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