Effects of adjuvant ozone autohemotherapy combined with routine treatment on clinical and paraclinical features of mechanically ventilated COVID-19 patients in the intensive care unit: a pilot randomized controlled trial.

Until the availability of an effective and practical vaccine, there is a serious need to recognize alternative treatments for coronavirus disease 2019 (COVID-19). This study aimed to determine whether major ozonated autohemotherapy (MOAH) can improve the clinical and paraclinical parameters in critically-ill patients with COVID-19 requiring mechanical ventilation. In this controlled trial, we enrolled 40 critically ill COVID-19 patients receiving invasive mechanical ventilation. The enrolled patients were then randomized into the MOAH and control groups. The patients in the MOAH group received MOAH three times per week (10 times in total) in addition to routine treatment and standard critical supportive care. Patients in the control group were only given regular treatment and standard critical supportive care. The patients in the MOAH group had more days of breathing with no aid than those in the control group. Moreover, the length of stay in the intensive-care unit was significantly lower in the MOAH group than in the control group. MOAH resulted in higher ventilation-free days and less intensive-care unit stay compared with the control treatment. In COVID-19 patients undergoing mechanical ventilation, MOAH with routine treatment resulted in more ventilator-free days and less intensive-care unit stay compared with the standard therapy.

Autologous conditioned serum (Orthokine) injection for treatment of classical trigeminal neuralgia: results of a single-center case series.

BACKGROUND: Despite some advances, treatment of trigeminal neuralgia remains a significant challenge. This study determines the efficacy and safety of autologous conditioned serum (Orthokine) injection into the foramen oval to treat refractory trigeminal neuralgia. CASE PRESENTATION: This is a consecutive case series from the Pain and Palliative Care Department of Imam Reza University Hospital, Tabriz, Iran. Eleven Iranian patients, eligible according to the inclusion and exclusion criteria, aged 45.64 ±â€Š11.58 years (Four male and seven female, all Iranian) with established classical trigeminal neuralgia were injected with Orthokine (2 mL per injection) once a week for three consecutive weeks (total of four injections). Numeric rating scale scores for facial pain intensity and also carbamazepine daily dose were confirmed at pretreatment (T0) and at week 1 (T1), week 2 (T2), week 3 (T3), week 4 (T4), and month 2 (T5) posttreatment. Pain intensity was significantly reduced in the first 3 weeks of follow-up in comparison with baseline (T0 to T3) (8.18 ± 1.99 to 2.82 ± 2.13, p < 0.001), an effect that was retained at week 4 (T4) and month 2 (T5) follow-ups (2.82 ± 2.13 to 3.36 ± 2.69, p = 0.886). Carbamazepine consumption was significantly reduced in the first 3 weeks of follow-up in comparison with baseline (T0 to T3) (636.36 ± 307.48 to 200.00 ± 296.64, p = 0.003), an effect that was retained at week 4 and month 2 follow-ups (200.00 ± 296.64 to 200.00 ± 282.84, p = 0.802). There were no serious adverse events in participants. CONCLUSION: Orthokine injection led to consistent pain relief and reduced carbamazepine dosage in patients with trigeminal neuralgia, with acceptable safety.

The Preventive Effects of Boron-Based Gel on Radiation Dermatitis in Patients Being Treated for Breast Cancer: A Phase III Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Radiation dermatitis (RD) is a side effect of radiation therapy (RT) which is experienced by over 90% of patients being treated for breast cancer. The current clinical trial was conducted to measure the preventative effects of a boron-based gel on several different clinical outcomes (dermatitis, erythema, dry desquamation, and moist desquamation) after 25 radiotherapy sessions. METHODS: This research used a double-blind parallel-group design with a placebo control (n = 76) and randomized group (n = 181), with all participants being between 18 and 75 years old. Fifteen minutes before each radiotherapy, participants in the intervention group were given a gel containing 3% sodium pentaborate pentahydrate, while those in the placebo group received a gel with no chemical substance. Dermatitis, erythema, dry desquamation, and moist desquamation were compared between the 2 groups. RESULTS: At baseline, there were no significant differences between the groups (p > 0.05), except for body mass index. After 14 days of treatment, dermatitis (98.7% vs. 9.9%; p < 0.001), erythema (96.1% vs. 12.2%; p < 0.001), dry desquamation (50% vs. 3.9%; p < 0.001), and moist desquamation (18.4% vs. 0.6%; p < 0.001) were much more common in the placebo group than the intervention group. To prevent dermatitis, erythema, dry desquamation, and moist desquamation in 1 patient, on average, 1.1 (95% confidence interval [CI]: 1.1-1.2), 1.2 (95% CI: 1.1-1.3), 2.2 (95% CI: 1.7-2.9), and 5.6 (95% CI: 3.8-11.0) patients need to be treated, respectively. CONCLUSION: The boron-based gel has a significant preventive effect on several categories of RD which might be used by clinicians in breast cancer.

Lower serum levels of alpha tocopherol and lycopene are associated with higher pain and physical disability in subjects with primary knee osteoarthritis: A case-control study.

Background: We aimed to determine dietary intake and serum concentration of α-tocopherol and lycopene in subjects with knee osteoarthritis (KOA) in relation to pain intensity and functional status and comparing them with healthy controls. Methods: This case-control study was conducted among 35 patients with primary KOA and 35 matched healthy subjects selected using convenience sampling method. Dietary intakes of alpha-tocopherol and lycopene were estimated from 24-hour dietary records. Visual Analogue Scale (VAS) and Western Ontario and McMaster (WOMAC) index were used to assess the pain and functional status, respectively. Results: Serum concentrations of alpha-tocopherol (0.024 ± 0.005 vs. 0.028 ± 0.007 µmol/ml, p-value =  0.021) and lycopene (0.616 ± 0.191 vs. 0.727 ± 0.159 µmol/l, p-value = 0.011) were significantly lower in OA patients in comparison with healthy controls. Dietary intake of alpha-tocopherol was negatively associated with total WOMAC score (r = -0.401, p-value = 0.021) and pain (r = -0.356, p-value = 0.042) and physical function (r = -0.355, p-value = 0.043) subscales. Dietary intake of lycopene was negatively associated with total WOMAC score (r = -0.616, p-value < 0.001) and pain (r = -0.348, p-value = 0.047) and physical function (r = -0.606, p-value < 0.001) subscales. Additionally, serum concentration of alpha-tocopherol was negatively associated with total WOMAC score (r = -0.574, p-value < 0.001) and physical function subscale (r = -0.571, p-value < 0.001). Serum concentration of lycopene was negatively associated with total WOMAC score (r = -0.360, p-value = 0.040) and physical function subscale (r = -0.350, p-value = 0.046) Conclusion: Serum concentrations of α-tocopherol and lycopene were significantly lower in patients with KOA than in healthy controls. Significant negative association was detected between serum concentration and dietary intake of α-tocopherol and lycopene with functional disability in patients with KOA.

Nutraceutical supplements in management of pain and disability in osteoarthritis: a systematic review and meta-analysis of randomized clinical trials.

This study designed to evaluate the effect of nutraceutical supplementation on pain intensity and physical function in patients with knee/hip OA. The MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, Google Scholar, Science direct, and ProQuest in addition to SID, Magiran, and Iranmedex were searched up to March 2020. Records (n = 465) were screened via the PICOS criteria: participants were patients with hip or knee OA; intervention was different nutritional supplements; comparator was any comparator; the outcome was pain intensity (Visual analogue scale [VAS]) and physical function (Western Ontario and McMaster Universities Arthritis [WOMAC] index); study type was randomized controlled trials. The random effects model was used to pool the calculated effect sizes. The standardized mean difference (SMD) of the outcome changes was considered as the effect size. The random effects model was used to combine the effect sizes. Heterogeneity between studies was assessed by Cochran's (Q) and I2 statistics. A total of 42 RCTs were involved in the meta-analysis. Nutritional supplementation were found to improve total WOMAC index (SMD = - 0.23, 95% CI - 0.37 to - 0.08), WOMAC pain (SMD = - 0.36, 95% CI - 0.62 to - 0.10) and WOMAC stiffness (SMD = - 0.47, 95% CI - 0.71 to - 0.23) subscales and VAS (SMD = - 0.79, 95% CI - 1.05 to - 0.05). Results of subgroup analysis according to the supplementation duration showed that the pooled effect size in studies with < 10 months, 10-20 months and > 20 months supplementation duration were 0.05, 0.27, and 0.36, respectively for WOMAC total score, 0.14, 0.55 and 0.05, respectively for WOAMC pain subscale, 0.59, 0.47 and 0.41, respectively for WOMAC stiffness subscale, 0.05, 0.57 and 0.53, respectively for WOMAC physical function subscale and 0.65, 0.99 and 0.12, respectively for VAS pain. The result suggested that nutraceutical supplementation of patients with knee/hip OA may lead to an improvement in pain intensity and physical function.

Dietary inflammatory index is associated with pain intensity and some components of quality of life in patients with knee osteoarthritis.

OBJECTIVES: We aim to measure dietary inflammatory index (DII) and its association with functional status, pain intensity and quality of life (QOL) in patients with knee osteoarthritis (KOA). Dietary information from 220 qualified patients with KOA was collected by a 168-item food frequency questionnaire. The functional status, pain intensity and QOL were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, Visual Analogue Scale (VAS) and SF36 questionnaire respectively. RESULTS: Linear regression analysis showed that the DII was significantly associated with VAS (p = 0.040; ß = 0.151), and physical function (p = 0.039; ß = - 0.184), emotional wellbeing (p = 0.048; ß = - 0.158) and pain (p = 0.020; ß = 0.161) scales and physical health (p = 0.047; ß = 0.110) subscale of QOL after adjusting for age, sex, body mass index, and physical activity. There was no significant differences concerning WOMAC across the DII tertiles with and without adjustment to probable confounders (Ptrend = 0.091 and 0.181, respectively). After adjustment, a significantly increased severe pain odds was observed in the highest tertile of DII score in comparison with the lowest tertile (OR tertile 3 vs. 1 = 1.55, 95% CI 1.04-2.31; Ptrend = 0.04).

Pilot prospective open-label one-arm trial investigating intrathecal Adenosine in neuropathic pain after lumbar discectomy.

OBJECTIVES: Adenosine has an analgesic and anti-inflammatory role and its injections are used for perioperative pain management. We aimed to study efficacy of intrathecal injection of adenosine for post-operative radicular pain after lumbar discectomy. Forty patients with unilevel lumbar discectomy who had radicular lower limb pain were treated by 1000 micrograms of intrathecal injection of adenosine in this single-arm prospective open-label trial between November 2015 to October 2016. Radicular pain severity using visual analogue scale (VAS) and pain killer consumption per day were assessed during a 3 months follow up period. RESULTS: Radicular pain severity was significantly reduced in 3 month follow-up period in comparison to the baseline (F = 19,760, df = 2.53, p-value < 0.001). Further, painkiller medication consumption rate in average during 3 month follow-up period after injection was significantly lower in comparison to baseline (F = 19.244, df = 1.98, p-value < 0.001). This study suggests that intrathecal injection of 1000 micrograms adenosine is a safe and effective method for post-operative neuropathic pain management after uni-level disk surgeries. Trial registration IRCT201608171772N20, Retrospectively registered on 2016-08-28.

Ginger (Zingiber officinale) and turmeric (Curcuma longa L.) supplementation effects on quality of life, body composition, bone mineral density and osteoporosis related biomarkers and micro-RNAs in women with postmenopausal osteoporosis: a study protocol for a randomized controlled clinical trial.

OBJECTIVES: Phytomedicine is widely suggested for the prevention of chronic disease, but evidence for a favorable effect on bone health is lacking. The present study will investigate the Zingiber officinale (ZO) and Curcuma longa L. (CL) supplementation effects on quality of life, body composition, bone mineral density (BMD) and osteoporosis related biomarkers and micro-RNAs in women with postmenopausal osteoporosis (PMO). METHODS: This study protocol is designed as prospective triple-blind randomized controlled trial. One hundred and 20 patients with PMO will be enrolled in a 4 month, prospective, triple-blind, placebo-controlled trial and randomly assigned to four groups: ZO (500 mg b.i.d.) + CL (500 mg b.i.d.) (ZO + CL); ZO (500 mg b.i.d.) + placebo CL (b.i.d.) (ZO + P); placebo ZO (b.i.d.) + CL (500 mg b.i.d.) (CL + P); and placebo ZO (b.i.d.) + placebo CL (b.i.d.) (P + P). Quality of life, body composition and BMD will be defined as the primary endpoints and osteoporosis related serum biomarkers and circulating micro-RNAs will be defined as the secondary endpoints. The ANCOVA statistical method will be used to investigate the effect of the interventional variables on the response variable. CONCLUSION: To our knowledge, this trial is the first clinical study exploring the effect of Ginger and turmeric on quality of life, body composition, BMD and osteoporosis related biomarkers and micro-RNAs in women with PMO. The findings of this trial could be the basis for the development of harmless and inexpensive preventive and therapeutic approaches for PMO.

Nutrition knowledge and attitude in medical students of Tabriz University of Medical Sciences in 2017-2018.

OBJECTIVES: In this cross-sectional study among 220 medical students we aimed to determine the nutritional knowledge and attitude of medical students through clinical training courses (externship and internship) of Tabriz University of Medical Sciences, Iran. A nutritional knowledge questionnaire included 51 questions was used to determine the correct, perceived and accuracy of knowledge of the participant in different aspects of nutrition sciences. The nutrition attitude questionnaire included 30 questions. Both questionnaires were confirmed in terms of the validity and reliability for assessing nutritional knowledge and attitude in this sample of Iranian medical students. Nutritional knowledge and attitude were calculated as percentage of correct or appropriate responses. RESULTS: The correct knowledge was not significantly different among externs and interns (68.20 ± 7.50% and 67.87 ± 6.04% respectively, p = 0.729). Results showed that most of the participants (49.61% of externs and 57.14% of inters) had a poor nutritional knowledge, significantly varied by age (p = 0.035). The attitude index of the subjects was not significantly different among externs and interns (73.36 ± 9.42% and 74.59 ± 9.20%, p = 0.335). Most students (92.7%) had a very appropriate attitude toward nutrition, significantly varied by sex (p = 0.010). These findings indicate that there are multiple deficiencies in nutrition knowledge of medical students.

The effects of probiotic Saccharomyces boulardii on the mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in patients with multiple sclerosis: study protocol for a double-blind randomized controlled clinical trial.

BACKGROUND: The relationship between gut dysbiosis and inflammatory diseases including multiple sclerosis (MS) is presently recognized as an important health issue. It has been established that some bacterial probiotic strains are effective in treating MS. This study will investigate the effect of yeast probiotic Saccharomyces boulardii (SB) supplements on mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in MS patients. METHODS/DESIGN: In this double-blind randomized controlled two-group parallel trial, 50 MS patients who meet the inclusion criteria will be recruited from outpatient settings. They will be randomly allocated to 4 months of daily placebo or the SB probiotic intervention. Blood samples will be taken from each participant at the baseline and after the intervention period to assess inflammation and oxidative stress. The primary endpoint will be the changes in their mental health evaluated by the 28-item General Health Questionnaire. The secondary endpoints include changes in: (1) quality of life, evaluated by the 36-item Short Form Questionnaire, (2) fatigue, evaluated by the Fatigue Severity Scale, (3) pain, evaluated by a visual analogue scale, and (4) serum levels of indices of inflammatory stress (high-sensitivity C-reactive protein) and oxidative stress (malondialdehyde and total antioxidant capacity). Moreover, any adverse events and side effects due to the intervention will be documented. DISCUSSION: There is a need to discover safe and practical methods for managing the symptoms of MS. This trial will gather evidence on the effects of a probiotic. TRIAL REGISTRATION: Iranian Clinical Trial Registry, IRCT20161022030424N1 . Registered on 9 April 2018.

Classic versus Inguinal Approach for Obturator Nerve Block in Transurethral Resection of Bladder Cancer under Spinal Anesthesia: A Randomized Controlled Trial.

Single spinal anesthesia in transurethral resection of bladder tumor (TURBT) has been reported to be unable to prevent obturator nerve stimulation and adductor muscle contraction, which can cause complications like bladder perforation. The present study aimed to compare the effectiveness of the classic and inguinal approaches for obturator nerve block (ONB ). Seventy patients with cancers of the lateral wall of the bladder, scheduled to undergo TURBT at Imam Reza Hospital (Tabriz, Iran) during a 6-month period as of June 2016, were randomly allocated to groups of inguinal and classic methods (n=35). After the infusion of 500 mL of normal saline, spinal anesthesia was commenced using 3 mL (15 mg) of bupivacaine. Then ONB was performed using 10 mL of 1% lidocaine via the inguinal or classic approach in the inguinal group or the classic group, respectively. The success rate, defined as lack of post-block contraction with stimulation or during surgery, number of puncture attempts, time of block onset, and patient and surgeon satisfaction, was compared between the 2 methods using SPSS, version 19. The success rate of ONB was significantly higher in the inguinal group (97.1% vs. 71.4%; P=0.003). The number of puncture attempts in the classic group was more than that in the inguinal group (3.71±1.10 vs. 1.66±0.68, respectively; P<0.001). The block onset time was shorter in the inguinal group (1.5±0.66 min vs. 2.9±1.18 min; P<0.001). Dissatisfaction of the patient (19 cases vs. 2 cases) and the surgeon (10 cases vs. no case) was higher in the classic group (P<0.001). Compared to the classic approach, the inguinal approach for ONB appeared to be an easily performable, effective block with a high success rate, rapid onset, and good patient and surgeon satisfaction. TRIAL REGISTRATION NUMBER: IRCT 201608171772N21.

Novel treatment in refractory tic douloureux.

A patient with refractory trigeminal neuralgia (tic douloureux) was treated by intravenous magnesium sulfate successfully. Parenteral magnesium sulfate is an analgesic that expresses its analgesic effects through a noncompetitive blockade of the N-methyl-D-aspartate (NMDA) receptors, which in turns inhibits calcium entry into the cells.

Assessment of Mini-dose Succinylcholine Effect on FacilitatingLaryngeal Mask Airway Insertion.

INTRODUCTION: Laryngeal Mask Airway (LMA) has gained wide acceptance for routine airway management and with increasing emphasis on day care surgery it is widely used. The aim of this study was to assess the effects of mini dose succinylcholine (0.1mg/kg) with semi-inflated cuff on facilitation of laryngeal mask airway insertion in order to achieve more satisfaction yet less complications . METHODS: In a randomized double-blinded study, sixty ASA 1, 2 and 3 patients aged 20-60 years scheduled for urologic surgical procedures were included. Thirty patients received succinylcholine (Group S), and thirty received 0.9% sodium choride as a placebo (Group C). RESULTS: Coughing occured in 33.3% of patients in the control group and there was no incidence in succ group (P=0.002). Head or limb movement occurred in 70% of the patients in the control group vs. 10% in succ group (P<0.001). Laryngospasm occurred in 36.6 % of the patients in the control group but there was no incidence in succ group (P=0.004). Additional propofol was required in 53% of the patients in control group vs. 10% for succ group (P=0.001). Ease of insertion and first successfull attempt of LMA were achieved in 93.3% and 90% of the patients respectively in group S (P<0.05). Myalgia and sore throat occurred in 66.7 % of patients in the group C in comparison with 33.3% in group S (P=0.06). CONCLUSION: The combination of propofol with mini dose succinylcholine, provided a significantly better method for LMA insertion, while reduced propofol doses were needed and number of attempts decreased.

Effect of low level laser application at the end of surgery to reduce pain after tonsillectomy in adults.

INTRODUCTION: Tonsillectomy is among commonest otorhinolaryngologic surgeries. Many methods have been used to control post surgical pain, but despite it, pain is still one of the problems related to this operation. Recently, due to the non invasiveness of low level lasers, this modality has attracted attention. The purpose of this study is to evaluate the effects of low level laser irradiation at the end of surgery on reduction of pain after tonsillectomy in adults. METHODS: In a clinical trial, 60 adult patients, candidates for tonsillectomy were randomly assigned to two groups, A and B, and both groups were anesthetized similarly by the same technique. At the end of surgery, in the case group, the tonsils' bed were irradiated by infrared laser with 980nm wavelength, 100Hz, 4J/cm(2) from the infra mandibular angle. In the control group, the tonsils' bed had laser therapy with a turned off probe. Following laser treatment, the patients were reversed and extubated and consciousness achieved, pain and odynophagia were assessed at 2, 4, 6, 8, 12 and 24h post surgery based on visual analog scale for pain (VAS) and analgesic consumption. RESULTS: In the laser group frequency of patients with pain sensation in each evaluated hour was lower than in the control group. The amount of pain decrease and analgesic consumption reduction was significantly higher in patients who received laser (P=0.01). CONCLUSION: Based on the results of this study, use of low level lasers is effective in reducing tonsillectomy post surgical pain in adults.

Effectiveness of intravenous dexamethasone versus propofol for pain relief in the migraine headache: a prospective double blind randomized clinical trial.

BACKGROUND: There are many drugs recommended for pain relief in patients with migraine headache. METHODS: In a prospective double blind randomized clinical trial, 90 patients (age ≥ 18) presenting to Emergency medicine Department with Migraine headache were enrolled in two equal groups. We used intravenous propofol (10 mg every 5-10 minutes to a maximum of 80 mg, slowly) and intravenous dexamethasone (0.15 mg/kg to a maximum of 16 mg, slowly), in group I and II, respectively. Pain explained by patients, based on VAS (Visual Analogue Scale) was recorded at the time of entrance to ED, and after injection. Data were analyzed by paired samples t test, using SPSS 16. P < 0.05 was considered to be statistically significant. RESULTS: The mean of reported pain (VAS) was 8 ± 1.52 in propofol group and 8.11 ± 1.31 in dexamethasone group at presenting time (P > 0.05). The VAS in propofol group was obviously decreased to 3.08 ± 1.7, 1.87 ± 1.28 and 1.44 ± 1.63 after 10, 20 and 30 minutes of drug injection, respectively. The VAS in dexamethasone group was 5.13 ± 1.47, 3.73 ± 1.81 and 3.06 ± 2 after 10, 20 and 30 minutes of drug injection, respectively. The mean of reported VAS in propofol group was less than dexamethasone group at the above mentioned times (P < 0.05). The reduction of headache in propofol group, also, was very faster than dexamethasone group (P < 0.05). There were no adverse side effects due to administration of both drugs. CONCLUSIONS: Intravenous propofol is an efficacious and safe treatment for patients presenting with Migraine headache to the emergency department. TRIAL REGISTRATION: Clinical Trials IRCT201008122496N4.

An Evaluation of the Effect of Morphine on Abdominal Pain and PeritonealIrritation Signs in Patients with Acute Surgical Abdomen.

INTRODUCTION: Acute surgical abdomen is one of the most common emergency surgical causes all over the world and also one of the most important abdominal pain causes which is sometimes intolerable for the patients referring to the emergency departments. Diagnosis and planning for operation in these cases is based on time-demanding serial examinations and results of paraclinical data. In this waiting period, patients have to tolerate pain.Therefore, we aimed to study the hypothesis that relieving pain has no influence on valuable findings in physical examination. METHODS: This double blind randomized clinical trial was carried out on 120 patients above 12 years old referred to an emergency department of a referral hospital with acute abdomen. Patients were divided into two groups of receiving intravenous placebo and Morphine randomly. Pain score, change in tenderness as well as change in rebound tenderness before and after receiving morphine or placebo were measured based on Numeric Pain Assessment Scale. RESULTS: Statistically significant difference was observed between both groups regarding the mean pain score. Prevalence of tenderness and rebound tenderness after medication administration revealed a significant difference between two groups. Furthermore, pain and tenderness showed a significant decrease in patients receiving morphine also a significant difference occurred in rebound tenderness between two groups. CONCLUSION: Despite the fact that opioid analgesics decrease pain in patients with acute surgical abdomen, they do not tend to eliminate required diagnostic data being obtained from physical examination like tenderness and rebound tenderness. Surprisingly, all the acute abdomen cases had rebound tenderness after morphine administration. Therefore, this research advises a cautious usage of morphine in patients with acute abdomen.

Multimodal preincisional premedication to prevent acute pain after cholecystectomy.

INTRODUCTION: Postoperative pain as an important medical concern is usually treated by opioids which also are of various inevitable side effects. The aim of this study was to assess the efficacy of multimodal preincisional premedication on preventing post-cholecystectomy acute pain. METHODS: In a randomized clinical trial, sixty patients undergoing open cholecystectomy were randomized into two groups. Before anesthesia induction, Diclofenac suppository (100 mg) and oral Clonidine (0.2 mg) were administered in the first group. Immediately before operation, patients received Ketamine (1 mg/kg IV) while the control group received placebo. The site of incision was infiltrated by the surgeon with 20 mL Bupivacaine 0.25% in both groups. Anesthesia induction and maintenance were similar in both groups. The severity of pain was recorded 2, 4, 6, 12, 24 and 48 hours after operation according to Visual Analogue Scale. RESULTS: The severity of pain at two defined stages (6 and 12 hours later) was significantly less in the intervention group than the control group (P<0.005). The average pain severity score was less than the control group (P<0.005). CONCLUSION: In our study, the administration of Clonidine, Diclofenac and Ketamine and bupivacaine infiltration to the site of incision, altogether was associated with a significant decrease in pain score and opioid requirement after cholecystectomy in comparison to bupivacaine infiltration to the site of incision.