|Year : 2017 | Volume
| Issue : 1 | Page : 28-33
Perioperative magnesium sulfate: an adjuvant to patients undergoing video-assisted thoracoscopic surgery
Assem A Moharram1, Aktham A Shoukry1, Nirvana A Elshalakany2, Ahmed M Mostafa3
1 Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Anesthesia and Intensive Care, Faculty of Medicine, October Six University, Cairo, Egypt
3 Department of Cardiothoracic Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Assem A Moharram
Department of Anesthesia and Intensive care, Faculty of Medicine, Ain Shams University, Cairo, 11828
Source of Support: None, Conflict of Interest: None
Background This randomized, prospective, double-blind, placebo-controlled study was designed to assess perioperative magnesium sulfate, an N-methyl-d-aspartate receptor blocker, as an anesthetic adjuvant reducing intraoperative anesthetic requirement, with a decrease in postoperative analgesic requirement and less adverse events.
Patients and methods A total of 24 patients undergoing video-assisted thoracoscopic surgery were included in two parallel groups − the magnesium group (group M, n=12) received magnesium sulfate 40 mg/kg intravenously before induction of anesthesia followed by 15 mg/kg/h continuous intravenous infusion during the operation. The same volume of isotonic solution was administered to the control group (group C, n=12). Primary outcome measures were postoperative analgesic requirement (doses of morphine and ketorolac). Secondary outcomes included intraoperative anesthetic requirements (fentanyl, sevoflurane, and vecuronium), postoperative visual analog score, Ramsay sedation score, and postoperative adverse events.
Results In the magnesium group, there was a reduction in intraoperative fentanyl (P=0.01), sevoflurane (P=0.02), and vecuronium (P=0.008), with a significant reduction in the postoperative dose of morphine (P=0.02), the need for rescue ketorolac (P=0.02), and a significant reduction in visual analog score and Ramsay sedation score compared with group C at 2, 3, 4, 6, and 8 h. There was a significant reduction in the number of patients who suffered an episode of tachyarrhythmia (P=0.03) with a decrease in nausea (P=0.06), vomiting (P=0.06), and pruritus (P=0.3), but did not reach statistical significance in group M compared with group C.
Conclusion Magnesium sulfate as an anesthetic adjuvant decreased postoperative analgesic requirement with a decrease in intraoperative anesthetic doses, with less adverse events.
Keywords: adverse events, analgesic requirement, anesthetic requirement, lobectomy, magnesium sulfate
|How to cite this article:|
Moharram AA, Shoukry AA, Elshalakany NA, Mostafa AM. Perioperative magnesium sulfate: an adjuvant to patients undergoing video-assisted thoracoscopic surgery. Ain-Shams J Anaesthesiol 2017;10:28-33
|How to cite this URL:|
Moharram AA, Shoukry AA, Elshalakany NA, Mostafa AM. Perioperative magnesium sulfate: an adjuvant to patients undergoing video-assisted thoracoscopic surgery. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2019 Jun 18];10:28-33. Available from: http://www.asja.eg.net/text.asp?2017/10/1/28/238467
| Introduction|| |
Video-assisted thoracoscopic surgery (VATS) is considered to be a less invasive surgery used to spare patients the large thoracotomy incision . The potential advantages of VATS include less postoperative pain, earlier mobilization, lower overall morbidity, a shortened hospital stay with reduced costs, a cosmetic incision, and, for some procedures, reduced operating time . However, the incidence of postoperative moderate-to-severe pain is still experienced in patients ,. Postoperative pain management includes administration of opioids and/or NSAIDs . Various anesthetic and analgesic techniques are used to decrease pain and improve outcomes . Magnesium sulfate an N-methyl-d-aspartate (NMDA) receptor anatgonist was studied as an adjuvant in perioperative analgesia in various operations . This study aimed to evaluate perioperative magnesium sulfate as an anesthetic adjuvant in patients undergoing VATS, decreasing intraoperative anesthetic requirement as well as postoperative analgesic consumption and adverse events.
| Patients and methods|| |
After approval from the institutional medical board and obtaining written informed consent, 24 patients aged above 18 years, American Society of Anesthesiologists physical status I and II, undergoing VATS in Ain Shams University Hospitals during the study period from December 2012 to December 2013 were included in the study. Exclusion criteria included coagulopathy, hepatic, renal, and cardiovascular dysfunction, neurological disease, chronic obstructive pulmonary disease, asthma, and patients treated with calcium channel blockers. Immediately after admission, patients were instructed to use a 10-point linear visual analog score (VAS) with a scale from 0 to 10, with the 0 representing no pain and the 10 representing the worst possible pain. Immediately before the operation, patients were randomised into two groups − group M (n=12) and group C (n=12) using a computer-generated program and opening a closed, sealed envelope. The magnesium group received 10% magnesium sulfate, and the control group received 0.9% sodium chloride in a double-blind manner. The solutions were prepared by the coordinator of the study, and the anesthetist who was in charge of the patients during the operation was unaware of the study medication.
Before induction, patients were monitored using standard monitoring (pulse oximetry, electrocardiogram, noninvasive arterial blood pressure monitoring, and capnography).The magnesium group (group M) received magnesium sulfate 40 mg/kg, administered as a slow intravenous bolus over a 10 min period before the induction of anesthesia, and 15 mg/kg/h by continuous intravenous infusion during the operation till the end of surgery. The same volume of isotonic saline was administered to the control group during the operation till the end of surgery (group C). Induction of anesthesia was achieved with 1–2 mg/kg of propofol, 2–3 µg/kg of fentanyl, and 0.1 mg/kg of vecuronium. A double-lumen endobronchial tube was placed for lung isolation. Maintenance of anesthesia consisted of oxygen, sevoflurane, and intermittent intravenous bolus doses of fentanyl 0.5 µg/kg. Dose adjustments of sevoflurane and fentanyl were based on standard clinical signs and hemodynamic measurements. Signs of inadequate analgesia were defined as an increase in heart rate (HR) and mean arterial pressure (MAP) of more than 20% from baseline. Hypotension was defined as a MAP of less than 20% from baseline. Supplemental vecuronium was administered if indicated by monitoring muscle relaxation with a nerve stimulator (model NS242; Fisher Paykel, Auckland, New Zealand. +6495740100). During the perioperative period, both groups received intravenous fluid (lactated Ringer solution) at 5 ml/kg/h.
Pressure-controlled ventilation was applied with FiO2 of 0.5 in air. During one-lung ventilation, FiO2 was increased to 0.8. At the end of surgery, residual neuromuscular block was reversed with neostigmine (0.04 mg/kg) and atropine (0.01 mg/kg), and the endotracheal tube was removed when the patient met criteria for extubation. Patients were transferred to the postanesthesia care unit (PACU) at the end of surgery. The final fentanyl dose was given ∼20 min before the end of surgery. After extubation, patients received 0.45–0.5% nebulized oxygen by facemask. Patients were monitored in the PACU for 2 h, and the need for reintubation in the postoperative period was recorded. Patients were then transferred to the high dependency unit for the rest of the 24 h follow-up. Patients who completed the 24 h follow-up were transferred to the ward. All the operations were performed by the same surgical team. The anesthetic technique for surgery was performed similarly for all patients by the same anesthetic team. On arrival at the PACU, all patients received intravenous PCA morphine (0.1 mg/kg/infusion). If VAS was more than 4, additional morphine of 2 mg intravenously was given, and the total amount of morphine given was recorded. HR, MAP, and peripheral oxygen saturation were monitored and recorded at 8, 16, and 24 h during the study period. Pain was assessed using VAS scores at rest and recorded at 1, 2, 3, 4, 6, 8, 16, and 24 h. Sedation was assessed at 1, 2, 3, 4, 6, 8, 16, and 24 h in the PACU according to the Ramsay sedation score (RSS)  ([Table 1]). Sedative drugs were not allowed during the study period. An investigator who was blinded to the study recorded levels of sedation, pain, total morphine consumption, and hemodynamic variables. Postoperative analgesia was assessed by a blinded observer using VAS. VAS was recorded after surgery at 1, 2, 3, 4, 6, 8, 12, and 24 h. Patients with VAS more than 4 received a morphine bolus dose. If the VAS was still more than 4 after the morphine dose, 30 mg of ketorolac was administered, which was repeated every 6 h with a maximum daily dose of 120 mg. The total analgesic doses required during the first 24 h. postoperatively were also recorded. Adverse events such as hypotension (systolic blood pressure<90 mmHg), respiratory depression (rate<10), arrhythmia [bradyarrhthmia (HR<40 beats/min) or tachyarrhythmia (HR>100 beats/min], postoperative hemorrhage, nausea, vomiting, and pruritus were also recorded. In the presence of nausea, with or without vomiting, ondansetron 4 mg intravenously was given and repeated once again if nausea persisted (maximum dose 8 mg/day).
Data were analyzed using SPSS, version 15 (SPSS Inc., Chicago, Illinois, USA). Data are reported as mean values and SDs. Continuous variables such as patient demographics (age, height, and weight), duration of surgery, and morphine consumption were analyzed using Student’s t-test. Categorical data such as sex and type of surgery were analyzed using percentages and χ2-tests. VAS pain score and RSS were analyzed using the Mann–Whitney U-test; a P value of 0.05 was considered statistically significant in these analyses. A sample size of 10 patients per group was needed to detect a 25% decrease in morphine consumption (α=0.05 and β=0.05 according to a previous study; 20% were added for possible violation of study protocol or possible dropout).
| Results|| |
A total of 28 patients were scheduled for VATS at the cardiothoracic department. Among them, two patients refused to participate in the study, one patient had renal disease, and one patient had a history chronic obstructive airway disease; thus, 24 patients were included in this randomized, prospective, double-blinded study (group M, n=12 and group C, n=12).There were no significant differences in patient characteristics with respect to age, sex, weight, height, and type of surgery ([Table 2]).
During the operation, patients in group M required less fentanyl (P=0.01), sevoflurane (P=0.02), and vecuronium (P=0.008) than group C. There was no significant difference between groups with regard to duration of operation, extubation time, and intraoperative fluid requirement. None of the patients in the study groups had any episode of hypotension or bradycardia ([Table 3]).
|Table 3 Mean and SD of duration of operation, intraoperative analgesic requirement, intraoperative fluid requirement, and extubation time|
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Postoperative hemodynamics, HR, MAP, and peripheral oxygen saturation were not significantly different between groups at 8, 16, and 24 h ([Table 4]), with a significant reduction in the total dose of morphine and the need for rescue ketorolac in group M compared with group C ([Table 5]). None of the patients in the study group required reintubation or suffered hypotension, bradycardia, or hemorrhage during the study period. In group M, there was a significant reduction in VAS and RSS than group C, respectively, at 2 h (P=0.01, 0.04), 3 h (P=0.01, 0.03), 4 h (P=0.003, 0.04), 6 h (P=0.04, 0.003), and 8 h (P<0.0001, 0.04). On the contrary, both VAS and RSS were not significantly different between groups, respectively, at 1 h (P=0.4, 0.5), 16 h (P=0.7, 0.4), and 24 h (P=0.1, 0.4) ([Figure 1] and [Figure 2]).
|Table 4 Postoperative hemodynamic means (SD) of heart rate, mean arterial pressure, and peripheral oxygen saturation at 8, 16, and 24 h|
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|Table 5 Postoperative analgesic requirement of total dose of morphine and ketorolac [mean (SD)]|
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|Figure 1 Bar charts represent the visual analog score during the postoperative period. Data are presented as median. *P<0.05 is considered significant.|
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|Figure 2 Bar charts represent the Ramsay sedation score during the postoperative period. Data are presented as median. *P<0.05 is considered significant.|
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During the postoperative period, there was a significant reduction in the number of patients who suffered an episode of tachyarrhythmia (four cases in group C and no cases in group M, P=0.03), with a decrease in the number of patients who suffered nausea (five cases in group C and only one case in group M, P=0.06) and vomiting (only three cases in group C, P=0.06); only one case of pruritus was present in group C (P=0.3), but did not reach statistical significance. No patient in the study group suffered intraoperative or postoperative hemorrhage or any sign of hypermagnesemia.
| Discussion|| |
This study evaluated magnesium sulfate as an adjuvant to patients undergoing VATS. Administration of magnesium sulfate resulted in a significant reduction in intraoperative anesthetic requirements (fentanyl, sevoflurane, and vecuronium), lower doses of morphine, and need for ketorolac postoperatively, with improvement in both VAS and RSS measured at 2, 3, 4, 6, and 8 h.
Thoracotomies are painful operations, and well-planned pain management is crucial for decreasing morbidity after major thoracic surgery for lung resection. In our study, we used VATS because of the potential advantages of less postoperative pain ,. Although postoperative systemic opioids are easy to use, cheap, and preferred by many clinicians for postoperative pain management, opioids still carry the risk of unwarranted side-effects such as respiratory depression, nausea, vomiting, and pruritus. Thus, various adjuvant analgesics to opioids are being studied to decrease the dose and the consequent unwarranted adverse effects.
Magnesium sulfate has been previously studied for its analgesic effect yielding conflicting results ,,,,,, Magnesium sulfate has been reported to reduce analgesic consumption both intraoperatively , and postoperatively ,,. The study by Levaux et al.  showed that a single dose of magnesium given at induction to patients undergoing lumber orthopedic surgery reduced postoperative opioid consumption during the 24-h study period. In addition, the study by Tramer et al.  administering perioperative magnesium sulfate to patients undergoing elective abdominal hysterectomy found a reduction in analgesic requirement, with a better quality of sleep in the postoperative period but without adverse effects. Moreover, Seyhan et al.  studied the effects of three different magnesium regimens in patients undergoing gynecological surgery and found that magnesium 40 mg/kg bolus followed by 10 mg/kg/h infusion reduced intraoperative anesthetic use (intraoperative propofol and atracurium) as well as postoperative morphine consumption during the 24 h period, and that increasing the dosage did not have any added advantages, but rather induced hemodynamic consequence.
Magnesium sulfate is also known for its sedative, antiarrhythmic, and bronchodilator effects , which would be beneficial in patients undergoing VATS both intraoperatively as well as postoperatively. We thus used magnesium sulfate 40 mg/kg as a slow intravenous bolus for a 10 min period before induction of anesthesia and 15 mg/kg/h by continuous intravenous infusion during VATS and similarly found significant reduction in intraoperative anesthetic requirements (fentanyl, sevoflurane, and vecuronium), with lower doses of morphine and need for ketorolac. Using this dose of magnesium sulfate was not associated with any episode of hypotension or bradycardia intraoperatively with no difference in postoperative hemodynamics between groups during the 24-h study period.
Although there are concerns regarding the effect of magnesium sulfate on platelet functions (in vitro and in vivo) and bleeding time ,,,, none of the patients in the study group suffered intraoperative or postoperative hemorrhage or any sign of hypermagnesemia. Moreover, during the postoperative period, there was a significant reduction in the number of patients who suffered an episode of tachyarrhythmia with a decrease in the number of patients who suffered nausea, vomiting, and pruritus in the magnesium group compared with the control group but did not reach statistical significance.
The possible mechanisms for the reduction in anesthetic requirements are antagonism of NMDA receptors in the central nervous system by magnesium  and reduction in catecholamine release by sympathetic stimulation, thus decreasing peripheral nociceptor sensitization or stress response to surgery . In addition, the actions of magnesium at the neuromuscular junction include a reduction in acetylcholine release from motor nerve terminals, a decrease in the depolarizing action of acetylcholine at the end-plate, and depression of muscle fiber membrane excitability ,,,. Moreover, magnesium could modulate postoperative pain by preventing nociception associated with central sensitization via blockade of NMDA receptor calcium ionophore ,. In addition, calcium channel blockers have shown antinociceptive effects in animals and a morphine-enhancing effect in patients with chronic pain .
A study by Ozcan et al.  was conducted using postoperative magnesium sulfate infusion for patients undergoing thoracotomy. In their study, Ozcan et al.  administered magnesium sulfate only postoperatively in a bolus dose of 30 mg/kg bolus, followed by10 mg/kg/h infusion for 48 h, and found that postoperative magnesium sulfate decreased morphine consumption after 4, 8, and 24 h with stable postoperative hemodynamics and no difference in VAS and RSS; they also reported an equal incidence of side-effects between their groups. The difference in results from our study may be because of the difference in dose and the magnesium sulfate regimen, as we administered magnesium sulfate as a bolus 40 mg/kg bolus followed by 15 mg/kg/h intraoperatively and the infusion was stopped by the end of surgery; moreover, our study was conducted on patients undergoing VATS, which is known to be less painful than conventional thoracotomy.
This study, although placebo-controlled, lacked measurement of serum magnesium levels, and comparison of different doses of magnesium sulfate or use of magnesium sulfate in the postoperative period. We conclude that magnesium sulfate as an anesthetic adjuvant decreased postoperative analgesic requirement with a decrease in intraoperative anesthetic doses, with less adverse events.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]