Effect of Adding Magnesium Sulphate to Epidural Bupivacaine Compared to Addition of Fentanyl in Patients undergoing Lower Limb Orthopedic Surgery under Combined Spinal Epidural Anathesia

Background The use of opioids in intrathecal or epidural anesthesia has become popular to optimize postoperative analgesia. However, opioid-induced side effects, such as respiratory depression, nausea, vomiting, urinary retention and pruritus, limit their use. Objectives The purpose of this study was to assess the postoperative analgesic requirements and the analgesic effect of adding magnesium sulphate to epidural bupivacaine compared to addition of fentanyl in patients undergoing lower limb orthopedic surgery under combined spinal epidural anathesia. Patients and Methods After approval of ethical committee in our study and obtaining written informed consent from eligible patients the study was conducted on 60 patients classified to ASA I and II scheduled for lower limb orthopedic surgery. The study presents double armed randomized interventional prospective study including patients allocated into two equal groups each consists of 30 patients. Group (A): patients received magnesium sulphate added to bupivacaine in epidural, Group (B): patients received fentanyl added to bupivacaine in epidural Results The results of their study showed that the maximum level of sensory blockade was significantly higher in the combined fentanyl with magnesium group as compared with fentanyl group alone and magnesium sulphate group alone. The duration of sensory blockade of the combined fentanyl and magnesium group was significantly prolonged as compared to the other two groups as for the other two group the difference in the blockade duration was insignificant Conclusion We concluded that either magnesium sulfate (75 mg) combined with (10 ml) 0.25% Bupivacaine or fentanyl (1 µg/kg) combined with (10 ml) 0.25% Bupivacaine in combined spinal epidural improves intraoperative analgesia and prolongs early postoperative analgesia in lower limb orthopedic surgeries. The duration of analgesia was more prolonged in magnesium sulphate group than in the fentanyl group and this difference was statistically significant.

Comparison of Mean Glasgow Outcome Score in Patients with Traumatic Brain Injury after Magnesium Sulphate Therapy and Placebo. A Prospective Study of Shaikh Zayed Hospital Lahore

Objective: We evaluated the effectiveness of magnesium sulphate treatment for the management and outcome of TBI. Material and Methods: The prospective cases (n = 112) of TBI were included from Department of Neurosurgery, Shaikh Zayed Hospital, Lahore. Patients were split into two groups. Magnesium sulphate treatment group (n = 56) and placebo group (n = 56). Detailed history of patients was taken along with comprehensive examinations with CT scans.56 TBI patients were given standard treatment plus magnesium sulphate and remaining 56 patients received just standard treatment. Results: Mean age of the magnesium supplement therapy group was 36.83 ± 13.45 years while in the placebo group was 33.64 ± 12.88 years). Majority 28 (67.9%) were male in the magnesium sulphate group while 37 (66.1%) were in the placebo group. Mean duration passed between hospital presentation and traumatic brain injury was 4.98 ± 2.32 hours in the magnesium sulphate group while it was 5.05 ± 2.48 in the placebo group. Mean Glasgow outcome score was 3.57 ± 1.33 in the magnesium sulphate group while 2.78 ± 1.23 in the placebo group and this difference was statistically significant. Conclusion: There is significant improvement in GOS after magnesium sulphate therapy in patients with traumatic brain injury versus placebo group as noted in the results.

Effect of dermatan sulphate on a C57-mouse model of pulmonary fibrosis

Objective To test the antifibrotic effect of dermatan sulphate in a bleomycin-induced mouse model of pulmonary fibrosis. Methods C57 mice were randomly divided into four experimental groups: saline-treated control group, bleomycin-induced fibrosis group, prednisolone acetate group and dermatan sulphate group. Lungs were assessed using the lung index, and the extent of interstitial fibrosis was graded using histopathological observation of haematoxylin & eosin-stained lung tissue. Lung tissue hydroxyproline levels and blood fibrinogen levels were measured using a hydroxyproline colorimetric kit and the Clauss fibrinogen assay, respectively. Tissue-type plasminogen activator (tPA) was measured using a chromogenic tPA assay kit. Results Lung index values were significantly lower in the dermatan sulphate group versus the fibrosis group. Histopathological analyses revealed that dermatan sulphate treatment ameliorated the increased inflammatory cell infiltration, and attenuated the reduction in interstitial thickening, associated with bleomycin-induced fibrosis. Hydroxyproline and fibrinogen levels were decreased in the dermatan sulphate group versus the fibrosis model group. Dermatan sulphate treatment was associated with increased tPA levels versus controls and the fibrosis group. Conclusions Damage associated with bleomycin-induced pulmonary fibrosis was alleviated by dermatan sulphate.

Magnesium sulfate decreases the dose of rocuronium for satisfactory double lumen tube placement condition in patients with myasthenia gravis

Background: Titrating a low dose of non-depolarizing neuromuscular blockers for induction of general anesthesia for patients with myasthenia gravis (MG) is a popular accepted practice. This practice may confront with unsatisfactory intubation conditions, especially for double lumen tube (DLT). This double-blind randomised study was to investigate whether magnesium sulfate could decrease the rocuronium demand and improve the DLT placement conditions for MG patients who scheduled for video-assisted thoracoscopic (VATS) thymectomy. Methods: The patients were randomly assigned into the magnesium sulfate or normal saline group. After acquiring the adequate sedative depth, magnesium sulfate(60mg.kg-1) or normal saline(control) was given to the patients in two groups respectively. After that, the same Train of Four (TOF) value was obtained with one or more doses of 0.05 mg.kg-1 rocuronium with 3 minutes interval, then DLT was intubated. The primary and secondary observational outcomes were the cumulative rocuronium dose and the intubation condition for DLT placement respectively. Results: 23 patients in the magnesium sulphate group and 22 patients in the control group completed the study. The amount of rocuronium used to meet the setting value of TOF were 0.10 (0.05)mg.kg-1 and 0.28(0.17) mg.kg-1 in the magnesium sulphate and control group respectively (P<0.0001). Under a similar depth of neuromuscular blockade and sedation, 23 patients in magnesium sulphate group and 16 patients in control group showed excellent intubation condition. The patients in both groups showed similar characteristics of recovery from neuromuscular blockade. Conclusions: Our research showed that magnesium sulfate could decrease the rocuronium demand for satisfactory DLT intubation condition in MG patients.

Magnesium sulfate decreases the dose of rocuronium for satisfactory double lumen tube placement condition in patients with myasthenia gravis

Background: Titrating a low dose of non-depolarizing neuromuscular blockers for induction of general anesthesia for patients with myasthenia gravis (MG) is a popular accepted practice. This practice may confront with unsatisfactory intubation conditions, especially for double lumen tube (DLT). This double-blind randomised study was to investigate whether magnesium sulfate could decrease the rocuronium demand and improve the DLT placement conditions for MG patients who scheduled for video-assisted thoracoscopic (VATS) thymectomy. Methods: The patients were randomly assigned into the magnesium sulfate or normal saline group. After acquiring the adequate sedative depth, magnesium sulfate(60mg.kg-1) or normal saline(control) was given to the patients in two groups respectively. After that, the same Train of Four (TOF) value was obtained with one or more doses of 0.05 mg.kg-1 rocuronium with 3 minutes interval, then DLT was intubated. The primary and secondary observational outcomes were the cumulative rocuronium dose and the intubation condition for DLT placement respectively. Results: 23 patients in the magnesium sulphate group and 22 patients in the control group completed the study. The amount of rocuronium used to meet the setting value of TOF were 0.10 (0.05)mg.kg-1 and 0.28(0.17) mg.kg-1 in the magnesium sulphate and control group respectively (P<0.0001). Under a similar depth of neuromuscular blockade and sedation, 23 patients in magnesium sulphate group and 16 patients in control group showed excellent intubation condition. The patients in both groups showed similar characteristics of recovery from neuromuscular blockade. Conclusions: Our research showed that magnesium sulfate could decrease the rocuronium demand for satisfactory DLT intubation condition in MG patients.

FUCOIDAN FROM BROWN SEAWEED AND ITS BIOACTIVITY

Fucoidan is a polysaccharide which substantially consists of L-fucosa and ester sulphate group and is mainly contained in brown seaweed. For the past ten years, bioactivity studies of fucoidan has been conducted. Recently, fucoidan has been examined for its application in drugs. In a couple of years, fucoidan structure was succesfully identified and its bioactivity was revealed. Fucoidan exhibits various bioactivities such as anticoagulant, antioxidant, anticomplementary, anti-inflamation, gastric protector, and blood lipid level control. This review gives some brief progress in isolation and bioactivity study of fucoidan from brown seaweeds.

Intraperitoneal magnesium sulphate plus bupivacaine for pain relief after laparoscopic cholecystectomy

Background: Multimodal analgesia is necessary for management of pain after laparoscopic cholecystectomy. Magnesium sulphate is a new emerging drug for management of acute pain. This study was performed to study the analgesic efficacy of intraperitoneal bupivacaine and bupivacaine plus magnesium sulphate for postoperative pain relief after laparoscopic cholecystectomy. Methods: At the end of laparoscopic cholecystectomy, 60 patients were randomized to one of the following groups: bupivacaine group receiving intraperitoneal instillation of 30 ml of 0.25% bupivacaine and magnesium sulphate group receiving intraperitoneal instillation of 0.25% bupivacaine plus 50 mg/kg magnesium sulphate to total volume of 30 ml. Postoperative pain was evaluated by using visual analogue scale (standard Visual Analogue Scale pain score of 0-10). Time duration of first analgesia demanded was noted and rescue analgesic was given as tramadol 50 mg intravenously and on demand. Pain, Visual Analogue Scale score and total analgesic consumption was recorded for 24 hours and analysed. Results: The patients who were given intraperitoneal bupivacaine plus magnesium sulphate at the end of surgery had better pain relief in first 24 hours, Visual Analogue Scale score of 0-5 compared to sole bupivacaine group who had Visual Analogue Scale score of 3-7. The magnesium sulphate group had longer pain free period of average 5.53±4.33 hours after surgery compared to 3.16±1.59 hours in sole bupivacaine group. Total analgesic consumption in magnesium sulphate group was also less compared to bupivacaine group (125.0±36.5 and 75.0±25.0 in bupivacaine and magnesium sulphate group respectively). All the results show highly significant differences between the groups. Conclusion: The combined instillation of bupivacaine and magnesium sulphate into the peritoneal cavity at the end of laparoscopic surgery renders patients better pain control and less consumption of analgesics in first 24 hours compared to sole bupivacaine group. DOI: http://dx.doi.org/10.3126/jkmc.v1i1.7251 Journal of Kathmandu Medical College, Vol. 1, No. 1, Issue 1, Jul.-Sep., 2012 pp.21-25

Substrate specificities of mouse heparan sulphate glucosaminyl 6-O-sulphotransferases

Glycosaminoglycan heparan sulphate interacts with a variety of proteins, such as growth factors, cytokines, enzymes and inhibitors and, thus, influences cellular functions, including adhesion, motility, differentiation and morphogenesis. The interactions generally involve saccharide domains in heparan sulphate chains, with precisely located O-sulphate groups. The 6-O-sulphate groups on glucosamine units, supposed to be involved in various interactions of functional importance, occur in different structural contexts. Three isoforms of the glucosaminyl 6-O-sulphotransferase (6-OST) have been cloned and characterized [H. Habuchi, M. Tanaka, O. Habuchi, K. Yoshida, H. Suzuki, K. Ban and K. Kimata (2000) J. Biol. Chem. 275, 2859–2868]. We have studied the substrate specificities of the recombinant enzymes using various O-desulphated poly- and oligo-saccharides as substrates, and using adenosine 3′-phosphate 5′-phospho[35S]sulphate as sulphate donor. All three enzymes catalyse 6-O-sulphation of both -GlcA-GlcNS- and -IdoA-GlcNS- (where GlcA represents d-glucuronic acid, NS the N-sulphate group and IdoA the l-iduronic acid) sequences, with preference for IdoA-containing targets, with or without 2-O-sulphate substituents. 6-OST1 showed relatively higher activity towards target sequences lacking 2-O-sulphate, e.g. the -GlcA-GlcNS- disaccharide unit. Sulphation of such non-O-sulphated acceptor sequences was generally favoured at low acceptor polysaccharide concentrations. Experiments using partially O-desulphated antithrombin-binding oligosaccharide as the acceptor revealed 6-O-sulphation of N-acetylated as well as 3-O-sulphated glucosamine residues with each of the three 6-OSTs. We conclude that the three 6-OSTs have qualitatively similar substrate specificities, with minor differences in target preference.

MAGNESIUM SULPHATE VERSUS PHENYTOIN FOR ECLAMPSIA: ONE YEAR PROSPECTIVE STUDY

Aim: Eclampsia is one of the important preventable causes of maternal mortality.This study aims to review the clinical profile of eclamptic women and compare thematernal mortality, recurrence of convulsions, other morbidities including the neonataloutcome with Magnesium Sulphate versus Phenytoin used for its management.Material and Methods: Prospective study was carried out in all the eclamptic patientadmitted in Gynae ward from April 2000 - April 2001 (Baisak 2057 to Chaitra 2057).Results: There were total of 30 patients.Most of the them (53.3%) were of the 15-20years of age group and three fourth (73%) were primigravidas. More than half (56%)were unbooked and one fourth were nonimmunised and illiterate .Blood pressure hadnever been measured in 63% of the patient . In the Phenytoin Group 68.75% hadrecurrences of fits where as in the Magnesium Sulphate Group only 21.43 % hadreccurence. In the Magnesium Sulphate group, 50% delivered normally whereas 42.5%needed caesarean section in the Phenytoin group Only 6.2% delivered normally andin 37.5 % forceps had to be applied. There were 37.50% admission to NeonatalIntensive Unit (NICU) for various complications in Phenytoin group whereas therewere only 14.2% NICU admission in Magnesium Sulphate group. There were twocases of neonatal deaths out of 16 neonates in the Phenytoin group whereas only oneout of 14 cases in Magnesium Sulphate group. There was only one maternal death inthese thirty patients and it belonged to the Phenytoin group.Conclusion: As proved in many other studies this study also showed that MagnesiumSulphate was superior to Phenytoin in terms of recurrence of fits, maternal and neonataloutcome. In our country where many deaths still occur due to Eclampsia the valuablerole of magnesium Sulphate should not be ignored and health personnels should betrained for its frequently than it is practiced to-day.Key Words: Eclampsia, Preeclampsia, Magnesium Sulphate, Phenytion.

Crystal structure of human carbonic anhydrase II complexed with ananti-convulsant sugar sulphamate

The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the widely used anti-epileptic drug topiramate, possesses anti-convulsant and carbonic anhydrase-inhibitory activities. We have studied the binding interactions of RWJ-37497 in the active site of human carbonic anhydrase II by X-ray crystallography. The atomic positions of the enzyme inhibitor complex were refined at a resolution of 2.1 Å (1 Å = 0.1 nm) to the final crystallographic R and Rfree values of 0.18 and 0.23, respectively. The inhibitor co-ordinates to the active-site zinc ion through its oxygen atom and the ionized nitrogen atom of the sulphamate group by replacing the metal-bound water molecules, although the sulphamoyl oxygen atom provides a rather lengthyco-ordination. The 4,5-cyclic sulphate group is positioned in a hydrophobic pocket of the active site, making contacts with the residues Phe-131, Leu-198, Pro-201 and Pro-202. Since the ligand was found to be intact, concerns about RWJ-37947 irreversibly alkylating the enzyme through its 4,5-cyclic sulphate group were dispelled.