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Hypotension Drug-InducedPhase 4NCT02967029

Effect of Controlled Hypotension on Cerebral Oxygen Saturation

A Phase 4 study testing Esmolol Hydrochloride and Remifentanil Hydrochloride in people with Hypotension Drug-Induced and Cerebral Oxygen Saturation, run by Istanbul University at 1 site in Turkey (Türkiye).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
What is being tested?
Esmolol Hydrochloride and Remifentanil Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
1 siteTurkey (Türkiye)
Study dates
1 Nov 2016to 1 Aug 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Turkey (Türkiye)1 site
  • Istanbul University, Department of Anesthesiology

    Istanbul, 34093

Other trials in Turkey (Türkiye)

About this study

Official title: Effect of Controlled Hypotension on Cerebral Oxygen Saturation in Patients Undergoing Functional Endoscopic Sinus Surgery: a Prospective Randomized Single Blind Clinical Trial

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.

Read more

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.

Read the 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.

Being tested
Esmolol Hydrochloride, Remifentanil Hydrochloride
Medical subject headings
Hypotension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Esmolol HydrochlorideDrug

    Also called Brevibloc 10 MG/ML Injectable Solution

    the influence of brevibloc as a hypotensive agent on rSO2

  • Remifentanil HydrochlorideDrug

    Also called ultiva

    the influence of remifentanyl as a hypotensive agent on rSO2

Study groups in NCT02967029
Study groupRoleWhat they receive
b groupActive comparatorb group controlled hypotension with esmolol hydrochloride
Receives: Drug: Esmolol Hydrochloride
r groupActive comparatorr group controlled hypotension with remifentanil hydrochloride
Receives: Drug: Remifentanil Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. cerebral desaturation

    reduction of cerebral oxygen saturation to higher than 20 % of baseline for ≥ 15 seconds were recorded when MAP reached the desired range (50-60 mmHg)

    Measured: reduction of cerebral oxygen saturation to higher than 20 % of baseline for ≥ 15 seconds through surgery completion

Secondary outcomes (10)
  1. the quality of the surgical field

    the quality of the surgical field was recorded in terms of blood loss and dryness using a 10 point scale (0= no bleeding, virtually bloodless field; 10= uncontrolled bleeding) When MAP reached the desired range (50-60 mmHg) and was maintained for at least 10 minutes

    Measured: When MAP reached the desired range (50-60 mmHg) and was maintained for at least 10 minutes

  2. Arterial blood pressure

    Hemodynamic parameters as systolic, diastolic and mean arterial blood pressures were recorded preoperative, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents

    Measured: arterial blood pressure at baseline, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents through surgery completion

  3. Heart rate

    Hemodynamic parameters as heart rates were recorded preoperative, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents

    Measured: Heart rate at baseline, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents through surgery completion

  4. SPO2 value

    Hemodynamic parameters as SPO2 values were recorded preoperative, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents

    Measured: SPO2 value at baseline, after induction, peroperative and 5 and 10 minutes after stoppage of hypotensive agents through surgery completion

  5. cognitive function of the patients

    The cognitive function of the patients was assessed using Mini Mental State Examination (MMSE) test was recorded 1 hour before surgery and 120 minutes after the discontinuation of the drugs

    Measured: cognitive function of the patients were assessed 1 hour before surgery and 120 minutes after the discontinuation of the drugs

  6. the duration of surgery

    duration of the surgery was recorded from the beginning of the surgery to the end of the surgery

    Measured: duration of the surgery from the beginning of the surgery up to the end of the surgery

  7. duration of anesthesia

    duration of anesthesia was recorded from the monitoring of the patient to the extubation of the patient

    Measured: Intraoperative

  8. the consumption dose of hypotensive agents

    the consumption dose of hypotensive agents were recorded from the from the beginning of the infusion to the stoppage of the drugs

    Measured: Intraoperative

  9. desaturated and not desaturated patients among the groups

    desaturated and not desaturated patients were recorded patients among the groups during the controlled hypotension

    Measured: Intraoperative

  10. cerebral oxygen saturation

    cerebral oxygen saturation was recorded when mean arterial pressure reached the target range (50-60 mmHg)

    Measured: Intraoperative

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2016 (estimated)
  2. Study start1 Nov 2016
  3. Primary completion1 Jul 2017
  4. Study completion1 Aug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Screening
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02967029
Sponsor's protocol ID
IstanbulUn
Status last verified
Aug 2021
First submitted
7 Nov 2016
Last updated
1 Sep 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Esmolol Hydrochloride and Remifentanil Hydrochloride in people with Hypotension Drug-Induced and Cerebral Oxygen Saturation, run by Istanbul University at 1 site in Turkey (Türkiye).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

cerebral desaturation (time frame: reduction of cerebral oxygen saturation to higher than 20 % of baseline for ≥ 15 seconds through surgery completion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2021.

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