The Effects of Dexmedetomidine on Reducing Emergence Coughing in Thyroidectomy Patients: A Randomized Clinical Trial

doi:10.21203/rs.3.rs-5007017/v1

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The Effects of Dexmedetomidine on Reducing Emergence Coughing in Thyroidectomy Patients: A Randomized Clinical Trial

https://doi.org/10.21203/rs.3.rs-5007017/v1

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Background

Emergence from anesthesia could be associated with complications such as bleeding. Such complications are more common among specific surgeries such as thyroidectomy. We aimed to study if a single-dose of dexmedetomidine given 10 minutes before emergence from anesthesia would decrease emergence cough among thyroidectomy patients.

Methods

This double-blind randomized clinical trial was conducted on patients aged 18–68 years old referred to Imam Khomeini Hospital, Urmia, Iran. The Ethics Committee of Urmia University of Medical Sciences approved the present study. Simple randomization was used in this study. The patients were randomly assigned into intervention and control groups. The baseline characteristics of the patients was recorded at baseline and systolic and diastolic blood pressure and mean arterial blood pressure were measured before the operation. In the ending 10 minutes of the operation, the intervention group received 0.5 micrograms/kg of dexmedetomidine and the control group received the same volume of saline. Then, the frequency and intensity of cough, heart rate, systolic and diastolic blood pressure, and shivering were measured. Chi-square and Fisher’s exact test were used for data analysis.

Results

Dexmedetomidine significantly reduced the frequency of coughing during recovery compared to the control group (p < 0.05). However, there were no significant differences in heart rate, blood pressure, or shivering between the two groups.

Conclusion

In conclusion, dexmedetomidine administration during surgery under general anesthesia significantly reduced the frequency of coughing during recovery in thyroidectomy patients.

Trial registration

IRCT code IR20211209053338N1

Dexmedetomidine

emergence cough

clinical trial

Emergence from anesthesia can be associated with a set of risks, one of which is coughing. Previous studies have reported a 40% prevalence of emergence coughing among patients undergoing general anesthesia (1). Emergence coughing can lead to postoperative complications such as bleeding, hemodynamic instability, laryngospasm, increased intra-abdominal pressure, and decreased functional residual capacity (2–4). Although emergence coughing might not lead to significant sequelae among most patients, the mentioned complications pose significant threats to certain surgeries, such as thyroid surgeries, given that a complicated bleeding could lead to airway obstruction in patients (5). Furthermore, most cases of post-thyroidectomy hemorrhages are induced by the severe emergence coughing (6).

Different agents have been used in clinical trials to alleviate emergence coughing, including remifentanil, lidocaine, alfentanil, and dexmedetomidine (7, 8). Dexmedetomidine is a highly selective α2-receptor agonist which has recently received attention as an intraoperative adjuvant therapy (9). There are positive attributes to dexmedetomidine; (i) a small dose of the agent has been shown to alleviate emergence cough; (ii) dexmedetomidine exerts its function without causing respiratory suppression (9); (iii) the use of the drug has been approved for bronchoscopic purposes; and (iv) the resultant decreased coughs then leads to decreased risk of bleeding (10).

In this randomized double-blind placebo-controlled study, we aimed to examine the effects of a single-dose dexmedetomidine before emergence from general anesthesia on alleviating emergence cough in patients undergoing thyroidectomy.

The present study was a double blind clinical trial conducted on patients aged 18–68 years old referred to Imam Khomeini Hospital, Urmia, Iran in 2021. The present study was approved by the Ethics Committee of Urmia University of Medical Sciences (IR.UMSU.REC.1400.211.). The study protocol was registered with the registry of Clinical Trials (IRCT code: IR20211209053338N1). A written informed consent was obtained from all study participant before the trials were started. The patients were allowed to leave the study at any moment and no charges were upon them. Furthermore, patient privacy was followed throughout the study by using an anonymous checklist for each patient. The exclusion in this study were (i) known allergy to vasopressors or local anesthetics, (ii) systemic diseases such as cardiovascular, liver or kidney and lung diseases including asthma, (iii) smoking, and (iv) patients receiving antitussives treatment for operations lasting longer than 2.5 hours.

Randomization

Seventy patients who matched the inclusion criteria were included in the current investigation. Simple randomization was used to divide the patients into two groups—dexmedetomidine (A) and the control group (B)—with 30 patients in each group and a 1:1 allocation ratio. For the randomization technique, blocks of four were made (AABB, ABAB, BBAA, BABA, ABBA, and BAAB). Then, an envelope was sealed around each block before placement. One of these envelopes was opened for the first patient, and the individuals in each group were assigned. Following the implantation of the fourth patient, a different envelope was once more chosen, and the process was repeated.

Study protocol

After obtaining written consent from the patients and obtaining the approval of the Ethics Committee of Urmia University of Medical Sciences, a number of patients underwent surgery under general anesthesia. The subjects were randomly divided into two equal groups of 35 people using computer numbers. After entering the operating room, the individual characteristics of the patient, including age, sex, and physical condition, were recorded, and systolic and diastolic blood pressure and mean arterial blood pressure were recorded. After the patient was transferred to the operating room, blood pressure and cardiovascular monitoring were performed and the patient's arterial blood oxygen saturation was measured by pulse oximetry and all the measured variables were recorded as baseline. In the last 10 minutes of surgery, each patient received 0.5 micrograms/kg of dexmedetomidine according to their group and the same volume of saline in the control group. The premedication consisted of midazolam 1–2 mg IV and fentanyl 2 mcg/kg. Upon entering the operating room, standard vital sign monitors (pulse oximetry, electrocardiogram and non-invasive blood pressure) were applied to the patients. Anesthesia was induced with propofol 1.5 mg/kg. After confirming adequate muscle relaxation by administering atracurium 0.5 mg/kg IV, an endotracheal tube (ETT) with an internal diameter of 7 mm (female) or 8 mm (male) were inserted into the trachea. ETT cuff pressure was maintained at 20–25 cmH2O. Mechanical ventilation was adjusted using a volume of 8 ml/kg (ideal body weight) to maintain ETCO2 at 35–40 mmHg. During the surgery, isoflurane 1.2 MAC was used to maintain the heart rate (HR) and mean arterial pressure (MAP) at 20% of the baseline value before the operation. The frequency and intensity of cough, heart rate, systolic and diastolic blood pressure, and shivering in two groups were evaluated analogically when regaining consciousness and during recovery, and the results were evaluated by a person who did not know the contents of the patient's medications. In this study, the severity of cough was divided as (0: no cough, 1: one cough, 2: more than one cough, 3: repeated coughs with raising the head (24).

Sample size and statistical analysis

The sample size was determined using the ratio of cough in the two investigated groups in the study of Lee et al. (5). After data collection, descriptive statistical methods including frequency-percentage and mean ± standard deviation were used for statistical analysis. Chi-Square test (if necessary, Fisher test) was used to compare frequency using SPSS version 17. A significance threshold of < 0.05 was considered as the significance level.

Ethics

All stages of the study were approved by the Ethics Committee of Urmia University of Medical Sciences and the code of ethics was obtained (IR.UMSU.REC.1400.211). All the patients were explained about the study and all the patients’ data remained confidential.

In this study, 70 patients who underwent thyroidectomy were examined. Examining the gender distribution of the patients showed that 11.4% of thyroidectomy patients were men and 88.6% of them were women. The study participants were divided into two groups; (a) the intervention group (35 individuals receiving dexmedetomidine) and (b) control group (35 individuals). The average age of the intervention group was 50.7 ± 10.2 years and the average age the control group was 46.4 ± 12.3 years.

Table 1

The baseline characteristics of study participants
Gender, n (%)	Male	8 (11.4)
Gender, n (%)	Female	62 (88.6)
Age, mean ± SD	Dexmedetomidine	50.7 ± 10.2
Age, mean ± SD	Control	46.4 ± 12.3

In this section, in order to check the research hypotheses, statistical inferential tests have been used. Before a test is considered for the analysis, it is necessary to obtain information about the parametric or non-parametric nature of the data, for which the Kolmogorov Smironov test was used. According to the significance level of the variables (systolic blood pressure/diastolic blood pressure/heart rate) which is more than 0.05, the null hypothesis based on the normality of the data was accepted and it can be concluded that these variables have a normal distribution and can be tested used a parameter to analyze them. The chi-square test showed a significant difference between the frequency of cough in the patients of the two groups (P < 0.05) with the group receiving dexmedetomidine having less cough than the control group. The chi-square test showed no significant difference between the frequency of shivering in the patients of the two groups postoperatively (P > 0.05) (Table 2).

Table 2

The presence/absence of cough and shivering among dexmedetomidine and control groups
		Dexmedetomidine	Control
Cough	Yes	14 (40%)	25 (71%)
Cough	No	21 (60%)	10 (29%)
p-value: 0.008
Shivering	Yes	7 (20%)	4 (11%)
Shivering	No	28 (80%)	31 (89%)
p-value: 0.971

Table 3

The comparison of cough severity, blood pressure, and pulse rate between dexmedetomidine and control groups
	Dexmedetomidine	Control
Cough severity (mean)	27.60	43.40
p-value: 0.001
Systolic blood pressure, mean ± SD	73.3 ± 14.3	73.2 ± 15.2
p-value: 0.987
Diastolic blood pressure, mean ± SD	135.9 ± 17.2	135 ± 13.6
p-value: 0.812
Mean pulse rate, mean ± SD	89.1 ± 10.2		87 ± 13.3
p-value: 0.465

The results showed a significant difference between the severity of cough in the patients of the two groups receiving dexmedetomidine and placebo in the postoperative recovery in patients undergoing thyroidectomy (P < 0.05). Also, there was no significant difference between the mean systolic and diastolic blood pressure and the average heart rate in the two groups receiving dexmedetomidine and placebo in post-operative recovery in thyroidectomy patients (P > 0.05 for both).

This study consisted of 70 patients, divided into two groups of 35, 8 patients (11.4% male) and 62 patients (88.6% female) with the average age of the dexmedetomidine group 50.7 ± 10.2 years and the control group 46.4 ± 12.3 years. The prevalence of emergence coughing was 40% in the present study in the intervention group and 71% in the control group, which showed a significant difference (p-value: 0.008). The prevalence of emergence cough in the present study was comparable to previous studies (11, 12). There was a significant difference between the frequency and severity of cough in the two groups receiving dexmedetomidine and placebo in postoperative recovery (P < 0.05), but there was no significant difference between the frequency of shivering, the average systolic/diastolic blood pressure and the average heart rate (P > 0.05).

Post-operative bleeding is an uncommon yet critical complication of thyroidectomy, which may necessitate intensive care (13). The risk factors of post-operative bleeding include male sex, older age, and post-operative coughing (2). The bleeding that precedes coughing can be explained by (a) the fact that the cough lifts the thyroid cartilage and (b) that severe cough increases venous return (10). Furthermore, thyroidectomy is a surgery inherently associated with increased risk of emergence cough and post-operative bleeding (11 and 2). Therefore, the importance of alleviating emergence cough seems of paramount importance in these patients. Therefore, this study examined the effect of dexmedetomidine on preventing emergence cough among thyroidectomy patients.

So far, different drugs have been applied to attenuate emergence coughing, including use of lidocaine either locally before intubation or intravenously after the surgery and administration of opioids such as remifentanil and sufentanil (14). In fact, use of lidocaine/prilocaine and tetracaine spray is currently the most commonly used alternative (15). However, despite the benefits, application of each of these potions is faced by challenges; opioids on the one hand, are perceived to cause delayed emergence, increased risk of vomiting, and suppressed respiration (11). On the other hand, the application of tetracaine on mucosal surface could be limited due to its inconvenience particularly among patients with respiratory infectious diseases. Moreover, administering anesthetics prior to the surgery provides only a limited time because these compounds are easily absorbed by the endotracheal mucus (16, 17). Overall, the debate is still going, as the significantly more optimal choice has not yet been introduced. A systematic review and meta-analysis in 2020 compared the use of dexmedetomidine, remifentanil, fentanyl, lidocaine i.v., intracuff lidocaine, and lidocaine via tracheal or topical route in reducing emergence coughing. The results showed that there is no significant difference between the outcome (18). Therefore, the research on this matter is still ongoing.

The sedative, analgesic, and non-respiratory-suppressive attributes of dexmedetomidine make it a potentially useful alternative. Several studies have used dexmedetomidine either alone or in conjunction with another drug. Kim et al. administered a 0.4 µg/kg/h intraoperative infusion of dexmedetomidine during nasal surgery. Their results showed that dexmedetomidine caused a smooth and hemodynamically stable emergence, but at the same time did not lead to decreased cough severity (19). Furthermore, another study reported that co-administration of remifentanil and dexmedetomidine significantly decreased emergence cough while the use of dexmedetomidine alone did not have such effect (20). These results were not consistent with our findings, which could be explained by the differences in the study population (age and gender distribution, ethnicity) and the type of surgery. However, another study backed our finding, reporting that the use of dexmedetomidine alone significantly decreased the emergence cough. Kim et al. mentioned the fact that there is controversy between their findings and those of others in this regard, and they perceived that because their study population was consisted of only females, this could explain the difference (21); and given that the majority of our study population were female, the explanation could be used here.

The present study had some limitations. The sample size of this study was relatively small and larger sample size might provide more statistical power and enhance the generalizability of the results to a broader population of thyroidectomy patients. Also, this research was conducted on a single research which could lead to a set of biases. Finally, the gender distribution of the patients was significantly imbalanced. Therefore, the results may not be fully generalizable.

The results of the study showed that there was a significant difference between the frequency and severity of cough in the dexmedetomidine and control groups, so that the frequency and severity of cough in the dexmedetomidine group was less than the placebo.

ETT: endotracheal tube

HR: heart rate

MAP: mean arterial pressure

Ethics approval

All stages of the study were approved by the Ethics Committee of Urmia University of Medical Sciences and the code of ethics was obtained (IR.UMSU.REC.1400.211).

Consent to participate

Informed consent was obtained from all study participants.

Data Availability Statement

The data supporting this study's findings are available from the corresponding author upon reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

None.

Author participation

All the research, including data collection, data analysis, and writing the manuscript was conducted by Sonia Mahmoudi Azar.

Acknowledgments

The authors would like to express their profound gratitude to the Department of Anesthesiology in Imam Khomeini Training Hospital.

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No competing interests reported.

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You are reading this latest preprint version

The Effects of Dexmedetomidine on Reducing Emergence Coughing in Thyroidectomy Patients: A Randomized Clinical Trial

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Trial registration

Introduction

Methods and materials

Randomization

Study protocol

Sample size and statistical analysis

Ethics

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1