Low Tidal Volume and EVLWI During OLV
Condition: Lung Diseases
MeSH terms: Lung Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      The use of low tidal volume (TV) during one lung ventilation (OLV) for thoracic surgery
      decreases the incidence of postoperative acute lung injury (ALI). We postulated that the use
      of low TV during OLV for video-assisted thoracoscopic surgery (VATS) would decrease the
      extravascular lung water content index (EVLWI). After local ethics committee approval and
      informed consent, we will randomly allocate 60 patients scheduled for elective VATS to
      ventilate the dependent lung with VT of 4, 6, or 8 mL/kg (n= 20 for each), I: E ratio 1: 2.5,
      PEEP of 5 cm H2O, recruitment maneuvers and respiratory rate will be adjusted to maintain
      normocapnia. Perioperative changes in EVLWI, hemodynamics, oxygenation index will be
      recorded. Also, the incidence of postoperative ALI, morbidity, hospitalization and mortality
      will be recorded
    

Detailed description: 
      Nowadays most thoracic procedures are performed via video-assisted thoracoscopic surgery
      (VATS) which necessitates the use of one lung ventilation (OLV).

      Acute lung injury (ALI) is the most serious pulmonary complication after lung resection which
      may be aggravated with the use of large tidal volume (TV) and high peak airway pressures
      (Paw) during one-lung ventilation (OLV). In a large multicenter trial included 861 patients
      at 10 university centers of the Acute Respiratory Distress Syndrome Network of the National
      Heart, Lung, and Blood Institute, the use of lower tidal volumes from 4 to 6 ml/kg of the
      predicted body weight (PBW) during ventilation in patients with acute lung injury and the
      acute respiratory distress syndrome may reduce injurious lung stretch, the release of
      inflammatory mediators, days of mechanical ventilation and mortality (P=0.007).

      By the late 1990s the standard VT for managing thoracic surgical patients had already been
      adjusted downwards [from 10 to 12 ml/kg in the 1980s] to 8 to 10 ml/kg, although no specific
      guidelines existed for one-lung ventilation.

      The implementation of lung protective strategy during OLV using low TV [5-6 ml/kg PBW],
      pressure-controlled ventilation, limiting inspiratory plateau pressures and adding
      end-expiratory positive pressure (PEEP) with or without recruitment maneuvers has been shown
      to attenuate the incidence of ALI by 76-82% and satisfactory gas exchange after lung surgery
      without inducing a possible inflammatory/remodeling response.

      The use of lower tidal volumes for OLV with subsequently decreased peak airway pressures may
      be associated with less production of tumor necrosis factor (TNF)-alpha and soluble
      intercellular adhesion molecule (sICAM)-1.8 Recent data have highlighted the role of extra
      vascular lung water index (EVLWI) as a useful good parameter for early diagnosis of pulmonary
      complication including acute lung injury after thoracic surgery. The diagnosis of
      postoperative ALI is often delayed because clinical signs of pulmonary edema present only
      once the extra vascular lung water (EVLW) exceeds 7 ml/kg (ideal body weight).

      EVLWI may be measured with thermal dilution pulse index continuous cardiac output (PiCCO)
      (pulse contour cardiac output, Pulsion Medical Systems; Munich, Germany). The EVLWI
      represents both interstitial and alveolar fluid.

      Many studies used the ratio of EVLWI and the intrathoracic blood volume (ITBV) within the
      lungs to derive the pulmonary vascular permeability index. A high EVLW/ITBV ratio will
      support an increased permeability as the cause of ALI, whereas a low ratio will suggest
      hydrostatic pulmonary edema.

      Up to our knowledge, there is no available study of the efficacy of low tidal volumes during
      OLV in reducing the EVLWI, incidence of acute lung injury and the hospital cost of stay after
      thoracoscopic surgery.

      The investigators assume that the changes in tidal volume during OLV by 1 ml/kg (e.g. 70 ml
      in a 70 kg body weight patient) make no sense. So, they hypothesize that the use of lower
      tidal volumes of 4 ml/kg and 6 ml/kg will be associated with less lung water content than the
      use of larger tidal volume of 8 ml/kg.

      Interventions:

      In all patients, standard monitors including three leads electrocardiograph, noninvasive
      pressure and pulse oximeter, will be applied, fentanyl (1.0 μg/kg) and midazolam (0.03 mg/kg)
      will be given and femoral artery will be catheterized with a 5 Fr. Thermodilution catheter
      under local anesthesia and will be connected to a computer for pulse contour monitor (PiCCO2,
      Pulsion Medical Systems; Munich, Germany). This catheter will be used for blood gasometry and
      beat to beat monitoring of arterial blood pressure.

      Anesthetic technique will be standardized in all studied patients. Anesthesiologists who will
      give the anaesthetic will be not involved in the patient's assessment. General anaesthesia
      will be induced with propofol (2-3 mg/kg), fentanyl (2-3 µg/kg), and cisatracurium (0.2
      mg/kg) will be given to facilitate tracheal intubation with a left-sided double-lumen tube
      (DLT). The correct position of its tip will be confirmed with a fiberoptic bronchoscope after
      intubation and after positioning the patient in the lateral decubitus position (LDP).
      Anesthesia will be maintained with sevoflurane 1-1.5 MAC and fentanyl increments of 0.5 µg/kg
      to maintain the response entropy (RS) values < 50 and the difference between RE and state
      entropy (SE) < 10. Suppression of the second twitch in the train-of-four stimulation of the
      ulnar nerve will be maintained with 0.03 mg/kg increments of cisatracurium.

      The patients' lungs will be mechanically ventilated using fraction of inspired oxygen (FiO2)
      of 0.5 in air, tidal volume (VT) of 8 mL/kg (predicted body weight), inspiratory to
      expiratory [I: E] ratio of 1:2.5, a positive end-expiratory pressure (PEEP) of 5 cm H2O,
      respiratory rate (R.R) will be adjusted to achieve an PaCO2 of 35-45 mm Hg, peak inspiratory
      pressures (Ppk) will be limited to 35 cm H2O and a low fresh gas flow (FGF) (<2 L/min) in a
      semi closed circuit system.

      A central venous catheter will be inserted in the right internal jugular vein with
      ultrasonography guidance. EVLWI and ITBV will be calculated with the PiCCO2 monitor. Three 20
      ml blouses of iced saline will be injected through the central venous catheter and the change
      in the temperature will be measured with the thermistor-tipped femoral arterial catheter.

      All operations will be performed by the same surgeons. The VATS procedure will begin with the
      exploration of the pleural cavity using a 30° video thoracoscopic camera through a 1.5-cm
      single skin incision with the use of 1-3 trocars which enables the thoracoscopic instruments
      to move the lung.

      Intraoperative fluid therapy will include intravenous infusion of 2 ml/kg/hour of Lactated
      Ringer's solution and blood losses will be compensated with colloids and with red blood cell
      concentrates if the hemoglobin levels decreases below 8 to 9 g/dL. Mean arterial blood
      pressure will be maintained greater than 60 mm Hg using boluses of ephedrine 5 mg or
      phenylephrine 100 ug. Urine output will be maintained greater than 0.5 ml/kg/hour.

      At the end of surgery, the nondependent will be re-expanded and TLV will be resumed as before
      surgery. At the end of surgery, sevoflurane will be discontinued, the residual neuromuscular
      block will be antagonized, and the patient will be extubated. Postoperative analgesia will be
      accomplished with the use of patient-controlled morphine analgesia, lornoxicam and
      paracetamol. A restrictive fluid and transfusion policy will be adopted throughout the study
      periods, with targeted fluid balance of maximum 500 ml/day and transfusion triggers ranging
      between 8 and 9 g/dL.

      The development of ALI, defined according to the American-European Consensus Conference
      criteria as sudden onset of respiratory distress within the first 48 hours after surgery;
      infiltrates on the chest radiograph consistent with pulmonary edema; impaired oxygenation
      with an PaO2/FIO2 ratio less than 300 mmHg for ALI; and absence of cardiac insufficiency or
      fluid overload, based on PICCO2, echocardiogram and/or clinical evaluation

      Statistical Analysis:

      Data will be tested for normality using the Kolmogorov-Smirnov test. Fisher exact test will
      be used for categorical data. Repeated measure analysis of variance (ANOVA) and Tukey's
      Honestly Significant Difference post hoc tests will be used to evaluate the effects of time,
      group, and interaction in the continuous data of the primary (EVLWI and EVLWI/LTBV ratio) and
      secondary endpoints in each group. Kruskal-Wallis one-way ANOVA and posthoc Wilcoxon rank sum
      tests will be done for intergroup comparisons for the nonparametric variables. univariate
      analysis for the risk factors for increases in EVLWI after OLV for VATS will be done
      including age, sex, preoperative pulmonary function, duration of surgery and OLV, tidal
      volume, and FiO2. Data will be expressed as mean ± SD, number (%), or median [range]. A value
      of P < 0.05 will be considered to be statistically significant.
    

Intervention name(s): The VT 4 ml/kg group; The VT 6 ml/kg group; The VT 8 ml/kg group
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): the dependent lung will be ventilated with a TV of 4 mL/kg (predicted body weight), respectively, whereas FiO2, I: E ratio, PEEP, frequency, Ppk, and a FGF will be maintained as during two-lung ventilation (TLV) and the lumen of the nondependent lung will be left open to air. Dependent lung recruitment maneuvers will be repeated at 30-minute intervals by raising the inspiratory pressure up to 35 cmH2O for 10 seconds.; the dependent lung will be ventilated with a TV of 6 mL/kg (predicted body weight), respectively, whereas FiO2, I: E ratio, PEEP, frequency, Ppk, and a FGF will be maintained as during two-lung ventilation (TLV) and the lumen of the nondependent lung will be left open to air. Dependent lung recruitment maneuvers will be repeated at 30-minute intervals by raising the inspiratory pressure up to 35 cmH2O for 10 seconds.; the dependent lung will be ventilated with a TV of 8 mL/kg (predicted body weight), respectively, whereas FiO2, I: E ratio, PEEP, frequency, Ppk, and a FGF will be maintained as during two-lung ventilation (TLV) and the lumen of the nondependent lung will be left open to air. Dependent lung recruitment maneuvers will be repeated at 30-minute intervals by raising the inspiratory pressure up to 35 cmH2O for 10 seconds.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Video-assisted thoracoscopic surgery; one lung ventilation; low tidal volume; acute lung injury; lung water content