Abstract
Background
Emergence agitation (EA) is a phenomenon commonly occurring in otorhinolaryngology surgery. It may increase the risk of injury and prolong recovery. Dexmedetomidine is the standard preventive agent, but limited due to its high cost, limited accessibility, extubation time, and incidence of bradycardia and hypotension. Magnesium sulphate (MgSO4) is considered a potential alternative but is there is insufficient research available. This study aimed to compare the effectiveness of intravenous MgSO4 and dexmedetomidine in reducing EA.
Methods
This study is a multicentered, double‐blinded, randomized controlled trial involving 64 adult patients undergoing otorhinolaryngology surgery. They were divided into two groups in a 1:1 ratio, with one group receiving MgSO4 20 mg/kgBW/h and another receiving dexmedetomidine 0.5 μg/kgBW/h from induction until the procedure ends. We measured the proportion of EA, onset, and duration of EA, intraoperative ephedrine dose, perioperative heart rate and mean arterial pressure (MAP), pain scores, perioperative fentanyl use, intraoperative sevoflurane use, and extubation time.
Results
The proportion of EA was not significantly different between the MgSO4 and dexmedetomidine groups (12.5% vs. 15.6%, p > 0.05). No differences in the severity, onset and duration of EA. The reduction of MAP and heart rate were greater in the dexmedetomidine group. The intraoperative ephedrine was significantly lower in the MgSO4 group (0 vs. 5 mg, p < 0.05). No significant differences in fentanyl and sevoflurane use, postoperative pain scores, and extubation time.
Conclusion
Intravenous MgSO4 and dexmedetomidine showed no statistically significant difference in the incidence of EA in adult patients undergoing otorhinolaryngologic surgery.
Trial Registration: ClinicalTrials.gov: NCT07544173
Keywords: adult, dexmedetomidine, emergence agitation, magnesium sulphate, otorhinolaryngology
1. Background
Emergence agitation (EA) involves a state of restlessness, disorientation, and purposeless movements in the early recovery phase from general anesthesia (GA). In the adult population, its incidence ranges from 21.3% to 45.9% globally. EA may cause significant clinical consequences, such as injury to patient or medical staff, accidental medical equipment dislodge, respiratory depression, and increased healthcare costs [1, 2]. Otorhinolaryngology surgeries carry a high risk of EA. A study by Yu in China reported an incidence of 55.4% in adult patients, primarily due to endotracheal tube use and nasal packing, which can cause a choking sensation. Other risk factors include obesity, sevoflurane anesthesia, smoking, advanced age, and a history of psychological disorders [3, 4].
EA typically begins 2–5 min after the cessation of inhaled anesthetic agents and can last for 30–45 min postextubation [4, 5]. Currently, there is no specific diagnostic test to confirm EA in adult patients. Most studies use the Riker Sedation‐Agitation Scale (RSAS), the Richmond Agitation‐Sedation Scale (RASS), or the 4‐point Aono scale to assess it [6–8]. At our teaching hospital, Rumah Sakit dr. Cipto Mangunkusumo (RSCM), RASS is the standard tool for evaluating agitation and delirium. A study by Suhandoko and Maskoen in Indonesia also found that the RASS demonstrated better reliability and validity compared to the Ramsay scale [9].
Dexmedetomidine is a highly selective α2 agonist. Various studies have shown that different doses of dexmedetomidine are consistently effective in reducing the incidence of EA [10, 11]. It is superior to propofol in preventing agitation and has a lower risk of respiratory depression compared to fentanyl, making it the preferred standard for managing EA [12–14]. However, its high cost, limited availability, risk of hypotension and bradycardia, and prolonged extubation time are notable limitations [10, 15].
Another drug that can be administered to reduce EA incidence is MgSO4. It enhances postoperative analgesia, provides sedation, reduces postoperative agitation, and facilitates better recovery after GA [1, 16, 17]. In addition, MgSO4 is more cost‐effective compared to dexmedetomidine and is more widely available across our country, Indonesia.
Direct comparative evidence between magnesium sulphate and dexmedetomidine for the prevention of EA in adults remains limited. Most previous comparative studies were conducted in nonotorhinolaryngologic surgical populations. To the best of our knowledge, no multicenter randomized controlled trial from Southeast Asia has directly compared continuous intraoperative magnesium sulphate and dexmedetomidine infusions for the prevention of EA in adult patients undergoing otorhinolaryngologic surgery. The present study therefore addresses an important regional and clinical evidence gap. In addition, given the lower cost and wider availability of magnesium sulphate, establishing whether it provides comparable effectiveness to dexmedetomidine may have important implications for perioperative practice in resource‐limited settings.
2. Methods
This study is an experimental double‐blinded, randomized controlled trial. Participants were consecutively selected from adult patients undergoing elective otorhinolaryngology surgery at the central operating theatre of Cipto Mangunkusumo Hospital (RSCM) and Universitas Indonesia Hospital (RSUI) from May to August 2024. Based on previous literature and an anticipated difference in EA incidence, with a significance level of 5% and power of 80%, a minimum of 58 participants was required. To account for potential dropouts, 10% was added, resulting in a total sample size of 64 participants. Sampling was conducted after receiving approval from the Health Research Ethics Committee of RSCM‐Faculty of Medicine Universitas Indonesia and the RSUI Research Ethics Committee. This trial was prospectively registered at ClinicalTrials.gov.
Patients scheduled for elective otorhinolaryngology surgery were assessed for eligibility. Inclusion criteria included adults aged 18–70 years, ASA physical status of 1 or 2, undergoing GA, and willing to participate in the research. Exclusion criteria were pregnant patients, severe cognitive impairment, allergies to study drugs, drug contraindications (atrioventricular block, sinoatrial node dysfunction, and renal failure), neuromuscular disorders, regular use of beta‐blockers or clonidine, not extubated in operating room (OR) nor postanesthesia care unit (PACU) after procedure, and BMI ≥ 40.
Subjects who met the inclusion and exclusion criteria signed the informed consent, and their information, including psychological history and smoking habits, was documented. They were then prepared for otorhinolaryngology surgery under GA. Randomization was performed using computer‐generated block randomization (block size of four) in a 1:1 ratio for drug allocation: MgSO4 (20 mg/kgBW/h) or dexmedetomidine (0.5 μg/kgBW/h). Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes prepared by an independent investigator not involved in patient care or data collection. The pharmacy team prepared the drugs according to the envelope instructions and labelled them with a research code, ensuring the researchers remained unaware of the drug identities. Both drugs were diluted in normal saline to make a total volume of 40 mL in identical syringes. With a similar infusion mL/h rate, ensuring a double‐blind study design. Data were collected by the researchers during the procedure, while the anesthesia team monitored the patients throughout the surgery.
An intravenous line was established before entering the OR. In the OR, standard monitoring equipment, including blood pressure, ECG, oxygen saturation, etCO2, and temperature devices, was set up. Mean arterial pressure (MAP), heart rate (HR), and sevoflurane consumption were recorded. The study drug infusion (MgSO4 20 mg/kgBW/h or dexmedetomidine 0.5 μg/kgBW/h) was initiated during the preoxygenation phase, prior to induction of anesthesia, and continued throughout the maintenance phase until the end of surgery. Therefore, both agents were administered as a continuous intraoperative infusion spanning induction and maintenance phases, ensuring consistent plasma levels during the emergence period. Dosages were calculated based on total body weight (TBW). Anesthesia was induced with a bolus of fentanyl 2 mcg/kgBW and propofol 2 mg/kgBW, followed by sevoflurane to deepen the anesthesia. The train of four (TOF) was measured if available. Rocuronium 0.6 mg/kgBW was administered once the patient was unconscious, followed by intubation. After intubation, 5 mg of IV dexamethasone and 1 g of IV paracetamol were administered. Anesthesia maintenance was achieved with sevoflurane at a minimum alveolar concentration (MAC) of 0.6–1.1. Fentanyl 1 mcg/kgBW and rocuronium 0.2 mg/kgBW were given intermittently as needed. If MAP or HR decreased by more than 30% from baseline values, 5 mg of ephedrine was administered. All fentanyl and ephedrine doses were recorded in the case report form.
At the end of the procedure, 30 mg of IV ketorolac and 10 mg of IV metoclopramide were administered. Before extubation, neostigmine and atropine were given when the TOF count was 4 and the TOF ratio was at least 0.4 or when the patient had resumed spontaneous breathing. Once the patient’s spontaneous ventilation was adequate, sevoflurane and the study drug were discontinued, and 80% oxygen at 6 L per minute was delivered. Extubation was performed while the patient was conscious. Extubation time was defined as the time from discontinuation of sevoflurane to eye opening on verbal command, obeying simple commands, achievement of a train‐of‐four (TOF) ratio ≥ 0.9, and removal of the endotracheal tube. The researcher assessed the EA using the RASS, with EA defined when RASS ≥ 2. Severe EA was defined as a RASS score ≥ +3, corresponding to very agitated or combative behavior requiring pharmacological intervention. If RASS was ≥ 3, propofol bolus of 0.5 mg/kgBW would be administered to the patient. The onset and duration of agitation, as well as the propofol dosage, were documented in the study report. EA onset is measured when both the study drug and sevoflurane are ceased until the RASS reaches ≥ 2, while EA duration is measured from when agitation begins until RASS < 2.
After the surgery, patients were transferred to the recovery room or PACU for assessment of postoperative pain using a numeric rating scale (1–10 scale), MAP and HR, and EA. Tendon reflexes and muscle strength were also evaluated. If necessary, calcium gluconate was administered if hyporeflexia or areflexia happened. Patients were discharged from the PACU once their Aldrete score reached ≥ 9.
Data analysis was performed using the Fisher’s exact test due to small expected cell counts. The Kolmogorov–Smirnov test was used to assess the normality of numerical data. Normally distributed data were presented as mean and standard deviation (SD) and analyzed using the independent Student’s t‐test. Nonnormally distributed data were reported by using median and minimum–maximum (min–max) ranges, and the Mann–Whitney test was applied. A risk difference with 95% confidence interval was calculated for the primary outcome. A p value < 0.05 was considered statistically significant. For repeated measurement data, such as MAP, HR, and sevoflurane MAC, the general estimating equations (GEE) were used.
3. Results
Data collection was done from May to August 2024 at the Central Operating Theatre of RSCM and RSUI. A total of 82 patients were assessed for eligibility. Eighteen patients were excluded, and 64 patients were randomized into two groups. The participant flow is shown in Figure 1. The baseline demographic and clinical characteristics of the participants are summarized in Table 1.
FIGURE 1.
CONSORT 2010 flow diagram.
TABLE 1.
Subjects characteristics.
| Variable | MgSO4 (n = 32) | Dexmedetomidine (n = 32) | p value |
|---|---|---|---|
| Age (years) α | 35 (18–68) | 45 (19–65) | 0.162 |
| Geriatric (> 60 years old) β | 1.000 | ||
| Yes | 5 (15.6%) | 4 (12.5%) | |
| No | 27 (84.4%) | 28 (87.5%) | |
| Sex β | 1.000 | ||
| Male | 14 (43.8%) | 15 (46.9%) | |
| Female | 18 (56.2%) | 17 (53.1%) | |
| Body weight (Kg) γ | 61.6 ± 12.7 | 62.3 ± 14.6 | 0.842 |
| Height (Cm) α | 160 (145–181) | 165 (141–183) | 0.522 |
| Body mass index (BMI) | 23.4 ± 4.4 | 23.4 ± 5.4 | 0.990 |
| Obesity β | 1.000 | ||
| Obese | 3 (9.4%) | 4 (12.5%) | |
| Nonobese | 29 (90.6%) | 28 (87.5%) | |
| ASA physical status β | |||
| ASA 1 | 10 (31.2%) | 9 (28.1%) | 1.000 |
| ASA 2 | 22 (68.8%) | 23 (71.9%) | |
| Surgery duration (min) α | 210 (50–570) | 175 (50–420) | 0.336 |
| Smoking status β | |||
| Smokers | 6 (18.8%) | 7 (21.9%) | 1.000 |
| Nonsmokers | 26 (81.2%) | 25 (78.1%) | |
| Psychologic status β | |||
| With psychological disorder | 2 (6.3%) | 1 (3.1%) | 1.000 |
| Without psychological disorder | 30 (93.8%) | 31 (96.9%) | |
| Surgery types β | 0.930 | ||
| Otology | 13 (40.6%) | 13 (40.6%) | |
| Rhinology | 14 (43.8%) | 15 (46.9%) | |
| Larynx and pharynx | 5 (15.6%) | 4 (12.5%) |
αNonnormally distributed data, presented as median (min–max), tested by the Mann–Whitney test.
βData presented as n (%), tested by chi‐square test or Fisher exact if cell expectation count < 5.
γNormally distributed data, presented as means ± SD, tested by unpaired student’s T‐test.
The occurrence of EA (Table 2) was observed in 12.5% of the MgSO4 group, compared to 15.6% of the dexmedetomidine group. The risk difference was −3.1% (95% CI −20.1% to 13.9%). Fisher’s exact test demonstrated no statistically significant difference between groups (p = 1.000). In the MgSO4 group, 1 subject (3.1%) experienced severe agitation, while 2 subjects (6.2%) in the dexmedetomidine group experienced the same, with no statistically significant difference (p = 1.000) (Table 2). Although severe EA occurred in a small number of patients (1 in MgSO4 group and 2 in the dexmedetomidine group), the overall median propofol requirement remained 0 mg in both groups, as most patients did not develop agitation requiring pharmacological treatment. The median propofol dose required for all study participants was 0 mg, with no statistically significant difference (p = 1.000). There were no statistically significant differences in the onset or duration of EA between the MgSO4 and dexmedetomidine groups (p = 0.73 and p = 0.19, respectively).
TABLE 2.
EA proportion, severity, propofol use, onset, and duration of EA.
| EA proportion α | |||||
|---|---|---|---|---|---|
| Group | EA | Without EA | p | Risk difference | 95% CI |
| MgSO4 | 4 (12.5%) | 28 (87.5%) | 1.000 | −3.1% | −20.1%–13.9% |
| Dexmedetomidine | 5 (15.6%) | 27 (84.4%) | |||
| Severe EA proportion β | |||||
| Group | Severe EA | Without severe EA | p | Risk difference | 95% CI |
| MgSO4 | 1 (3.1%) | 31 (96.9%) | 1.000 | −3.2% | −16.8%–10.6% |
| Dexmedetomidine | 2 (6.3%) | 30 (93.8%) | |||
| Propofol use γ | |||||
| Variable | MgSO 4 (n = 32) | Dexmedetomidine (n = 32) | p | ||
| Propofol dose | 0 (0–30) | 0 (0–30) | 1.000 | ||
| Onset and duration of EA δ | |||||
| Variable | MgSO 4 (n = 4) | Dexmedetomidine (n = 5) | p | ||
| Onset (min) | 10 (9–13.5) | 8 (5–13) | 0.73 | ||
| Duration (min) | 2 (2–3) | 5 (1.5–5) | 0.19 | ||
αCell expectation count < 5. Analysis was performed using Fisher exact test.
βCell expectation count < 5. Analysis was performed using Fisher exact test.
γNonnormal data distribution. Analysis was performed using Mann–Whitney test.
δNonnormal data distribution. Analysis was performed using Mann–Whitney test.
The MAP was measured in mmHg and HR was measured in beats per minute (bpm). Several measurement points were taken, including baseline, preinduction, postinduction, postintubation, postincision, 30 min postincision, postextubation, and 1‐h postoperative. The analysis of the GEE for MAP showed a significant interaction (p < 0.005) between dexmedetomidine use and time at postincision, 30 min postincision, and postextubation (Table 3). At postincision, the dexmedetomidine group experienced a 9.4 mmHg decrease in MAP from baseline compared to the MgSO4 group (p = 0.036). This was also observed at 30 min postincision, with an 8.28 mmHg decrease in the dexmedetomidine group (p = 0.032). At postextubation, the dexmedetomidine group showed another reduction of 10.12 mmHg from baseline (p = 0/010).
TABLE 3.
Intraoperative MAP change.
| Predictor | Coefficient | Standard error | p |
|---|---|---|---|
| Constants | 92.78 | 1.50 | < 0.001 |
| Drug | |||
| MgSO4 | 0.0 | — | |
| Dexmedetomidine | −0.281 | 2.48 | 0.910 |
| Observation | |||
| Baseline | 0.0 | ||
| Preinduction | 3.43 | 1.71 | 0.045 |
| Postinduction | −13.81 | 2.44 | < 0.001 |
| Postintubation | −3.84 | 2.94 | 0.192 |
| Postincision | −8.99 | 3.18 | 0.005 |
| 30 min postincision | −12.40 | 2.32 | < 0.001 |
| Postextubation | 0.87 | 2.94 | 0.767 |
| 1 h postoperative | −5.46 | 1.88 | 0.004 |
| Drug and time interactions | |||
| Dexmedetomidine ∗ baseline | 0.0 | ||
| Dexmedetomidine ∗ preinduction | 4.71 | 2.64 | 0.075 |
| Dexmedetomidine ∗ postinduction | −2.93 | 3.62 | 0.418 |
| Dexmedetomidine ∗ postintubation | −5.68 | 3.90 | 0.145 |
| Dexmedetomidine ∗ postincision | −9.40 | 4.47 | 0.036∗ |
| Dexmedetomidine ∗ 30 min postincision | −8.28 | 3.85 | 0.032∗ |
| Dexmedetomidine ∗ postextubation | −10.12 | 3.95 | 0.010∗ |
| Dexmedetomidine ∗ 1 h postoperative | −2.53 | 2.84 | 0.374 |
Note: Tested by GEE and exchangeable correlation matrix.
∗statistically significant (p < 0.05).
The GEE for HR showed a significant interaction between dexmedetomidine use and time at postincision and postextubation (Table 4). At postincision, the dexmedetomidine group had a significant average heart rate reduction of 8.18 bpm from baseline compared to the MgSO4 group (p = 0.022). This difference reoccurred at postextubation, with an average heart rate drop of 8.84 bpm in the dexmedetomidine group (p = 0.008).
TABLE 4.
Intraoperative HR change.
| Predictor | Coefficient | Standard error | p |
|---|---|---|---|
| Constants | 78.15 | 1.84 | < 0.001 |
| Drug | |||
| MgSO4 | 0.0 | — | |
| Dexmedetomidine | −4.31 | 2.74 | 0.910 |
| Observation | |||
| Baseline | 0.0 | ||
| Preinduction | 3.34 | 2.00 | 0.095 |
| Postinduction | −2.78 | 2.00 | 0.165 |
| Postintubation | 8.78 | 2.56 | 0.001 |
| Postincision | 4.84 | 2.69 | 0.072 |
| 30 min postincision | −2.50 | 2.34 | 0.287 |
| Postextubation | 12.75 | 2.71 | < 0.001 |
| 1 h postoperative | 1.93 | 1.82 | 0.287 |
| Drug and time interactions | |||
| Dexmedetomidine ∗ baseline | 0.0 | ||
| Dexmedetomidine ∗ preinduction | 0.15 | 2.81 | 0.976 |
| Dexmedetomidine ∗ postinduction | 3.75 | 3.02 | 0.215 |
| Dexmedetomidine ∗ postintubation | −1.12 | 3.14 | 0.742 |
| Dexmedetomidine ∗ postincision | −8.18 | 3.58 | 0.022∗ |
| Dexmedetomidine ∗ 30 min postincision | 0.59 | 2.97 | 0.842 |
| Dexmedetomidine ∗ postextubation | −8.84 | 3.34 | 0.008∗ |
| Dexmedetomidine ∗ 1 h postoperative | −4.06 | 2.43 | 0.096 |
Note: Tested by GEE and exchangeable correlation matrix.
∗statistically significant (p < 0.05).
The most frequent side effects of both study drugs were bradycardia and hypotension (Table 5). When these occurred, 5 mg of ephedrine was given as a rescue agent. The incidence of bradycardia between the dexmedetomidine and MgSO4 groups was not statistically significant (p = 0.238) according to the Fisher exact test. However, the difference in the proportion of hypotension was significant based on the chi‐square test (p = 0.023). Hypotension was observed in 9 cases (28.1%) in the MgSO4 group, with a relative risk (RR) 0.474 times lower than in the dexmedetomidine group, which had 19 cases (59.4%). Additionally, dexmedetomidine required a median of 5 mg of ephedrine per surgery, compared to 0 mg for the MgSO4 group (p = 0.003). No cases of respiratory depression, arrhythmia, or clinically significant hypermagnesemia were observed in either group during the intraoperative or immediate postoperative period.
TABLE 5.
Proportion of bradycardia and hypotension, intraoperative ephedrine use.
| Proportion of bradycardia α | |||||
|---|---|---|---|---|---|
| Group | Bradycardia | No bradycardia | p | RR | 95% CI |
| MgSO4 | 0 (0%) | 32 (100%) | 0.238 | — | — |
| Dexmedetomidine | 3 (9.4%) | 29 (90.6%) | |||
| Proportion of hypotension β | |||||
| Group | Hypotension | No hypotension | p | RR | 95% CI |
| MgSO4 | 9 (28.1%) | 23 (71.9%) | 0.023 | 0.474 | 0.254–0.884 |
| Dexmedetomidine | 19 (59.4%) | 13 (40.6%) | |||
| Ephedrine intraoperative use γ | |||||
| Variable | MgSO 4 (n = 32) | Dexmedetomidine (n = 32) | p | ||
| Ephedrine dose (mg) | 0 (0–30) | 5 (0–30) | 0.003 | ||
αCell expectation count < 5. Analysis was performed using Fisher exact test.
βCell expectation count ≥ 5. Analysis was performed using chi–square test.
γNonnormal data distribution. Analysis was performed using Mann–Whitney test.
The use of intraoperative sevoflurane was measured in MAC (Table 6). The sevoflurane MAC is recorded after intubation, during incision, 30 min after the incision, and just before cessation of sevoflurane. The distribution of sevoflurane usage data is not normal. The Mann–Whitney test results indicate no significant difference in MAC between the two groups, and no interaction between MAC and time was found based on the GEE (p = 0.075).
TABLE 6.
Intraoperative sevoflurane use.
| MAC | MgSO4 (n = 32) | Dexmedetomidine (n = 32) | p |
|---|---|---|---|
| Postintubation | 0.8 (0.5–1.1) | 0.8 (0.6–1.1) | 0.188 |
| During incision | 0.9 (0.6–1.1) | 0.8 (0.6–1.1) | 0.201 |
| 30 mins after incision | 0.9 (0.6–1.1) | 0.8 (0.6–1.1) | 0.070 |
| Just before sevoflurane cessation | 0.7 (0.4–1.1) | 0.6 (0.3–1.1) | 0.073 |
| Interaction MAC ∗ time | 0.075 |
Note: Nonnormal distribution. Analysis was performed using the Mann–Whitney test. The MAC ∗ time interaction was tested by GEE.
The analysis of fentanyl dosage was based on the intraoperative fentanyl amount in micrograms/kgBW/h and the proportion of patients receiving fentanyl postoperatively as rescue analgesia for severe pain (Table 7). An independent t‐test revealed no significant difference in intraoperative fentanyl dosage between the groups (p = 0.255). A chi‐square test on postoperative fentanyl use also showed no statistically significant difference between the groups (p = 1.000). Postoperative pain scores were assessed using the numeric pain scale, with pain defined as a score of 4 or higher. In both groups, 6.2% of patients reported pain, with no significant difference in proportions (p = 1.000).
TABLE 7.
Intraoperative and postoperative fentanyl use, postoperative pain proportion.
| Intraoperative fentanyl use α | |||||
|---|---|---|---|---|---|
| Variable | MgSO4 (n = 32) | Dexmedetomidine (n = 32) | p | ||
| Intraoperative fentanyl (microgram/kgBW/h) | 1.28 ± 0.71 | 1.09 ± 0.64 | 0.255 | ||
| Postoperative fentanyl use β | |||||
| Group | With fentanyl | Without fentanyl | p | RR | 95% CI |
| MgSO4 | 1 (3.1%) | 31 (96.9%) | 1.000 | — | — |
| Dexmedetomidine | 1 (3.1%) | 31 (96.9%) | |||
| Postoperative pain β | |||||
| Group | Pain | No pain | p | RR | 95% CI |
| MgSO4 | 2 (6.2%) | 30 (93.8%) | 1.000 | — | — |
| Dexmedetomidine | 2 (6.2%) | 30 (93.8%) | — | — | |
αNormal data distribution. Analysis was performed using unpaired student’s t‐test.
βCell expectation count < 5. Analysis was performed using Fisher exact test.
Extubation time was recorded in minutes, starting from the discontinuation of sevoflurane and the study drug until the patient was fully awake and extubated (Table 8). As the data distribution was nonnormal, the Mann–Whitney test was used for analysis, revealing no significant difference between the two groups (p = 0.503).
TABLE 8.
Extubation time.
| Variable | MgSO4 (n = 32) | Dexmedetomidine (n = 32) | p |
|---|---|---|---|
| Extubation time (min) | 10 (4.5–23) | 10 (4–30) | 0.503 |
Note: Nonnormal data distribution. Analysis was performed using Mann–Whitney Test.
4. Discussion
The overall characteristics of the subjects in both groups were considered comparable, as there were no statistically significant differences (p > 0.05). The results showed no significant difference between MgSO4 and dexmedetomidine in reducing EA (p > 0.05). These findings are consistent with Salman et al., who reported comparable effectiveness between the two agents. In contrast, Ahmed et al. found MgSO4 to be superior during percutaneous nephrolithotomy [18]. Variability in surgical type, anesthetic technique, and agitation definitions may explain these differences across studies.
EA has been attributed to asynchronous cortical recovery, where motor and auditory functions return earlier than higher cognitive processing. Dexmedetomidine reduces sympathetic activity through central alpha‐2 receptor stimulation, whereas MgSO4 primarily acts as an NMDA receptor antagonist and calcium channel modulator [4, 19]. Despite different mechanisms, both agents may reduce neuronal excitability during anesthetic emergence, which may explain their similar clinical performance.
The overall incidence of EA in this study was relatively low. A meta‐analysis by Shen et al. reported no significant reduction in EA with MgSO4; however, only eight studies were included, and postoperative pain was not evaluated [16]. Mahmoud et al. demonstrated dexmedetomidine superiority in pediatric patients, suggesting age‐related differences in neurophysiological response. The low event rate observed in the present study may have limited the ability to detect modest between‐group differences [20].
No significant difference was found in propofol requirements or severe agitation incidence. Similar reductions in EA severity have been reported with dexmedetomidine and MgSO4 in previous studies by Kim et al. [7, 21]. Hussein Fahmy Kahla et al. also demonstrated that MgSO4 reduced agitation severity and postoperative opioid consumption, indicating combined sedative and analgesic effects [22]. In our cohort, postoperative pain incidence was low, which may have contributed to the overall low agitation rate.
In this study, the dexmedetomidine group demonstrated a more significant reduction in MAP and heart rate compared to the MgSO4 group. Based on the GEE analysis, dexmedetomidine produced greater reductions in MAP and heart rate compared with MgSO4. Its sympatholytic action via presynaptic alpha‐2 receptor stimulation explains this effect [23–25]. These findings align with previous studies and meta‐analyses demonstrating significant MAP and HR reductions with dexmedetomidine [26–28]. In contrast, MgSO4 was administered without a loading dose and at a lower maintenance infusion (< 30 mg/kg), which may explain its milder hemodynamic effect. The greater magnitude of hemodynamic reduction observed with dexmedetomidine is clinically relevant, as it likely contributed to the higher incidence of hypotension and increased requirement for ephedrine in this group [29–31]. Although postoperative hypotension did not differ significantly between groups, dexmedetomidine‐induced hypotension has been reported at higher cumulative doses [15].
Ephedrine was required more frequently in the dexmedetomidine group, likely reflecting stronger sympatholytic activity. Ahmed et al. similarly reported bradycardia requiring vasoactive intervention [18]. However, other studies found no significant difference in hypotension incidence [28, 32]. Overall, MgSO4 appeared to provide greater hemodynamic stability, which may be advantageous in patients sensitive to blood pressure fluctuations.
Sevoflurane is known to increase EA risk [2]. In this study, MAC values were comparable between groups. Experimental data suggest that sevoflurane increases neuronal excitability, which may be attenuated by NMDA antagonists or sedative agents [33]. Both MgSO4 and dexmedetomidine may reduce anesthetic requirements and contribute to smoother emergence [23, 34]. However, anesthetic depth monitoring was not used, and MAC adjustments were based on hemodynamic parameters, which may introduce variability.
At extubation, MAC values were 0.7 in the MgSO4 group and 0.6 in the dexmedetomidine group, with no significant difference observed. High end‐of‐surgery sevoflurane concentrations have been associated with increased agitation and delayed recovery [35, 36]. Although depth‐of‐anesthesia monitoring (e.g., bispectral index or Conox) may optimize volatile agent titration and reduce EA risk, anesthetic depth in this study was guided by hemodynamic parameters rather than EEG‐based monitoring. While MAC values were comparable between groups, variability in individual anesthetic sensitivity may have influenced emergence characteristics and represents a potential confounding factor.
No significant differences were found in intraoperative or postoperative fentanyl consumption. Although dexmedetomidine has demonstrated opioid‐sparing effects in other surgical settings, otorhinolaryngologic procedures generally require lower opioid requirements [23, 37]. Postoperative pain is a recognized risk factor for EA [38, 39]. In this study, postoperative pain occurred in only 6.2% of patients, with postoperative opioid administration in 3.1%, which may partly explain the overall low incidence of agitation.
Median extubation time was 10 min in both groups, with no significant difference. Extubation time was defined as the interval from discontinuation of sevoflurane to eye opening on verbal command, ability to obey simple commands, achievement of TOF ratio ≥ 0.9, and removal of the endotracheal tube. Salman and Mohamed reported longer extubation with dexmedetomidine, whereas other studies have shown no consistent prolongation [1, 40]. The absence of delayed recovery in this study may be related to the continuous low‐dose infusion of dexmedetomidine (0.5 μg/kg/h) without a loading dose [35, 41].
This study provides novel evidence by evaluating magnesium sulphate and dexmedetomidine specifically in adult otorhinolaryngologic surgery, a population at high risk for EA. In addition, the multicenter design enhances the generalizability of the findings. The comparable effectiveness observed between the two agents suggests that magnesium sulphate may serve as a practical and accessible alternative to dexmedetomidine, particularly in resource‐limited healthcare settings.
Several limitations should be acknowledged. The inclusion of different surgical procedures may have introduced heterogeneity in pain intensity and operative duration. The relatively low incidence of EA resulted in a limited number of events, which may have reduced the statistical power to detect moderate between‐group differences. Preoperative anxiety was also not assessed, and intraoperative blood loss, which may have contributed to hypotensive episodes, was not quantified. Additionally, although MAC values were recorded, total sevoflurane consumption and objective anesthetic depth were not measured, leaving residual confounding related to anesthetic depth. Formal assessment of blinding accuracy was not performed; however, identical drug preparation, labeling, and allocation concealment procedures were implemented to minimize the risk of unblinding. Future studies incorporating more homogeneous surgical populations and depth‐of‐anesthesia monitoring may provide more precise estimates of comparative effectiveness.
5. Conclusion
This study demonstrated that MgSO4 and dexmedetomidine showed comparable effectiveness in reducing EA in adult patients undergoing otorhinolaryngologic surgery. There were no significant differences in the proportion of EA events or the propofol dose required for severe agitation between the two groups. The onset and duration of agitation were also comparable. Patients in the dexmedetomidine group experienced greater decrease in MAP and HR and required higher doses of ephedrine. There were no significant differences in intraoperative use of fentanyl or sevoflurane between the groups. Similarly, postoperative pain and fentanyl use were comparable. The extubation times were also similar, averaging around 10 min for both groups.
Author Contributions
Riyadh Firdaus: conceptualization, methodology, supervision, investigation, formal analysis, manuscript drafting, and final approval of the manuscript.
Aino Nindya Auerkari: study design, data collection, interpretation of data, manuscript review, and critical revision.
Girhanif Amri Yunda: data collection, statistical analysis, literature review, manuscript editing, and interpretation of data.
Funding
The authors receive no sponsorship and financial support.
Disclosure
All authors read and approved the final manuscript.
Ethics Statement
This study was approved by the Health Research Ethics Committee of Rumah Sakit Universitas Indonesia (RSUI), Indonesia, with ethical approval number S‐064/KETLIT/RSUI/IV/2024 and protocol number 2024‐04‐065, approved on 17 April 2024. Research permission was also granted by Dr. Cipto Mangunkusumo National General Hospital (RSCM), Jakarta, Indonesia, under document number YR.02.01/D.IX.2.3/462/2024. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants prior to enrollment in the study.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
The authors thank the staff of Dr. Cipto Mangunkusumo Hospital and Universitas Indonesia Hospital for their support during this study.
Yunda, Girhanif Amri , Firdaus, Riyadh , Auerkari, Aino Nindya , Comparison on the Effectiveness of Intravenous Magnesium Sulphate and Intravenous Dexmedetomidine in Reducing Emergence Agitation in Adults Undergoing Otorhinolaryngology Surgery, Anesthesiology Research and Practice, 2026, 5531396, 10 pages, 2026. 10.1155/anrp/5531396
Academic Editor: Srijoni Sengupta
Contributor Information
Riyadh Firdaus, Email: riyadh.firdaus@ui.ac.id.
Srijoni Sengupta, Email: ssengupta@wiley.com.
Data Availability Statement
Research data are not shared.
References
- 1. Salman O. H. and Mohamed H. S. A., Comparison Between Dexmedetomidine Versus Magnesium Sulfate Infusions for Mitigating Emergence Agitation in Obese Adults Undergoing Nasal Surgery, Ain-Shams Journal of Anaesthesiology. (2022) 14, no. 1, 4–11. [Google Scholar]
- 2. Tolly B., Waly A., Peterson G., Erbes C. R., Prielipp R. C., and Apostolidou I., Adult Emergence Agitation: A Veteran-Focused Narrative Review, Anesthesia and Analgesia. (2021) 132, no. 2, 353–364, 10.1213/ane.0000000000005211. [DOI] [PubMed] [Google Scholar]
- 3. Yu D., Chai W., Sun X., and Yao L., Emergence Agitation in Adults: Risk Factors in 2000 Patients, Canadian Journal of Anesthesia. (2010) 57, no. 9, 843–848, 10.1007/s12630-010-9338-9. [DOI] [PubMed] [Google Scholar]
- 4. Lee S. J. and Sung T. Y., Emergence Agitation: Current Knowledge and Unresolved Questions, Korean Journal of Anesthesiology. (2020) 73, no. 6, 471–485, 10.4097/kja.20097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Kusnugroho D. and Pardede B., Pencegahan Emergence Agitation Pasca-Operasi Pada Pasien Anak, Cermin Dunia Kedokteran. (2020) 47, no. 1, 16–23. [Google Scholar]
- 6. Talih G., Yüksek A., and Şahin E., Evaluation of Emergence Agitation After General Anesthesia in Rhinoplasty Patients: Inhalation Anesthesia Versus Total Intravenous Anesthesia, American Journal of Otolaryngology–Head and Neck Medicine and Surgery. (2020) 41, no. 3, 10.1016/j.amjoto.2020.102387. [DOI] [PubMed] [Google Scholar]
- 7. Kim J. C., Kim J., Kwak H., and Ahn S. W., Premedication with Dexmedetomidine to Reduce Emergence Agitation: A Randomized Controlled Trial, BMC Anesthesiology. (2019) 19, no. 1, 4–9, 10.1186/s12871-019-0816-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Jo J. Y., Jung K. W., Kim H. J. et al., Effect of Total Intravenous Anesthesia vs. Volatile Induction With Maintenance Anesthesia on Emergence Agitation After Nasal Surgery: A Randomized Clinical Trial, JAMA Otolaryngology–Head and Neck Surgery. (2019) 145, no. 2, 117–123, 10.1001/jamaoto.2018.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Suhandoko E. P. and Maskoen T. T., Reliabilitas Dan Validitas Penilaian Skala Sedasi Richmond Agitation Sedation Scale (RASS) Dan Ramsay Pada Pasien Kritis Dengan Ventilasi Mekanik di Ruang Perawatan Intensif, Jurnal Anestesi Perioperatif. (2014) 2, no. 3, 186–193, 10.15851/jap.v2n3.330. [DOI] [Google Scholar]
- 10. Zhang J., Yu Y., Miao S. et al., Effects of Peri-Operative Intravenous Administration of Dexmedetomidine on Emergence Agitation After General Anesthesia in Adults: A Meta-Analysis of Randomized Controlled Trials, Drug Design, Development and Therapy. (2019) 13, 2853–2864, 10.2147/dddt.s207016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Ye Q., Wang F., Xu H., Wu L., and Gao X., Effects of Dexmedetomidine on Intraoperative Hemodynamics, Recovery Profile and Postoperative Pain in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Controlled Trial, BMC Anesthesiology. (2021) 21, no. 1, 1–10, 10.1186/s12871-021-01283-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Han X., Sun X., Liu L., and Wang Q., Single Bolus Dexmedetomidine Versus Propofol for Treatment of Pediatric Emergence Delirium Following General Anesthesia, Pediatric Anesthesia. (2021) 32, no. 3, 446–451, 10.1111/pan.14381. [DOI] [PubMed] [Google Scholar]
- 13. Sultana S. P., Saikia D., and Dey S., Fentanyl Versus Dexmedetomidine for the Prevention of Emergence Agitation in Children After Sevoflurane Anesthesia: A Comparative Clinical Study, Cureus. (2022) 14, no. 8, 1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Huang L., Wang L., Peng W., and Qin C., A Comparison of Dexmedetomidine and Propofol on Emergence Delirium in Children Undergoing Cleft Palate Surgery With Sevoflurane-Based Anesthesia, Journal of Craniofacial Surgery. (2022) 33, no. 2, 650–653, 10.1097/scs.0000000000008343. [DOI] [PubMed] [Google Scholar]
- 15. Yang S. S., Gelinas C., Yim E. et al., Association of Intraoperative Dexmedetomidine Use With Postoperative Hypotension in Unilateral Hip and Knee Arthroplasties: A Historical Cohort Study, Canadian Journal of Anesthesia. (2022) 69, no. 12, 1459–1470, 10.1007/s12630-022-02339-5. [DOI] [PubMed] [Google Scholar]
- 16. Shen Q. H., Shen X., Lai L., Chen Y. J., Liu K., and Sun L. J., The Effect of Magnesium Sulfate on Emergence Agitation in Children Undergoing General Anesthesia: A Systematic Review and Meta-Analysis, Journal of Clinical Anesthesia. (2022) 78, 10.1016/j.jclinane.2022.110669. [DOI] [PubMed] [Google Scholar]
- 17. Su Y. H., Luo D. C., and Pang Y., Effects of Intraoperative Magnesium Sulfate Infusion on Emergency Agitation During General Anesthesia in Patients Undergoing Radical Mastectomy: A Randomized Controlled Study, BMC Anesthesiology. (2023) 23, no. 1, 1–7, 10.1186/s12871-023-02288-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Ahmed A. A., Mohammed M. H. E. D., Alsagheer G. A., and Ismail M. M. A., Magnesium Sulphate Versus Dexmedetomidine for Prevention of Emergence Agitation After Sevoflurane in Adult Patients Undergoing Percutaneous Nephrolithotomy, Egyptian Journal of Hospital Medicine. (2022) 88, no. 1, 3434–3438, 10.21608/ejhm.2022.248722. [DOI] [Google Scholar]
- 19. Liu G. Y., Chen Z. Q., and Zhang Z. W., Comparative Study of Emergence Agitation Between Isoflurane and Propofol Anesthesia in Adults After Closed Reduction of Distal Radius Fracture, Genetics and Molecular Research. (2014) 13, no. 4, 9285–9291, 10.4238/2014.january.24.9. [DOI] [PubMed] [Google Scholar]
- 20. Mahmoud E., Zahaby H., Moharram A., and Asaad A., The Effect of Dexmedetomidine Infusion Versus Magnesium Sulphate Infusion on Emergence Delirium in Pediatric Patients Undergoing Lower Abdominal Surgery, QJM: International Journal of Medicine. (2021) 114, no. 1. [Google Scholar]
- 21. Koo C.-H., Koo B.-W., Han J., Lim D., Shin H.-J., and Shin H., The Effects of Intraoperative Magnesium Sulfate Administration on Emergence Agitation and Delirium in Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Pediatric Anesthesia. (2021) 32, no. 4, 522–530, 10.1111/pan.14352. [DOI] [PubMed] [Google Scholar]
- 22. Hussein Fahmy Kahla A., Mohamed El-Mahdi Ibrahim W., and Mahmoud Shehata El-Sayed A., The Efficacy of Magnesium Sulphate on Emergence Agitation in Adults Following Nasal Surgeries, Al-Azhar Medical Journal. (2019) 48, no. 4, 467–478, 10.21608/amj.2019.64953. [DOI] [Google Scholar]
- 23. Menshawi M. A. and Fahim H. M., Dexmedetomidine Versus Magnesium Sulfate as Adjunct to General Anesthesia in Patients Undergoing Video-Assisted Thoracoscopy, Ain-Shams Journal of Anaesthesiology. (2022) 14, no. 1, 10.1186/s42077-021-00209-8. [DOI] [Google Scholar]
- 24. Noor El-Din T., Madian M., Salem E., and Hamed A., Magnesium Sulfate Versus Nitroglycerin in Controlled Hypotensive Anesthesia in Middle Ear Surgeries, International Journal of Medical Arts. (2020) 2, no. 3, 661–667. [Google Scholar]
- 25. Sanad H. A., Mohamed A. Z., and Abd-elraouf A. A., Comparative Study Between Three Different Doses of Magnesium Sulfate as a Technique of Hypotensive Anesthesia During Functional Endoscopic Sinus Surgery, Egyptian Journal of Hospital Medicine. (2019) 74, no. 8, 1759–1768, 10.21608/ejhm.2019.28676. [DOI] [Google Scholar]
- 26. Chhabra A., Saini P., Sharma K., Chaudhary N., Singh A., and Gupta S., Controlled Hypotension for FESS: A Randomised Double-Blinded Comparison of Magnesium Sulphate and Dexmedetomidine, Indian Journal of Anesthesia. (2020) 64, no. 1, 24–30, 10.4103/ija.ija_417_19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Lang B., Zhang L., Lin Y., Zhang W., Li F. S., and Chen S., Comparison of Effects and Safety in Providing Controlled Hypotension During Surgery Between Dexmedetomidine and Magnesium Sulphate: a Meta-Analysis of Randomized Controlled Trials, PLoS One. (2020) 15, no. 1, 1–18, 10.1371/journal.pone.0227410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Aboelsuod M. A. A. and Seyam S. H., Dexmedetomidine Versus Magnesium Sulfate for Controlled Hypotension During Rhinoplasty Surgeries: A Prospective Randomized Comparative Study, Egyptian Journal of Anesthesia. (2023) 39, no. 1, 657–664, 10.1080/11101849.2023.2242645. [DOI] [Google Scholar]
- 29. Moharram A. A. and Mostafa R. H., Efficacy of Dexmedetomidine Infusion Without Loading Dose as a Potent Hypotensive Agent in Lumbar Fixation Surgery, Open Anesthesiology Journal. (2019) 13, no. 1, 68–74, 10.2174/2589645801913010068. [DOI] [Google Scholar]
- 30. Ibrahim I. M., Hassan R., Mostafa R. H., and Ibrahim M. A., Efficacy of Dexmedetomidine Infusion Without Loading Dose on Hemodynamic Variables and Recovery Time During Craniotomy: A Randomized Double-Blinded Controlled Study, Anesthesiology and Pain Medicine. (2021) 11, no. 2, 10.5812/aapm.113410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Zhang J., Wang Y., Xu H., and Yang J., Influence of Magnesium Sulfate on Hemodynamic Responses During Laparoscopic Cholecystectomy: A Meta-Analysis of Randomized Controlled Studies, Medicine. (2018) 97, 10.1097/md.0000000000012747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Bafna U., Gurjar S. S., and Nagal J. B., Dexmedetomidine Versus Magnesium Sulfate for Induced Hypotension During Functional Endoscopic Sinus Surgery: A Randomized, Double-Blind Study, Bali Journal of Anesthesiology. (2020) 4, no. 6, S39–S43, 10.4103/bjoa.bjoa_35_20. [DOI] [Google Scholar]
- 33. Yang L., Ton H., Zhao R. et al., Sevoflurane Induces Neuronal Activation and Behavioral Hyperactivity in Young Mice, Scientific Reports. (2020) 10, no. 1, 1–14, 10.1038/s41598-020-66959-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Jain N., Surendran N., Kumari N., Kumar P., Patodi V., and Kavita P., A Comparison of Postoperative Analgesic Efficacy of Opioid-Free Anesthesia Using Intravenous Paracetamol, Lignocaine, and Magnesium Sulfate Versus Standard Opioid Anesthesia Using Intravenous Tramadol for Preemptive Analgesia, Indian Journal of Health Sciences and Biomedical Research KLEU. (2023) 16, no. 2, 219–224, 10.4103/kleuhsj.kleuhsj_168_22. [DOI] [Google Scholar]
- 35. Frelich M., Lečbychová K., Vodička V. et al., Effect of BIS-Guided Anesthesia on Emergence Delirium Following General Anesthesia in Children: A Prospective Randomized Controlled Trial, Anesthesia Critical Care and Pain Medicine. (2024) 43, no. 1, 10.1016/j.accpm.2023.101318. [DOI] [PubMed] [Google Scholar]
- 36. Dutta H., Mallick S., Laha B., Swaika S., Mandal U. S., and Ghosh S., Monitoring of General Anesthesia by qCON and qNOX Indices Versus Conventional Clinical Parameters in Urological Surgery: A Randomized Controlled Clinical Trial, Asian Journal of Medical Sciences. (2024) 15, no. 3, 20–25, 10.3126/ajms.v15i3.59955. [DOI] [Google Scholar]
- 37. Sommer M., Geurts J. W. J. M., Stessel B. et al., Prevalence and Predictors of Postoperative Pain After Ear, Nose, and Throat Surgery, Archives of Otolaryngology—Head and Neck Surgery. (2009) 135, no. 2, 124–130, 10.1001/archoto.2009.3. [DOI] [PubMed] [Google Scholar]
- 38. Kim H., Kim H., Choi S., and Kim J. K., Risk Factors of Emergence Agitation in Adults Undergoing General Anesthesia for Nasal Surgery, Clinical and Experimental Otorhinolaryngology. (2015) 8, no. 1, 46–51, 10.3342/ceo.2015.8.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. He M., Zhu Z., Jiang M. et al., Risk Factors for Postanesthetic Emergence Delirium in Adults: A Systematic Review and Meta-Analysis, Journal of Neurosurgical Anesthesiology. (2024) 36, no. 3, 190–200, 10.1097/ana.0000000000000942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Kim S. Y., Kim J. M., Lee J. H., Song B. M., and Koo B. N., Efficacy of Intraoperative Dexmedetomidine Infusion on Emergence Agitation and Quality of Recovery After Nasal Surgery, British Journal of Anaesthesia. (2013) 111, no. 2, 222–228, 10.1093/bja/aet056. [DOI] [PubMed] [Google Scholar]
- 41. Bagle A., Hasnain S., and Suryawanshi C., Comparison Between the Effect of Bispectral Index and Minimum Alveolar Concentration Monitoring on Recovery After General Anesthesia: A Prospective, Randomized, Clinical Study, Bali Journal of Anesthesiology. (2023) 7, no. 4, 224–229, 10.4103/bjoa.bjoa_177_23. [DOI] [Google Scholar]
Associated Data
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Data Availability Statement
Research data are not shared.