Clinical trial NCT03850093: Preoperative Gabapentin Versus Bisoprolol for Hemodynamic Optimization During Sinus Surgery
Official title: Preoperative Gabapentin Versus Bisoprolol for Intraoperative Hemodynamic and Surgical Field Optimization During Endoscopic Sinus Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Blood Pressure
Keywords: gabapentin
bisoprolol
hemodynamic
surgical field
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2019-02-21
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: the current study hypothesized that Gabapentin can be effective as Bisoprolol in reduction of intraoperative bleeding, improving the operative's field visibility and increase the surgeon satisfaction via optimization of blood pressure and heart rate .

A prospective randomized double blinded controlled study. Eligible patients were randomized according to random list generated software and allocated into 3 equal and matched groups (15 patients in each group):-

* Group G: gabapentin group in which Patients were premedicated with oral gabapentin 1200 mg (Conventin 400mg; Evapharm) with sips of water, 2 hours before induction of anesthesia.
* Group B: bisoprolol group in which Patients were premedicated with oral bisoprolol 2.5 mg ( Concor 2.5mg ; Merck/Amoun ) with sips of water, 2 hours before induction of anesthesia.
* Group C: control group in which Patients were premedicated with oral placebo with sips of water, 2 hours before induction of anesthesia.

Detailed description: Hypothesis:

Gabapentin can be effective as Bisoprolol in reduction of intraoperative bleeding, improving the operative's field visibility and increase the surgeon satisfaction via optimization of blood pressure and heart rate.

Objectives Compare the effect of preoperative Gabapentin with Bisoprolol on hemodynamics, surgical field optimization during endoscopic nasal surgeries.

Technical design:

A) Site of study :

The study was conducted at Anesthesia and Surgical intensive care and Otorhinolaryngology departments, faculty of medicine, Zagazig University.

B) Sample Size :

According to 80% power of the study, 95% CI and calculated volume of blood loss 200±40 ml and 150±55ml on Gabapentin (22) and Bisoprolol (15) premedication respectively, the estimated Sample size was 54 patients (open EPI) , 63 patients were included in the study to compensate for drop out.

Randomization was carried out on 63 patients to compensate for drop out . All planned ESS procedures was managed by the same anesthetist and surgeon who were blinded to the used study's premedication. The surgeon was blinded to the monitor recording the hemodynamic variables.

All patients had been preoperatively evaluated according to standard local protocol. Preoperative surgical preparation and proper management of infection were confirmed to every patient.

Patient was premedicated by IV ranitidine 50 mg, midazolam 0.05 mg/kg and atropine 20µg/kg immediately before admission to the operating room.

On admission to the operating room, Standard monitoring included 5 leads ECG, non-invasive blood pressure, Pulse Oximetry and End-tidal carbon dioxide (ETCO2) trace were applied (B40i Monitor - GE Healthcare, Finland).

Anesthesia was induced with IV propofol 2 mg/kg and fentanyl 1 µg/kg was given for analgesia. Cisatracurium 0.15 mg/kg IV was given to facilitate direct laryngoscopy and orotracheal intubation. The patient was ventilated at tidal volume 6-8mL/kg and respiratory rate that achieved ETCO2 of 30-35 mmHg. Oropharyngeal pack was inserted.

Anesthesia was maintained by isoflurane based on MAC 1.2 % until a steady state of anesthesia was achieved (defined as a state of anesthesia when no changes in hemodynamic variables take place for at least 10 min). An increase of ≥ 20% of basal value in both HR and MAP was treated with increasing the concentration of isoflurane by 0.5% and increments of fentanyl 1 μg/kg. Muscle relaxation was confirmed by cisatracurium 0.03mg/kg every 20 mins. IV lactated ringer solution was infused at approximately 6ml/kg/hr till the end of the procedure.

All patients were positioned supine and the bed-head of the surgical table was raised by 30° to improve venous drainage.

Before the beginning of surgical procedure, well wrung out cotton pledgets soaked with 4 ml of 2% lignocaine with 1:200,000 adrenaline were topically applied to the nasal mucous membrane for 10 min (no infiltration).

Technique for hemodynamic optimization:

Target mean arterial pressure (MAP) was 60-70 mmHg during the surgical procedure to achieve Fromm and Boezaart category scale of 2 or 3 which is judged to be optimal for surgery (20).

If the MAP was still ˃70mmHg in spite of increasing isoflurane inhalation to 2.5%, nitroglycerine (1-10 μg/kg/min.) titrated to effect.

If the heart rate was more than 100 beats/ minute, propranolol was titrated 1-3 mg/hour to achieve target MAP.

If mean arterial pressure (MAP) decreased to less than 60 mm Hg, ephedrine in increments of 3 mg was given.

Withdrawal vasoactive agents:

After recording the surgeons' opinion regarding the surgical field and about 15 minutes before ending surgery, the infusion of any vasoactive medication (if used) was stopped and the anesthetic agent was decreased allowing HR and MAP to return to their basal value. If Hypotension (defined as SAP\< 90mmHg and bradycardia less than 60 bpm) persisted, they was treated by ephedrine in increments of 3 mg .

On compilation of surgical procedure, anesthesia was discontinued and reversal of neuromuscular blockade was achieved using IV neostigmine 0.08 mg/kg and atropine 20µg/kg. After removal of oropharyngeal pack, oropharyngeal suction was performed. On the start of obeying commands, patients were extubated and shifted to recovery room.

Patients were discharged to the ward after reaching a score ≥ 9 on the Modified Aldrete Scoring System.

During postoperative period up to 6 hours, the patient was monitored for conscious level, oxygen saturation, heart rate and mean arterial blood pressure.

On ward admission, IM diclofenac sodium 75mg was given then every 12 hours. If the patient complained moderate to severe pain (VAS≥ 4) meperidine 25mg increments up to pain relief (maximum 100mg as a single dose) was given.

Eligibility criteria: Inclusion Criteria:

* patients who underwent functional endoscopic sinus surgery
* ability to swallow tablets

Exclusion Criteria:

* suspected difficult airway
* basal HR \<60/min.
* chronic cardiovascular or cerebrovascular disease
* bronchial asthma or COPD
* DM
* bleeding disorders
* anemia (Hb level\< 10 gm/dl)
* renal or hepatic insufficiency
* psychiatric disorders
* chronic treatment by BBs, gabapentin or drugs that affect coagulation
* acute nasal infection
* allergy/contraindications to any of the study's drugs.

Primary outcomes:
measure: Changes in Surgical Field Visibility
timeFrame: scale was assessed by the surgeon every 15 minutes from the start of surgical procedure till the end
measure: Blood Loss
timeFrame: at the end of surgery
Secondary outcomes:
measure: Heart Rate Change
timeFrame: were recorded before oral premedication (baseline), pre-induction, after induction of anesthesia, 1, 5, 10, 15 minutes after intubation and then every 15 minutes until the end of surgery
measure: Mean Arterial Blood Pressure Change
timeFrame: were recorded before oral premedication (baseline), pre-induction, after induction of anesthesia, 1, 5, 10, 15 minutes after intubation and then every 15 minutes until the end of surgery
Other outcomes:
measure: Surgeon Satisfaction (Categorical)
timeFrame: at the end of surgery
measure: Number of Patients Who Recieved Intraoperative IV Nitroglycerin During Operative Procedure
timeFrame: at the end of surgery
measure: Number of Patients Who Recieved Intraoperative IV Propranolol During Operative Procedure
timeFrame: at the end of surgery
measure: Number of Patients Who Recieve Both IV Nitroglycerin and Propranolol During Operative Procedure
timeFrame: at the end of surgery
measure: Visual Analogue Scale (VAS) for Postoperative Pain
timeFrame: 1, 3 and 6 hrs. after recovery
measure: Visual Analogue Scale (VAS) for Postoperative Pain
timeFrame: 0n full recovery, 3 and 6 hrs. after recovery
measure: Time to 1st Postoperative Rescue Analgesia
timeFrame: on administration of 1st postoperative rescue analgesia
Locations:
Study officials:
affiliation: faculty of medicine - Zagazig university
name: Abeer M. Elnakera, doctorate
role: PRINCIPAL_INVESTIGATOR
affiliation: Zagazig University
name: Ayman A. Hassan, doctorate
role: STUDY_CHAIR
affiliation: Zagazig University
name: Maram wagdy, Master
role: STUDY_CHAIR
affiliation: Zagazig University
name: Mohamed W. El-Anwar, doctorate
role: STUDY_CHAIR
References: