Download EIT-project - clinical trial of the newborn and premature infant

R Sindelar
FOT Protocol
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Clinical trial of premature newborn infants with ventilatory assistance
and different levels of PEEP measured by FOT
Background:
Preterm newborn infants are at risk of developing lung diseases such as transient
tachypnoea of the newborn (TTN i.e. “wet lung”) or respiratory distress syndrome (RDS),
which usually necessitates ventilatory support/assistance such as nasal continuous
positive airway pressure (CPAP) or intermittent mandatory ventilation (IMV), surfactant
treatment and supplementary oxygen (FiO2).
The lung mechanics in term, and foremost preterm infants, are characterized by
low functional respiratory capacity (FRC), low tidal volumes (VT), low lung compliance (CL)
and high airflow resistance (R).
To estimate and optimize the right level of positive end expiratory pressure
(PEEP) is difficult and might lead to either overextension (barotrauma) or collapse
(atelectasis; atelectrauma) of the lung. Barotrauma and atelectrauma in addition to
exposure to high FiO2 predispose for developing chronic lung disease (CLD) /
bronchopulmonary dysplasia (BPD) with increased long term morbidity and mortality.
The factors identified with decreased risk of developing BPD in preterm infants
have been mainly reduced time on mechanical ventilation i.e. early weaning, and low tidal
volume ventilation. It’s still unclear, though, how to maintain an adequate ventilation and
oxygenation without invasive ventilation, and the correct level of tidal volume to be set. In
some studies, high frequency oscillatory ventilation (HFOV) have shown short term
benefits on lung inflammatory response but no difference has been seen in long term
follow up in the incidence of BPD, time on mechanical ventilation or neurological outcome.
Different recruitment maneuvers have been applied to achieve an adequate level
of FRC, the most commonly used being PEEP in preterm newborns, with less evident
effects of increased peak inspiratory pressure (PIP) and prolongation of inspiratory time or
higher ventilatory rates, all with the aim of increasing mean airway pressure (MAP)
without overextending the lungs.
The tools to set the adequate PEEP level during IMV and nCPAP or MAP during
HFOV are arbitrary, as no objective ventilatory measurement is sufficient in preterm
infants with small tidal volumes and FRC, non-cuffed tubes with leakage and variable lung
mechanical changes depending on stage of lung development and thoracic cage
instability.
The forced oscillatory technique (FOT) is a method to measure the reactance of
the lung and thereby the oscillatory compliance (Cx5). In animal models, FOT has been
shown to be both a reliable and a non-invasive method in estimating the correct airway
R Sindelar
FOT Protocol
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opening pressure i.e. the correct level of FRC, by setting the correct level of PEEP. FOT
has also been shown to be able to separate non-homogenous lung injury form unilateral
lung collapse. Also, FOT can be applied both invasively and non-invasively and during
spontaneous breathing.
Aim:
Observational study of lung mechanics (oscillatory compliance) by FOT in
preterm newborn infants during different stages of lung development and
lung injury related to different clinical settings of PEEP both during
invasive and non-invasive ventilatory assistance
Purpose:
Obtain optimal PEEP levels and thereby optimal ventilation without
overdistension or derecruitment of the lung
Inclusion:
Preterm newborn infants with need of invasive and non-invasive
ventilatory assistance
Exclusion:
Major congenital anomalies, hemodynamic instability, seizures, or ongoing
sepsis or meningitis
Protocol:
A. Daily sequential FOT measurements during mechanical ventilation at different
PEEP levels over 14 days (or until weaning off ventilatory assistance) in
extremely premature newborn infants in need of mechanical ventilation from
day 1 in order to estimate the optimal recruitment level and lung mechanics
changes over the first 2 weeks of postnatal age. No other intervention should
be made during the registration.

During ventilatory settings made by the attending physician

Independent of invasive or non-invasive ventilatory assistance

PEEP will be changed within the range of 3 to 7 cm H2O, in any case no
more than ±2 cm H2O from the original clinical settings

FOT frequencies 5, 10 and 15 Hz will used
1. Connect external FOT monitoring device to 3 analogue ports for air
flow, pressure or signal of choice on Stephanie Ventilator
2. Calibrate pressure transducer
3. Connect pressure transducer at Y-piece of patient???
4. Position patient in supine
5. Apply tcPCO2 and tcPO2, besides SaO2 and ECG
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FOT Protocol
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6. Patient on ex. A/C=23/5 cm H2O, freq=60/min, Tinsp=0.33, Texp=0.67
7. Set fHFOV sinusoidal 50% and set HFOV P-P range to 1:3 instead of
1:1 (decreased scaling of amplitude=P-P knob: 1-6 scaling will be 0.3-2
scaling). Be aware that PEEP must be adjusted during the different
fHFOV frequencies
8. Increase PEEP up to 7 cmH2O
9. Stabilize for 5 minutes
10. Set fHFOV at 10 Hz and P-P at 1 (equals ±2 cm H2O) and apply HFOV
11. Stabilize 2-4 ventilatory breaths
12. Registration for 10-20 breaths
13. Increase fHFOV to 15 Hz (same P-P and ventilatory settings)
14. Stabilize 2-4 ventilatory breaths
15. Register 10-20 breaths
16. Decrease fHFOV to 5 Hz (same P-P and ventilatory settings)
17. Stabilize 2-4 ventilatory breaths
18. Register 10-20 breaths
19. Increase expiratory time from 0.67 s to 0.8 s (Tinsp=0.33, RR=53
bmp)
20. Stabilize 2-4 ventilatory breaths
21. Register 10-20 breaths
22. Decrease PEEP to 6 cmH2O
23. follow from 9 to 21
24. Decrease PEEP to 5 cmH2O
25. follow from 9 to 21
26. Decrease PEEP to 4 cmH2O
27. follow from 9 to 21
28. Decrease PEEP to 3 cmH2O??
29. Go back to the starting settings
30. Switch off HFOV
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FOT Protocol
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
If patient is on nasal CPAP put the pneumotachograph in place trying to
avoid leaks hopefully with the mouth closed, then a continuous registration
from 8. with increases of fHFOV 5 – 10 – 15 Hz, 2-4 breaths stabilization per
fHFOV and 10-20 breaths per registration

If the patient is triggering more than 60 bpm during A/C, then necessary to
switch to S-IMV with the same settings as during A/C. If too large clinical
changes during manipulations with PEEP, might be necessary to go back to
baseline in between changes in

Same procedure can be made on nasal CPAP and PAV
B. To validate differences in FOT measurements between invasive and nasal
CPAP

Invasive CPAP prior to extubation and then during nasal CPAP (5 patients)

HFOV frequencies 5, 10 and15 Hz
1. 1. to 7. as in A.
2. Set fHFOV at 10 Hz and P-P at 1 (equals ±2 cm H2O) and apply HFOV
3. Compute the resistance of the ETT and unload the patient from the tube
unless it has an ETT with a diameter > 3.0 mm
4. Set CPAP 5 cm H2O (same PEEP level as during A/C) or the supposed set
CPAP after extubation which is usually PEEP +1-2 cm H2O
5. Stabilize 2-4 ventilatory breaths
6. Registration for 5 breaths
7. Set back A/C as previously
8. Increase fHFOV to 15 Hz (same P-P and ventilatory settings)
9. Set CPAP 5 cm H2O (same PEEP level as during A/C)
10. Stabilize 2-4 ventilatory breaths
11. Register 5 breaths
12. Set back A/C as previously
13. Decrease fHFOV to 5 Hz (same P-P and ventilatory settings)
14. Stabilize 2-4 ventilatory breaths
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15. Register 5 breaths
16. Set back A/C as previously
17. Switch off HFOV
18. Extubation to nasal CPAP
19. After stabilization of the patient on nasal CPAP set by the clinician (usually
PEEP +1-2 cm H2O), a continuous registration with increases of fHFOV 5 –
10 – 15 Hz, 2-4 breaths stabilization and registration of 5 breaths per fHFOV
setting
20. Switch off

If patient is stable during invasive CPAP, then a continuous registration with
increases of fHFOV 5 – 10 – 15 Hz, 2-4 breaths stabilization and registration of 5
breaths per fHFOV
Measurements:

FOT
–
5 / 10 / 15 Hz
–
HFOV sinusoidal 50% superimposed on A/C, S-IMV, nCPAP or short
duration during PAV on CPAP only
–
HFOV with P-P 4 or 2 cm H2O (if lower see “Scale” and then 1:1 HFOV,
button represents 0-2 instead of 1-6 for P-P)
–
Connect pressure sensor to Y-piece; calibration
–
During 5 Hz FOT, at least 0.8 s expiratory time during 15 seconds; other
FOT frequencies according to ventilatory rate i.e. 60/min

Supine position with head straight forward

tcPCO2 and tcPO2 (infants < 25 GA with immature skin will start tc measurements
after 3rd day of life), SaO2, heart rate (ECG), episodes of apnea and bradycardia
registered by attending physician

Arterial blood gases at the beginning of the daily measurements

Ventilatory settings; PAV, nCPAP, PIP/PEEP, ventilatory frequency, MAP, FiO2

Tidal volume (exp/insp) as provided from Stephanie

BW, APGAR, GA, day of age, sedatives, other medications vital for breathing or
lung mechanical changes, present weight
R Sindelar
FOT Protocol
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tube size and length

Electrical diaphragm (Edi) activity as measured by feeding gavages electrodes to
assess influence of different PEEP levels on breathing activity
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Collaborators
Raffaele Dellaca PhD
Richard Sindelar MD PhD
Peter Frykholm MD PhD
Emanuela Zannin PhD
Linda Wallström MD PhD student
Ilaria Milesi PhD student
Chiara Veneroni PhD student
References
1. Dellaca R, Andersson Olerud M, Zannin E, Kostic P, Pompilio P, Hedenstierna G, Pedotti A,
and Frykholm P. Lung recruitment assessed by total respiratory system input reactance.
Intensive Care Med (2009) 35:2164–2172
2. Dinger J, Töpfer A, Schaller P, and Schwarze R. Effect of positive end-expiratory pressure on
functional residual capacity and compliance in surfactant-treated preterm infants. J. Perinat.
Med. 29 (2001) 137-143
3. Thome U, Töpfer A, Schaller P, and Pohlandt F. The effect of positive end-expiratory
pressure, peak inspiratory pressure, and inspiratory time on functional residual capacity in
mechanically ventilated preterm infants. Eur J Pediatr (1998) 157: 831-837
4. Alegria X, Claure N, Wada Y, Esquer C, D’Ugard C, and Bancalari E. Acute effects of PEEP
on tidal volume and respiratory center output during synchronized ventilation in preterm
infants. Pediatric Pulmonology (2006) 41:759–764