March 2017 by ejima

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

MARCH 2017

Original Article Effect of magnesium sulphate infusion on intraoperative propofol requirements in neurosurgical patients receiving balanced anaesthesia Sankari Santra , Ratul Basu , Santa Saha-Roy , Bibhu Kalyani Das 1

Magnesium, one of the N-methyl-D-aspartate (NMDA) antagonists, may be a useful adjunct to anaesthesia and analgesia. The present randomized placebo controlled, double blind study was designed to investigate whether an intravenous administration of magnesium sulphate reduces propofol consumption during balanced anaesthesia in neurosurgical patients. Sixty adult patients undergoing elective craniotomy under general anaesthesia were randomly divided into two groups (n=30 per group). The patients in ‘magnesium group’ received magnesium sulphate (30mg/kg as a bolus, then 10mg/kg/hour) whereas the patients in the ‘control group’ received same volume of 0.9% sodium chloride. Controlled ventilation through oral endotracheal tube with nitrous oxide in oxygen was done. Anaesthesia was maintained with propofol (administered according to the bi-spectral index), fentanyl (adjusted according to heart rate and mean arterial pressure) and rocuronium (adjusted to provide complete depression of the first twitch after train-offour stimulation). To maintain a predetermined anaesthetic depth, mean hourly dose requirements of propofol in the magnesium group was 4.1 ± 0.48mg/kg/hour versus 7.73 ± 0.49mg/kg/hour in the control group (p<0.001). No adverse effect was observed magnesium with administration. The magnesium group required significantly less fentanyl and rocuronium (p<0.001). Intravenous administration of magnesium sulphate reduces propofol infusion requirements. These results suggest that magnesium administration may have an effect on anaesthesia or analgesia and may be a useful adjunct in balanced anaesthesia during elective craniotomy. [J Indian Med Assoc 2017; 115: 10-14]

Key words : Magnesium sulphate, propofol, balanced anaesthesia, elective craniotomy.

and cardiac depression. On the other hand, 60% reduction in minimum alveolar concentration of halothane was demonstrated in magnesium treated rats. This result was due to central effect of the ion, but this has not been substantiated . Recently, the importance of magnesium in anaesthetic practice has been highlighted . It has been suggested that magnesium has the potential to treat and prevent pain by acting as an antagonist of N-methyl-D aspartate (NMDA) receptors . In some clinical studies, peri-operative administration of magnesium sulphate reduced intraoperative and post-operative analgesic requirements in patients undergoing arthroscopic knee surgery or elective abdominal hysterectomy . In one of the studies, when propofol infusion rate was held constant and the fentanyl dose was adjusted to haemodynamic end points, opioid requirements were reduced . In other studies, magnesium has been used as an adjuvant during general anaesthesia . However there are limited studies regarding effects of magnesium sulphate infusion in reducing anaesthetic requirements in elective craniotomy.

agnesium is the fourth most abundant cation in the body and the second most abundant intracellular cation . It has numerous physiological activities including activating many enzymes involved in energy metabolism and protein synthesis .Magnesium acts as a natural calcium antagonist by regulating calcium access into the cell . At the beginning of last century, magnesium sulphate was proposed as a general anaesthetic . Although magnesium was regarded as a central nervous system (CNS) depressant, its anaesthetic effect was shown to result from cerebral hypoxia after progressive respiratory 1,2

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Department of Anaesthesia, Bangur Institute of Neurosciences, Kolkata 700025 1 MD, Post Doctoral Certificate Course (Neuroanaesthesia), Associate Professor 2 MD, Post Doctoral Certificate Course (Neuroanaesthesia), RMO, Department of Anaesthesia, NRS Medical College, Kolkata 700014 3 MD, Assistant Professor, Department of Biochemistry, Bangur Institute of Neurosciences, Kolkata 700025 4 MD, Retired Professor and Ex Head of the Department of Anaesthesia, Bangur Institute of Neurosciences, Kolkata 700025, at present Director of Academic Development, Institute of Neurosciences, Kolkata 700017

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Accordingly, the present study was designed to assess the effect of intra-operatively administered magnesium sulphate infusion on propofol requirement during elective craniotomy. MATERIALS AND METHODS The study was carried out at Bangur Institute of Neurosciences, IPGME&R, Kolkata, after approval of the Institutional Ethics Committee. Sixty adult patients of 2060 years of age, ASA grade I and II, undergoing supratentorial craniotomy were selected for the study. Patients, allergic to study drug, or suffering from cardiac, pulmonary, renal, hepatic or haematological disorders were excluded. Patients having pregnancy, obesity and prior treatment with calcium channel blocker or anticoagulants were also excluded from the study. Informed consents were taken from the potential subjects prior to including them in the study during pre-anaesthetic check up. They were randomly allocated into two groupsMagnesium group (n=30) and Control group (n=30). Thorough pre-anaesthetic check- up and counseling had been done prior to anaesthesia. Before induction of anaesthesia, routine monitoring [heart rate (HR), arterial oxygen saturation (SpO2), electrocardiography (ECG)] was started. An arterial line was inserted in radial artery to measure systemic blood pressure and blood sampling. The level of anaesthesia was monitored with bi-spectral index (BIS). The BIS electrodes were placed on the forehead and were connected to BIS (A-2000 BISTM monitor, Aspect TM Medical System Inc., Norwood, MA, USA). Magnesium group was received magnesium sulphate 30mg/kg, administered as a slow intravenous (IV) bolus before the induction of anaesthesia and then 10mg/kg/hour by continuous infusion till the closure of dura mater. The same volume of isotonic saline (0.9%) was administered to the control group. After pre-oxygenation for 3minutes, anaesthesia was induced with fentanyl 2µg/kg and propofol in increments of 20mg every 5seconds until BIS reached a predetermined value of 60. Lignocaine 1% (1mg/kg) was given to all patients to reduce pain caused by injection of propofol. After induction of anaesthesia supramaximal train-of-four (TOF WatchR, Organon Ltd, Dublin, Ireland) had been measured at 20 seconds interval. When a stable twitch response was established (at least three successive equal responses to TOF stimulation) rocuronium 1mg/kg was administered via a fast flowing IV infusion over 5seconds. Orotracheal intubation was performed after complete (T1 = 0%) single twitch depression. The time from the start of anaesthesia induction to reaching a BIS level of 60 had been recorded. Anaesthesia was maintained by N2O in O2 and Propofol infusion and intermittent fentanyl injection. Propofol infusion was started at the rate of 10mg/kg/hour and titrated to maintain BIS in the range of 45-60. The hourly

MARCH 2017

consumption of propofol was recorded as mg/kg/hour. Dose adjustment of fentanyl was based on standard clinical signs and haemodynamic measurements. Inadequate analgesia defined as an increase in heart rate and mean arterial pressure (MAP) of more than 20% of baseline and was managed with fentanyl (0.5-1mg/kg), if BIS is within standard anaesthetic range. Muscle relaxation was achieved by rocuronium adjusted to provide complete depression of the first twitch after TOF stimulation. Throughout the operation PaCO2 level between 30-35mm Hg and normothermia were maintained. Approximately 30 minutes before the end of surgery or when dura was closed, magnesium infusion and rocuronium were discontinued. Patients were allowed to recover spontaneously until the return of T1 = 25%. Propofol was discontinued on skin closure. Patients were reversed with glycopyrolate 0.004mg/ kg and neostigmine 0.05mg/kg when BIS reached 80. After return of TOF ratio (T4/T1) to 70% and BIS 80 patients were extubated. Patients were transferred to recovery unit and were assessed neurologically for any signs of hypermagnesemia or any adverse effects. Pre- and post-operative serum magnesium level was estimated by Calmagite Dye method13. Data were expressed as mean ± SD. The requirement of propofol was compared between the two groups by Student’s unpaired t-test. Within each group, changes in haemodynamic parameters were assessed by repeated measures of analysis of variance (ANOVA) followed by Student’s paired t-test for comparison between two individual time points. Categorically variables were compared by Chi-square test or Fisher’s exact test, whichever is appropriate. The analysis was conducted on an intention to treat basis. A two tailed ‘p’ value <0.05 was considered statistically significant. RESULTS This is a prospective parallel group, double blind and controlled study involving 60 patients divided into two groups. In magnesium group (N = 30), patients received magnesium sulphate and those in control group (N = 30) received normal saline, along with propofol as continuous infusion. The patient characteristics in both groups were comparable with respect to age, weight, and duration of surgery (Table 1). All patients underwent the same type of surgery. Time interval between start of induction and achieving of BIS60 and recovery time are shown in Table 1. Induction of anaesthesia (BIS = 60) was achieved in 54.5 ± 2.39 sec in magnesium group and in 81.8 ± 3.25sec in control group (p<0.0001). The recovery time was shorter in control group, 7.34min versus 9.56min (p<0.001). The mean intraoperative propofol consumption in the control group was significantly higher than that in magne-