Mohamed A. Wadod 1 , Walaa Y. Elsabeeny* 1
Abstract
Background: Direct laryngoscopy is a day case procedure used for diagnosis and sometimes in treatment of laryngeal tumors. It is a short procedure that requires complete relaxation and rapid recovery. Rocuronium emerged as a good alternative to succinylcholine with better profile. Adding magnesium sulphate (MgSO4) to rocuronium can accelerate its onset of action with better relaxation. The aim of this study is to investigate the effect of MgSO4 when added to low dose of rocuronium on neuromuscular blockade and anesthetic profile.
Methodology: Sixty ASA I-II patients, scheduled for direct laryngoscopy were randomly allocated to group R: received rocuronium dose of 0.6 mg/kg and group RM: low dose rocuronium 0.4 mg/kg and MgSO4 50 mg/kg.
Results: RM group showed shorter onset, and less time to achieve deep level of neuromuscular blockade but prolonged duration when compared to R group (P value = 0.035, <0.001 and <0.001 respectively). Heart rate, mean arterial blood pressure and BIS values were lower in RM group compared to R group.
Conclusions: Adding MgSO4 to low dose rocuronium hastens its onset of action and shorten the time needed to achieve deep blockade but with prolonged duration. It had a favorable anesthetic profile when compared to conventional anesthesia.
Key words: Magnesium sulfate, rocuronium, neuromuscular blockade, anesthesia.
Trial registration: The trial was registered at ClinicalTrials.gov with registration number (NCT 04510337) https://clinicaltrials.gov/ct2/show/NCT04510337.
Citation: Wadod MA, Elsabeeny WY. The effect of adding magnesium sulfate to low dose rocuronium on neuromuscular blockade and anesthesia for direct laryngoscopy: A randomized controlled trial. Anaesth. pain intensive care 2021;25(5):607–612; DOI: 10.35975/apic.v25i5.1628 Received: June 28, 2021, Reviewed: August 19, 2021, Accepted: August 26, 2021
Introduction
Clinical staging of cancer larynx using direct laryngoscopy is performed under general anesthesia for accurate determination of tumor extent and proper pathological diagnosis.1 Direct laryngoscopy with excisional biopsy has a therapeutic role in management of hyperplastic epithelial lesions of the larynx.2 It is a day case procedure done under general anesthesia.3 Operating through the larynx carries an anesthetic challenge of being a shared airway procedure. 4 Although it is a short procedure, but it needs full relaxation and rapid recovery. Succinylcholine was the muscle relaxant of choice for such procedures because of its rapid onset, short duration and full relaxation effect.5 Rocuronium evolved as a better choice with less side effects and longer duration of action.5 Addition of magnesium sulphate (MgSO4) to low dose rocuronium can accelerate rocuronium onset of action and obtain good relaxation with shorter muscle relaxant duration,6 shorter onset of action can be attributed to the effect of MgSO4 on decreasing the median effective dose of non-depolarized muscle relaxants.7 Additionally, MgSO4 effectively attenuates the hemodynamic response to laryngoscopy and endotracheal intubation.8 The use of MgSO4 as an anesthetic adjuvant has been increasingly introduced in anesthetic management secondary to its role in inhibiting catecholamine release and as a calcium channel antagonist as well as its N- methyl D aspartate (NMDA) antagonist.9,10 The aim of this study is to investigate the effect of magnesium sulphate when added to low dose of rocuronium on neuromuscular blockade action and anesthetic management.
Methodology
Formal approval of the Institutional Review Board of the National Cancer Institute, Cairo University (IRB 201617031.2P) was obtained and the trial was registered at clinicaltrials.gov (NCT 04510337) https://clinicaltrials.gov/ct2/show/NCT04510337.
This double blinded (participant and assessor) was done in the period from April 2018 to February 2021 after a written informed consent taken from all patients enrolled in the study. The study was conducted according to the principles of the Declaration of Helsinki and followed Consolidated Standards of Reporting Trials (CONSORT) guidelines.
Eighty-six cancer patients referred to the anesthesia department in our institute requiring direct laryngoscopy for staging and diagnosis of laryngeal cancer were assessed for eligibility in preoperative anesthesia clinic, 26 patients were excluded, 19 of them did not meet the inclusion criteria and 7 refused to participate. Sixty patients were randomly allocated using closed envelop method into one of the two study groups by anesthesia resident in the holding area. (Figure 1)
.
Random number list was generated using computer generated random list. The study included American Society of Anesthesiologist (ASA) I and II cancer patients with laryngeal tumors aged from 30 to 70 years. Patients with renal or hepatic insufficiency, neuromuscular disease, known allergy to any of the study drugs as well as large glottic and/or supra-glottic lesions with or without breathing difficulties were excluded from the study.
Routine preoperative assessment was conducted as standard (complete blood count, liver and kidney function tests, coagulation profile and chest x-ray) in addition to indirect laryngoscopy airway assessment. Upon arrival to the holding area all the patients were monitored by standard monitoring (electrocardiogram, pulse oximetry and non-invasive automated arterial blood pressure), all patients had a 20 G cannula inserted. On arrival to the operating theatre Group R: received 100 ml saline infusion 15 min prior to induction of anesthesia and Group RM: received 100 ml saline with 50 mg/kg MgSO4 infusion 15 min prior to induction of anesthesia. Induction of anesthesia was done with propofol 2 mg/kg and fentanyl 2 µ/kg. Then Group R: received rocuronium 0.6 mg/kg and Group RM: received rocuronium 0.4 mg/kg followed by single lumen endotracheal intubation by an expert anesthesiologist who was blind to the study group. Anesthesia was maintained using controlled mechanical ventilation with 50% Fio2, and sevoflurane to achieve end tidal MAC 2- 3% according to each patient hemodynamic response, top up doses of rocuronium 0.15 mg/kg were given as needed to keep at least 3 TOF responses suppressed. Starting from induction of anesthesia heart rate (HR) and oxygen saturation (Spo2) were continuously monitored, mean arterial blood pressure (MAP) were measured every 5 min. In case of elevation of MAP or HR ≥ 20% from baseline, a rescue fentanyl of 25 µg was given and reported.
Intubating conditions were assessed according to good clinical research practice 11 from excellent to poor using ease of laryngoscopy, vocal cord position and/or movement and response to intubation or cuff inflation (cough or diaphragmatic movement). Intubating conditions were considered as acceptable (excellent or good) or unacceptable (poor). (Table 1)
.
Electrodes were placed on the forehead to monitor bispectral index (BIS) (BIS™ LoC 2 Channel monitor, COVIDIEN llc, 15 Hampshire Street, Mansfield, MA, USA). BIS values were continuously monitored, and inhalational anesthetic mac value were adjusted accordingly to maintain values between 40-60. Neuromuscular block was monitored using accelomyography peripheral nerve stimulator [TOF- Watch® SX, Organon (Ireland) Ltd)] measuring the response to ulnar nerve stimulation at the thumb using (2 Hz every 12 s). After induction of anesthesia onset of rocuronium was assessed by train of four (TOF) stimulation and was defined as reaching 95% suppression of TOF first twitch. Duration of action was defined as time from rocuronium injection to time to return of first TOF twitch. Post tetanic count was assessed after reaching TOF 0. Deep neuromuscular blockade was defined as PTC count ≤ 5. At the end of the procedure extubation was done when TOF ratio ≥ 0.9 was attained, after reversal of rocuronium induced muscle relaxation by sugammadex (2 mg/kg) for moderate block (TOF ≥2) and 4 mg/kg for deep block (PTC≤ 5). Recovery time from sugammadex injection to TOF 0.9 was assessed.
Our primary outcome was duration of muscle relaxant in minutes. Secondary outcomes were onset time, depth of blockade, intraoperative hemodynamics including HR, MAP, BIS values, intubating conditions, and recovery time.
Sample size calculation was based on the previous paper by Choi et al., 2017 6, the difference between 2 groups in duration of neuromuscular blockade is 8 ± 7.5 min. Using power 95% and 5% significance level, 24 patients are required. We added 6 cases in each group to overcome drop out. Therefore, we recruited 30 patients in each group. Sample size calculation was achieved using PS: Power and Sample Size Calculation software Version 3.1.2 (Vanderbilt University, Nashville, Tennessee, USA.
Data were analyzed using IBM SPSS version 21 (SPSS Inc., Chicago, IL). Data were explored for normality using Shapiro-Wilk test and histograms. Numerical data were described as mean and standard deviation and were compared using the Student’s t-test. Categorical data were described as numbers and percentages and were compared using the chi-square test and fisher exact as appropriate. A two tailed p-value less than or equal to 0.05 was considered statistically significant.
Results
Patients' characteristics (age, weight, height, BMI, sex and ASA) were insignificantly different between both groups. (Table 2)
.
Onset time of neuromuscular blockade was significantly shorter in RM group compared to R group (85.63 ± 11.23 and 93.47 ± 16.42 sec. respectively, p = 0.035) and duration of neuromuscular blockade was significantly prolonged in group RM than group R (35.40 ± 4.12 and 30.70 ± 3.49 min. respectively, p < 0.001). There was significant difference in time needed to achieve deep block in RM group when compared to R group (10.77 ± 1.92 and 15.07 ± 2.70 min. respectively, p < 0.001). There was no significant difference in duration of surgery, duration of anesthesia and recovery time between both groups (p = 0.233, 0.182, 0.104 respectively). (Table 3)
.
No patient in RM group versus 7 patients in R group needed a single dose of 25 µg rescue fentanyl (p = 0.011). (Table 4) Intubating conditions were better in RM group than R group although it was not statistically significant (p = 0.237). (Table 4)
.
Heart rate was significantly lower in RM group than R group at all time measurement except at baseline. (Figure 2)
.
Mean arterial blood pressure was significantly lower in RM group than R group at all time measurement except at baseline. (Figure 3)
.
Peripheral oxygen saturation was comparable in both groups at all time measurement. (Figure 4)
.
BIS values were significantly lower in RM group than R group at all time measurement except baseline and end was insignificantly different between both groups. (Figure 5) Only two patients in MR group reported burning sensation during MgSO4 infusion which resolved spontaneously.
Discussion
Monitoring neuromuscular block allows more precise muscle relaxant dose titration according to drug dose effect, as well as proper estimation of accurate timing for reversing the drug effect when needed.12 Studies on different doses of rocuronium were conducted to assess different doses effect on intubating conditions.6,13,14 Obtaining rapid onset of muscle relaxant can be achieved by increasing the intubating dose, yet this would result in the drawback of longer duration.15 On the other hand, adding magnesium sulphate (MgSO4) to rocuronium is thought to shorten the onset by inhibiting acetylcholine presynaptic release.16 The current study results demonstrated that pre-treatment infusion of MgSO4 50 mg/kg added to low dose rocuronium 0.4 mg/kg was superior to rocuronium 0.6 mg/kg regarding onset of action, depth of neuromuscular block and depth of anesthesia with more hemodynamic stability in cancer larynx patients undergoing rigid/direct laryngoscopy procedures. Although, it is reported previously that MgSO4 augments muscle relaxation through its calcium antagonist effect without prolonging its duration of action.6,17 but our results demonstrated significant increase in block duration which is supported with other former studies.18,19 Choi and colleagues reported that adding MgSO4 to low dose rocuronium resulted in augmented action and faster onset without prolonging neuromuscular block duration, such difference in duration of action with our results may be attributed to the difference in the dose of MgSO4 they used being 30 mg/kg.6 Czarnetzki et al., used 60 mg/kg MgSO4 added to rocuronium 0.6 mg/kg and stated that pre-treatment with MgSO4 15 min prior to induction of anesthesia while speeds the onset of NMB by 35 % but adversely prolongs its recovery time by 25%, although this is consistent with our results, but we demonstrated only 26% hastened onset and 15% increase in duration, such difference may be attributed to the higher doses of rocuronium and MgSO4 they used.20 On the other hand, Kussman and his colleagues reported that although pretreatment of rocuronium 0.6 mg/kg with MgSO4 60 mg/kg prolonged its duration of action, but it didn’t hasten its onset, this might be explained by the timing of MgSO4 administration being given only 1 min prior to the muscle relaxant.21 Thus, different doses of both rocuronium and MgSO4 as well as the timing of MgSO4 administration have an important role in modification of rocuronium action. Regarding the effect of MgSO4 as an anesthetic adjuvant, we found that patients who received pre-treatment with MgSO4 showed significant attenuation in hemodynamic response to intubation, clinically better intubating conditions and lower BIS values with faster onset to reach deeper level of anesthesia. MgSO4 pretreatment can effectively improve intubating conditions when compared to other methods, it can be considered as a useful adjuvant to general anesthesia that helps in lower BIS values.8,22,23 This is consistent with the results reported by Amer et al., who stated that adding MgSO4 resulted in significantly lower BIS values with less time to reach values below 60 in pediatric patients under general anesthesia.24 MgSO4 can efficiently reduce intraoperative hemodynamics alteration, provides cardiovascular stability and attenuates the response to laryngoscopy and endotracheal intubation.8,25 Adding MgSO4 50 mg/kg to low dose rocuronium 0.4 mg/kg resulted in hastened onset of action with shorter time to achieve deep block but with prolonged duration of action which although not favored in short procedures but might be of benefit in longer ones. It had a favorable anesthetic profile when compared to conventional anesthesia.
Conclusion
Adding MgSO4 to low dose rocuronium hastens the onset of rocuronium, shorten the time needed to achieve deep blockade with good intubating conditions and better intraoperative hemodynamic profile but showed prolonged duration of action when compared to standard dose rocuronium.
Limitations
Limitations to the current study included that we did not study adding same dose of magnesium to standard dose rocuronium. Also, we used inhalational anesthetics which might play a role in augmenting the effect of muscle relaxant used. Additionally, we used different doses of sugammadex for reversal of residual muscle relaxant according to depth of blockade, we think further studies on same dose of reversing drug might help in assessing the actual effect or mechanism of magnesium on depth of blockade and recovery time.
Conflict of interests
None declared by the authors.
Authors’ contribution
All authors read and approved the final version of the manuscript
MW: Study idea, Patient recruitment, Interpretation and analysis of data
WE: Study idea, Patient recruitment, Interpretation and analysis of data, writing and editing the manuscript
References
- Lecturer, Department of Anesthesiology & Pain Management, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, Egypt 11796.
Abstract
Background: Direct laryngoscopy is a day case procedure used for diagnosis and sometimes in treatment of laryngeal tumors. It is a short procedure that requires complete relaxation and rapid recovery. Rocuronium emerged as a good alternative to succinylcholine with better profile. Adding magnesium sulphate (MgSO4) to rocuronium can accelerate its onset of action with better relaxation. The aim of this study is to investigate the effect of MgSO4 when added to low dose of rocuronium on neuromuscular blockade and anesthetic profile.
Methodology: Sixty ASA I-II patients, scheduled for direct laryngoscopy were randomly allocated to group R: received rocuronium dose of 0.6 mg/kg and group RM: low dose rocuronium 0.4 mg/kg and MgSO4 50 mg/kg.
Results: RM group showed shorter onset, and less time to achieve deep level of neuromuscular blockade but prolonged duration when compared to R group (P value = 0.035, <0.001 and <0.001 respectively). Heart rate, mean arterial blood pressure and BIS values were lower in RM group compared to R group.
Conclusions: Adding MgSO4 to low dose rocuronium hastens its onset of action and shorten the time needed to achieve deep blockade but with prolonged duration. It had a favorable anesthetic profile when compared to conventional anesthesia.
Key words: Magnesium sulfate, rocuronium, neuromuscular blockade, anesthesia.
Trial registration: The trial was registered at ClinicalTrials.gov with registration number (NCT 04510337) https://clinicaltrials.gov/ct2/show/NCT04510337.
Citation: Wadod MA, Elsabeeny WY. The effect of adding magnesium sulfate to low dose rocuronium on neuromuscular blockade and anesthesia for direct laryngoscopy: A randomized controlled trial. Anaesth. pain intensive care 2021;25(5):607–612; DOI: 10.35975/apic.v25i5.1628 Received: June 28, 2021, Reviewed: August 19, 2021, Accepted: August 26, 2021
Introduction
Clinical staging of cancer larynx using direct laryngoscopy is performed under general anesthesia for accurate determination of tumor extent and proper pathological diagnosis.1 Direct laryngoscopy with excisional biopsy has a therapeutic role in management of hyperplastic epithelial lesions of the larynx.2 It is a day case procedure done under general anesthesia.3 Operating through the larynx carries an anesthetic challenge of being a shared airway procedure. 4 Although it is a short procedure, but it needs full relaxation and rapid recovery. Succinylcholine was the muscle relaxant of choice for such procedures because of its rapid onset, short duration and full relaxation effect.5 Rocuronium evolved as a better choice with less side effects and longer duration of action.5 Addition of magnesium sulphate (MgSO4) to low dose rocuronium can accelerate rocuronium onset of action and obtain good relaxation with shorter muscle relaxant duration,6 shorter onset of action can be attributed to the effect of MgSO4 on decreasing the median effective dose of non-depolarized muscle relaxants.7 Additionally, MgSO4 effectively attenuates the hemodynamic response to laryngoscopy and endotracheal intubation.8 The use of MgSO4 as an anesthetic adjuvant has been increasingly introduced in anesthetic management secondary to its role in inhibiting catecholamine release and as a calcium channel antagonist as well as its N- methyl D aspartate (NMDA) antagonist.9,10 The aim of this study is to investigate the effect of magnesium sulphate when added to low dose of rocuronium on neuromuscular blockade action and anesthetic management.
Methodology
Formal approval of the Institutional Review Board of the National Cancer Institute, Cairo University (IRB 201617031.2P) was obtained and the trial was registered at clinicaltrials.gov (NCT 04510337) https://clinicaltrials.gov/ct2/show/NCT04510337.
This double blinded (participant and assessor) was done in the period from April 2018 to February 2021 after a written informed consent taken from all patients enrolled in the study. The study was conducted according to the principles of the Declaration of Helsinki and followed Consolidated Standards of Reporting Trials (CONSORT) guidelines.
Eighty-six cancer patients referred to the anesthesia department in our institute requiring direct laryngoscopy for staging and diagnosis of laryngeal cancer were assessed for eligibility in preoperative anesthesia clinic, 26 patients were excluded, 19 of them did not meet the inclusion criteria and 7 refused to participate. Sixty patients were randomly allocated using closed envelop method into one of the two study groups by anesthesia resident in the holding area. (Figure 1)
.Random number list was generated using computer generated random list. The study included American Society of Anesthesiologist (ASA) I and II cancer patients with laryngeal tumors aged from 30 to 70 years. Patients with renal or hepatic insufficiency, neuromuscular disease, known allergy to any of the study drugs as well as large glottic and/or supra-glottic lesions with or without breathing difficulties were excluded from the study.
Routine preoperative assessment was conducted as standard (complete blood count, liver and kidney function tests, coagulation profile and chest x-ray) in addition to indirect laryngoscopy airway assessment. Upon arrival to the holding area all the patients were monitored by standard monitoring (electrocardiogram, pulse oximetry and non-invasive automated arterial blood pressure), all patients had a 20 G cannula inserted. On arrival to the operating theatre Group R: received 100 ml saline infusion 15 min prior to induction of anesthesia and Group RM: received 100 ml saline with 50 mg/kg MgSO4 infusion 15 min prior to induction of anesthesia. Induction of anesthesia was done with propofol 2 mg/kg and fentanyl 2 µ/kg. Then Group R: received rocuronium 0.6 mg/kg and Group RM: received rocuronium 0.4 mg/kg followed by single lumen endotracheal intubation by an expert anesthesiologist who was blind to the study group. Anesthesia was maintained using controlled mechanical ventilation with 50% Fio2, and sevoflurane to achieve end tidal MAC 2- 3% according to each patient hemodynamic response, top up doses of rocuronium 0.15 mg/kg were given as needed to keep at least 3 TOF responses suppressed. Starting from induction of anesthesia heart rate (HR) and oxygen saturation (Spo2) were continuously monitored, mean arterial blood pressure (MAP) were measured every 5 min. In case of elevation of MAP or HR ≥ 20% from baseline, a rescue fentanyl of 25 µg was given and reported.
Intubating conditions were assessed according to good clinical research practice 11 from excellent to poor using ease of laryngoscopy, vocal cord position and/or movement and response to intubation or cuff inflation (cough or diaphragmatic movement). Intubating conditions were considered as acceptable (excellent or good) or unacceptable (poor). (Table 1)
.Electrodes were placed on the forehead to monitor bispectral index (BIS) (BIS™ LoC 2 Channel monitor, COVIDIEN llc, 15 Hampshire Street, Mansfield, MA, USA). BIS values were continuously monitored, and inhalational anesthetic mac value were adjusted accordingly to maintain values between 40-60. Neuromuscular block was monitored using accelomyography peripheral nerve stimulator [TOF- Watch® SX, Organon (Ireland) Ltd)] measuring the response to ulnar nerve stimulation at the thumb using (2 Hz every 12 s). After induction of anesthesia onset of rocuronium was assessed by train of four (TOF) stimulation and was defined as reaching 95% suppression of TOF first twitch. Duration of action was defined as time from rocuronium injection to time to return of first TOF twitch. Post tetanic count was assessed after reaching TOF 0. Deep neuromuscular blockade was defined as PTC count ≤ 5. At the end of the procedure extubation was done when TOF ratio ≥ 0.9 was attained, after reversal of rocuronium induced muscle relaxation by sugammadex (2 mg/kg) for moderate block (TOF ≥2) and 4 mg/kg for deep block (PTC≤ 5). Recovery time from sugammadex injection to TOF 0.9 was assessed.
Our primary outcome was duration of muscle relaxant in minutes. Secondary outcomes were onset time, depth of blockade, intraoperative hemodynamics including HR, MAP, BIS values, intubating conditions, and recovery time.
Sample size calculation was based on the previous paper by Choi et al., 2017 6, the difference between 2 groups in duration of neuromuscular blockade is 8 ± 7.5 min. Using power 95% and 5% significance level, 24 patients are required. We added 6 cases in each group to overcome drop out. Therefore, we recruited 30 patients in each group. Sample size calculation was achieved using PS: Power and Sample Size Calculation software Version 3.1.2 (Vanderbilt University, Nashville, Tennessee, USA.
Data were analyzed using IBM SPSS version 21 (SPSS Inc., Chicago, IL). Data were explored for normality using Shapiro-Wilk test and histograms. Numerical data were described as mean and standard deviation and were compared using the Student’s t-test. Categorical data were described as numbers and percentages and were compared using the chi-square test and fisher exact as appropriate. A two tailed p-value less than or equal to 0.05 was considered statistically significant.
Results
Patients' characteristics (age, weight, height, BMI, sex and ASA) were insignificantly different between both groups. (Table 2)
.Onset time of neuromuscular blockade was significantly shorter in RM group compared to R group (85.63 ± 11.23 and 93.47 ± 16.42 sec. respectively, p = 0.035) and duration of neuromuscular blockade was significantly prolonged in group RM than group R (35.40 ± 4.12 and 30.70 ± 3.49 min. respectively, p < 0.001). There was significant difference in time needed to achieve deep block in RM group when compared to R group (10.77 ± 1.92 and 15.07 ± 2.70 min. respectively, p < 0.001). There was no significant difference in duration of surgery, duration of anesthesia and recovery time between both groups (p = 0.233, 0.182, 0.104 respectively). (Table 3)
.No patient in RM group versus 7 patients in R group needed a single dose of 25 µg rescue fentanyl (p = 0.011). (Table 4) Intubating conditions were better in RM group than R group although it was not statistically significant (p = 0.237). (Table 4)
.Heart rate was significantly lower in RM group than R group at all time measurement except at baseline. (Figure 2)
.Mean arterial blood pressure was significantly lower in RM group than R group at all time measurement except at baseline. (Figure 3)
.Peripheral oxygen saturation was comparable in both groups at all time measurement. (Figure 4)
.BIS values were significantly lower in RM group than R group at all time measurement except baseline and end was insignificantly different between both groups. (Figure 5) Only two patients in MR group reported burning sensation during MgSO4 infusion which resolved spontaneously.
Discussion
Monitoring neuromuscular block allows more precise muscle relaxant dose titration according to drug dose effect, as well as proper estimation of accurate timing for reversing the drug effect when needed.12 Studies on different doses of rocuronium were conducted to assess different doses effect on intubating conditions.6,13,14 Obtaining rapid onset of muscle relaxant can be achieved by increasing the intubating dose, yet this would result in the drawback of longer duration.15 On the other hand, adding magnesium sulphate (MgSO4) to rocuronium is thought to shorten the onset by inhibiting acetylcholine presynaptic release.16 The current study results demonstrated that pre-treatment infusion of MgSO4 50 mg/kg added to low dose rocuronium 0.4 mg/kg was superior to rocuronium 0.6 mg/kg regarding onset of action, depth of neuromuscular block and depth of anesthesia with more hemodynamic stability in cancer larynx patients undergoing rigid/direct laryngoscopy procedures. Although, it is reported previously that MgSO4 augments muscle relaxation through its calcium antagonist effect without prolonging its duration of action.6,17 but our results demonstrated significant increase in block duration which is supported with other former studies.18,19 Choi and colleagues reported that adding MgSO4 to low dose rocuronium resulted in augmented action and faster onset without prolonging neuromuscular block duration, such difference in duration of action with our results may be attributed to the difference in the dose of MgSO4 they used being 30 mg/kg.6 Czarnetzki et al., used 60 mg/kg MgSO4 added to rocuronium 0.6 mg/kg and stated that pre-treatment with MgSO4 15 min prior to induction of anesthesia while speeds the onset of NMB by 35 % but adversely prolongs its recovery time by 25%, although this is consistent with our results, but we demonstrated only 26% hastened onset and 15% increase in duration, such difference may be attributed to the higher doses of rocuronium and MgSO4 they used.20 On the other hand, Kussman and his colleagues reported that although pretreatment of rocuronium 0.6 mg/kg with MgSO4 60 mg/kg prolonged its duration of action, but it didn’t hasten its onset, this might be explained by the timing of MgSO4 administration being given only 1 min prior to the muscle relaxant.21 Thus, different doses of both rocuronium and MgSO4 as well as the timing of MgSO4 administration have an important role in modification of rocuronium action. Regarding the effect of MgSO4 as an anesthetic adjuvant, we found that patients who received pre-treatment with MgSO4 showed significant attenuation in hemodynamic response to intubation, clinically better intubating conditions and lower BIS values with faster onset to reach deeper level of anesthesia. MgSO4 pretreatment can effectively improve intubating conditions when compared to other methods, it can be considered as a useful adjuvant to general anesthesia that helps in lower BIS values.8,22,23 This is consistent with the results reported by Amer et al., who stated that adding MgSO4 resulted in significantly lower BIS values with less time to reach values below 60 in pediatric patients under general anesthesia.24 MgSO4 can efficiently reduce intraoperative hemodynamics alteration, provides cardiovascular stability and attenuates the response to laryngoscopy and endotracheal intubation.8,25 Adding MgSO4 50 mg/kg to low dose rocuronium 0.4 mg/kg resulted in hastened onset of action with shorter time to achieve deep block but with prolonged duration of action which although not favored in short procedures but might be of benefit in longer ones. It had a favorable anesthetic profile when compared to conventional anesthesia.
Conclusion
Adding MgSO4 to low dose rocuronium hastens the onset of rocuronium, shorten the time needed to achieve deep blockade with good intubating conditions and better intraoperative hemodynamic profile but showed prolonged duration of action when compared to standard dose rocuronium.
Limitations
Limitations to the current study included that we did not study adding same dose of magnesium to standard dose rocuronium. Also, we used inhalational anesthetics which might play a role in augmenting the effect of muscle relaxant used. Additionally, we used different doses of sugammadex for reversal of residual muscle relaxant according to depth of blockade, we think further studies on same dose of reversing drug might help in assessing the actual effect or mechanism of magnesium on depth of blockade and recovery time.
Conflict of interests
None declared by the authors.
Authors’ contribution
All authors read and approved the final version of the manuscript
MW: Study idea, Patient recruitment, Interpretation and analysis of data
WE: Study idea, Patient recruitment, Interpretation and analysis of data, writing and editing the manuscript
References
- Licitra L, Bernier J, Grandi C, Locati L, Merlano M, Gatta G, et al. Cancer of the larynx. Crit Rev Oncol Hematol. 2003 Jul;47(1):65-80. [PubMed] DOI: 1016/s1040-8428(03)00017-9
- Koltsidopoulos P, Kountakis S, Skoulakis C. ENT: Core Knowledge. Springer, Cham; 2017.
- Marioni G, Marchese-Ragona R, Cartei G, Marchese F, Staffieri A. Current opinion in diagnosis and treatment of laryngeal carcinoma. Cancer Treat Rev. 2006;32(7):504-515. [PubMed] DOI: 1016/j.ctrv.2006.07.002
- Hsu J, Tan M. Anesthesia considerations in laryngeal surgery. Int Anesthesiol Clin. 2017;55(1):11-32. [PubMed] DOI: 1097/AIA.0000000000000126
- Mallon WK, Keim SM, Shoenberger JM, Walls RM. Rocuronium vs. succinylcholine in the emergency department: a critical appraisal. J Emerg Med. 2009;37(2):183-188. [PubMed] DOI: 1016/j.jemermed.2008.07.021
- Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017;36:102-106. [PubMed] DOI: 1016/j.jclinane.2016.10.020
- Ghodraty MR, Saif AA, Kholdebarin AR, Rokhtabnak F, Pournajafian AR, Nikzad-Jamnani AR, et al. The effects of magnesium sulfate on neuromuscular blockade by cisatracurium during induction of anesthesia. J Anesth. 2012;26(6):858-863. [PubMed] DOI: 1007/s00540-012-1439-x
- Shin YH, Choi SJ, Jeong HY, Kim MH. Evaluation of dose effects of magnesium sulfate on rocuronium injection pain and hemodynamic changes by laryngoscopy and endotracheal intubation. Korean J Anesthesiol. 2011;60(5):329-333. [PubMed] DOI: 4097/kjae.2011.60.5.329
- James MFM. Magnesium: An emerging drug in anesthesia. Br J Anaesth. 2009;103 (4):465-467. [PubMed] DOI: 1093/bja/aep242
- Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anesthesia. Br J Anaesth. 2008;100(3):397-403. [PubMed] DOI: 1093/bja/aem407
- Fuchs-Buder T, Claudius C, Skovgaard LT, Eriksson LI, Mirakhur RK, Viby-Mogensen J. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: The Stockholm revision. Acta Anaesthesiol Scand. 2007;51(7):789-808. [PubMed] DOI: 1111/j.1399-6576.2007.01352.x
- McGrath CD, Hunter JM. Monitoring of neuromuscular block. Continuing Edu Anesth Crit Care Pain. 2006;6(1):7-12. DOI: 1093/bjaceaccp/mki067
- Kwan W, Chen B, Sun S, Lee C, Chang P. Rapid tracheal intubation with rocuronium 0.3 mg/kg. Anesth Analg. 1998;86(Supplement):475S. DOI: 1097/00000539-199802001-00473
- Sudha P, Manju B. Comparison of the effect of two different doses of rocuronium on intubating conditions. Int Surg J. 2016;3(2):582-585. DOI: 18203/2349-2902.isj20161126
- El-Orbany M, Connolly LA. Rapid sequence induction and intubation: Current controversy. Anesth Analg. 2010;110(5):1318-1325. [PubMed] DOI: 1213/ANE.0b013e3181d5ae47
- Krendel DA. Hypermagnesemia and neuromuscular transmission. Semin Neurol. 1990;10(1):42-45. [PubMed] DOI: 1055/s-2008-1041252
- Gulhas N, Durmus M, Demirbilek S, Togal T, Ozturk E, Ersoy MO. The use of magnesium to prevent laryngospasm after tonsillectomy and adenoidectomy: A preliminary study. Paediatr Anaesth. 2003;13(1):43-47. [PubMed] DOI: 1046/j.1460-9592.2003.00927.x
- Sinatra RS, Philip BK, Naulty JS, Ostheimer GW. Prolonged neuromuscular blockade with vecuronium in a patient treated with magnesium sulfate. Anesth Analg. 1985 Dec;64(12):1220-2. [PubMed]
- Gupta K, Vohra V, Sood J. The role of magnesium as an adjuvant during general anesthesia. Anesthesia. 2006;61(11):1058-1063. [PubMed] DOI: 1111/j.1365-2044.2006.04801.x
- Czarnetzki C, Lysakowski C, Elia N, TramÈr MR. Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: A randomised study. Acta Anaesthesiol Scand. 2010;54 (3):299-306. [PubMed] DOI: 1111/j.1399-6576.2009.02160.x
- Kussman B, Shorten G, Uppington J, Comunale ME. Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block. Br J Anaesth. 1997 Jul;79(1):122-4. [PubMed] DOI: 1093/bja/79.1.122
- Kim MH, Oh AY, Han SH, Kim JH, Hwang JW, Jeon YT. The effect of magnesium sulphate on intubating condition for rapid-sequence intubation: A randomized controlled trial. J Clin Anesth. 2015;27(7):595-601. [PubMed] DOI: 1016/j.jclinane.2015.07.002
- Altıparmak B, Çelebi N, Canbay Ö, Toker MK, Kılıçarslan B, Aypar Ü. Effect of magnesium sulfate on anesthesia depth, awareness incidence, and postoperative pain scores in obstetric patients. A double-blind randomized controlled trial. Saudi Med J. 2018 Jun;39(6):579-585. [PubMed] DOI: 15537/smj.2018.6.22376
- Amer MM, Abdelaal Ahmed Mahmoud A, Abdelrahman Mohammed MK, Elsharawy AM, Ahmed DA, Farag EM. Effect of magnesium sulphate on bi-spectral index (BIS) values during general anesthesia in children. BMC Anesthesiol. 2015 Sep 22;15:126. [PubMed] DOI: 1186/s12871-015-0108-7
- Vicković S, Pjević M, Uvelin A, Pap D, Nikolić D, Lalić I. Magnesium sulfate as an adjuvant to anesthesia in patients with arterial hypertension. Acta Clin Croat. 2016;55(3):490-496. [PubMed] DOI: 20471/acc.2016.55.03.20