2) NIV use has been shown to prevent
endotracheal intubation and improved hospital and ICU survival. NIV decreases the work of
breathing by unloading the respiratory muscles through assisting the inspiratory phases and
counterbalancing the intrinistic positive end expiratory positive pressure (ipeep)(3).
NIV is delivered through face mask, although newer interfaces like helmet available(3).
Tradionally pressure targeted mode is used in NIV therapy and is often given intermittently
rather than continuously(4). NIV therapy via face mask was first used by Meduri et. Al in
acute respiratory failure patients. Subsequent multiple randomized control trials established
the role of NIV therapy in better gas exchange, reducing PCO2, reducing endotracheal
intubation thereby reducing mortality, length of stay in hospital(3).
NIV-PSV (pressure support ventilation) consists of 2 pressures. IPAP (inspiratory positive
airway pressure) and EPAP (expiratory positive airway pressure) or PEEP. Pressure support is
usually the pressure added above PEEP. Pressure support is usually started with 8-10 cm H2O
to obtain a tidal volume of 6-8ml/kg ideal body weight. EPAP/PEEP is adjusted to
counterbalance the iPEEP. It is usually kept at 4-6cm H2O. Fio2 is kept to maintain
saturation of 88-92%. Inspiratory trigger is usually set at 1 L/min. Expiratory trigger kept
at 50%. Back up rate should always be kept usually lower than the patient respiratory rate
10-12 breaths/min(5).
Adaptive support ventilation (ASV) is a new method of closed loop ventilation which can
switch back between pressure support and pressure control modes of ventilation. Based on the
ideal body weight and % of minute volume ventilation given, the ASV mode choses the best
tidal volume and respiratory rate according to the patient lung mechanics by calculating
expiratory time constant (RCe) through expiratory flow volume curve(6). Since closed loop
system, being a completely automated system, prevent frequent adjustment by clinician and
thereby increasing the time and capacity of medical staff. The first application of such
closed loop system in mechanical ventilation was done by saxton in1953 in iron lung for
regulation of etCO2(7). Studies published on ASV as non-invasive mode of ventilation is
limited. In a feasibility study, it has been shown that ASV can be used in non-invasive mode
of ventilation with similar results to PSV in COPD patients(8).
Description:
Acute exacerbation of chronic obstructive pulmonary disease are periods of acute worsening
during the course of illness which increase hospital admission and mortality. Intensive care
unit admission and mortality are higher among elderly and those with co-morbidities(9).
Non-invasive methods of ventilation can be used in mild to moderate exacerbation of COPD.
They prevent most of the complications of invasive mechanical ventilation and has also
reduces mortality in acute exacerbations of COPD. In mild to moderate COPD
exacerbations(pH-7.25 to 7.35), non-invasive ventilation (NIV) failure rate is found to be
15% to 20%. In severe COPD exacerbations, NIV failure rate approaches upto 52% to 62%(9).
Adaptive support ventilation (ASV) and pressure support ventilation (PSV) are among the
non-invasive modes of ventilation used in COPD exacerbations.
Adaptive support ventilation:
Adaptive support ventilation is a closed loop ventilation in which it provides both pressure
support and pressure controlled ventilation as per the patient needs(10). The mode was first
described by Hewlett in 1977 in form of mandatory minute ventilation with adaptive pressure
control(11). Later Dr. fleur T Tehrani invented this mode, which was later introduced in
Galileo ventilator(11). This mode supports patient with pressure support when patient has
spontaneous breath and when target ventilation is not reached it delivers pressure control
breath to achieve adequate ventilation. In this mode, minute volume is controlled via Vt/RR
combination based on respiratory mechanics of the patient to keep the work of breathing at
minimum(10). This mode calculates the tidal volume and respiratory rate to be delivered by
otis equation in its algorithm after %minute volume being set by the clinician to ensure
effective ventilation at the alveolar level. The inputs provided by the clinician in this
mode is %minute volume based on ideal body weight, ETS, flow trigger, maximum pressure
limit(12). The mode after being initiated will deliver a series of 5 pressure limited breaths
and deliver a inspiratory pressure15 cm h2o above the baseline pressure during which it
calculates dynamic compliance, RCe, tidal volume and respiratory rate. These measurements are
used to determine the initial targets of breath rate and tidal volume(12). After which based
on respiratory rate and effort of the patient, inspiratory pressure, mandatory breath are
adjusted automatically to meet the set %minute volume. ASV mode can be used as initiation,
maintenance and weaning phases of mechanical ventilation and it provides full, partial or
minimal ventilator support during any of these phases(12). The number of manual ventilatory
adjustments are less compared to conventional mode of ventilation in ASV(13). Some randomized
controlled trials performed in Non-COPD suggest shorter weaning time with ASV mode of
ventilation. Shorter weaning is attributed to automated inspiratory pressure change according
to patient efforts, thereby reducing ventilator patient dysynchrony and frequency of manual
manipulation. In a randomized control study done by c. kirakli et. Al found out that in COPD
patients ASV mode of ventilation(24 hours) has shorter weaning duration compared to pressure
support mode of ventilation(72 hours) (p-value 0.041). But, this study has not found any
difference in the duration of mechanical ventilation, length of stay in ICU, weaning failures
when ASV and PSV mode were compared(p-value>0.05)(10) A randomized controlled trial conducted
among 80 patients by Bialais et. al comparing safety, efficacy and workload of intellivent-
ASV and conventional mode of ventilation (pressure assist mode and pressure support mode)
found out that tidal volume delivery and spo2 were most of the time in the optimal range
(6-10ml/kg IBW, spo2-92 to 96% for normal lung/ ARDS and 95-99% for brain injury) for
intellivent-ASV compared to conventional mode of ventilation(p-value-0.001 and 0.005).
However it was found that Pmax (maximum inspiratory pressure measured) was higher (24±5
versus 22±6) with intellivent-ASV mode than conventional ventilation(p-value-0.042). There
was no significant difference between intellivent-ASV and conventional mode of ventilation in
terms of time spent in optimal range of parameters like respiratory rate, PETCO2, PEEP,
minute ventilation, FIO2 , RCexp. There was also no difference in length of mechanical
ventilation, length of ICU stay, length of hospital stay, ICU mortality, hospital mortality
and total mortality. There was comparative less need for ventilator adjustment with
intellivent-ASV mode compared with conventional mode of ventilation(14).
A randomized control trial by kirakli et. Al among 229 patients found out that median
mechanical ventilation duration until weaning(67{43-94} vs 92{61-165}) p-value-0.003, weaning
duration(2{2-2} vs 2{2-80}hours p value-0.001) and total mechanical ventilation duration
(4{2-6} days vs 4 {3-9} days, p value-0.016) were shorter in ASV group compared to pressure
assist/control ventilation. Also the number of patients succeeding first attempt of
extubation was higher in ASV group (p value-0.001). Weaning success and mortality were
comparable between the two groups(15).
NIV-PSV:
Mechanical ventilation in its first form was used at the end of 1930s called tank ventilator.
Later in 1950s during the polio epidemics, modern mechanical ventilators began to emerge.
Intermittent positive pressure application via anaesthesia mask in treatment of acute
respiratory illness was studied in motley and colleagues at Bellevue hospital in 1940s. The
first application of NIV as CPAP via nasal mask to obstructive sleep apnea patients was done
by Sullivan et. Al in 1981. Successful application of NIV via full face mask for respiratory
failure in COPD patients, heart failure patients in 1989 avoided intubation. The use of NIV
has increased with the introduction of ventilators with effective compensation for air leaks.
NIV are most commonly used in obstructive sleep apnea, COPD and cardiac failure patients and
to some extent in failed extubation. Although invasive mechanical ventilation has kept the
NIV at second place, still it is used in above clinical settings(16).
In a study conducted by Hilbert et. Al, NIV-PSV was compared with standard medical treatment
in COPD patients. It was found out that the days of ventilator assistance and length of ICU
stay has significantly lower with NIV-PSV treated group (7±4 days vs 10±15 days, p<0.01) &
(9±4 days vs 21±12 days, p <0.01) respectively. Also NIV support prevented tracheal
intubation in acute exacerbation of COPD patients significantly (26% vs 71%) compared to
standard medical therapy(17).
Randomized control study conducted by laurent et.al suggested that non-invasive ventilation
compared to standard medical treatment for COPD exacerbation could reduce the intubation
rates, length of stay in hospital(18). Another study by plant et. Al replicated the same
results that early NIV therapy would reduce the number of intubation needed in mild to
moderate exacerbation of COPD patients and improvement in paco2 and respiratory rate. This
study suggested that NIV therapy can be effectively administered in general respiratory wards
also(19).
NIV therapy was used in hypoxemic respiratory failure in post-abdominal surgery patients
compared with oxygen therapy alone by jaber et. Al. NIV therapy has significantly reduced
tracheal reintubation rates within 7 days following surgery (33.1% vs 45.5%, p value - 0.03)
and also it provided more invasive ventilation free days compared with standard oxygen
therapy(25.4 vs 23.2 days). Gas exchange was found to be similar with NIV and standard oxygen
therapy in hypoxemic respiratory failure in this study. Also, the NIV group had fewer
pulmonary infections compared with oxygen therapy group(20).
A randomized study by Nava et. Al conducted to study the effectiveness of NIV to prevent
reintubation suggested that early institution of NIV after extubation especially in high risk
patients ie) COPD, Cardiac failure, hypercapneic patients may prevent reintubation rates(4/48
vs 12/49, p-value-0.027). The delayed delivery of NIV after extubation can cause increase in
mortality. So , timely delivery of NIV support can reduce mortality upto 60%. In this study
NIV support was given atleast 8 hours/day after extubation(21).
Patient-ventilator asynchrony is well known in patients who are mechanically ventilated.
Although there are no studies that suggest direct patient related outcome due to asynchrony,
it is well known patient-ventilator asynchrony prolong the duration of mechanical
ventilation(22). Although correlation with oesophageal pressure is the standard way of
detecting the patient-ventilator asynchrony, a trained eye can detect most of the
asynchronies using pressure-time or flow-time waveform analysis(23).Multiple studies has
suggested better patient-ventilator interactions with adaptive support mode of ventilation
requiring less manipulations from the clinician and also facilitating early liberation from
mechanical ventilation compared to other modes of ventilation(24-26).
