Comparative Study Between the Efficacy of Verapamil and Bisoprolol on Reduction of Bleeding During Endoscopic Sinus Surgery Under General Anaesthesia.

Early Phase 1

• Conditions: Heart Rate; Endoscopic Sinus Surgery; Blood Loss
• Interventions: Drug: Placebo oral tablet; Drug: Verapamil; Drug: Bisoprolol

• Registration Number: NCT04356196
• Lead Sponsor: Assiut University

Brief Summary

The study aims to compare the effect of addition of verapamil and Bisoprolol to general anasthesia aimed reduction in heart rate and blood loss during endoscopic sinus surgery.

Detailed Description

Intra-operative bleeding presents a larger obstacle to endoscopic visualization. Blood obscures the anatomy of the surgical field and dirties the endoscope lens causing greater difficulty with visualization. This situation increases the risk of complications, including brain injury, orbital or optic nerve injury, and catastrophic bleeding from major vessels (e.g., internal carotid artery) 1.

Endoscopic sinus surgery (ESS) is a minimally invasive technique used to restore sinus ventilation and function in patients with recurrent acute or chronic infective sinusitis in whom medical therapy has failed. The term ESS is used to draw attention to the potential for reestablishing natural mucociliary clearance mechanism, drainage and aeration of sinuses, whilst maintaining as much of the normal anatomy as possible. Over last few years this technique has become popular worldwide due to its minimally invasive nature and preservation of mucosa2.

Continued bleeding into the surgical field during ESS not only impairs endoscopic vision but can lead to complications3. Compared with conventional anesthesia, total intravenous anesthesia (TIVA) has been previously reported to result in reduced blood loss when used for FESS. However, few recent studies point out that TIVA may not significantly reduce blood loss 4-5.

Controlled hypotension has been used to reduce bleeding and the need for blood transfusions, and provide a satisfactory bloodless surgical field . Controlled hypotension is defined as a reduction of the systolic blood pressure to 80-90 mm Hg, a reduction of mean arterial pressure (MAP) to 50-65 mm Hg or a 30% reduction of baseline MAP 6. The physiological principle which underlies hypotensive anesthesia is a natural survival mechanism. When profuse bleeding occurs, the blood pressure drops. This drop leads to a reduction or cessation of the bleeding, blood pressure stabilization, and recovery. Accordingly, reducing the patient's blood pressure during surgery can potentially reduce

overall bleeding. Since bleeding in the surgical field is also reduced, the surgical field operating conditions are improved 7 .

Pharmacological agents used for controlled hypotension include those agents that can be used successfully alone and those that are used adjunctively to limit dosage requirements and, therefore, the adverse effects of the other agents. Agents used successfully alone include inhalation anaesthetics, sodium nitroprusside, nitroglycerin, trimethaphan camsilate, alprostadil (prostaglandin E1), adenosine, remifentanil, and agents used in spinal anaesthesia. Agents that can be used alone or in combination include calcium channel antagonists (e.g. nicardipine), beta-adrenoceptor antagonists (beta- blockers) \[e.g. bisoprolo, propranolol, esmolol\] and fenoldopam. Agents that are mainly used adjunctively include ACE inhibitors and clonidine. New agents and techniques have been recently evaluated for their ability to induce effective hypotension without impairing the perfusion of vital organs 8.

Calcium channel blockers are drugs that block the entry of calcium into the muscle cells of the heart and arteries. Thus, by blocking the entry of calcium, calcium channel blockers reduce electrical conduction within the heart, decrease the force of contraction (work) of the muscle cells, and dilate arteries which reduces blood pressure and thereby the effort the heart must exert to pump blood 9.

Although calcium channel blockers have a similar mechanism of action, they differ in their ability to affect heart muscle vs. arteries, and they differ in their ability to affect heart rate and contraction. For example; verapamil (Covera-HS, Verelan PM, Calan), reduces the strength and rate of the heart's contraction and are used in treating abnormal heart rhythms10.

Beta-blockers antagonise the effects of sympathetic nerve stimulation or circulating catecholamines at beta-adrenoceptors which are widely distributed throughout body systems. Beta1-receptors are predominant in the heart (and kidney) while beta2- receptors are predominant in other organs such as the lung, peripheral blood vessels and skeletal muscle11.

Study Timeline

• Study First Submitted: 2020-04-18
• Study First Submitted QC: 2020-04-21
• Study First Posted: 2020-04-22
• Study Start: 2021-06-15
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-21
• Last Update Posted: 2021-12-03
• Primary Completion: 2021-12-28
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

• Age of 18 - 60 years.
• patients of both genders.
• ASA grade I - II.

Exclusion Criteria

• Patient refusal.

• Any contraindication of B- blocker:

  1. Athma , COPD
  2. Bradycardia , Heart block
  3. Acute decompensated heart failure
  4. Peripheral vascular disease

• Any contraindication of calcium channel blocker:

  1. AV conduction defects (2nd and 3rd degree AV block).
  2. Sick sinus syndrome .
  3. Wolf-Parkinson-White Syndrome.
  4. History of congestive heart failure.
  5. Patients on long-term ß-blocker therapy.
  6. Patients with allergy to medication included in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo group	Placebo oral tablet	45 patients will receive placebo tablet PO 3 hours preoperative .
Verapamil group	Verapamil	45 patients will receive 80 mg oral verapamil 3 hours pre-operative
Bisoprolol group	Bisoprolol	45 patients will receive Bisoprolol 5mg PO 3 hours preoperative

Primary Outcome Measures

Name	Time	Method
Estimated Blood Loss	end of operation assessment	Estimated blood loss in milliliters per hour is calculated by subtracting the volume of total irrigation used during the case from the total amount of fluid in the suction canister at the end of surgery dividing by surgical time in hours.
Heart Rate	intraoperative	heart beats for minutes

Secondary Outcome Measures

Name	Time	Method
plasma norepinephrine concentrations	baseline before Anastasia ( in the holding area with insertion of I.V. cannula) and three hours after the end of surgery.	plasma norepinephrine concentrations measured by enzyme immunoassay as venous blood samples about 4ml will be collected from each patient under aseptic condition
serum cortisol concentrations	baseline before Anastasia ( in the holding area with insertion of I.V. cannula) and three hours after the end of surgery.	serum cortisol will be measured by enzyme immunoassay as venous blood samples about 4ml will be collected from each patient under aseptic condition
The Boezaart and van der Merwe intraoperative surgical field scale	Every 15 minutes for the duration of surgery	Boezaart Bleeding Scale (BBS) (0 - no bleeding (cadaveric conditions), 1 - Slight bleeding, no suctioning required, 2 - Slight bleeding, occasional suctioning required, 3 - Slight bleeding, frequent suctioning required; bleeding threatens surgical field a few seconds after suction is removed, 4 - Moderate bleeding, frequent suctioning required, and bleeding threatens surgical field directly after suction is removed, 5 - Severe bleeding, constant suctioning required; bleeding appears faster than can be removed by suction; surgical field severely threatened and surgery usually not possible).

Trial Locations

Locations (1)

Faculty of medicine Assiut university; 🇪🇬 Assiut, Egypt