The effect of MS dose calculated using the actual body weight was similar to that calculated using the corrected ideal body weight in obese patients in terms of the blood concentration of magnesium, postoperative analgesia and recovery of neurmomuscular block.
The increase in adipose tissue and muscle mass results in changes in the pharmacokinetics of many medications21–24. Moreover, diseases associated with obesity reduct the physiological reserves this population27.
Despite the benefits of MS in various areas of medicine1–8 it has side effects11,27,28, such as delayed recovery of neuromuscular function and orotracheal extubation29.
The low-level pain at awakening has bias related to multimodal analgesic strategy used.
In this trial, patients in groups receiving MS showed lower mean postoperative pain scores and morphine consumption. This result, already reported in other studies9–12, is attributed to the action of magnesium in the calcium channels and N-methyl-D-aspartate (NMDA) receptors4,5.
There was a difference of 21.6% between the actual body weight and the corrected ideal body weight in the corrected ideal body weight group participants in the present study. Although receiving proportionally less MS these participants showed similar analgesic outcomes, compared to the real body weight group. That lower dose might have decreased the risk of adverse effects.
The onset of the cisatracurium effect in this trial was not altered by MS. Germano et al.30 did not find difference in latency of rocuronium 0.6 mg·kg− 1 after MS. Czarnetzki et al.15 found a significant reduction in the latency (average of 77 versus 120 s) rocuronium 0.6 mg·kg− 1 after MS at higher doses than in Germano’s and in the present study (60 mg·kg− 1). The difference in the time gap between the administration of MS and the administration of rocuronium might have interfered in the results. In the aforementioned studies rocuronium was the neuromuscular blocker agent, whereas cisatracurium was the neuromuscular blocker agent in our study. Thus, the absolute times in this study cannot be compared to those found by them.
In the current study, the groups showed no differences in the total duration of the neuromuscular block. This result is different from that reported by Czarnetzki16, who found that the average total recovery time was 73.2 min (SD = 22 min) with previous administration of MS 57.8 min (SD = 14.2 min) in the control group. However, a MS dose of 60 mg·kg− 1 was used before administration of rocuronium 0.6 mg·kg− 1. The absolute times in this study could not be compared to those found in ours.
The 21.6% difference in the MS dose administered in the groups did not result significant difference in the resulting magnesium blood concentrations. These concentrations were always within the safe values for patients in the study31.
This study included a nonobese group of 10 patients, who received MS at a dose of 40 mg·kg− 1, as a reference for the average magnesium concentration in the non-obese population. The comparison between the magnesium concentrations in obese patients and the nonobese group did not show any significant difference. The concentrations were also similar to those reported by Taheri et al.17.
Each gram of MS contains 98.6 mg of magnesium (Fresenius Kabi Canada, Toronto ON). In the current study, the real body weight group participants had an average actual body weight of 94.32 kg, while corrected ideal body weight group participants, had an average corrected ideal body weight of 73.54 kg. Therefore, average total doses of 3,772.8 mg and 2,941.6 mg were administered to the real body weight group and the corrected ideal body weight group participants, respectively. Based on the calculated total blood volume of 70 mL.kg− 1 of ideal body weight22,24,32−34 we estimated an average plasma volume of 2700 mL in both groups. Based on the information above, we calculated that the corrected ideal body weight group and the real body weight group participants received 290 mg and 372 mg of magnesium, respectively. Accordingly, and ignoring the tissue distribution volume, it is expected an increase in magnesium concentration of 1.07 mg.mL− 1 and 1.38 mg.mL− 1, respectively. It is similar to concentrations reached after 30 min of administration, after the highest peak in the first 15 min.
The average body content of magnesium is 24 g in an individual weighing 70 kg35,36. Only about 0.3% of this content is distributed in the plasma35,36. This is a possible cause for the rapid balance in the concentration and similar analgesia between the groups that received MS. The patients had an average increase in body magnesium of 1.2% in the corrected ideal body weight group and 1.55% in the real body weight group. Pascoal et al.37 compared two groups of 31 patients undergoing treatment with MS to prevent pre-eclampsia. After an initial dose of 6 g of MS patients received a continuous infusion of 1 g.h− 1 or 2 g.h− 1. The initial concentration was statistically equal between the groups (3.7 mEq.L− 1; p = 0.96). Thereafter, concentrations increased in the group that received an infusion of 2 g.h− 1 and decreased in the group that received 1 g.h− 1. The authors concluded that infusion of 1g.h− 1 can be as effective as infusion of 2 g.h− 1, with a small reduction in side effects. This knowledge may be transferred to the use of MS for analgesic purposes.
Finally, there is a huge variety of volume of distribution among patients as shown in the literature. This fact might have been an important bias affecting every outcome assessed in this study8. But, because of the safety concerns, the present study included relatively low BMI range of the participants. Studies with participants with a higher BMI range are needed to assess behavior with even more different doses between groups.
Sugimoto et al.38 recorded a reduction in the production of inflammatory cytokines (tumor necrosis factor and interleukin 6) in pregnant women submitted to MS, a mechanism that needs to be investigated in the context of the use of the substance for analgesic purposes.
Future research may clarify advantages and disadvantages of MS infusion association, the main mechanism of magnesium elimination, the role of reduction of inflammatory cytokines induced by MS in analgesia and the therapeutic window of this medication.
In conclusion, MS decreased postoperative pain and morphine consumption without affecting the recovery time of cisatracurium in obese patients undergoing laparoscopic cholecystectomy. Compared to dose based on actual weight in obese patient, the dose of MS based on corrected ideal weight induces similar analgesia. On the other hand, the resultant magnesium blood concentration is not different with both strategies.