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Magnesium Research 2012; 25 (2): 72-8 ORIGINAL ARTICLE

The effects of magnesium sulphate ondesflurane requirement, earlyrecovery and postoperative analgesiain laparascopic cholecystectomyBilge Olgun, Gonca Oguz, Mensure Kaya, Serpil Savl, Hamit Erdal Eskicrak,

Ihsan Gney, Nihal Kadogullar

Dr A.Y. Ankara Oncology Education and Research Hospital, Department of Anesthesiology,Ankara, TurkeyCorrespondence: G. Oguz, Hukukcu Dostlar Sitesi 495. Sok. No: 13, Cayyolu Yenimahalle/Ankara, Turkey

Abstract. Purpose: we evaluated the effects of magnesium sulphate infu-sion on anesthetic requirement, early recovery and postoperative analgesia indesflurane-remifentanil-based,balancedanaesthesia.Methods: 60, ASA(Ameri-can Society of Anesthesiologists) group 1-2 patients who were scheduled forlaparoscopic cholecystectomy were randomly divided into two groups. Beforeanesthesia, the magnesium-treated group (n = 30) received a 15 min infusion of40 mg/kg of magnesium sulphate followed by 10 mg/kg/h by continuous i.v. infu-sion during the operation. The same volume of isotonic saline was adminis-tered to the control group (n = 30). Anesthesia was induced with propofol,

remifentanil and vecuronium, and maintained with desflurane 3-6%, O2/airand remifentanil infusion. Desflurane was titrated to maintain BIS (bispectralindex) values of 40-60. The times from cessation of anesthesia to spontaneousbreathing, eye opening, extubation, reaching BIS 70, and Aldrete scores wererecorded. After surgery, patients received a patient-controlled, morphine anal-gesia device. Results: demographic variables were similar. During the 15 mininfusion of magnesium sulphate, the BIS value was significantly lower in themagnesium sulphate-treated group. The amounts of propofol and desfluraneused were less in the magnesium sulphate-treated group, by 18% and 22%respectively (p


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Effects of magnesium on anesthetic requirement

The anesthetic effect of magnesium is thoughtto be related to several mechanisms, such asantagonism of NMDA receptors in the centralnervous system, decrease of the stress responseto surgery by reducing catecholamine release [3]

and inhibition of acetylcholine release at motornerve terminals [4]. A competitive antagonism inhippocampal presynaptic calcium channels thatregulate neurotransmitter release in the centralnervous system has also been suggested [5].

Perioperative analgesia, an important compo-nent of anesthesia, is an effective factor in therecovery process. The demonstration of an inverserelationship between the severity of pain and theserum magnesium concentration has led to fur-ther investigation of magnesium [6]. Inhibitionof calcium influx, antagonism of NMDA recep-

tors, and prevention of central sensitization afterperipheral tissue injury or inflammation by inhi-bition of dorsal horn NMDA receptors have beensuggested as the analgesic mechanisms [7]. Also,NMDA antagonists have been shown to poten-tiate the analgesic effect of opioids by delayingor reducing the development of acute tolerance[8].

We hypothesized that a magnesium sul-phate infusion would reduce the amount ofanesthetic agents needed. The primary aim

of this double-blind, randomised, placebo-controlled study was to assess the effects of aperioperatively-administered, magnesium sul-phate infusion on anesthetic requirement indesflurane-remifentanil-based, balanced anesthe-sia. Early recovery parameters and postoperativemorphine use were also investigated.

Methods and materials

After obtaining approval of the InstitutionalEthics Committee and the patients informed con-sent, 60, ASA physical status 1-2 patients, aged20-70, scheduled for laparoscopic cholecystectomywere included in this double blind, randomized,prospective study.

Exclusion criteria included hepatic, neuro-muscular, renal, respiratory and cardiovascularsystem disorders, prior treatment with calciumchannel blockers, opioids or magnesium, andknown allergy to the study drugs.

Patients were randomly allocated into one of thegroups using a computer-generated, random list

of numbers (magnesium sulphate-treated group(n = 30), control group receiving saline (n = 30)).Before surgery, all patients were informed aboutthe use of a patient-controlled analgesia device(Abbott APM Provider pump, North Chicago, IL,

USA) and the Visual Analogue Scale (VAS 0:no pain, VAS 10: most severe pain experienced).After premedication with midazolam 0.07 mg/kgi.m., monitoring of standard ECG, pulse oxymetryand non-invasive blood pressure was establishedon arrival at the operating room. The depth ofanesthesia was monitored with a bispectral indexmonitor (BIS), which uses processed electro-encephalogram signals to measure the depth ofsedation on a unitless scale from 0 to 100. A PEN-LON (SIGMA ALPHA, AYBO, Eczacbas, Baxter,UK) vaporizator was used to measure desfluraneconsumption. This automatically calculates theamount of desflurane use.

Fifteen minutes before the induction of anes-thesia, a continuous, i.v. infusion of 40 mg/kgof magnesium sulphate, 15% in 100 mL saline,and then 10 mg/kg bwt/h was administered tothe magnesium-treated group and was continuedthroughout the operation. The same volume ofisotonic salinewas administered, at the same infu-sion rate, to the control group.

In both groups, anesthesia was induced with

remifentanil 1 g/kg and propofol 1 mg/s until aBIS value of 40 was reached. Orotracheal intuba-tion was undertaken 3 min after administrationof vecuronium 0.1 mg/kg. Remifentanil infusionwas started at an infusion rate of 0.25 g/kg//minafter the induction of anesthesia, and reduced to0.125 g/kg/min, 10 min after intubation. Anes-thesia was maintained with desflurane 3-6%,O2/air and remifentanil infusion. Desflurane wastitrated to maintain BIS values between 40-60,during anesthesia.

Baseline MAP (mean arterial pressure), HR(heart rate), BIS and SpO2 values were recordedinitially, at 5, 10 and 15 min before induction,1, 3 and 5 min after intubation and at 5 minintervals during the surgery. If MAP and HRexceeded 20% of baseline values while BIS waswithin the targeted range, a bolus of remifen-tanil 1 g/kg bwt was given. If the situation wasnot resolved 5 min later, the infusion rate wasincreased to 0.25 g/kg bwt/min after another1 g/kg bwt bolus. Nitroglycerine was adminis-tered when needed. An MAP 20% lower than base-

line was treated with ephedrine 5 mg, and anHR


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All of the anesthetics and the magnesium infu-sion were discontinued at the end of skin closure,and the total consumption of drugs was noted.Neuromuscular block was antagonized with intra-

venous neostigmine 0.04 mg/kg and atropine

0.02 mg/kg bwt. The time from cessation of anes-thesia to the beginning of spontaneous breathing,eye opening, extubation and reaching a BIS valueof 70 was recorded. Patients were extubated whenBIS 70. Postoperative recovery was assessedusing the Aldrete scoring system. Blood sampleswere taken from patients before infusion and10 min after cessation of infusion of magnesiumsulphate in order to measure serum magnesiumconcentrations.

Following surgery, all patients received apatient-controlled analgesia device (PCA)

adjusted to deliver a 5 mg loading dose ofmorphine, a bolus of 1 mg, and a 10 min lock-outperiod. An additional 5 mg bolus dose of morphinewas given when VAS4.

MAP, HR, respiratory rate and VAS pain scoreswere evaluated at postoperative 0, 1, 2, 4, 6, 12and 24 h. Patient satisfaction, side-effects suchas nausea-vomiting and pruritis, and the need forre-intubation were also recorded. Patient satisfac-tion was assessed using a 4-point scale (1 = bad,2 = moderate, 3 = good, 4 = excellent). Nausea

and vomiting were treated with ondansetron 4 mgi.v.The primary outcome of this study was to

obtain a decrease in the desflurane requirement.Allowing an error of 0.01 and a error of0.10, it was estimated that a minimum of 27patients per group would be required to show a20% decrease in desflurane requirement. Thus, 30patients were recruited for each group in case ofpossible drop-outs from the study. Secondary out-come variables included propofol and morphineconsumption, patient satisfaction and occurrence

of side-effects.

Statistical analysis was performed using SPSSstatistical software (version 15.0, SPSS, Chicago,IL, USA) and MedCalc version 11.2.0.0. Thedistribution of the data was analyzed usingthe Kolmogorov Smirnov test. The independent

sample T-test was used to make between-groupcomparisons. Side-effects were analyzed using the2 test. P-values below 0.05 were considered sig-nificant. Values expressed as means aregiven withthe standard error of the mean.

Results

The demographic variables and duration ofsurgery were similar between the two groups. Thedemographic characteristics are shown in table 1.

During the 15 min infusion period of the studydrugs, prior to the induction of anesthesia, therewere no differences between MAP and HR, how-ever, BIS values were significantly lower in themagnesium sulphate-treated group (table 2).

The amount of propofol used for the induc-tion of anesthesia was low in magnesium-treatedpatients (p = 0.016). The magnesium sulphate-treated group received 114.3 29.3 mg ofpropofol, while the group receiving saline received

137.7 42.2 mg. The total consumption of desflu-rane was also found to be significantly lower in themagnesium sulphate-treated group (p = 0.005).Propofol and desflurane consumption rates areshown in table 3.

MAP, HR and BIS values were similar betweenthe groups throughout the surgery. Five patientsin the magnesium sulphate-treated group andeight patients in the saline group receivedatropine because of bradycardia. Intraoperativeuse of atropine and ephedrine were similar.

The groups did not differ with respect to thetime taken to reach a BIS value of 70 following;

Table 1. Demographic characteristics of patients in the group receiving magnesium sulphatetreatment compared to controls receiving saline.

Magnesium sulphate Saline(n = 30) (n = 30)

Age (yr) 47.7 11.4 45.4 12.4Weight (kg) 76.0 12.7 75.9 13.0Gender (F/M) 25 / 5 25 / 5

ASA (I/II) (20 / 10) (16 / 14)

Duration of operation (min) 64.1

20.8 70.6

16.5Mean SD; ASA: American Society of Anesthesiologists

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Table 2. BIS values before anesthesia in magnesium sulphate-treated group compared to controlsreceiving saline.

Magnesium sulphate Saline T P(n = 30) (n = 30)

BIS 0 min 95 10.6 97.3 1.9 -0.049 0.961BIS 5 min 92.6 9.2 97 2.0 2.512 0.015*BIS 10 min 89.9 9.9 95.9 3.8 3.049 0.003*BIS 15 min 86.4 11.5 93.8 6.3 3.077 0.003*

Mean SD; *P


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Table 5. Postoperative VAS pain scores in the magnesium sulphate-treated group compared to controlsreceiving saline.

Magnesium sulphate Saline T P(n = 30) (n = 30)

0 min 5.9 2.3 7.3 2.3 2.397 0.020*1 h 4.3 2.1 6.4 2.1 3.826 0.000*2 h 2.9 1.8 4.2 1.9 2.726 0.008*4 h 1.8 1.1 3.2 1.9 3.373 0.001*8 h 1.4 1.0 2.3 1.5 2.721 0.009*12 h 1.1 0.4 1.8 1.3 2.669 0.010*24 h 1.0 0.1 1.4 1.0 2.317 0.024*

Mean SD; *P


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postoperative serum magnesium levels of thesepatients were within the therapeutic range andthey did not receive any anesthetic or anal-gesic drugs that were outside the study protocol.

Although we did not use neuromuscular monitor-

ing, we believe that the effects of magnesium onthe neuromuscular junction may be responsiblefor this consequence.

Modified Aldrete scores on leaving the operat-ing room were also low in the magnesium group.This result is in accordance with the other studies[13].

Magnesium is known to inhibit the release ofcatecholamine from peripheral adrenergic nerveterminals and adrenal gland, and produce vaso-dilatation by calcium antagonistic effects on blood

vessel smooth muscle [18]. Several studies have

been performed looking at the effects of magne-sium on hemodynamics [18, 19]. Although Ryu

et al. found magnesium to decrease significantlyMAP and HR during total intravenous anesthe-sia [20], Tramer et al. have not demonstratedany hemodynamic differences between the groups[21]. In our study, the response to intubationand surgery, and intraoperative hemodynamicparameters were similar. The discrepanciesbetween the results from these studies might bedue to differences in methodology or the dosages

of magnesium and anesthetics used.It is known that the plasma magnesium concen-tration does not reflect the magnesium content ofthe tissues; however, magnesium toxicity has beenreported to start at serum magnesium concen-trations of 2.5-5 mmol/L, resulting in cardiacarrest at 12.5 mmol/L [22]. We therefore measuredthe serum magnesium concentrations and showedthat the concentration increased 1.5-2-fold post-operatively, without reaching toxic levels.

Postoperative pain control is an importantfactor for recovery and perioperative morbidity.

Serum magnesium concentration has beenreported to decrease during anesthesia andreturn to baseline 1-3 days after surgery [12].Magnesium produces a voltage-dependent block-ade of NMDA receptors, and its potential effectson postoperative opioid consumption have beenwidely investigated [23, 24]. In one of the primaryinvestigations involving the analgesic effects ofmagnesium, Tramer et al. demonstrated thatperioperative magnesium reduced postopera-tive analgesic use, provided better sleep quality

and patient comfort, without any side effects[21]. In the same study, they showed a 30%

decrease in postoperative morphine consumptionin magnesium-treated group. Pickering et al.showed that magnesium alone did not improvethe pain indicators in patients with neuropathicpain, but diminished the frequency of pain parox-

ysms and improved the emotional componentwhen compared to the placebo group [25].In our study, we obtained a 21% decrease in

postoperative morphine consumption by addingmagnesium as an adjuvant to anesthesia. VASpain scores were also lower in the magnesiumgroup at all time intervals measured. Althoughwe used a patient-controlled analgesia device andadministered a bolus dose of morphine when VAS4, patients reported high pain scores in thefirst two, postoperative hours. We believe that theresidual effects of intraperitoneal insufflation of

gases during the surgery, leading to abdominaldiscomfort, might be responsible for these highscores.

Studies report a feeling of flushing especiallyduring rapid infusion rates [26]. We observedflushing in four patients in the magnesiumsulphate-treated group. The side effect profile wassimilar in both groups. Although Tramer et al.have suggested that magnesium reduced nauseaand vomiting by decreasing postoperative opi-oid consumption [21], many investigators have

reported that magnesium did not offer any advan-tage [13]. Similarly, we did not demonstrate anydifference in the incidence of nausea-vomitingthat could be linked to the decrease in morphineuse. Patient satisfaction rates were also similarbetween the two groups. With the exception of onepatient, even those who were re-intubated scoredtheir anesthesia experience as good. We think thatpostoperative analgesia seems to be more impor-tant for the patients. However, in addition to thefact that patients might be reluctant to share theirreal thoughts with their doctors, , showing close

attention to the patient, and frequent questioningregarding pain and side effects might have alsoincreased the levels of satisfaction, particularlyfor those who were re-entubated.

In this study, the perioperative use of magne-sium sulphate reduced propofol and desfluraneconsumption and the postoperative morphinerequirement, while causing a delay in recovery asshown by a decreased Aldrete score. We suggestthat magnesium has a significant analgesic andanesthetic-sparing effect, but special care must be

taken as it can also lead to inadequate respirationand a delay in recovery.

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