The Effect of Different Ventilation Strategies on Cerebral Oxygenation Using Near Infrared Spectroscopy (NIRS) in Pediatrics Undergoing Posterior Fossa Tumor Surgery
Condition: Infratentorial Neoplasms; Hyperventilation; Craniotomy
MeSH terms: Infratentorial Neoplasms; Hyperventilation
Study type: Interventional

Summary: 
      The aim of this study is to evaluate the changes of cerebral oxygen saturation during
      hyperventilation and normo-ventilation (using near-infrared spectroscopy) in pediatrics
      undergoing posterior fossa tumor resection.
    

Detailed description: 
      Introduction:

      Hyperventilation has been used for intraoperative brain relaxation for decades,
      Interestingly, this common practice is not based on robust evidence .

      The mechanism of brain relaxation secondary to hyperventilation is attributed to the
      hypocapnia induced cerebral vasoconstriction and the subsequent reduction of cerebral blood
      volume (CBV) and intracranial volume. The CBV reduction is accompanied by the reduction in
      cerebral blood flow that could render the brain at ischemic risk, if the cerebral metabolic
      activity remains the same before and after hyperventilation. So, it is possible that
      inadvertent cerebral ischemia may outweigh the benefits of hyperventilation and should be
      subjected for further investigation.

      Cerebral near-infrared spectroscopy (NIRS) is a useful non-invasive tool for regional
      cerebral oxygen saturation (rScO2) monitoring, which provides continuous, real time
      information on the balance between cerebral oxygen delivery and consumption.

      Cerebral oximetry monitoring had the ability to detect clinically silent episodes of cerebral
      ischemia in a variety of clinical settings which could be an important safeguard for cerebral
      function.

      Hyperventilation had been shown to significantly reduce cerebral oxygenation using
      near-infrared spectroscopy in patients undergoing elective abdominal surgery.

      Multiple studies have shown that prolonged hyperventilation correlated with poor outcome
      especially in brain injured patients. 5,6 However, there is still a lack of evidence on the
      relationship between hyperventilation and neurological outcome in patients having craniotomy.

      However, to the best of the investigator's knowledge no previous randomized controlled trials
      had studied the effect of hyperventilation versus normo-ventilation on cerebral oximetry in
      pediatrics undergoing posterior fossa tumor surgeries.

      V. Study procedure:

      This is a prospective, randomized controlled trial with a two-period crossover design so that
      the patient can act as a control to himself. Enrolled patients are children (1-6 years old)
      undergoing posterior fossa tumor resection. Prior to anesthetic induction, the two sensors
      (SAFB-SM, Covidien, Dublin, Ireland) for near-infrared spectroscopy (INVOS 5100C, Covidien,
      Dublin, Ireland) will be applied on the left and right sides of the forehead with the caudal
      border approximately 1 cm above the eyebrows to measure regional oxygen saturation (rSO2). A
      bispectral index (BIS) sensor will also be fixed on the left forehead (Model QUATRO,
      Covidien, Dublin, Ireland) to monitor the depth of anesthesia. Both sensors will be fixed to
      their positions using adhesive pads to avoid removal during positioning and soaking with
      betadine solution. Baseline values for cerebral oxygen saturation will be obtained using NIRS
      monitor, Standard monitors (electrocardiogram, non-invasive blood pressure, pulse oximeter)
      will be applied to all patients. The anesthetic management will be standardized for all
      patients as follows:

      General anesthesia will be induced by inhalational agent 'sevoflurane' until intravenous line
      is secured then Fentanyl (1-2 µg/kg), Propofol (1-2 mg/Kg) will be given intravenously.
      Intubation will be facilitated by Atracurium (0.5 mg/kg) and confirmed by capnography.
      Nasopharyngeal temperature probe will be inserted for monitoring of core body temperature
      which will be kept between 36.5-37 C using warming blankets. A 22 G arterial cannula will be
      placed in the left radial artery and baseline ABG will be obtained to correlate value of
      Etco2 and Paco2. Anesthesia will be maintained with isoflurane in oxygen 40% and will be
      adjusted to maintain BIS between 40 and 60 and Atracurium infusion (0.5 mg/kg/hr). Central
      venous line will be inserted in the right internal jugular vein under complete aseptic
      condition under ultrasound guidance, wide bore peripheral cannula will be inserted for fluid
      management and a Foley's catheter will be inserted in the urinary bladder for urine output
      monitoring. Patients will be positioned in the prone position with the arms positioned and
      secured at the patient's side and after careful padding of the pressure points; the patient
      head will be supported on the forehead using a horseshoe adapter. Slight neck flection will
      be permitted till the anesthetist can pass two fingers easily between the chin and the chest
      to allow for optimum surgical exposure. Patients will be randomly assigned using concealed
      envelopes, according to a computer-generated random number to one of the following two
      treatment sequences:

        -  Group 1: hyperventilation (ETco2 25-30 mm Hg) for 20 minutes that will start immediately
           after skin incision followed by normoventilation (ETco2 31-35 mm Hg) for another 20
           minutes.

        -  Group 2: normoventilation (ETco2 31-35 mm Hg) for 20 minutes immediately after skin
           incision followed by hyperventilation (ETco2 25-30 mm Hg) for another 20 minutes. The
           ventilation strategies will be achieved using volume-controlled mode with a tidal volume
           of 8 ml/kg, I/E ratio:1/2 and ETco2 will be maintained at the desired range by adjusting
           the respiratory rate. Positive end-expiratory pressure (PEEP) will not be applied. After
           removal of the bone flap and exposure of the dura matter, a 20-gauge plastic cannula
           will be inserted into the subdural space along the surface of the brain. This will be
           connected to a calibrated pressure transducer via a length of polyethylene high pressure
           tubing filled with normal saline. The transducer will be zeroed at ear level. During the
           study period, the mean subdural pressure will be recorded at 2 minutes intervals at the
           end expiratory phase.

      Assessment phase 1: An arterial blood sample will be obtained immediately after skin incision
      for blood gas analysis to determine the difference between arterial and end-tidal carbon
      dioxide tension (Pa-ETCO2). Ventilation and ETCO2 will be kept constant for at least 20 min,
      which is long enough for stabilization of any vascular responses to the change in Paco2. At
      the end of the equilibration period (20 minutes), another arterial blood sample will be
      obtained to confirm that the targeted Paco2 (was achieved. The neurosurgeon, unaware of the
      anesthetic and ventilatory management provided, will be then asked to score the brain bulk
      according to a four-point scale as follows:

        1. Excellent with no swelling

        2. Minimal swelling, acceptable

        3. Swollen but no treatment required

        4. Swollen, needing treatment. After this assessment, ventilation will be changed
           immediately according to group assignment.

      Assessment phase 2: Another 20 min of equilibration will be allowed and measurements will be
      repeated as previously described. During the whole period of study (40 minutes), the cerebral
      oximetry will be recorded at 5 minutes intervals. During this period factors that may affect
      cerebral oximeter will be controlled by maintaining position of the patient head,
      (normothermia with temperature at 36.5-37 C), within 20% of the base line blood pressure
      using increments of ringer solution and ephedrine boluses as appropriate, maintain PH
      7.35-7.45, Hb level around 10 gm/dl guided by blood loss and repeated measurements of Hb in
      ABG and blood glucose level between 80-180 mg/dl. The study will be ended at this point, the
      subdural cannula will be removed, and surgery will proceed as normal. Specific or routine
      interventions for brain swelling such as a change in body position or diuretic therapy with
      mannitol or furosemide will not be administered until the study had ended. However, for
      ethical reasons, interventions will be made if requested by the surgeon and the patient will
      be then withdrawn from the study. Data will be collected by an independent blinded
      anesthesiologist using a data collection form.

      • Measurement tools:

        -  Demographic and categorical characteristics including patient's age in years, weight in
           Kg, gender, type of the procedure( 4th ventricular, medulloblastoma,... )

        -  Both NIRS values at baseline and every 5 minutes during each phase of the study

        -  Subdural intracranial pressure (ICP) every 2 minutes during each phase of the study

        -  End tidal co2 every 5 minutes during each phase of the study

        -  Paco2 baseline and at the end of each phase of ventilation (20 minutes following start
           of phase 1 assessment and 20 minutes after start of phase 2 assessment)

        -  Heart rate and mean arterial blood pressure every 10 minutes.

        -  Brain relaxation score
    

Intervention name(s): cerebral oximetry
Intervention type(s): Device
Intervention description(s): evaluation of the changes of cerebral oxygen saturation during hyperventilation and normo-ventilation (using near-infrared spectroscopy) in pediatrics undergoing posterior fossa tumor resection.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The aim of this study is to evaluate the changes of cerebral oxygen saturation during hyperventilation and normo-ventilation (using near-infrared spectroscopy) in pediatrics undergoing posterior fossa tumor resection.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: posterior fossa; cerebral oximetry; hyperventilation; children