Clinical trial NCT02967029: Effect of Controlled Hypotension on Cerebral Oxygen Saturation
Official title: Effect of Controlled Hypotension on Cerebral Oxygen Saturation in Patients Undergoing Functional Endoscopic Sinus Surgery: a Prospective Randomized Single Blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypotension Drug-Induced
Cerebral Oxygen Saturation
Lead sponsor: Istanbul University
Sponsor class: OTHER
First posted: 2016-11-17
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief 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.

Eligibility criteria: Inclusion Criteria:

* American Society of Anesthesiology (ASA) I and II patients
* aging between 18 and 65,
* undergoing for elective FESS
* requiring general anesthesia with endotracheal intubation

Exclusion Criteria:

* hypertension,
* coronary artery diseases and cerebral insufficiency,
* severe hypovolemia and anemia,
* body mass index over 30 kg/m2,
* anticoagulation therapy
* previous hypersensitivity to any of the study drugs

Primary outcomes:
measure: cerebral desaturation
timeFrame: reduction of cerebral oxygen saturation to higher than 20 % of baseline for ≥ 15 seconds through surgery completion
Secondary outcomes:
measure: the quality of the surgical field
timeFrame: When MAP reached the desired range (50-60 mmHg) and was maintained for at least 10 minutes
measure: Arterial blood pressure
timeFrame: arterial blood pressure at baseline, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents through surgery completion
measure: Heart rate
timeFrame: Heart rate at baseline, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents through surgery completion
measure: SPO2 value
timeFrame: SPO2 value at baseline, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents through surgery completion
measure: cognitive function of the patients
timeFrame: cognitive function of the patients were assessed 1 hour before surgery and 120 minutes after the discontinuation of the drugs
measure: the duration of surgery
timeFrame: duration of the surgery from the beginning of the surgery up to the end of the surgery
measure: duration of anesthesia
timeFrame: Intraoperative
measure: the consumption dose of hypotensive agents
timeFrame: Intraoperative
measure: desaturated and not desaturated patients among the groups
timeFrame: Intraoperative
measure: cerebral oxygen saturation
timeFrame: Intraoperative
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istanbul University, Department of Anesthesiology
Study officials:
affiliation: Istanbul University
name: Demet Altun
role: PRINCIPAL_INVESTIGATOR
References: