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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 3  |  Page : 171-176

Comparison of dexmedetomidine, lidocaine, magnesium sulfate, and remifentanil in cough suppression during endotracheal extubation: A double-blind, randomized clinical trial


1 Students Research Committee, Arak, Iran
2 Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak, Iran
3 Department of Otolaryngology, Arak University of Medical Sciences, Arak, Iran
4 Department of Epidemiology, Arak University of Medical Sciences, Arak, Iran

Date of Submission05-Feb-2022
Date of Decision28-Apr-2022
Date of Acceptance01-May-2022
Date of Web Publication10-May-2022

Correspondence Address:
Hesameddin Modir
Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoa.bjoa_47_22

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  Abstract 

Background: This study was undertaken to compare the effects of several drugs on attenuation of stimulatory responses and cough suppression at the end of endotracheal extubation under general anesthesia. Patients and Methods: This trial was conducted on 120 patients who were candidates for general anesthesia in Arak, Iran. The patients were randomly assigned into four groups. All groups received the study drugs 10 min prior to the end of surgery in the following manner: group 1, 0.5 μg/kg intravenous (IV) dexmedetomidine; group 2, 1.5 mg/kg IV lidocaine; group 3, 1 μg/kg IV remifentanil; and group 4, 30 mg/kg IV magnesium sulfate 50%. Laryngospasm, the presence of cough, mean arterial pressure, heart rate (HR), arterial oxygen saturation, and sedation were assessed and recorded. Results: No significant difference was observed in the number of coughs (P = .740) among the study groups. Although the dexmedetomidine group showed more sedation, the lowest increase in HR (P = .001) was observed in lidocaine and dexmedetomidine groups, respectively. The lowest and highest HR was observed in lidocaine and magnesium sulfate groups, respectively. The patients did not have laryngospasm during the assessment. In addition, dexmedetomidine had the highest Ramsay score (P = .019). Conclusion: There was no difference in the amount of laryngospasm and cough in the groups, and due to the lack of no serious complication requiring treatment, the study drugs can be recommended to be used for attenuating and suppressing stimulatory responses during endotracheal extubation.

Keywords: Cough, dexmedetomidine, general anesthesia, laryngospasm, lidocaine, magnesium sulfate, remifentanil


How to cite this article:
Jafarzadeh E, Modir H, Moshiri E, Zamani Barsari F, Almasi-Hashiani A. Comparison of dexmedetomidine, lidocaine, magnesium sulfate, and remifentanil in cough suppression during endotracheal extubation: A double-blind, randomized clinical trial. Bali J Anaesthesiol 2022;6:171-6

How to cite this URL:
Jafarzadeh E, Modir H, Moshiri E, Zamani Barsari F, Almasi-Hashiani A. Comparison of dexmedetomidine, lidocaine, magnesium sulfate, and remifentanil in cough suppression during endotracheal extubation: A double-blind, randomized clinical trial. Bali J Anaesthesiol [serial online] 2022 [cited 2022 Aug 10];6:171-6. Available from: https://www.bjoaonline.com/text.asp?2022/6/3/171/344954




  Introduction Top


Physiological responses at the end of anesthesia and during endotracheal extubation are common, which can cause complications such as cough, laryngospasm, bronchospasm, and tachycardia.[1] Problems and complications of the airway after surgery, such as sore throat, cough, and sputum, are common following anesthesia. Numerous reports have contributed cough after endotracheal extubation to mechanical stimuli such as external pressure or the method of endotracheal intubation, tracheal cuff, endotracheal tube size, and other factors.[2] Coughing caused by endotracheal extubation, although usually not a serious or abundant complication of anesthesia, occurs explosively and spasmodically at times, increasing intracranial, intraocular, and intra-abdominal pressures.[3] Coughing after endotracheal intubation, which occurs for a variety of reasons including the type of laryngoscope blade, bucking by the patient during endotracheal extubation, and smoking, is reduced by the administration of intravenous lidocaine. Endotracheal intubation is commonly used during general anesthesia. After endotracheal intubation, inflating the tube cuff will close the space around the tube and stimulate the trachea. This will cause coughing when the anesthesia depth is shallow. Stimulation of the endotracheal tube and its cuff is the main mechanism of coughing. Rapidly acting receptors are abundant in the trachea, and these receptors appear to play an important role in association with coughing.[4] During general anesthesia, the stimulations are blocked, which accounts for the reason why the patients do not cough.[1] Coughing after emergence from general anesthesia causes increased blood pressure and heart rate (HR), myocardial ischemia, bronchospasm, and bleeding.[5],[6] Coughing also increases surgical pain as well as intracranial pressure and intraocular pressure.[7]

There are several methods to reduce coughing, such as the topical and intravenous use of local anesthetics. Although the intravenous use of opioid and endotracheal extubation when the patient is not fully awake have also been used as an alternative to reducing cough, this method has not been desirable in many cases. The use of local anesthetics before endotracheal intubation is effective only for a limited period of time during the surgery because it will be absorbed via the tracheal mucus. For its prolonged use, another alternative method should be used via the administration of intracuff local anesthetics.[8] The use of lidocaine reduces the secretion of goblet cells by controlling the neural pathway, and water absorption is also reduced by the ion transfer effect of lidocaine. It appears that the use of lidocaine affects the results in different ways.[9],[10] Khezri et al. reported the effectiveness of lidocaine on reducing the patients’ cough.[11]

Dexmedetomidine, an α-2 adrenergic agonist, is a sedative that reduces blood pressure. Its infusion leads to reduced HR, systemic vascular resistance, and blood pressure. In addition, it has potent anesthetic and analgesic effects, thus reducing the need for opioid requirements and their complications as well as decreasing the stress response and improving the quality of recovery.[12] Lee et al. found that the patients who had received dexmedetomidine had lower mean arterial pressure (MAP) and HR.[13] Fan et al. maintained that dexmedetomidine led to decreased coughing in the patients.[14]

Magnesium sulfate plays a role in cellular functions and is considered as a treatment for asthmatic patients due to its relaxing effect on airway smooth muscles and prevention of cough as well.[15] An et al. stated that magnesium sulfate can be as effective as remifentanil in suppressing cough and stimulating airways in patients undergoing general anesthesia.[16]

Remifentanil is used as an adjunct drug in general anesthesia. Previous studies have demonstrated that it can prevent the increase of stimulatory responses of airway and hemodynamic changes.[17],[18],[19] Chen et al. stated that remifentanil can suppress coughing following endotracheal extubation, while not prolonging the recovery from anesthesia.[17]

There has been no study on comparing the four abovementioned drugs so far, and sometimes, research in this regard has yielded differing results arising from binary comparisons. As such, this study was undertaken to compare the effects of dexmedetomidine, lidocaine, magnesium sulfate, and remifentanil on attenuation of stimulatory responses and cough suppression at the end of endotracheal extubation under general anesthesia. Provided that positive results—in the absence of any side effects—are obtained from this study, it is hoped that various options might be introduced for controlling cough and stimulatory responses.


  Materials and Methods Top


This double-blind, randomized, clinical trial study was carried out on 120 patients aged 20–60 years who were candidates for general anesthesia in Valiasr Hospital, Arak, Iran, in 2021. Four parallel groups including 30 patients in each group were included in the study. The study protocol was registered in the Iranian Registry of Clinical Trials (registration no. IRCT20141209020258N149) on September 23, 2020. The CONsolidated Standards of Reporting Trials Statement was followed to preparing the article. Patient’s recruitment lasted from July 2020 to November 2020.

The patients entered the study based on eligibility criteria and after giving informed written consent. Inclusion criteria were aged 20–60 years, American Society of Anesthesiologists grade I and II, Mallampati class I or II, being of either sex, lack of substance abuse and smoking, absence of active airway infection or history of tracheal and laryngeal surgery, absence of lower esophageal sphincter incompetence (and absence of reflux), body mass index less than 30, lack of increased intracranial and intraocular pressure, duration of surgery between 60 and 120 min, absence of pulmonary and cardiovascular diseases, and lack of use of cough-inducing medications. The exclusion criterion was patient dissatisfaction.

All patients were hospitalized for at least 1 day before surgery and kept fasting for 8 h. The patients were randomly assigned to four groups by the block method with block sizes of four and eight. All patients underwent the same anesthesia protocol in which they received 5 mL/kg of Ringer’s crystalloid fluid before induction of anesthesia. Then, 1 μg/kg fentanyl and 2 mg midazolam were injected intravenously, and after preoxygenation, anesthesia was induced with 5 mg/kg sodium thiopental and 0.5 mg/kg atracurium. Direct laryngoscopy was performed with an appropriate sized Macintosh blade, and endotracheal intubation was carried out (Flexicare Co., Mountain Ash, UK) with appropriate size for each patient. To maintain the same amount of air in endotracheal tube cuff in all patients, we inflated the cuff by a special gauge up to a volume that showed a pressure of 25 cmH2O, so that all patients were in the same conditions with regard to endotracheal tube cuff stimulation. Maintenance of anesthesia was performed by 75–150 μg/kg propofol infusion per minute, and a repetition of muscle relaxants and opioids. About 10 min before the end of surgery, the patients were assigned to the four groups and received the study drugs in the following manner: the dexmedetomidine group (D) received 0.5 μg/kg dexmedetomidine (Exir Co., Lorestan, Iran), the lidocaine group (L) received 1.5 mg/kg lidocaine (Caspian Tamin, Rasht, Iran), the remifentanil group (R) received 1 μg/kg intravenous (IV) remifentanil (Normon, SA; Madrid; Spain), and the magnesium sulfate group (S) received 30 mg/kg IV magnesium sulfate 50% (Shahid Ghazi Pharmaceutical Co., Tabriz, Iran).

After calculating the doses for each patient, all the study drugs were increased to 10 mL with normal saline and infused slowly for 10 min. At the end of the surgery, after clearing the airway secretions and the return of spontaneous breathing and its adequacy and complete awakening of the patient (responding to verbal commands such as opening the eyes, raising the head for 5 s), the endotracheal tube was removed. Laryngospasm and the presence of cough in all patients were measured and recorded by one person at 0 and 10 min after endotracheal extubation and in recovery up to 40 min after endotracheal extubation based on observation and the incidence of coughing and laryngospasm. Cough here signifies real and audible coughing in which the patient exhales spontaneously, involuntarily, and rapidly.

MAP, HR, arterial oxygen saturation (O2Sat), and electrocardiogram were all measured by Datascope Passport 2 monitor (Montvale, NJ, USA) from the patient’s arrival at the operating room to the end of surgery at 5-min intervals. The abovementioned measurements were also carried out and recorded at the end of surgery at 0, 5 and every 5 min up to 40 min after endotracheal extubation. In case of continuous hypotension (defined as a decrease in blood pressure <20% of baseline), bradycardia (as an HR of <45 beats per minute [bpm]), and a decrease in oxygen saturation (<92%), an appropriate course of treatment was performed and recorded as well. In all, 5 mg ephedrine was administered for controlling hypotension; 0.5 mg atropine for bradycardia and 4 L/min oxygen for SaO2 <92% were administered via the nasal cannula.

By an epidemiologist, the permuted balanced block randomization method with block sizes 4 and 8 was used to allocate the patients into four groups. In order to double blind the study, the interested outcomes were assessed and recorded by a medical intern who was unaware of the groupings. In addition, the preparation and administration of drugs in each group was done by an anesthesiologist other than the research team. Additionally, the patients were not aware of the group to which they had been assigned.

Number (percentage) and mean (standard deviation) as well as tables and figures were used to describe the data. One-way analysis of variance (ANOVA) and repeated measures ANOVA were used to analyze the data. All statistical analyses were done by Stata software version 13 (Stata Corp, College Station, Texas). P value less than .05 was considered statistically significant.


  Results Top


In this study, of 120 patients recruited, 183 patients were screened in terms of inclusion criteria and 63 patients were not eligible to be included in the study; the selected patients were randomly allocated into four groups. All of 120 included patients were followed until the end of study and were included in the analysis. The demographic and clinical characteristics at the baseline are reported in [Table 1] by groups. The age range of participants was 24–51 years with mean of 37.7 years. The mean values of MAP, HR, and O2Sat were 99.7 mmHg, 90.1 bpm, and 97.1%, respectively.
Table 1: Baseline demographic and clinical characteristics by study groups

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According to [Table 2], there was a statistically significant difference in HR among the study groups (P = .001). The minimum HR was observed in lidocaine and dexmedetomidine groups, and the maximum HR was observed in the magnesium sulfate group [Figure 1]. Based on the repeated measures ANOVA test, a statistically significant difference was observed, and the HR in lidocaine and dexmedetomidine groups was lower than that in the other groups (P = .001). However, the results suggested no statistical significance among study groups in terms of MAP (P = .102) and O2Sat (P = .692).
Table 2: Comparison of mean and SD of HR, MAP, and O2 Sat in the study groups

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Figure 1: Comparison of mean of mean HR among the study groups

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As is shown in [Table 3], based on repeated measure ANOVA test, there was not statistically significant difference in the mean of coughs among the study groups (P = .740). However, the results revealed that there was a statistically significant difference in Ramsay score during the study time between the groups (P = .019) and the dexmedetomidine group had the highest Ramsay score [Figure 2] compared to other groups. The mean duration of surgery was similar between the four groups, and there was no significant difference between the groups in this regard (P = .930).
Table 3: Comparison of mean and SD of number of coughs and Ramsay score in the study groups

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Figure 2: Comparison of mean of Ramsay score among the study groups

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  Discussion Top


This double-blind clinical trial was carried out on 120 patients who were candidates for general anesthesia in Valiasr Hospital, Arak, Iran. The patients were randomly assigned to four groups (dexmedetomidine, remifentanil, magnesium sulfate, and lidocaine). No statistically significant difference was found in the mean oxygen saturation percentage, arterial pressure, duration of surgery, and number of coughs among the groups. None of the patients had laryngospasm during the assessment time. Furthermore, HR and Ramsay score were statistically different among groups, and the lowest HR was observed in lidocaine and dexmedetomidine groups, and also the dexmedetomidine group had the highest Ramsay score. In general, it can be said that dexmedetomidine results in more sedation in patients. However, the groups were similar in that there was no difference in the number of coughs and laryngospasm among them.

In a study conducted in 2019 on comparing the cough-suppressing effect of dexmedetomidine and lidocaine during anesthesia emergence, Saidie et al. reported that dexmedetomidine reduced HR and the number of coughs in the patients, but no difference was found in Ramsey score between dexmedetomidine and lidocaine groups. They maintained that dexmedetomidine seems to be a suitable drug for suppressing patients’ coughs on emergence from anesthesia due to its lack of side effects.[20] The results of their study are not in line with those of this study in that dexmedetomidine caused more sedation in patients, but there was no difference in the number of coughs and laryngospasm between the groups. This could be attributed to the differences in the number of samples and the number of groups under the study. In the study by Saidie et al.,[20] the samples size was more than that in this study and the two intervention groups were compared with placebo, but in this study, four drug groups were compared.

In 2015, Sane et al. conducted a study on evaluating the effect of intravenous and intracuff lidocaine on MAP, HR, and cough after endotracheal extubation. They came up with no difference in the incidence of cough compared to the control group after endotracheal extubation.[21] The results of their study were consistent with those of this research, except that in our study, different drugs were compared in the study groups, but the study by Sane et al. compared lidocaine and placebo. Kim et al.[22] conducted a study on comparing the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic changes during recovery. They stated that dexmedetomidine and remifentanil had equal effectiveness in attenuation of coughing and that dexmedetomidine proved more effective in the management of hemodynamic changes than remifentanil. The results of their research were in tandem with those of this study. Lee et al. investigated the effect of a single dose of dexmedetomidine on cough suppression during anesthesia. They found the incidence of cough to be lower in the dexmedetomidine group; in addition, the mean cough grade at the end of the endotracheal extubation was lower in this group as well. They went on to say that there was no difference between MAP and HR, and compared with the remifentanil dose alone, a single dose of dexmedetomidine significantly attenuated coughing without further respiratory depression in patients.[13] The difference between their results and those of this study could be ascribed to the larger sample size in their study.

In their study in 2011 that was carried out on 60 patients aged 15–60 years who were candidates for general surgery, Khezri et al.[11] compared the effect of intravenous lidocaine on airway responses during endotracheal extubation. There was no significant difference in cardiovascular variables between the two groups. The effect of intravenous and endotracheal lidocaine on the amount of bucking, coughing, and extubation time during emergence from anesthesia was almost similar. The results of their study were consistent with those of this study. Finally, Guler et al.[23] evaluated the effect of single-dose dexmedetomidine on reducing agitation and smooth extubation after surgery. They found that agitation and pain were lower in the dexmedetomidine group. In addition, the number of coughs was significantly lower in the dexmedetomidine group. Nausea and vomiting were similar in both groups. They reported that dexmedetomidine reduced coughing and agitation in patients. The reason for this difference could be that this study compared different drugs, whereas in the study by Guler et al., dexmedetomidine was compared with placebo.


  Conclusion Top


Considering the results of this study and the fact that there was no difference in the amount of laryngospasm in the groups and no serious complication requiring medical intervention was observed, the intervention drugs in this study can be recommended to be used to attenuate and suppress stimulatory responses during endotracheal extubation. However, the selection of the desired drug for each patient depends on his/her special conditions and the discretion of the anesthesiologist.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Hu S, Li Y, Wang S, Xu S, Ju X, Ma L. Effects of intravenous infusion of lidocaine and dexmedetomidine on inhibiting cough during the tracheal extubation period after thyroid surgery. BMC Anesthesiol 2019;19:66.  Back to cited text no. 1
    
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Hu B, Bao R, Wang X, Liu S, Tao T, Xie Q, et al. The size of endotracheal tube and sore throat after surgery: A systematic review and meta-analysis. PLoS One 2013;8:e74467.  Back to cited text no. 2
    
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Lee JS, Choi SH, Kang YR, Kim Y, Shim YH. Efficacy of a single dose of dexmedetomidine for cough suppression during anesthetic emergence: A randomized controlled trial. Can J Anaesth 2015;62:392-8.  Back to cited text no. 13
    
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