Evaluation of fully automated ventilation:
A randomized controlled study in post-cardiac surgery patients
François Lellouche, Pierre-Alexandre Bouchard, Serge Simard,
Erwan L’Her, Marc Wysocki
ELECTRONIC SUPPLEMENTARY MATERIAL
DETAILED MATERIAL AND METHODS
From July 2009 to December 2009, we conducted a prospective randomized controlled study comparing automated ventilation to protocolized ventilation in post-cardiac surgery patients at the Institut Universitaire de Cardiologie et de Pneumologie de Québec. Study approval was obtained from the local ethics committee and signed informed consent was obtained from all patients before surgery.
Patients
Patients were screened by the research coordinator before surgery. Only patients who were scheduled for morning surgery were considered. Pre-inclusion criteria were the following: (i) elective cardiac surgery scheduled for morning surgery, (ii) age between 18 and 90 years old, (iii) body mass index < 40 kg/m², (iv) baseline PaCO2 < 50 mmHg, (v) serum creatinine < 200 µMol/L.
The patients were included after surgery if by 15 minutes after their arrival in the ICU they were hemodynamically stable (epinephrine or norepinephrine < 1 mg/hour, bleeding <100 ml within the preceeding 15 minutes and < 3 transfused red blood cell units) and had a urine output > 50 mL/hour.
They were excluded if an unexpected surgical procedure was required or if extubation was expected within 60 minutes after ICU arrival. Patients were also excluded if a broncho-pleural fistula was present or if the study ventilator was not available. Figure 1 provides a flow chart of the study (main manuscript).
Study Protocol
As soon as patients met the inclusion criteria, they were randomized to fully automated ventilation (AV arm) and were connected to a S1 Hamilton ventilator (modified G5 with an embedded IntelliVent™ algorithm) (Hamilton Medical AG, Rhazuns, Switzerland) or to conventional ventilation (PV arm) and were connected to a G5 ventilator. The concealed randomization was performed by sealed and opaque envelopes. Randomisation with 1:1 allocation and block randomization scheme was obtained from random.org.
Automated ventilation group
IntelliVent (Hamilton Medical AG, Rhazuns, Switzerland) is a fully automatic ventilator adjusting tidal volume (TV), respiratory rate (RR), FiO2 and PEEP based on the patient’s respiratory mechanics, EtCO2 and SpO2. Cycles are pressure delivered and this mode is classified as pressure control intermittent mandatory ventilation (PC-IMV) [1]. Optimal TV and RR are defined based on the patient’s respiratory mechanics as it is with adaptive support ventilation (ASV) [2, 3]. In contrast to ASV, minute ventilation (MV) is automatically adjusted based on the patient’s EtCO2 and RR. Safety limits for TV are based on the pressure limitation set by the clinician. The system always attempts to find the optimal combination of TV and RR to deliver the appropriate MV based on Otis equations [4] within the safety range set by the clinician [5]. IntelliVent™ also automatically adjusts the FiO2 and PEEP based on SpO2. The choice between FiO2 and PEEP is based on predefined PEEP-FiO2 tables [6, 7] but maximum PEEP was limited to 10 cmH2O in this population. In addition to the PEEP limitation, the only manual setting after the inclusion in the AV group was the patient’s height and gender to determine initial MV.
Protocolized ventilation group
Protocolized ventilation was administered according to the local written protocol which was based on recommendations coming from anesthesiology textbooks [8, 9]. At ICU arrival, patients were connected to the ventilator and the initial settings were prescribed by the treating anesthesiologist using volume control intermittent mandatory ventilation (VC-IMV) which is equivalent to Volume Control Ventilation in sedated non-triggering patients. A plateau of 0.3 seconds was set to continuously record plateau pressures. Tidal volumes were set at 10 ml/kg, respiratory rate at 10 breaths/minute, PEEP at 5 cmH2O, and the FiO2 ranged from 70 to 100%. The ventilatory protocol for the post-operative period was managed by respiratory therapists for the FiO2 weaning (decreased by 10% each 10 minutes if SpO2 95% to reach 40%) and for the switch to pressure support ventilation (PSV) as soon as patients were deemed to be able to breath spontaneously. PSV was used during the weaning phase when the patients were deemed to be ready by the respiratory therapists or by the physicians. Modifications of respiratory rate and tidal volume were managed by intensive care physicians based on arterial blood gas results collected at inclusion and after any adjustments in ventilator settings. Three full-time respiratory therapists were in the ICU during the post-operative course dedicated to the ventilator management (8 to 10 patients were admitted daily after cardiac surgery in this ICU). In addition 2 senior intensive care physicians and 2 to 4 residents were in the ICU during the post-operative time period (closed-unit organization).
Features common to both groups
Patients were managed using fast-track extubation procedures, with early termination of sedation (propofol) and use of minimal doses of analgesic (fentanyl) after rewarming to 36˚C [10]. Patients were extubated if they had stable respiratory parameters (with a PSV level of 10 to 12 cmH2O, PEEP 5 cmH2O and FiO2 40%), adequate neurologic state (obeys commands) and haemodynamic parameters (low levels of inotropes and vasopressor to maintain cardiac index above 2.2 l/min/m2 and adequate mean arterial pressure) and with blood loss below 50 ml per hour.
Data recorded
A research assistant was at the patients’ bedside during the entire duration of the study (4 hours) to assess patient safety, to chronometer the time that the patient passed in the different predefined zones of ventilation (table 1,main manuscript) and to record the number and duration of interventions required to set the ventilator. All ventilator data were stored in the ventilators for both groups. In the control group, the plateau pressure was recorded continuously and stored. In the Intellivent group, we assumed that the peak pressure was equal to the plateau pressure considering that cycles are delivered in pressure with decelerating flow.
Endpoints
The study was designed to assess safety. The primary endpoint was the number of episodes and the time in the predefined “not acceptable zone of ventilation” defined as a tidal volume greater than 12 ml/kg of predicted body weight, plateau pressure above 35 cmH2O, EtCO2 below 25 or above 51 mmHg and a SpO2 below 85% for a minimum of 30 seconds (table 1, main manuscript). These targets were based on the concordance between the above criteria and a multicentre survey involving 53 physicians and respiratory therapists [11].
The secondary endpoints were the time spent by the patients with safe ventilation (predefined zones of optimal and acceptable ventilation) (table 1), the number of manipulations required to set MV, FiO2 and PEEP, and the time needed for these manipulations. We also assessed the time to extubation, duration of ICU stay and mortality.
Statistical Analysis
This is a prospective study and no information is available to estimate the sample size. We analyzed results from 30 subjects per group to get information about the primary end-point. Based on previous data on high tidal volumes in this population [12], our sample size was sufficient to detect a reduction from 20% to 1% for this parameter [2, 5], with a power of 80% and alpha risk of 5%. Only 50 patients would be required to demonstrate the difference of time in the not acceptable zone of ventilation from 15 minutes to 1 minute with a standard deviation of 20 minutes with a power of 90% and alpha risk of 5%.
Continuous variables are expressed as mean (SD) or median (min-max) depending on variable distribution. Group comparisons were analyzed using Student’s t-test or Wilcoxon rank-sum test for continuous variables. Categorical variables were expressed in percentage and were analyzed using Chi-square or Fisher’s exact tests. A mixed model was involved to analyse Tidal volume, Pplateau, PaCO2 and PaO2 with one experimental fixed factors associated to the comparison between protocolized and automated ventilation at inclusion and at each hour until 4. This level was analysed as a repeated-measure. A heterogeneous autoregressive structure (ar(1)) was used to measure the dependence among repeated measurements [13]. The multivariate normality assumptions were verified with the Shapiro-Wilk tests after a Cholesky factorization. The results were declared significant with p-values < 0.05. The data were analyzed using the statistical package program SAS v9.2 (SAS Institute Inc., Cary,NC).
ADDITIONNAL FIGURES
Figure E1: Tidal volume distribution at inclusion and after one hour in both study groups
Tidal volume distribution at inclusion (upper panel) and after one hour (lower panel) in the automated ventilation group (black bars) and in the protocolized ventilation group (white bars) (expressed in ml/kg of predicted body weight).
Each bar represents a range of tidal volume (e.g. 9 is for tidal volumes between 9 and 9.99 ml/Kg of PBW).
Figure E2: Tidal volume reduction few cycles after initiation of automated ventilation
Tidal volume reduction occurred 5 cycles after initiation of the automated ventilation for this patient (subject#58), associated with a slight increase of the respiratory rate.
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