|Year : 2017 | Volume
| Issue : 1 | Page : 76-83
Hypotensive anesthesia for the correction of scoliosis under total intravenous anesthesia: comparison between dexmedetomidine and magnesium sulfate
Ibrahim A Nasr, Khaled M Elnaghy, Hesham F Soliman
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Ibrahim A Nasr
Sultan Bin Abdul-Aziz Humanitarian City, PO Box 64399, Riyadh 11536
Source of Support: None, Conflict of Interest: None
Context This study was designed to compare dexmedetomidine with magnesium sulfate as an adjunctive to total intravenous anesthesia (TIVA) as regards the efficacy and safety as hypotensive agents in scoliosis correction surgery.
Patients and methods This prospective randomized double-blinded study included 40 patients of American Society of Anesthesiology II who were scheduled for the correction of scoliosis under TIVA and divided into two groups of 20 patients each. The first group was the Dex group, which was administered dexmedetomidine infusion at a rate of 0.5 μg/kg/h, and the second group was the Mg group, which was administered magnesium sulfate infusion at a rate of 15 mg/kg/h. The target mean arterial pressure (MAP) was 60–70 mmHg. The two groups were compared as regards MAP, heart rate (HR), intraoperative blood loss, blood transfusion, quality of surgical field, need for vasodilators and analgesics, time to extubation, time to recover the hypotension, time to recover the full conscious level, and perioperative serum levels of calcium and magnesium.
Results Both groups could achieve the target MAP before skin incision. The Dex group showed more HR stability, less intraoperative blood loss, and less intraoperative blood transfusion with better surgical field quality. Moreover, the need for vasodilators was lesser in this group. However, the Mg group showed faster extubation time, faster reversibility of hypotension, and faster recovery of full conscious level. Need for intraoperative analgesia was comparable between the two groups. Intraoperative and postoperative serum magnesium were higher in the Mg group and intraoperative and postoperative serum calcium levels showed gradual drop in the Mg group compared with the Dex group and the preoperative level in the Mg group. Both electrolytes showed recovery to normal preoperative level 24 h postoperatively without interference.
Conclusion TIVA with both dexmedetomidine and magnesium sulfate could achieve the target MAP for hypotensive anesthesia. Dexmedetomidine can control MAP with lesser need for vasodilators and with better control of HR. It provided lesser blood loss and better quality of surgical field. Magnesium sulfate showed faster extubation and recovery of conscious level with faster reversibility of hypotensive state but with the risk for perioperative hypocalcemia.
Keywords: dexmedetomidine, hypotensive anesthesia, magnesium sulfate, scoliosis
|How to cite this article:|
Nasr IA, Elnaghy KM, Soliman HF. Hypotensive anesthesia for the correction of scoliosis under total intravenous anesthesia: comparison between dexmedetomidine and magnesium sulfate. Ain-Shams J Anaesthesiol 2017;10:76-83
|How to cite this URL:|
Nasr IA, Elnaghy KM, Soliman HF. Hypotensive anesthesia for the correction of scoliosis under total intravenous anesthesia: comparison between dexmedetomidine and magnesium sulfate. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2018 Oct 15];10:76-83. Available from: http://www.asja.eg.net/text.asp?2017/10/1/76/238468
| Introduction|| |
Correction of scoliosis is a major surgical procedure that is usually associated with a significant blood loss . Controlled hypotension is the most commonly used technique to reduce blood loss and to provide better surgical field visualization during spinal fixation  with consideration of spinal cord perfusion to minimize the risk for ischemic neurological deficit .
Many anesthetics and vasoactive drugs have been used to produce controlled hypotension, including volatile agents, direct vasodilators, ganglion blockers, calcium channels blockers, β-adrenergic blockers, α2 agonists (dexmedetomidine), and magnesium sulphate ,,.
Dexmedetomidine is a selective, short-acting, central α2-adrenergic agonist, which is characterized by a dose-dependent decrease in mean arterial blood pressure (MAP), heart rate (HR), cardiac output, and norepinephrine release . It also has a sedative, anxiolytic, and analgesic action without respiratory depression . It also mediates a peripheral vasoconstrictive effect that reduces skin and muscle bleeding .
Magnesium sulfate also has been used as a hypotensive agent . It mediates its hypotensive effect by limiting the outflow of calcium from the sarcoplasmic reticulum and produces a vasodilating effect by increasing the synthesis of prostacyclin and inhibiting angiotensin-converting enzyme activity . Magnesium also reduces the need for analgesic and sedative drugs as it is an N-methyl-d-aspartate receptor antagonist . However, magnesium sulfate has hypocalcemic effect through the suppression of parathyroid hormone secretion and increase in renal calcium excretion .
The aim of this study was to compare dexmedetomidine and magnesium sulfate as hypotensive agents with total intravenous anesthesia in scoliosis correction surgery as regards their efficacy (hemodynamic stability, blood loss, intraoperative analgesic effect, and surgical field quality) and safety (reversibility of hypotension, conscious level recovery, extubation time, and risk for hypocalcemia).
| Patients and methods|| |
This prospective randomized double-blinded study was conducted at Sultan Bin Abdul-Aziz Humanitarian City (the largest rehabilitation hospital in the Kingdom of Saudi Arabia) over a period of 12 months (from December 2014 to December 2015). After approval of the Research Ethics Committee and having obtained written informed consent from all patients, 40 patients of both sexes between 11 and 18 years of age and of American Society of Anesthesiology physical status II who were scheduled for the correction of scoliosis under general anesthesia were included in the study.
On arrival to the preanesthesia area, intravenous cannula 20 G was inserted and 6 ml of blood was drawn for the measurement of preoperative serum magnesium and calcium (S1). All patients had established intravenous line, and infusion of Ringer’s lactate solution was started at a rate of 7 ml/kg/h. Routine monitoring was started immediately with ECG, pulse oximetry, and noninvasive blood pressure monitoring every 5 min with very close observation of the conscious level and respiratory pattern. Thereafter, patients were randomly allocated using a computer-generated random list to one of the two parallel groups.
- Dex group (n=20): Patients were administered dexmedetomidine infusion started at preanesthesia room at a dose of 1 μg/kg over 10 min (precedex 200 μg/2 ml, diluted in 50 ml 0.9% saline infused over 10 min before induction of anesthesia) as a loading dose, followed by continuous infusion with 0.5 μg/kg/h until the end of the procedure.
- Mg group (n=20): Patients were administered 50 mg/kg of magnesium sulfate diluted in 50 ml of 0.9% saline over 10 min before induction of anesthesia, and then was sustained at a maintenance dose of 15 mg/kg/h. Infusion was performed through syringe pump.
We excluded patients with cardiac disease (hypertension, arrhythmia, and valve lesions), respiratory disorders, pre-existing coagulation defects, hepatic or renal dysfunction, diabetes mellitus, neuromuscular disorder, and seizure disorder and those with known allergy to any of the drugs used in the study.
The solutions were prepared by an anesthesia technician who was not involved in the study monitoring. Moreover, the anesthetist was blinded to the infused medication and group allocation.
In the operating room, anesthesia was induced with fentanyl 1 μg/kg and propofol 2 mg/kg intravenously, atracurium 0.5 mg/kg intravenously with 100% oxygen, and mask ventilation for 3 min to facilitate tracheal intubation.
All patients were mechanically ventilated with a tidal volume of 6–10 ml/kg, I : E ratio of 1 : 2, and a respiratory rate adjusted to maintain end-tidal carbon dioxide concentration of 33–38 mmHg (10–16 breaths/min). Adequate muscle relaxation was maintained with incremental bolus doses of 10 mg atracurium when indicated by the peripheral nerve stimulation (TOF guard).
Another intravenous line with (18 G) cannula was established for the administration of fluids and blood, and a 22 G cannula was inserted into a radial artery for invasive arterial blood pressure monitoring. Urinary catheter was inserted to monitor urine output, and then all patients were placed in prone position.
Patients were monitored for HR and MAP (invasive and noninvasive), five-lead ECG, pulse oximetry, urine output, and esophageal temperature. Heating air mattress and infusion of warm fluids were used to maintain normothermia. Moreover, the bispectral index (BIS) was used to monitor an adequate depth of anesthesia. Propofol infusion was adjusted to maintain BIS score 40–60 (surgical anesthesia).
Anesthesia was maintained with 50% oxygen in air and propofol infusion, which started at a rate 12 mg/kg/h and then decreased gradually to 6–10 mg/kg/h. The target MAP for all groups was 60–70 mmHg to minimize the risk for spinal cord hypoperfusion and ischemia .
Tranexamic acid 10 mg/kg intravenously was administered to all patients in both groups before skin incision as an operative protocol to control intraoperative bleeding.
The intraoperative blood loss was calculated by weighing the surgical gauze pads and measuring the contents of the suction bottle (with adjustment made for the amount of saline irrigation used) by an anesthesia technician who was unaware of the study details. Surgical field quality was assessed by surgeons using Fromme’s scale  ([Table 1]).
Packed red blood cell transfusion was started when the blood loss reached 15% of the patient’s blood volume. Second blood sample (S2) was obtained before blood transfusion or after 2 h of skin incision, which is first, to measure intraoperative serum magnesium and calcium.
In both groups, signs of inadequate anesthesia (e.g. increases in MAP greater than the target level, movement, tearing, or sweating, and BIS>70) were treated with additional intravenous boluses of fentanyl at a dose of 1 μg/kg and recorded. Hydralazine 5 mg intravenous bolus was administered if MAP was higher than 70 mmHg for 5 min after adjustment of propofol infusion. Tachycardia (HR>120 beats/min or 20% higher than baseline reading with adequate urine output) was recorded and treated by increasing the depth of anesthesia. Hypotension (MAP<60 mmHg for >10 min) was treated with a bolus of saline infusion and ephedrine 5 mg intravenous bolus if needed. Bradycardia (HR<50 beats/min for 10 min) was treated with atropine 0.5 mg intravenously.
Infusion of the study drugs was stopped with the starting of the muscle layer closure, and propofol infusion was stopped after skin closure. Time to reversibility of the hypotensive state was recorded, which was defined as time from stopping of hypotensive agent until restoration of the baseline MAP.
At the end of surgery, any residual neuromuscular blockade was reversed with neostigmine and atropine to achieve a train-of-four ratio of at least 0.9. Extubation time (time from stopping of propofol infusion until extubation) and time to total recovery from anesthesia (time from stopping propofol infusion until recovery to Modified Aldrete’s score 9 on a scale 0–10) were recorded . After extubation, patients were transferred to the recovery room where a third blood sample was taken (S3) to monitor serum calcium and magnesium. A fourth blood sample (S4) was taken 24 h postoperatively to monitor serum calcium and magnesium as well.
The two groups were compared with reference to patient’s characteristics (age, sex, preoperative hemoglobin%, and body weights), preoperative, intraoperative, and postoperative serum calcium and magnesium, and intraoperative clinical data (operative time, anesthesia time, intraoperative blood loss and blood transfusion, intraoperative MAP and HR, quality of the operative field, intraoperative hydralazine and fentanyl consumption, time to restoration of MAP, extubation time, and time to regain full conscious level).
Data were collected and analyzed using a statistical software package (GraphPad InStat, version 3.00; GraphPad Software Inc., San Diego, California, USA) for Windows and presented as mean±SD, n (%), or ratio, as appropriate. A power analysis of α=0.05 and β=0.90 showed that 15 patients were required per study group to detect a 30% difference in the MAP and HR changes between the two groups. Groups were compared using the parametric or the nonparametric versions of analysis of variance followed by appropriate post-hoc analysis if significance was detected. Nominal data were compared using the χ2-test or alternatively using Fisher’s exact test, as appropriate. P values less than 0.05 were considered significant.
| Results|| |
There was no significant difference between the two groups as regards the age, sex, and body weight, duration of surgery, and duration of anesthesia ([Table 2]).
Preoperative hemoglobin levels were comparable between the study groups. Intraoperative blood loss was lesser in the Dex group compared with the Mg group. Moreover, the volume of transfused blood was significantly lesser in the Dex group compared with the Mg group ([Table 3]).
Both groups had achieved the target MAP throughout the intraoperative period ([Table 4]). Intraoperative hydralazine consumption was lower in the Dex group, whereas intraoperative fentanyl consumption did not show a significant difference between the two study groups ([Table 3]).
Intraoperative HR showed a significant drop in the Dex group compared with the Mg group and the preoperative values in the same group ([Table 5]). Two patients in the Dex group required one intravenous atropine dose, one patient at 60 min and the other patient at 150 min.
Preoperative serum magnesium was comparable between the two study groups, but after 2 h of induction it was significantly higher in the Mg group. The same results were reported in recovery room as well. The 24 h postoperative samples showed its recovery to the preoperative levels ([Table 6]).
Preoperative serum calcium was comparable between the two study groups, but after 2 h of induction it showed a significant drop in the Mg group compared with the Dex group and the preoperative level in same group. The same results were reported in recovery room as well. The 24 h postoperative samples showed comparable serum calcium levels between the two groups compared with each other and with preoperative levels ([Table 7]).
The Dex group showed a better surgical field quality compared with the Mg group. However, extubation time, recovery time to full conscious level, and recovery time of hypotension were significantly earlier in the Mg group in comparison with the Dex group ([Table 8]).
|Table 8 Surgical field quality and recovery time of hypotension and conscious level|
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| Discussion|| |
Correction of scoliosis is an extensive surgical procedure associated with major blood loss up to 50% of patient’s blood volume with a high incidence of developing coagulopathy due to dilutional transfusion or consumption of coagulation factors .
Controlled hypotension is a widely used technique to reduce blood loss, but it is associated with an increased risk for neurological deficit due to reduced spinal cord perfusion . For that reason, we adopted in our study a conservative control of MAP (60–70 mmHg), which could be achieved effectively in both study groups at skin incision. That target MAP was decided on the basis of a balance between many studies that investigated the save MAP level during hypotensive anesthesia. Newton et al.  had concluded that MAP at 55 mmHg produces minimal endocrine and metabolic responses and does not affect tissue perfusion. Another study by Chiesa et al.  showed that perioperative hypotension with MAP less than 70 mmHg has a higher risk of developing spinal cord ischemia. However, Yashikawa and colleagues used a MAP of 60–70 mmHg as a target for induced hypotensive anesthesia in patients undergoing mandibular osteotomy. They concluded that hypotension can be induced safely if MAP is maintained between 60 and 70 mmHg based on the nonsignificant changes they detected in the serum levels of pyruvate, lactate, and glucose .
The efficacy of dexmedetomidine in providing better surgical field and less blood loss during controlled hypotension was reported in many studies ,,. It has a sympatholytic effect of α2 agonists, which regulate the autonomic and cardiovascular systems and inhibit norepinephrine release. It also reduces the sympathetic outflow and augments the cardiac vagal activity, thus reducing the HR and cardiac output . It also mediates a peripheral vasoconstrictive effect through α2 receptors, which are located on blood vessel wall; thus, it reduces skin and muscle bleeding .
Magnesium sulfate has also been used as a hypotensive agent to decrease MAP and HR and to reduce bleeding . It has analgesic and antiarrhythmic properties. It also has direct vasodilator effect on peripheral vessels through calcium channel blockade resulting in hypotension and reduced blood loss . Magnesium produces vasodilatation through a direct action, as well as indirectly through sympathetic blockade and inhibition of catecholamine release , which may be responsible for hypotension produced by magnesium administration.
Our study showed that both study groups (the Dex group and the Mg group) could achieve the target MAP throughout the intraoperative period, but the hemodynamic profile of the Dex group showed more stability. HR was lower in the Dex group and the quality of surgical field and blood loss was more controlled. The volume of transfused blood and the intraoperative need for vasodilators (hydralazine) was lower in the Dex group, whereas intraoperative fentanyl consumption did not show a significant difference. Extubation time and time to restore the baseline values of MAP and time for conscious level recovery (Aldrete’s score 9) were longer with dexmedetomidine than with magnesium sulfate.
In agreement with that, a previous study found that dexmedetomidine has showed a higher hemodynamic stability with slower and steadier HR when compared with magnesium sulfate for hypotensive anesthesia . Dexmedetomidine also provided a lesser intraoperative blood loss and better surgical field quality, whereas the emergence time and time to restore MAP to its basal values were longer compared with magnesium sulfate and nitroglycerine in deliberate hypotension during functional endoscopic sinus surgery (FESS) .
Tobias and Berkenbosch  effectively achieved the target MAP (55–60) with dexmedetomidine for controlled hypotension in a case of pediatric patient undergoing spinal fusion surgery, but they showed a shorter time to restore baseline values (7 min after discontinuation).
Jamaliya et al.  also reported an effective use of dexmedetomidine in minimizing blood loss and maintaining superior hemodynamic in posterior fixation spine surgeries, but they reported a longer time to restore the baseline MAP (10 min). The great affinity of dexmedetomidine to α2 receptors can explain the longer time for restoration of baseline MAP in the Dex group even after the hypotensive drugs are stopped. The hypotension in the Dex group can be reverted only when the drug diffused out of its receptors . This reason can explain the longer time to restore the baseline values of MAP in our study as well. However, gradual return of blood pressure may be helpful by preventing excess blood loss in the immediate postoperative period.
Many studies had showed that magnesium sulfate could reduce MAP to the target values without reflex tachycardia and provided a satisfactory surgical field ,,. Elsharnouby and Elsharnouby  concluded that magnesium sulfate reduced MAP, HR, and blood loss and was associated with less anesthetic requirements and emergence time for patients who underwent FESS. Yosri et al.  concluded that magnesium sulfate could produce deliberate hypotension and provided good surgical conditions for the resection of choroidal melanoma compared with nitroprusside with no need for adding potent hypotensive agents. However, when compared with dexmedetomidine, Akkaya et al.  had shown that dexmedetomidine is more superior to magnesium sulfate in providing better visual quality of the surgical field when used in FESS patients under general anesthesia.
The current study did not show a significant difference as regards the intraoperative fentanyl consumption between the two study groups. Several studies have demonstrated that perioperative use of dexmedetomidine was associated with a significant reduction in the consumption of fentanyl in a dose-dependent manner ,,. This could be explained by the sedative and analgesic sparing effects of dexmedetomidine through central actions in the locus coeruleus and in the dorsal horn of the spinal cord . Moreover, the analgesic action of magnesium sulfate had been reported by Ryu and colleagues. They proved that magnesium sulfate and remifentanil both can induce adequate deliberate hypotension for middle ear surgery, but magnesium sulfate was associated with better postoperative analgesia .
In agreement with our observations, dexmedetomidine was associated with significantly longer times to extubation and to total recovery from anesthesia . Kol et al.  reported that extubation time was significantly longer in patients receiving dexmedetomidine compared with those receiving esmolol for controlled hypotension during tympanoplasty. Moreover, many studies observed that recovery time was prolonged in patients who received dexmedetomidine for induced hypotension when compared with control groups ,. Another study observed that there was a prolonged recovery time in patients who received dexmedetomidine when compared with those who received remifentanil during gynecologic laparoscopic surgery . However, Zhou et al.  reported that the use of dexmedetomidine in aged patients with total hip replacement surgery under general anesthesia resulted in reduction in the extubation time and waking time after surgery.
Although the MAP could be controlled in both our study groups throughout the intraoperative time, patients in the Mg group showed higher values of blood loss and consequently higher volumes of blood transfusion. Some studies reported that bleeding in spinal fusion surgery is essentially venous  and it is highly dependent on the degree of venous congestion around the vertebral bodies ,.
Magnesium sulfate has a direct vasodilator effect on the venous plexus around the vertebral bodies, which may contribute to increased blood loss with its use for controlled hypotension , whereas the peripheral vasoconstrictive effect of dexmedetomidine may explain the minimal intraoperative bleeding with the same MAP range .
Relton and Hall  had reported the relation between the venous congestion and blood loss within the same MAP range. Moreover, Lee et al.  had detected a wide variation in local blood flow in paraspinal muscles during spine surgery with different hypotensive drugs reaching a similar degree of hypotension. This supports the fact that the blood loss is influenced by the degree of venous congestion in the epidural plexus .
The effect of magnesium sulfate on coagulation profile is another factor that might increase the intraoperative bleeding . Some studies have shown that magnesium sulfate causes a prolongation in bleeding time ,, whereas another study found it effective in bleeding reduction without having an effect on patients’ coagulation profile . Moreover, James and Neil  found that serum magnesium level less than 3 mmol/l has no significant effects on coagulation. Unfortunately, we did not monitor the coagulation profile as one of the study parameters.
In our study, serum magnesium levels showed gradual intraoperative and immediate postoperative increase (as expected), whereas serum calcium levels showed gradual intraoperative and immediate postoperative drop and both parameters had recovered to normal preoperative values 24 h postoperatively without interference.
Many studies had reported the correlation between magnesium therapy and serum calcium level ,. Administration of a large dose of magnesium sulfate as in the treatment of pre-eclampsia may cause transient hypocalcemia due to increased renal loss and inhibition of parathyroid hormone secretion . High urinary calcium excretion may be due to the competition of magnesium with calcium at Ca+-sensing receptors on the basolateral surface of the loop of Henle . Cholst et al.  reported high levels of parathyroid hormone with drop in serum calcium levels during magnesium therapy, which supports that hypermagnesemia might blunt the peripheral effect of parathyroid hormone. Another study by Suzuki et al.  had shown that infusion of magnesium sulfate for 120 min was accompanied by a gradual and progressive decrease in serum calcium level. It was mainly due to renal calcium excretion with only minimal role for the parathyroid hormone.
| Conclusion|| |
Total intravenous anesthesia with both dexmedetomidine and magnesium sulfate could achieve the target MAP for hypotensive anesthesia. Dexmedetomidine can control MAP with less need for vasodilators and with better control of HR. It provided less blood loss and better quality of surgical field. Magnesium sulfate showed faster extubation and recovery of conscious level with faster reversibility of hypotensive state but with the risk for perioperative hypocalcemia.
Our study has some limitations. To begin with, there was no control group, as all patients had to receive hypotensive agent. Second, we did not monitor the coagulation profile changes with both agents, which might contribute in blood loss control. Third, we could not detect the actual time of recovery of serum levels of calcium and magnesium to normal values as we had one blood sample in recovery room and then the following sample was taken 24 h postoperatively, whereas some studies reported the recovery time of magnesium to preoperative levels 6 h after surgery .
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]