Background:No drug, used as adjuvant to spinal bupivacaine, has yet been identified that specifically inhibits nociception without its associated side-effects.Aims:This prospective randomized double-blind study was conducted to evaluate the onset and duration of sensory and motor block as well as perioperative analgesia and adverse effects of dexmedetomidine and magnesium sulfate given intrathecally with 0.5% hyperbaric bupivacaine for spinal anesthesia.Materials and Methods:A total of 90 patients classified as American Society of Anesthesiologists status I and II scheduled for lower abdominal and lower limb procedures were prospectively studied. Patients were randomly allocated to receive intrathecally either 15 mg hyperbaric bupivacaine plus 0.1 ml (10 μg) dexmedetomidine (group D, n=30) or 15 mg hyperbaric bupivacaine plus 0.1 ml (50 mg) magnesium sulfate (group M, n=30) or 15 mg hyperbaric bupivacaine plus 0.1 ml saline (group C, n=30) as control. The onset time to reach peak sensory and motor level, the regression time for sensory and motor block, hemodynamic changes and side-effects were recorded.Statistical Analysis Used:All statistical analyses were performed using INSTAT for windows. Continuous variables were tested for normal distribution by the Kolmogorov-Smirnov test. Data was expressed as either mean and standard deviation or numbers and percentages. Continuous covariates (age, body mass index and height) were compared using analysis of variance (ANOVA). For the times to reach T10 dermatomes, Bromage 3 scale and the regression of the sensory block to S1 dermatome and Bromage scale 0, one-way ANOVA was used to compare the means. The level of significance used was P<0.05.Results:The onset times to reach T10 dermatome and to reach peak sensory level as well as onset time to reach modified Bromage 3 motor block were significantly different in the three groups. The onset time to reach peak sensory and motor level was shorter in group D as compared with the control group C, and it was significantly prolonged in group M. We also found that patients in group D had significant longer sensory and motor block times than patients in group M, which was greater than in the control group C.Conclusion:It was found that onset of anesthesia was rapid and of prolonged duration in the dexmedetomidine group (D). However, in the magnesium sulfate group (M), although onset of block was delayed, the duration was significantly prolonged as compared with the control group (C), but to a lesser degree than in the dexmedetomidine group (D). The groups were similar with respect to hemodynamic variables and there were no significant side-effects in either of the groups.

Background:Both magnesium and clonidine are known to inhibit catecholamine and vasopressin release and attenuate hemodynamic response to pneumoperitoneum. This randomized, double blinded, placebo controlled study has been designed to assess which agent attenuates hemodynamic stress response to pneumoperitoneum better.Materials and Methods:120 patients undergoing elective laparoscopic cholecystectomy were randomized into 4 groups of 30 each. Group K patients received 50 ml normal saline over a period of 15 min after induction and before pneumoperitoneum, group M patients received 50 mg/kg of magnesium sulfate in normal saline (total volume 50 ml) over same time duration. Similarly group C1 patients received 1 μg/kg clonidine and group C2 1.5 μg/kg clonidine respectively in normal saline (total volume 50 ml). Blood pressure and heart rate were recorded before induction (baseline value), at the end of infusions and every 5 min after pneumoperitoneum.Statistical Analysis:Paired t test was used for intra-group comparison and ANOVA for inter-group comparison.Results:Systolic blood pressure was significantly higher in control group as compared to all other groups during pneumoperitoneum. On comparing patients in group M and group C1, no significant difference in systolic BP was found at any time interval. Patients in group C2 showed best control of systolic BP. As compared to group M and group C1, BP was significantly lower at 10, 30 and 40 min post pneumoperitoneum. No significant episodes of hypotension were found in any of the groups. Extubation time and time to response to verbal command like eye opening was significantly longer in group M as compared to other groups.Conclusion:Administration of magnesium sulfate or clonidine attenuates hemodynamic response to pneumoperitoneum. Although magnesium sulfate 50 mg/kg produces hemodynamic stability comparable to clonidine 1 μg/kg, clonidine in doses of 1.5μg/kg blunts the hemodynamic response to pneumoperitoneum more effectively.

Background and Aims:This prospective, randomized, double-blind study was undertaken to establish the effect of addition of magnesium or dexmedetomidine, as an adjuvant, to epidural bupivacaine in lower limb surgeries.Materials and Methods:One hundred and twenty ASA (American Society of Anesthesiologists) class I and II patients undergoing lower limb surgeries were enrolled to receive either magnesium sulfate (Group M) or dexmedetomidine (Group D) along with epidural bupivacaine for surgical anesthesia. All the study subjects received an epidural anesthesia with 14 ml of 0.5% bupivacaine along with either MgSO4 50 mg (Group M) or dexmedetomidine 0.5 μg/kg (Group D) or saline (Group C). The onset of motor and sensory block, duration of block, hemodynamic parameters, and any adverse events were monitored.Results:Analgesia in the postoperative period was better in Group D, duration of sensory and motor blockade was significantly prolonged in Group D and incidence of sedation was more in Group D.Conclusion:Hence, addition of dexemedetomidine to epidural bupivacaine can be advantageous with respect to increased duration of motor and sensory blockade and arousable sedation.

Background:Anaesthesia for spine surgeries is not only concerned with relieving pain during surgeries but also during the post-operative period. A prospective randomised study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to ropivacaine, in epidural analgesia with special emphasis on their quality of analgesia and the ability to provide the smooth post-operative course.Methods:A total of 60 subjects, 33 were men and 27 were women between the age of 18 and 65 years of American Society of Anaesthesiologists (ASA) I/II class who underwent spine surgeries were randomly allocated into two groups, ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC), comprising 30 patients each. Group RD received 20 ml of 0.2% ropivacaine and 1 μg/kg of dexmedetomidine while group RC received 20 ml of 0.2% ropivacaine and 2 μg/kg of clonidine through the epidural catheter. Onset of analgesia, time of peak effect, duration of analgesia, cardiorespiratory parameters, side-effects and need of rescue intravenous (IV) analgesics were observed.Results:The demographic profile and ASA class were comparable between the groups. None of the patients needed rescue analgesics in either group. Group RD had early onset, early peak effect, prolonged duration and stable cardiorespiratory parameters when compared with group RC. The side-effects profile was also comparable with a little higher incidence of nausea and dry mouth in both groups.Conclusion:Epidural route provided acceptable analgesia in spine surgeries and avoided the need of IV analgesics in either group. Dexmedetomidine is a better neuraxial adjuvant compared with clonidine for providing early onset and prolonged post-operative analgesia and stable cardiorespiratory parameters.

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Background At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-d-glucose (2-DG) is a metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy and safety of 2-DG as adjunct to standard care in the treatment of moderate to severe COVID-19 patients. Methods We conducted a randomized, open-label, phase II, clinical study to evaluate the efficacy, safety, and tolerability of 2-DG administered as adjunct to standard of care (SOC). A total of 110 patients between the ages of 18 and 65 years with moderate to severe COVID-19 were included. Patients were randomized to receive 63, 90, or 126 mg/kg/day 2-DG in addition to SOC or SOC only. Times to maintaining SpO2 ≥ 94% on room air, discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO clinical progression scale, negative conversion on RT-PCR, requirement for intensive care, and mortality were analyzed to assess the efficacy. Results Patients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO2 ≥ 94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs. 5 days, Hazard ratio [95% confidence interval] = 2.3 [1.14, 4.64], p = 0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalization were significantly shorter for the 2-DG 90 mg group. All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild. Conclusions 2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefit over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase II study is encouraging for confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase III trial. Trial registration: CTRI, CTRI/2020/06/025664. Registered 5th June 2020, http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27.

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Introduction Centhaquine (Lyfaquin ® ) showed significant safety and efficacy in preclinical and clinical phase I and II studies. Methods A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock, systolic blood pressure (SBP) ≤ 90 mmHg, and blood lactate levels ≥ 2 mmol/L. Patients were randomized in a 2:1 ratio to the centhaquine group ( n = 71) or the control (saline) group ( n = 34). Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine 0.01 mg/kg) was administered in 100 mL of normal saline infusion over 1 h. The primary objectives were to determine changes (mean through 48 h) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, and vasopressors administered in the first 48 h, duration of hospital stay, time in intensive care units, time on ventilator support, change in acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and the proportion of patients with 28-day all-cause mortality. Results The demographics of patients and baseline vitals in both groups were comparable. The cause of hypovolemic shock was trauma in 29.4 and 47.1% of control group and centhaquine group patients, respectively, and gastroenteritis in 44.1 and 29.4%, respectively. Shock index (SI) and quick sequential organ failure assessment at baseline were similar in the two groups. An equal amount of fluids and blood products were administered in both groups during the first 48 h of resuscitation. A lesser amount of vasopressors was needed in the first 48 h of resuscitation in the centhaquine group. An increase in SBP from baseline was consistently higher up to 48 h (12.9% increase in area under the curve from 0 to 48 h [AUC 0–48 ]) in the centhaquine group than in the control group. A significant increase in pulse pressure (48.1% increase in AUC 0–48 ) in the centhaquine group compared with the control group suggests improved stroke volume due to centhaquine. The SI was significantly lower in the centhaquine group from 1 h ( p = 0.032) to 4 h ( p = 0.049) of resuscitation. Resuscitation with centhaquine resulted in a significantly greater number of patients with improved blood lactate (control 46.9%; centhaquine 69.3%; p = 0.03) and the base deficit (control 43.7%; centhaquine 69.8%; p = 0.01) than in the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. Conclusion Centhaquine is an efficacious resuscitative agent for treating hypovolemic shock. The e...