Influence of the End-inspiratory Pause on Mechanical Ventilation.
Condition: Anesthesia; Surgery
MeSH terms: Respiratory Aspiration
Study type: Interventional

Summary: 
      This study evaluates the influence of two different end-inspiratory pause (EIP) times on
      respiratory mechanics and arterial gases of surgical patients when ventilated under an open
      lung approach (OLA) strategy. The investigators evaluate the impact of using EIP 10% versus
      30% of the inspiratory time on a volume control model. The investigators also analyse the
      potential influence of these EIP on pulmonary gas distribution measured by electric impedance
      tomography.
    

Detailed description: 
      Prolonging the EIP while maintaining an adequate expiratory time has shown benefits in terms
      of improving alveolar effective ventilation and enhancing gas exchange in surgical and
      intensive care patients. However, there are no published studies addressing the effects of
      different EIP times on the respiratory mechanics and gas distribution of surgical patients
      when associated with OLA strategies for ventilation.

      Assuming the benefits of OLA, these investigators hypothesized about the potential effects of
      increasing the EIP when ventilating patients in a volume control mode. In the present study
      the investigators evaluated the influence of two different EIP (10% and 30% of the
      inspiratory time) on the respiratory mechanics of patients submitted to scheduled abdominal
      surgery under general anesthesia and ventilated with a protective lung strategy. The
      investigators studied the influence of EIP on driving pressure (Pdriv), plateau pressure
      (Pplat), respiratory static compliance (Crs) and open lung PEEP (OL-PEEP). We also assessed
      gas distribution by means of electric impedance tomography and studied its influence on gas
      exchange measured by means of serial gasometries.

      Study protocol. A forced spirometry was performed in all patients after accepting their
      inclusion.

      On the day of surgery, standard monitoring was initiated on arrival in the theatre, including
      electrocardiography, pulse oximetry, and noninvasive blood pressure monitoring. After light
      sedation with 1-2 mg of midazolam, a thoracic epidural catheter was placed under local
      anesthesia on anesthesiologist's criteria. A remifentanil infusion 0.03 mcg/kg/min was
      started before left radial artery catheterization under local anesthesia. After recording
      basal data during full consciousness on 21% inspired oxygen, all participants were
      preoxygenated via a facial mask for 5 min on spontaneous ventilation with fraction of
      inspired oxygen (FiO2) of 0.7 and fresh gas flow of 6 L/min. After induction with propofol
      ((1-1.5 mg/kg of predicted body weight (PBW)), 0.8 mg/kg of PBW of rocuronium were
      administered and proceeded with tracheal intubation. Patients were ventilated via a Primus
      (Drager, Telford, PA, USA) using a tidal volume of 7 ml/kg of PBW; volume control mode
      comprised an inspiration: expiration ratio of 1:2 and a respiratory rate of 12-14 breaths per
      minute to maintain the etCO2 at 35-40 mmHg, with an initial PEEP of 5 cmH2O. EIP was
      programmed according to randomization group. Fresh gas flow of 2 L/min with FiO2 of 0.7 was
      used throughout the procedure. Anesthesia was maintained with remifentanil 0.03-0.1
      mcg/kg/min and sevoflurane, with minimal alveolar concentration (MAC) of 0.7-1 adjusted for
      patient´s age. Bispectral Index monitoring was used throughout the entire procedure (BIS
      Quatro, Covidien Ilc, Mansfield, MA, USA). All ventilation parameters remained stable
      throughout the study except the EIP (diverted in function of study protocol assignation) and
      the PEEP, which was tailored according the principles of OLA ventilation previously
      published. A central venous line was inserted in all cases and continuous cardiac output
      monitoring, systemic vascular resistance and systolic volume variation were monitored
      throught out all procedure by means of FloTrac sensor (Edwards Lifesciences, Irvine,
      California, USA). Other monitoring included train of four (TOF) for neuromuscular relaxation.

      Dräger Primus (Dräger Medical, Lübeck, Germany) was used for ventilation with continuous
      monitoring of peak pressure (Ppk), Pplat, PEEP, Crs, FiO2, fraction of expired oxygen (FeO2),
      end-tidal CO2 (etCO2). For blood gases an ABL90 FLEX PLUS analyzer (Radiometer Medical,
      Copenhagen, Denmark) was used. If hemodynamic instability occurred during the ARM (fall> 20%
      of the cardiac index or mean arterial pressure), maneuver was discontinued and ephedrine or
      phenylephrine was administered and registered, restoring ARM on haemodynamics recovering.

      Ventilatory management Data collection was made in five different moments (moment 0 to 4);
      moment 0: after endotracheal intubation, on establishing mechanical ventilation and prior to
      ARM, with the EIP assigned to each group and a standard PEEP of 5 cm H2O. Subsequently an ARM
      was performed as previously described by Ferrando et al, with calculation of the optimal PEEP
      by means of a decremental titration trial followed of a new AMR and establishment of a
      tailored OL-PEEP, 2 cmH2O over optimal PEEP (moment 1). EIP was then crossed between groups
      (30% in Group 1 and 10% in Group 2), moment 2. Another ARM was then performed with the
      consequent re-assignation of a different OL-PEEP for each group (moment 3). Finally, EIP was
      crossed again (moment 4). All data were collected 5 minutes after changes implementation.

      Statistic analysis The investigators used the statistical software IBM SPSS Statistics for
      Windows, version 24 (IBM Corp., Armonk, N.Y., USA) for data analysis. An exploratory analysis
      of the data was performed using the mean and standard deviation or the median with
      interquartile ranges for quantitative variables. The investigators used the percentages for
      analysis of the qualitative variables. The investigators checked the normality of the
      distribution of data with the Kolmogorov-Smirnov test, or with the Shaphiro-Wilk test for
      variables with less than 50 records. The Student´s T test for paired samples was used to
      analyse the difference in the means of quantitative paired variables (intra-group
      differences), and the Student T test for independent samples to analyse the difference in the
      means of quantitative variables between both groups (inter-group differences).

      Finally, the investigators grouped records corresponding to the EIP applied after
      recruitment, independently of the original assignation according to Group, In this sense,
      investigators grouped data corresponding to Group 1 in moment 1 with Group 2 in moment 3
      (EIP10% after recruitment) and data of Group 1 in moment 3 with Group 2 in moment 1 (EIP 30%
      after recruitment), obtaining a sample of 32 registers in comparable paired conditions.

      Calculation of the sample size Given the absence of previously published works with an
      approach similar to the one proposed by investigators, the sample size was calculated based
      on the data obtained in a pilot sample of 5 patients submitted to surgical and anesthesia
      management similar to those of the protocol proposed. The investigators estimated the sample
      size assuming the differences in Crs when changing from an EIP 10 % to 30% in a sequential
      way (paired sample), determining an average difference 12 ml/cm H2O between both
      interventions. Sample size was calculated to obtain a power of 80 % to detect differences in
      the contrast of the null hypothesis h₀: μ₁ = μ₂ by means of a bilateral Student's T test for
      two related samples, taking into account a level of significance is of 5 %, and assuming a
      mean of the differences of 12 ± 20 units. Taking into account that the expected percentage of
      dropouts was 20.00% it would be necessary to recruit 30 pairs of experimental units in the
      study.
    

Intervention name(s): End-inspiratory pause 10%; End-inspiratory pause 30%
Intervention type(s): Procedure; Procedure
Intervention description(s): Percentage of the total inspiratory time in which there is no gas flow. It is the period of time between the cessation of the inspiratory flow and the start of expiration. In this intervention arm it would correspond to a 10% of the total inspiratory time; Percentage of the total inspiratory time in which there is no gas flow. It is the period of time between the cessation of the inspiratory flow and the start of expiration. In this intervention arm it would correspond to a 30% of the total inspiratory time
Other intervention name(s): Time of inspiratory pause 10%; Time of inspiratory pause 30%
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: end-inspiratory pause; lung protection; intraoperative ventilation; lung compliance