Effect of Selenium on Succinylcholine-Induced POM

Eligibility and type of the study: This prospective randomized placebo-controlled double-blind study will be conducted after approval from the Institutional Ethics Committee and obtaining written informed consent from patients scheduled for elective adult sinuscopic procedures under general anesthesia. This study will be conducted at Assiut University Hospital from April 2018 until April 2019.

Sample size: Sample size calculation is based on the pilot study, where the incidence of POM in outpatient cases is found to be more than 70% and intervention that can cause 25-50% reduction in incidence of POM will be interesting. With a power of 90% and type I error of 5%, 37 patients will be required in each group (α=0.05 and β=90%). But to avoid possible loss of samples (dropouts) during the study, the number of patients in each group will be increased to 40 to be a total of 80 patients.

Drugs coding and Randomization: Patients will be randomly allocated to two equal groups with the help of a computer-generated table of random numbers to receive the study drugs. All capsules will be removed from their strips and will be stored in envelopes numbered from 1 to 80. The envelopes will be numbered and randomized according to the computer-generated randomization tables to ensure an equal number of patients in each arm. Access to the envelopes codes will be only available to one anesthesiologist who will pack the envelopes. The anesthetic technique and outcome data will be collected by an anesthesiologist not included in giving study drugs or envelops coding.

Patients: Eighty patients will be enrolled in this study. They will be equally divided into two groups:

- Group C (control group): 40 patients will receive starch capsules orally with sips of water 2 hours before induction of anesthesia.

- Group S (Selenium group): 40 patients will receive Selenium (selenium NATURE'S BOUNTY, INC. Bohemia) 200 mcg orally with sips of water 2 hours before induction of general anesthesia.

Anesthetic Technique and Data Collection: Two days before surgery, patients will visit the outpatient clinic for history taken, clinical assessment and explanation about the study protocol. Laboratory investigations will be performed and patients will be informed that they can stop participation in the study at any time without any loss of service.

With no pre-medications and 2 hours before sinuscopies, the study drug will be given to all patients by another anesthesiologist blinded to the envelops coding. No IM injections will be administered during the perioperative period.

Inside the operating room, standard monitoring (electrocardiogram, non-invasive blood pressure, heart rate, peripheral oxygen saturation) will be attached and the preliminary values will be recorded. An intravenous cannula 18G will be inserted and secured in the dorsum of the non-dominant hand and intravenous fluids (NaCl 0.9%) was started at the calculated volume and rate. After 3 minutes of 100% pre-oxygenation via facemask, anesthesia will be induced with fentanyl 1 mcg/kg, propofol 2.0 mg/kg (diluted with normal saline 0.9%) and succinylcholine 1.5 mg/kg.

Fasciculations Assessment:

The intensity of fasciculations will be assessed by an anesthesiologist blinded to the patient's group allotment based on a four-point scale.

After end of fasciculations, the values of heart rate, non-invasive blood pressure and oxygen saturation will be measured and recorded.

Patients will be intubated with an appropriate size cuffed endotracheal tube under direct laryngoscopy after complete muscular relaxation. The endotracheal tube then will be fixed at the appropriate length, by adhesive tape at the angle of the mouth. After 5 minutes of tracheal intubation, the previous values in addition to the EtCO2 will be recorded. Subsequent values will be recorded every 5 minutes throughout the surgical procedure. Anesthesia will be maintained with oxygen 100% and sevoflurane (2-4% MAC). The respiratory tidal volume will be adjusted to keep end-tidal CO2 at 35-40 mmHg. The same surgical team will complete all surgical procedures. Atend of surgery and before extubation, all patients will receive infraorbital block by bupivacaine 0.25% 1 ml each side.

At the end of the procedure, sevoflurane inhalation will be discontinued and all patients will be ventilated by 100% oxygen until full consciousness regains and following verbal commands. At that point, endotracheal tubes will be removed after gentle suction of secretions through the tube and the oropharyngeal cavity. After the desired spontaneous ventilation, the patients will be transferred to post-anesthesia care unit (PACU).

In PACU, postoperative care will be standardized for all patients. Pain related to POM will be treated with paracetamol 1g intravenously (Perfalgan; Bristol-Myers Squibb, New York, USA) when NRS more than or equal 4. The total dose of analgesic requirement in the first 24 hours will be recorded. After meeting the discharge criteria, the patients will be discharged to be taken home and cared for, by a responsible adult.

Myalgia Assessment:The incidence and severity of myalgia in all patients will be determined 24 hours after surgery by an anesthesiologist who is unaware of the grouping. Myalgia is defined as "a pain with no surgical interference" and is graded based on a four-point scale.

Pain Assessment:

All pain scores will be obtained during rest. To assess postoperative pain, Numeric rating scale (NRS) will be used. The NRS is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of their pain. The common format is a horizontal bar or line. An 11-point numeric scale (NRS 11) with 0 representing one pain extreme (e.g., "no pain") and 10 representing the other pain extreme (e.g., "pain as bad as you can imagine" and "worst pain imaginable"). NRS will be used immediately at the recovery room, 1, 2, 4, 6, 12 and 24 hours postoperatively

Laboratory Study:

Glutathione peroxidase measurement in plasma will be assessed in venous blood sample of all included patients (4 ml) under complete aseptic conditions at two events; baseline before induction of anesthesia (in the holding area after IV canula insertion) and 6, 24 hours after induction of anesthesia.

Assessment of possible complications:

Any complications like postoperative nausea, vomiting, headache, dizziness, somnolence, vertigo, confusion will be recorded and managed accordingly. Nausea will be treated by 10 mg metoclopramide intravenously, vomiting will be treated by 4 mg ondansetron intravenously.

Statistical Analysis:

Data will be performed using a standard SPSS software package version 21 (SPSS Inc., Chicago, Illinois, USA). Data will be expressed as mean ± SD, numbers (n), percentages (%) and median (range). The demographic data will be analyzed by Student t-test. Patient data will be analyzed with the Chi square test. The consumption of analgesia in groups will be analyzed by using Student t-test. The incidence and severity of fasciculation and POM will be analyzed using Fisher's exact test. Pearson's r correlation will be used to test the correlation between fasciculations and postoperative myalgia. A p-value of <0.05 will be considered statistically significant.

Ethical Considerations:

- Patients will be informed about the nature and steps of the study.

- Any patient can stop participation in the study at any time without any loss of service.

- There is no risk affecting the patients participating in this study.

- Any data taken from all patient will be made confidential and available only to persons conducting the study.

- Written consent will be obtained from each patient after approval from our institutional ethical committee.

- All of the regulations of the local ethics committee of Faculty of Medicine, Assiut University will be followed.