Table of Contents  
Year : 2015  |  Volume : 8  |  Issue : 2  |  Page : 217-222

Addition of magnesium sulfate to caudal block for preventing emergence agitation in sevoflurane-based anesthesia in children

Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission07-Sep-2014
Date of Acceptance16-Dec-2014
Date of Web Publication8-May-2015

Correspondence Address:
Ashraf E El-Agamy
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, PO Box 11331, Cairo
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.156691

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Postoperative emergence agitation (EA) is still a problem in sevoflurane-based anesthesia in children. Among the solutions of this problem is giving caudal anesthesia during operations in the lower half of the body. The aim of this study was to evaluate the addition of magnesium sulfate to bupivacaine in caudal block for the prevention of EA.
Materials and methods
In this prospective, randomized, double-blind study, 80 children aged 1-6 years, ASA I, undergoing unilateral hernia repair/orchiopexy with sevoflurane-based anesthesia were allocated into one of two groups: either bupivacaine 1 ml/kg 0.25% plus magnesium 50 mg (BM group) or bupivacaine 1 ml/kg 0.25% (B group) received in caudal block. EA was evaluated in both groups using the Pediatric Anesthesia Emergence Delirium scale and Aono's scale. The sedation score, the recovery time, and the occurrence of complications were assessed during the stay in the postanesthesia care unit.
Only 72 children completed the study (36 in each group). There was a statistically significant difference in the Pediatric Anesthesia Emergence Delirium scale, the value being lower in the BM group than in the B group at 5 min [6 (5-17) compared with 8 (5-18)] (P < 0.001) and at 10 min [5 (4-16) compared with 6 (4-13)] (P < 0.001) postoperatively. Aono's scale showed that the incidence of EA was significantly lower in the BM group than in the B group (P = 0.003). The sedation score was significantly higher in the BM group than in the B group at 15 min (P = 0.001). In contrast, the duration of motor block after operation was similar in both groups.
The use of caudal magnesium sulfate (50 mg) combined with bupivacaine 0.25% was effective in reducing postoperative EA in preschool children undergoing hernia repair/orchiopexy procedures.

Keywords: caudal block, emergence agitation, magnesium sulfate, sevoflurane anesthesia

How to cite this article:
El-Agamy AE, El-Kateb AS, Mahran MG. Addition of magnesium sulfate to caudal block for preventing emergence agitation in sevoflurane-based anesthesia in children. Ain-Shams J Anaesthesiol 2015;8:217-22

How to cite this URL:
El-Agamy AE, El-Kateb AS, Mahran MG. Addition of magnesium sulfate to caudal block for preventing emergence agitation in sevoflurane-based anesthesia in children. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2021 Oct 24];8:217-22. Available from:

  Introduction Top

Sevoflurane is used widely in pediatric anesthesia because of its excellent physical characteristics of fast and well-tolerated inhaled induction, low hepatotoxicity, hemodynamic stability, and rapid emergence from anesthesia. However, up to 80% of pediatric patients undergoing anesthesia with sevoflurane may experience postoperative emergence agitation (EA) [1],[2] . EA is characterized by the dissociative state of consciousness, crying, excitation, incoherence, and delirium. EA is a self-limiting condition, but it carries the risk of self-injury, particularly at the site of surgery, and is annoying for people around the child [3] . Different techniques have been used to treat EA and its severity: for example, sedative drugs before induction, change in the maintenance technique of anesthesia, administration of pharmacological agents at the end of anesthesia, and analgesics [1],[2],[3],[4],[5] . Among these techniques is the use of caudal analgesia, which has become one of the most popular and commonly used techniques in anesthesia for pediatric patients since it was described by Campbel in 1933. It is a rapid, reliable, and safe technique that can be used with general anesthesia for intraoperative and postoperative analgesia in pediatric patients undergoing lower limb or abdominal surgery. There are many additives to the local anesthetic drug, bupivacaine, in the caudal block to improve the quality of block and prolong the duration of analgesia, such as α2 -agonists, clonidine, and dexmedetomidine [6] .

N-methyl-d-aspartate (NMDA) receptors play a major role in central nociceptive transmission, modulation, and sensitization of acute pain. Among NMDA receptor antagonists, magnesium has been shown to be useful in the reduction of acute postoperative pain, analgesic consumption, or both. There are different studies about the route of administration of magnesium, such as intrathecal or epidural, that improves the anesthetic and analgesic quality [7],[8],[9] .

The role of magnesium sulfate as a sedative has been analyzed in several studies, and a significant reduction has been observed in midazolam consumption during the operation period of magnesium-treated individuals [10],[11],[12] . However, these studies used magnesium sulfate through the intravenous route.

The purpose of this prospective randomized double-blinded study was to compare the effects of adding magnesium sulfate to bupivacaine in caudal block to antagonize the suspected postoperative EA in children undergoing unilateral inguinal hernia repair/orchiopexy using sevoflurane-based anesthesia and to evaluate its possible side effects.

  Materials and methods Top

After obtaining the ethics committee approval and parental written informed consent, 80 boys aged 1-6 years, ASA I, scheduled for unilateral inguinal hernia repair or orchiopexy at Ain Shams University Hospital from November 2013 to May 2014 were enrolled in this prospective, randomized, double-blinded study. The study has been performed according to the World Medical Association Declaration of Helsinki. Children with developmental delay, psychological or neurological disorders, difficult airway, hyperactive airway disease, or children in whom caudal block was contraindicated (e.g. infection at the site of block, bleeding disorder, or abnormalities of the sacrum) were excluded from the study. All patients were fasted at least 6 h before operation.

The enrolled children were allocated randomly into one of two groups to receive either caudal bupivacaine-magnesium (BM group) or caudal bupivacaine alone (B group) in a double-blinded manner according to a computer randomization method. The study drugs were prepared randomly by an anesthetist who was not involved in the study. Children were transferred to the operating room without premedication. Monitoring included pulse oximetry, ECG, and noninvasive blood pressure. Anesthesia was started by inhalational induction of 8% sevoflurane in 100% oxygen through a facemask. The induction quality was judged according to a four-point scale: 1, crying, needs restraint; 2, moderate fear and reassured with difficulty; 3, slight fear, but can be reassured easily; and 4, asleep or calm or awake and cooperative [3] . Children with a score of 1 were excluded from the study as they were severely agitated during induction. After the child's loss of consciousness, sevoflurane was decreased to 3-3.5% for several minutes to facilitate the insertion of an intravenous cannula. A laryngeal mask airway (LMA; Laryngeal Mask Company Limited, Broadway, UK) was inserted: the size of the LMA was 1.5, 2, or 2.5 according to the child's weight (5-10, 10-20, or 20-30 kg), respectively. If LMA insertion failed, intubation was performed and the child was withdrawn from the study. After LMA insertion and adequate spontaneous ventilation, the child was placed in the lateral position, and caudal block was given using a 23-G short-beveled needle by a completely sterile technique. Children in group BM received caudal block 1 ml/kg of bupivacaine 0.25% (Hospira Inc., Lake Forest, Illinois, USA) mixed with 1 ml of 50 mg magnesium (1 g in 2 ml, 50% conc.; Martindale, Pharmaceuticals Brampton Road, Harold HillRomford, RM3 8UG, England) prepared by aspirating 1 ml (500 mg) 50% concentration diluted in 9 ml normal saline to be 50 mg/ml (5% concentration). Group B received 1 ml/kg of bupivacaine 0.25% mixed with 1 ml of 0.9% of normal saline in the caudal space. Surgical intervention was started after 5 min of caudal block in both groups.

Skin incision was performed as a test for adequate caudal block. An increased heart rate of more than 20% from the basal heart rate of the child was considered as inadequate caudal block, and the child was withdrawn from the study. During surgery, maintenance of anesthesia was achieved by sevoflurane 2-2.5% in 100% oxygen with fresh gas flow 4-5 l/min; spontaneous ventilation was maintained in all children. At the completion of surgery, the sevoflurane concentration was decreased to 1%, the LMA was removed, sevoflurane was discontinued, 100% oxygen was continued through a face mask with observation of possible early respiratory complications such as breath holding, airway obstruction, or laryngeal spasms. When spontaneous breathing with patent airway was satisfactory with no evidence of early respiratory complications, the child was transferred to the postanesthesia care unit (PACU).

When the child arrived to the PACU, he was monitored by a nursing staff who was blinded to the drug given in the caudal block. Parents were not allowed to enter the PACU for the first 30 min postoperatively according to the policy of our hospital. Bedside monitoring of SpO 2 , noninvasive blood pressure, respiratory rate, and heart rate was performed every 5 min for the first 30 min; the EA was evaluated and recorded at the same period of time by an attending anesthesiologist who was blinded to the drug given in the caudal block. The highest recorded value of EA was used for evaluation. The evaluation of EA was performed using the Pediatric Anesthesia Emergence Delirium (PAED) scale ([Table 1]) [13] .
Table 1 The Pediatric Anesthesia Emergence Delirium scale [13]

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Children with a PAED score of 16 or greater were defined as having EA: the higher the total score, the more severe the EA. Children with EA were given a rescue medication of propofol 1 mg/kg intravenously. Another scale used for the assessment of EA was Aono's scale (1, calm; 2, easily consoled state; 3, moderate agitation; 4, severe agitation) [13] . Aono's state 3 or more was considered as EA and was treated by giving a rescue medication of propofol 1 mg/kg intravenously. Assessment of sedation was performed using an objective score based on eye opening (eyes open spontaneously = 0, eyes open in response to verbal stimulation = 1, and eyes open in response to physical stimulation = 2) [6] .

When the child was fully awake and had stable hemodynamics and O 2 saturation greater than 95% on room air, he was shifted from the PACU to the outpatient recovery room to be kept with his guardians, and the children stayed for at least 3 h before discharge from the hospital. The duration of motor block was recorded (the time between giving caudal block and the first spontaneous movement of the child's legs).

The occurrence of any side effects during the whole recovery period was monitored; nausea and vomiting were treated with ondansetron 0.1 mg/kg. Delayed voiding was also recorded. The time for discharge from the PACU and the time of discharge from the recovery unit were also recorded.

Statistical analysis

Using PASS for sample size calculation, it was calculated that a sample size of 29 per group will achieve 80% power to detect a difference of 40% reduction in the incidence of emergency delirium between the two groups with a significance level (a) of 0.05 using a two-sided two-sample t-test: 36 patients per group were included to replace any drop outs.

The statistical analysis was performed using a standard SPSS software package version 17 (SPSS Inc., Chicago, Illinois, USA). Data were expressed as mean values ± SD for parametric data, n (%) for categorical data, and median (interquartile range) for nonparametric data. Student's t-test was used to analyze the parametric data, and discrete (categorical) variables were analyzed using the χ2 -test; the Mann-Whitney U-test for nonparametric data, with P-values less than 0.05 considered statistically significant.

  Results Top

Flow chart

Of the 80 children enrolled, only 72 children completed the study successfully ([Figure 1]). There were no significant differences in the age, the weight, or the duration of anesthesia between the two groups ([Table 2]).
Figure 1: A consort flow chart diag ram. BM, bupivacaine magnesium group; B, bupivacaine group.

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Table 2 Children's characteristics and the duration of anesthesia

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In the present study, there was a statistically significant difference with a lower PAED score in the BM group compared with the B group at 5 and 10 min after operation [6 (5-17) vs. 8 (5-18), P < 0.001, and 5 (4-16) vs. 6 (4-13), P < 0.001, respectively]. Also, the BM group was lower in the PAED score compared with the B group at 15, 20, 25, and 30 min, but without statistically significant values ([Table 3]).
Table 3 The Pediatric Anesthesia Emergence Delirium score

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Aono's scale, presented as the highest recorded value, showed that the incidence of EA was significantly lower in the BM group than in the B group (P = 0.003) ([Table 4]).
Table 4 Aono's scale

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The duration of stay in the PACU was comparable between children in both groups; however, the sedation score was significantly higher in the BM group than in the B group [15 min {1 (1-1) vs. 0.5 (0-1)}, P = 0.001]. In contrast, the duration of motor block was similar in both groups ([Table 5]).
Table 5 Postoperative characteristics

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The incidence of laryngospasm, nausea, vomiting, and delayed voiding were similar between both groups, whereas the use of rescue for EA (propofol 1 mg/kg intravenously) was significantly lower in the BM group compared with the B group (3 vs. 7 patients) (P < 0.001) ([Table 6]).
Table 6 The incidence of postoperative complications

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  Discussion Top

In the present study, we have shown that the addition of magnesium sulfate to bupivacaine 0.25% as preoperative caudal analgesia to children for unilateral hernia repair/orchiopexy resulted in a decrease in postoperative EA when compared with bupivacaine 0.25% alone without significant postoperative complications.

Various drugs were used to antagonize the occurrence of postoperative EA in children undergoing sevoflurane-based anesthesia. A recent meta-analysis demonstrated that propofol, fentanyl, α2 -adrenergic receptor agonists, and ketamine play a role in the prevention of EA [14] . Another recent study by Kim et al. [15] found that small doses of propofol or fentanyl at the end of sevoflurane anesthesia reduces EA, with evidence that propofol was better for short-term PACU stay and a lower incidence of nausea and vomiting. Additives to caudal analgesics are numerous: use of opioids has its side effects, for example, respiratory depression, itching, nausea, and vomiting [16] . α2 -Adrenoreceptor agonists (dexmedetomidine) provide good analgesia, but cause prolonged sedation for up to 4 h postoperatively [6] .

Magnesium sulfate is a physiological calcium channel blocker and a noncompetitive NMDA receptor antagonist; these properties appear to play a major role in the prevention and the treatment of perioperative pain and could also be responsible for the modification of perioperative sedation [17] . Several studies have been conducted to evaluate the effect of either intrathecal or epidural magnesium; however, they concentrated on the effect of magnesium in prolonging the analgesic and antinociceptive effects of opioids [18],[19] .

Pain assessment scales in preschool children are observational scales and also incorporate agitation as a part of their assessment; however, none of the pain scales have been tested to differentiate between manifestations of EA and pain. Pain during emergence from general anesthesia may be a cause of EA; however, EA has also been recorded in patients undergoing nonpainful interventions, suggesting that pain may not be the sole etiology [20] . In the present study, preoperative caudal block was given to exclude pain, and children with unsatisfactory caudal block were excluded from the study. The results of the present study regarding EA in the BM and the B groups were 3/36 (8%) and 7/36 (19%), respectively, which are less than that found by Singh et al. [20] who found the incidence of EA after sevoflurane anesthesia with preoperative caudal block with bupivacaine to reach up to 40%. In other studies, preoperative caudal block was effective in decreasing the incidence and the severity of EA, with a varying incidence from 4.5 to 26%. The lower limit is actually lower than that found in the present study; this might be due to the use of midazolam as premedication and because of parental presence in the PACU [21],[22] . However, in the current study, the incidence of EA in the BM group was less than the incidence of EA (10%) with high single intravenous dexmedetomidine for the same types of operation, but with delayed discharge from PACU [78 (25) min compared with 35.9 (3.3) min in the present study] [1] .

In the present study, there was a significantly lower incidence of EA in the BM group than in the B group [three children compared with seven children, respectively (P < 0.001)], meaning that the caudal route of magnesium sulfate can decrease the incidence of EA in preschool children; this might be attributed to the central sedative effect of magnesium sulfate, which has been investigated in other studies [11],[23] . No other studies investigated the caudal route of magnesium sulfate; however, the central effect of magnesium has been assessed in either intrathecal or epidural routes, especially in adults [19],[20] .

The gradual decrease in PAED scores postoperatively in both groups coincides with other studies with regard to EA in preschool children [20],[24] . In the present study, caudal magnesium has two beneficial effects: a lower incidence of EA [3/36 patients (8%)] and also a decreased time of stay in the PACU in comparison with intravenous fentanyl 1 µg/kg at the end of sevoflurane-based anesthesia to antagonize EA [15] .

Postoperative sedation scores at different times were significantly higher in the BM group than in the B group at 15 min [1 (1-1) vs. 0.5 (0-1)] (P = 0.001). Our results are different from the sedation produced by caudal dexmedetomidine that caused up to 4 h postoperative sedation [6] . The duration of motor block was not prolonged in the BM group compared with the B group; this may be due to the low concentration of magnesium sulfate (5%) and the low dose of 50 mg only added to the conventional caudal bupivacaine 0.25%.

The incidence of postoperative complications was similar in both groups with regard to laryngospasm, nausea and vomiting, and delayed voiding. The significantly lower use of the rescue drug (propofol 1 mg/ml) in the BM group than in the B group (three vs. seven patients; P < 0.001, respectively), might be due to the central sedative effect of magnesium sulfate, but the use of propofol as a rescue medication did not prolong the stay of patients in the recovery room.

The PAED scale is considered as a valid and reliable scale to evaluate EA as supported by other studies, especially for the comparison of drugs for assessing their effects in the prevention of EA in preschool children [13, 15, 25]. However, other studies used other scales, besides the PAED scale, and the incidence of EA might be different depending on the evaluation scale [14],[26] . However, in the present study, Aono's scale was used to reinforce the results of EA found by the PAED scale and both were comparable.

There are several limitations to the present study. First, the dose of magnesium sulfate (50 mg) in the caudal block was fixed instead of varying with the variable body weight in children, but the aim of study was to prove the role of the drug in antagonizing postoperative EA after sevoflurane anesthesia, thus paving the way for other studies that can compare different doses of magnesium sulfate. Second, children with severe preoperative anxiety were excluded from the study, as preoperative anxiety may exacerbate postoperative EA; hence, further studies are needed to investigate the effect of caudal magnesium sulfate on children with preoperative anxiety. Finally, there is a lack of a long postoperative follow-up to evaluate whether there are other late-onset complications.

  Conclusion Top

The use of caudal magnesium sulfate (50 mg combined with bupivacaine 0.25%) is effective in reducing postoperative EA in preschool children undergoing hernia repair/orchiopexy in sevoflurane-based anesthesia procedures without remarkable side effects.

  Acknowledgements Top

Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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