Dexamethasone Versus Dexmedetomidine

PATIENTS AND METHODS:

This study will be performed on Fifty-four adult patients who will be undergone an abdominal hysterectomy after obtaining the approval of the local ethical committee and scientific institutional review board. written informed consents will be signed from each patient before enrollment and randomization into the study.

The patients will be randomly allocated to receive either a mixture of bupivacaine and dexamethasone 8 mg (group A, 27 patients) or a mixture of bupivacaine and dexmedetomidine 80 µg (group B, 27 patients). Randomization will be performed by using a computer-generated random number list. The random number for each patient will be concealed in opaque sealed envelope which will be opened by the investigators shortly after the admission of the patient into the operation room. The investigators sharing in the patients care and data acquisition will be blinded to groups allocation till full completion of statistical analysis.

Preoperative preparation:

Visual analog scale (VAS) will be explained to all the patients on preoperative visit (0-10 cm, in which 0 cm = no pain and 10 cm = worst pain) and the compulsory investigations according to the regular institutional protocol will be done [electrocardiogram (ECG), complete blood count (CBC), blood sugar level, serum urea and creatinine, liver function tests, and coagulation profile].

On the day of surgery, intravenous (IV) access will be inserted. The patient will be administered midazolam 0.03 mg/kg, metoclopramide 10 mg slowly, ranitidine 50 mg, and cefotaxime 1 gm intravenously (IV) as premedications.

Anesthetic technique:

All the patients will be received a standard general anesthesia with standard monitoring [ECG, noninvasive blood pressure (NIBP), capnography and pulse oximetry]. Anesthesia will be induced by using fentanyl 1μg/kg, propofol 1.5-2 mg/kg and Atracurium 0.5 mg/kg will be used for muscle relaxation to facilitate endotracheal intubation by cuffed endotracheal tube (internal diameter = 7 mm).

After induction of anesthesia and under a complete aseptic condition, the TAP blocks will be performed by the attending anesthesiologists who will not participate in this trial under real-time ultrasound guidance (Philips ClearVue 350 Ultrasound Machine, Philips healthcare, USA). At the level of the umbilicus, the high-frequency ultrasound linear array probe (L4 - 12) will be placed transversely on the anterolateral abdominal wall between the subcostal margin and the iliac crest. Identification of the external oblique, the internal oblique, and the transversus abdominis muscles and localization of the fascial plane between the internal oblique and the transversus abdominis muscle that appeared as a hypoechoic line will be done. The local anesthetic solution mixture will be injected with short bevel needle (22 Gauge, 90 mm sonoplex stim cannula, Pajunk® GmbH, Geisingen, Germany) under real-time ultrasound guidance after negative aspiration to avoid intravascular injection. The local anesthetic solution mixture will be observed separating the fascial plane during injection. The TAP block will be then performed on the opposite side, using the same technique and the same local anesthetic solution mixture volume. For the patients randomized to group A (dexamethasone group, 27 patients), the local anesthetic solution mixture consisted of a total volume of 40 ml bupivacaine 0.25 % and dexamethasone 8 mg, 20 ml injected on each side. Dexamethasone sodium phosphate (Epidron®, EIPICO, Cairo, Egypt) is supplied in 4 mg/ml ampule. For the patients randomized to group B (dexmedetomidine group, 27 patients), the local anesthetic solution mixture consisted of a total volume of 40 ml bupivacaine 0.25 % and dexmedetomidine 80 µg, 20 ml injected on each side. Dexmedetomidine hydrochloride (Precedex®, manufactured by Hospira, Inc. Lake Forest, IL, and USA) is supplied in 100 μg/ml ampule. the local anesthetic solution mixture will be prepared and coded by independent attending anesthesiologists who will not share in data collection or in patients care.

Anesthesia will be maintained with isoflurane 1.5 volume % and Atracurium 0.1 mg/kg will be administered as a maintenance dose every 30 minutes until completion of the procedure. Ventilation parameters will be adjusted as follows: tidal volume (TV) = 4-8 ml/kg, positive end-expiratory pressure (PEEP) = 5 cm H2O, respiratory rate (RR) = 12/min then it will be adjusted to maintain end-tidal CO2 between 35-40 mmHg, and fraction of inspired oxygen (FiO2) = 0.5-0.6.

Fentanyl 0.5μg/kg will be given intraoperatively when either heart rate or NIBP increased by more than 20% of the basal records and could be repeated till the desired effect. After completion of the procedure, anesthesia will be discontinued and tracheal extubation will be done once the extubation criteria will be fulfilled. The patients then will be transferred to the post-anesthesia care unit (PACU) for two hours' observation period. The patients will be discharged to the ward after fulfilling the discharge criteria based on modified Aldrete score ≥ 9.(17) As a part of standardized regular institutional postoperative pain control policy, Acetaminophen 1 gm every 6 hours by IV infusion and ketorolac 30 mg diluted in 100 ml normal saline through IV infusion over 20 minutes every 8 hours will be administered. Patients with VAS ≥ 5 received morphine sulfate IV at a bolus dose of 2-5 mg increments with a maximum dose of 15 mg per 4 hours or 45 mg per 24 hours. The criteria to stop morphine titration will be reasonable pain control or the patient became sedated (Ramsay sedation scale >2). Furthermore, respiratory rate < 10 / min, Oxygen saturation < 95%, or development of serious adverse effects (allergy, marked itching, excessive vomiting, and hypotension with systolic blood pressure ≤ 20% of baseline readings).

STATISTICAL ANALYSIS:

The normally distributed numerical data will be presented as mean (SD) and differences between groups will be compared using Student's t-tests. Continuous data with skewness and kurtosis as well as the ordinal data will be presented as median (interquartile range[IQR]) and compared for significance by using the Mann-Whit¬ney U test. The Kolmogorov-Smirnov test will be implemented to check the normality of Continuous data distribution (P ≤ 0.05). Categorical data will be presented as proportions and will be compared for significance by using the chi-square test. Fisher's exact test will be used instead if the minimum expected cell count less than five. We will use the log-rank test and Kaplan-Meier curves to compare data measuring time to an event. The level P ≤ 0.05 will be considered the cut-off value for significance. Statistical analysis will be performed using the statistical package for the social sciences (SPSS) version 16 (SPSS Inc., Chicago, IL, USA).

The sample size of 22 patients per group was found acceptable to detect a difference of 65 minutes between both groups in time for the first request of analgesia (primary outcome), assuming α = 0.05 (two tail), β = 0.2 (80 % power), and the standard deviation = 75 minutes (derived from Ammar et al. 2012). Recruitment of 27 patients per group will be done to account for possible data loss. Sample size calculation will be done by using G*Power software version 3.1.9.2 (Institute of Experimental Psychology, Heinrich Heine University, Dusseldorf, Germany).