Effect of Controlled Hypotension on Cerebral Oxygen Saturation
Condition: Hypotension Drug-Induced; Cerebral Oxygen Saturation
MeSH terms: Hypotension
Study type: Interventional
Phase: Phase 4

Summary: 
      For a successful functional endoscopic sinus surgery (FESS), it is crucial to provide
      effective controlled hypotension to reduce blood loss and provide a relatively blood-free
      surgical environment to facilitate surgery.

      The goal of controlled hypotension is to maintain an arterial blood pressure which is
      sufficiently low to allow a reduction in bleeding with offering a superior intraoperative
      hemodynamic stability during stressful surgical events to maintain intact cerebral
      microcirculatory auto-regulation.

      Auto-regulation impairment during controlled hypotension might increase oxygen extraction
      ratio. Thus monitoring the cerebral oxygen saturation (rSO2) to measure cerebral oxygenation
      becomes essential and it remains a challenge to clinically assess cerebral oxygenation on a
      routine basis.

      Various recent studies reported based on facilitating the induction of controlled
      hypotension, but the effects of hypotension on cerebral perfusion and oxygenation and its
      effects on postoperative cognitive function are still poorly characterized. Moreover, the
      relationship between rSO2 and controlled hypotension has not been established in patients
      undergoing FESS.

      Within the last decade, near infrared spectroscopy (NIRS) INVOS® monitors which is clinically
      most broadly spread technique, can be used for non-invasive assessment of cerebral perfusion
      by detecting changes in rSO2 by online monitoring of cerebral oxygenation.

      In our clinical routine for achieving a controlled hypotension, esmolol and remifentanyl are
      the most commonly used hypotensive agents. The aim of this prospective randomized single
      blind study was to investigate the influence of remifentanyl as a hypotensive agent in
      comparison to esmolol on rSO2 by using NIRS and postoperative cognitive function in patients
      undergoing FESS.
    

Detailed description: 
      For a successful functional endoscopic sinus surgery (FESS), it is crucial to provide
      effective controlled hypotension to reduce blood loss and provide a relatively blood-free
      surgical environment to facilitate surgery.

      The goal of controlled hypotension is to maintain an arterial blood pressure which is
      sufficiently low to allow a reduction in bleeding with offering a superior intraoperative
      hemodynamic stability during stressful surgical events to maintain intact cerebral
      microcirculatory auto-regulation.

      Auto-regulation impairment during controlled hypotension might increase oxygen extraction
      ratio. Thus monitoring the cerebral oxygen saturation (rSO2) to measure cerebral oxygenation
      becomes essential and it remains a challenge to clinically assess cerebral oxygenation on a
      routine basis.

      Various recent studies reported based on facilitating the induction of controlled
      hypotension, but the effects of hypotension on cerebral perfusion and oxygenation and its
      effects on postoperative cognitive function are still poorly characterized. Moreover, the
      relationship between rSO2 and controlled hypotension has not been established in patients
      undergoing FESS.

      Within the last decade, near infrared spectroscopy (NIRS) monitors which is clinically most
      broadly spread technique, can be used for non-invasive assessment of cerebral perfusion by
      detecting changes in rSO2 by online monitoring of cerebral oxygenation.

      In our clinical routine for achieving a controlled hypotension, esmolol and remifentanyl are
      the most commonly used hypotensive agents. The aim of this prospective randomized single
      blind study was to investigate the influence of remifentanyl as a hypotensive agent in
      comparison to esmolol on rSO2 by using NIRS and postoperative cognitive function in patients
      undergoing FESS.

      After receiving the local institutional research ethics committee approval and written
      informed consent from each patient, 140 American Society of Anesthesiology (ASA) I and II
      patients aging between 18 and 65, undergoing for elective FESS and required controlled
      hypotension were enrolled in this study. Patients with hypertension, coronary artery diseases
      and cerebral insufficiency, severe hypovolemia and anemia, body mass index over 30 kg/m2,
      anticoagulation therapy and previous hypersensitivity to any of the study drugs were excluded
      from the study.

      They were equally randomly assigned to receive either remifentanil or esmolol to maintain
      mean arterial blood pressure (MAP) between 55-65 mmHg.

      After insertion of a peripheral venous cannula upon arrival to the operating room, balanced
      electrolyte solution at 5 ml/kg/h was initiated. Following the premedication with intravenous
      midazolam 0.05 miligram/kg IV 15 min prior to the induction of anesthesia, and standard
      monitoring was applied consisting of electrocardiography (EKG), noninvasive blood pressure,
      peripheral oxygen saturation (SPO2). Further, cerebral oxygen saturation value (rSO2, using
      the NIRS with adult probe placed in the median frontal region) was continuously monitored
      using NIRS before the induction of anesthesia.

      After preoxygenation anaesthesia was induced with 2 miligram/kg propofol, 2 μg/kg fentanyl
      and to facilitate the endotracheal intubation 0.6 miligram/kg rocuronium was administered.
      Following orotracheal intubation, mechanical ventilation was adjusted to maintain PaCO2 at 35
      to 40 mm Hg.

      Anaesthesia maintenance was performed using sevoflurane (0.8 to 1 adjusted MAC) in a mixture
      of O2/Nitrous oxide 50%/50%. Then the treatment protocol consisting of remifentanil and
      esmolol were delivered in order to induce controlled hypotension that was considered
      effective when MAP reached the target pressure of 60 mmHg.

      Patients in the esmolol group (Group E) received esmolol 0.5 miligram/kg iv at induction
      followed by a continuous infusion of esmolol 5-15 miligram/kg/min and titrated to the maximum
      dose 300μg/kg/min to reach target MAP of 50-60 mmHg about a value of 5 mmHg. Patients in the
      remifentanil group (Group R) received remifentanil 0.5 μg/kg/min at induction followed by an
      infusion of remifentanil 0.1- 0.5 μg/kg/min and titrated between 0,1- 0,5 μg/kg/min to reach
      target MAP of 50-60 mmHg about a value of 5 mmHg.

      In both groups no surgical stress was applied during 5 min following start of hypotension.

      Cerebral desaturation was defined as a reduction of rSO2 to higher than 20 % of baseline for
      ≥ 15 seconds. When cerebral desaturation occurred, remifentanil and esmolol infusion doses
      were decreased and MAP was increased with intravascular fluid administration and ephedrine.
      When hypotension below the target MAP and bradycardia below the heart rate 45 beats/min
      longer than one minute in duration were occurred, a bolus of ephedrine 10 mg iv and atropine
      0.1 miligram/kg iv applied, respectively.

      All operations were performed by the same attending surgeon in order to ensure consistency in
      the estimation of the surgical field who was blinded to the hypotensive agent. When MAP
      reached the desired range (50-60 mmHg) and was maintained for at least 10 minutes, the
      quality of the surgical field was defined in terms of blood loss and dryness using a 10 point
      scale (0= no bleeding, virtually bloodless field; 10= uncontrolled bleeding).

      The cognitive function of the patients was assessed using Mini Mental State Examination
      (MMSE) test. Preoperative MMSE test was done at the premedication room 1 hour before surgery
      and 120 minutes after the discontinuation of the drugs for each patient. A decrease in the
      MMSE score ≥ 2 points from baseline was considered as an index of decline in cognitive
      function.

      Hemodynamics (Diastolic blood pressure (DBP), Mean blood pressure (MBP), systolic blood
      pressure (SBP) and heart rate (HR), SPO2 and rSO2 were recorded preoperatively (baseline),
      postinduction 5th min (after administration of hypotensive and anesthetic agent),
      intraoperatively (10, 20, 30, 45, 60, 90 minutes), 5 and 10 minutes after stoppage of
      hypotensive agents. Additionally, the duration of surgery, duration of anesthesia, the
      consumption dose of hypotensive agents, desaturated and not desaturated patients among the
      groups were also recorded.
    

Intervention name(s): Esmolol Hydrochloride; Remifentanil Hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): the influence of brevibloc as a hypotensive agent on rSO2; the influence of remifentanyl as a hypotensive agent on rSO2
Other intervention name(s): Brevibloc 10 MG/ML Injectable Solution; ultiva
Intervention MeSH terms: Remifentanil; Esmolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Screening