Non-dependent HFPPV Versus CPAP for Video-assisted Thoracoscopy
Condition: Elective Video-assisted Thoracoscopic Surgery; One-lung Ventilation Lasts at Least One Hour
Study type: Interventional
Phase: Phase 2

Summary: 
      Video-assisted thoracoscopic surgery (VATS) is usually performed using well-collapsed lung is
      essential for optimum surgical visualization and resection. However, one lung ventilation
      (OLV) is associated with deleterious impaired oxygenation secondary to the increases in shunt
      fraction.1 There are different approaches for the recruitment of the non-dependent lung (NL)
      during OLV such as the selective application of continuous positive pressure ventilation
      (CPAP) or high frequency positive pressure ventilation (HFPPV) to the non-dependent lung.2-4
      These strategies may improve arterial oxygenation and reduce shunt fraction,2-4 However, the
      use of high CPAP levels impaired the surgical conditions during thoracotomy.2-3 On contrary,
      the application of HFPPV either to both lungs5or to the non-dependent lung permits adequate
      surgical conditions during thoracotomy.4 The investigators hypothesize that the application
      of volume-controlled HFPPV to the non-dependent lung during OLV for video-assisted
      thoracoscopic surgery may provide better surgical field and adequate oxygenation than the use
      of CPAP 2 cm H2O.

      The investigators will evaluate the effects of the selective application of conventional one
      lung ventilation, HFPPV, or CPAP 2 cm H2O to the non-dependent lung on surgical field
      conditions, and arterial oxygen and carbon dioxide tensions (PaO2 and PaCO2, respectively)
      during OLV in the patients scheduled for video-assisted thoracoscopic surgery.
    

Detailed description: 
      Thirty patients aged 18-60 years (ASA physical status II-III) scheduled for elective
      video-assisted thoracoscopic surgery with at least one hour of one-lung ventilation (OLV)
      will be included in this randomized prospective placebo-controlled crossover study at the
      authors' center after obtaining approval of the institutional ethical committee and informed
      written consent. The patients will be randomized to a CPCP2-HFPPV group(n = 15)or a
      HFPPV-CPAP2 group(n = 15).

      A power analysis of the data obtained from our preliminary pilot study indicated that 26
      patients will be sufficient to detect a one SD changes in the visual analog scale assessment
      of the surgical field, with a type-I error of 0.05 and a power of 85%, with added 10% more
      patients, for a final sample size of 30 patients to account for patients dropping out during
      the study. All operations will be performed by the same surgeons.

      The patients will be premedicated with fentanyl (1.0 μg/Kg) and i.v. midazolam (0.03 mg/Kg).
      All patients will be monitored with five leads electrocardiography, pulse oximetry, and
      non-invasive blood pressure and 7mL/Kg of 6% Hydroxyethyl Starch 130/0.4 (Voluven, Fresenius
      Kabi, Bad Homburg, Germany) will be given intravenously before induction of general
      anesthesia. An arterial line (20 G) will be inserted under local anesthesia. A thoracic
      epidural catheter (T4-T7) will be inserted with the patient in sitting position, and a test
      dose (1.5% lidocaine 3 mL plus epinephrine 1:200.000) will be administered in order to
      exclude an intravascular or intrathecal position of the catheter. No more epidural local
      anesthetics will be used during the study in order to avoid effects on hypoxic pulmonary
      vasoconstriction.

      Anesthesiologists who gave the anesthetic will not be involved in the collection of the
      patient's data. General anesthesia will be induced with propofol (2-3 mg/kg), fentanyl (2-3
      µg/kg), and cisatracurium (0.2 mg/kg) was given for muscle relaxation.

      The trachea will be intubated with a left-sided double-lumen tube (DLT) [Broncho-Cath®;
      Mallinckrodt Medical Ltd., Dublin, Ireland]. The correct position of the tube will be
      confirmed with a fiberoptic bronchoscope after intubation and after positioning the patient
      in the lateral decubitus position. Other patient monitoring included end-tidal CO2,
      neuromuscular blockade, and nasopharyngeal temperature will be used. Anesthesia will be
      maintained with continuous infusions of propofol (6-8 mg/kg/h) and fentanyl (1 µg/kg/h).
      Increments of cisatracurium (0.03 mg/kg) will be given to maintain suppression of the second
      twitch using a train-of-four stimulation.

      In all patients,the patients' two lungs will be mechanically ventilated with intermittent
      positive pressure ventilation 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 arterial carbon dioxide tension (PaCO2) 35-45 mm Hg, peak inspiratory
      pressures will be limited to 35 cm H2O and a low flow of fresh gas (<2 L/min) in a semi
      closed circuit system.

      After positioning of the patient in the lateral decubitus position,the dependent
      non-operative lung will be ventilated conventionally(OLV)with a tidal volume of 6 mL/kg
      (predicted body weight), whereas FiO2, I: E ratio, PEEP, frequency, peak inspiratory
      pressures, and a flow of fresh gas will be maintained as during two-lung ventilation and the
      lumen of the non-dependent operative lung will be left open to air.

      The subjects will be allocated randomly to two groups (n=15 each) by drawing sequentially
      numbered sealed opaque envelopes containing a computer-generated randomization code.

      In CPAP2-HFPPV group, the non-dependent lung will be allowed to deflate to a CPAP of 2 cm H2O
      for 30 min, using a CPAP circuit (Bronchocath® CPAP system; Mallinckrodt Medical, Inc., St.
      Louis, MO) which will be connected to the flowmeter of an oxygen cylinder with a flow rate of
      5 L/min and FiO2 of 1.0.7 Then, the lumen of non-dependent lung will be connected to a second
      identical ventilator with low compliant internal circuit. HFPPV will be initiated for 30 min
      using a FiO2 of 1.0, VT 3 mL/kg (predicted body weight), I: E ratio <0.3 and R.R 60
      breaths/min.

      In HFPPV-CPAP2 group, the non-dependent lung will be ventilated using HFPPV of the
      non-dependent lung for 30 min followed with non-dependent lung CPAP of 2 cm H2O for 30 min,

      At the end of surgery, the nondependent lung will be re-expanded and two-lung ventilation
      will be resumed with a tidal volume of 8 mL/kg (predicted body weight). Twenty minutes before
      the skin closure, the infusions of propofol and fentanyl will be gradually decreased by 20%
      in every 5 minutes. At the end of surgery, the infusions will be discontinued, the residual
      neuromuscular block will be antagonized with neostigmine 50 μg/kg and atropine 20 μg/kg, and
      the patient will be extubated by the same anesthesiologists.

      The surgical field conditions, oxygenation and hemodynamic data will be recorded after
      induction of general anesthesia (baseline), 15 (NL-15), 30 (NL-30) and 60 minutes (NL-60)
      after the selective application of CPAP or HFPV to the nondependent lung, and 15 min after
      returning of two-lung ventilation (TLV).

      The surgeons will be asked to rate their satisfaction with the surgical field using a 10-cm
      VAS (0: worse; 10: excellent field). The ICU and hospital lengths-of-stay will be recorded.

      Perioperative hypoxemia (SaO2<90%), respiratory and cardiovascular events, and mortality will
      be recorded within 30 days of surgery because a shorter period may have missed complications
      and deaths directly related to events that occurred after thoracic surgery.

      Statistical analysis will be performed using the Statistical Package for the Social Sciences
      (Release 16, SPSS Inc., Chicago, IL, 2007). Data will be tested for normality using the
      Kolmogorov-Smirnov test. Repeated-measures analysis of variance will be used for analysis of
      serial changes in the patients' data at different times after the start of study
      intervention. Chi-square test will be used for categorical data. Dependent t-test and ANOVA
      will be used for continuous parametric variables. The Mann-Whitney U test will be performed
      for intergroup comparisons for the non-parametric values. 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): Non-dependent lung ventilation; Non-dependent lung ventilation
Intervention type(s): Procedure; Procedure
Intervention description(s): the dependent lung will be ventilated with conventional ventilation (OLV) a tidal volume of 6 mL/kg (predicted body weight), whereas FiO2, I: E ratio, PEEP, frequency, peak inspiratory pressures, and a flow of fresh gas will be maintained as during two-lung ventilation for 15 min.
Then the non-dependent lung will be allowed to deflate to a CPAP of 2 cm H2O, which will be connected to the flowmeter of an oxygen cylinder with a flow rate of 5 L/min and FiO2 of 1.0 for 30 min
Then, the non-dependent lung will be connected to a second identical ventilator, 15 min after OLV, using a FiO2 of 1.0, VT 3 mL/kg (predicted body weight), I: E ratio <0.3 and R.R 60 breaths/min for further 30 min.; the dependent lung will be ventilated with conventional ventilation (OLV) a tidal volume of 6 mL/kg (predicted body weight), whereas FiO2, I: E ratio, PEEP, frequency, peak inspiratory pressures, and a flow of fresh gas will be maintained as during two-lung ventilation for 15 min.
Then, the non-dependent lung will be connected to a second identical ventilator, 15 min after OLV, using a FiO2 of 1.0, VT 3 mL/kg (predicted body weight), I: E ratio <0.3 and R.R 60 breaths/min for further 30 min.
Then the non-dependent lung will be allowed to deflate to a CPAP of 2 cm H2O, which will be connected to the flowmeter of an oxygen cylinder with a flow rate of 5 L/min and FiO2 of 1.0 for 30 min
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: VATS; one lung ventilation; continuous positive pressure ventilation; high frequency positive pressure ventilation