The comparative effect of lidocaine-remifentanil intravenous infusion and gargle on hemodynamic responses and sore throat and cough after endotracheal extubation: A randomized clinical trial

Mohammad Shabani; Hesameddin Modir; Farzad Zamani Barsari

doi:10.4103/jhnps.jhnps_34_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 10 | Issue : 2 | Page : 142-147

The comparative effect of lidocaine-remifentanil intravenous infusion and gargle on hemodynamic responses and sore throat and cough after endotracheal extubation: A randomized clinical trial

Mohammad Shabani¹, Hesameddin Modir², Farzad Zamani Barsari³
¹ Students Research Committee, Arak University of Medical Sciences, 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

Date of Submission	07-Jun-2022
Date of Decision	17-Jul-2022
Date of Acceptance	19-Jul-2022
Date of Web Publication	15-Dec-2022

Correspondence Address:
Hesameddin Modir
Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak
Iran

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jhnps.jhnps_34_22

Abstract

Purpose: The present evidence-based clinical study addressed the therapeutic effectiveness of lidocaine-remifentanil intravenous infusion versus gargle on attenuation of hemodynamic responses and prevention of sore throat and cough after endotracheal extubation. Materials and Methods: In a double-blind clinical trial whereby 76 cases receiving endotracheal intubation under general anesthesia were classified into two intervention groups being treated with lidocaine-remifentanil mixture administered by either intravenous infusion or gargle using balanced block randomization. Hemodynamic parameters including heart rate and blood pressure during surgery and in recovery every 15 min and respiratory symptoms such as cough, hoarseness, and sore throat during recovery and at certain postoperative time points of 2, 4, 8, 12, and 24 h were gathered. Pain score was measured by a Visual Analog Scale. Statistical analysis was conducted using the software SPSS v22 by Chi-square and independent t-test. Results: No statistically significant observed intergroup in terms of oxygen saturation, heart rate, mean blood pressure, need for analgesic medication, duration of surgery, and the incidence of cough and hoarseness (P > 0.05), but not in pain score in recovery and eight postoperative hours. While the intergroup difference was found at other times, the intravenous infusion group was associated with less pain score, compared to the gargling group (P > 0.05). Conclusion: A reduction in sore throat observed in subjects receiving an intravenous infusion compared to those receiving the gargling intervention during recovery and 8 h after surgery. We have convincing evidence to support the superiority of intravenous therapy comprising of lidocaine and remifentanil; however, larger sample size is needed to establish whether or not the interventions are effective.

Keywords: Cough, gargling, hemodynamic responses, intravenous infusion, lidocaine, remifentanil, sore throat

How to cite this article:
Shabani M, Modir H, Barsari FZ. The comparative effect of lidocaine-remifentanil intravenous infusion and gargle on hemodynamic responses and sore throat and cough after endotracheal extubation: A randomized clinical trial. J Head Neck Physicians Surg 2022;10:142-7

How to cite this URL:
Shabani M, Modir H, Barsari FZ. The comparative effect of lidocaine-remifentanil intravenous infusion and gargle on hemodynamic responses and sore throat and cough after endotracheal extubation: A randomized clinical trial. J Head Neck Physicians Surg [serial online] 2022 [cited 2023 Jun 4];10:142-7. Available from: https://www.jhnps.org/text.asp?2022/10/2/142/363921

Introduction

Postoperative sore throat has been well documented and recognized as a leading complication still unsolved in patients undergoing endotracheal intubation.^[1] To our knowledge, tracheal intubation accounts for one primary cause of trauma to the airway mucosa leading to postoperative sore throat, whose prevalence is estimated to vary with a range between 14.4% and 80%^[1],[2] and known to be ranked the eighth highest adverse events in the postoperative period.^[3],[4] Although cough during endotracheal extubation is not typically a serious complication following anesthesia, it is an unpleasant experience and sometimes an attack and can increase intracranial, intraocular, and intra-abdominal pressures.^[5],[6]

Preceding prospective studies have established that intravenous lidocaine infusion reduces postoperative cough under general anesthesia with endotracheal intubation, occurring for a variety of reasons, including the inappropriate laryngoscope blade type, bucking during endotracheal extubation, and smoking.^[7],[8] The neural mechanism of coughing has been well documented and has been frequently reported to be associated with stimulation by the endotracheal tube and its cuff. Research suggests that high-speed receptors are found abundant in the trachea and these receptors seem to play a key role in causing coughing.^[9],[10] During general anesthesia, the irritation resulting from cuff pressure is blocked so that patients do not cough. Coughing on emergence from general anesthesia can cause increased blood pressure, heart rate, myocardial ischemia, bronchospasm, and bleeding, as well as amplified surgery-induced pain and intracranial and intraocular pressures.^[11],[12]

Various human studies aimed specifically at relieving postoperative sore throat have investigated a number of pharmacological and nonpharmacological interventions among which the latter ones are also proposed as the smaller endotracheal tube, intubation with an endotracheal tube lubricated with water-soluble gel, use proper airway, intubation after complete relaxation, gentle oropharyngeal suction, minimizing intra-cuff pressures, and extubation with the cuff fully deflated,^{[3],[4],[5],[13],[14]} while the first interventions are the beclomethasone inhalation, gargling with aspirin, topical lidocaine spray, and lidocaine given into the cuff.^[3],[15]

As evidenced by the literature, various methods such as local and intravenous administration of local anesthetics are suggested to suppress cough. A common analgesic option is intravenous opioids and endotracheal extubation performed while patients are not completely awake; it is not seen as a desirable method in many cases.^[16],[17] Due to the incidence of sore throat and cough during laryngoscopy and endotracheal intubation and the importance of relieving the postoperative complications and to a lack of comparative study examining the effect of lidocaine-remifentanil intravenous infusion versus gargle. The present study was designed to comparing the effectiveness of these two techniques on attenuation of the hemodynamic responses and prevention of sore throat and cough after laryngoscopy and endotracheal intubation.

Materials and Methods

Study setting and patients

This randomized, double-blind, clinical trial stratified the participants into two intervention groups undergone endotracheal intubation for surgery under general anesthesia. The inclusion criteria included patients aged 30–60 years, of both genders, American Society of Anesthesiologists Class I and II, no history of postoperative sore throat, no history of surgery on head and neck, especially throat, no addiction to any drug, no history of chronic consumption of analgesics, no sensitivity to the study drugs, no upper airway infection and cold, Mallampati score <2, no liver or kidney failure, no need to insert NG tubes during surgery and up to 24 postoperative hours, and finally duration of surgery more than 45 min and <120 min. The exclusion criteria were unwillingness to continue the study, bleeding during suctioning at the extubation, and requiring a second laryngoscopy for any reason.

The sample size calculation conducted by considering the study power 80%, confidence interval 95%, and pain score of our recent study.^[18]

Intervention

No analgesic or sedative medication was given to the study participants prior to surgery, who received induction of anesthesia with 2 mcg/kg fentanyl (Caspian Tamin Pharmaceutical Company, Rasht, Iran) and 2 mg midazolam (Iran Eksir, Tehran, Iran), 3–5 mg/kg thiopental sodium (VUAB Pharma Inc., Roztoky, Czech), and 0.5 mg/kg atracurium (Caspian Tamin Pharmaceutical Company).

An attempt was made at intubation using a Macintosh blade and a 7.0–7.5- and 7.5–8.0-mm endotracheal tube (for women and men, respectively). Endotracheal tube cuff pressure was adjusted to 25 cm H2O using a pressure gauge manometer in all patients. Endotracheal intubation was achieved with a polyvinylchloride (PVC) cuffed endotracheal tube (Flexicare Medical Ltd, UK, imported by Jahan Gostar Tejarat Co., Tehran, Iran). One person gently intubated all patients for which metal laryngoscope blades of appropriate size were used. They were randomly split into two groups using block randomization with randomly selected block sizes of 4 and 8. The first group received 0.5 mcg/kg remifentanil (Laboratorios Normon S.A. Madrid Spain) which was diluted to 5 mL, afterward 100 mg of lidocaine (5 mL, 2%) (Caspian Tamin Pharmaceutical Company), and lastly 10 mL of 20% dextrose (Shahid Ghazi Pharmaceutical Company, Tabriz, Iran) were added. Thus, the total volume of the gargling solution was adjusted to 20 mL for each group. Subjects in the two groups were requested to gargle 10 min before anesthetic induction. The gargling solution was split equally into two parts of 10 mL; the first 10 mL was gargled for 15 s and spit out, immediately followed by the second for the same length of time.^[19] The second group received intravenously 0.5 μg/kg remifentanil and 1.5 mg/kg lidocaine^[20],[21] at a total volume of 10 mL 10 min before surgery and the volume was infused over 10 min. To equalize the intervention, patients in the group receiving an intravenous infusion of remifentanil and lidocaine (the second group) gargled with a mixture of distilled water (Daroupakhsh Pharmaceutical Co., Tehran, Iran) and dextrose 20% (Shahid Ghazi Pharmaceutical Company, Tabriz, Iran) twice in 10 min before the surgery. The subjects who were given a solution of remifentanil and lidocaine as a gargle (the first group) received an intravenous injection of distilled water in a volume of 10 mL for 10 min. Throughout the surgery, pulse oximetry monitoring, noninvasive blood pressure, and heart rate and electrocardiography recordings were performed every 15 min.

Maintenance of anesthesia was provided by administrating 100–150 μg/kg/min propofol, repeated doses of muscle relaxants, and fentanyl, whereas the duration of surgery was recorded for all subjects. At the end of surgery, oral secretions were gently suctioned from the nasopharynx, then participants were transferred to the recovery room after endotracheal extubation, and the incidence of cough, hoarseness, and sore throat was recorded in recovery and at postoperative times of 2, 4, 8, 12, and 24 h. A Visual Analog Scale (VAS) was used to assess sore throat which was scored within the range of 1 (the lowest) to 10 (the highest), based on which VAS >5 was considered as pain and it was treated with 500 mg of oral acetaminophen, while the time of administration was recorded.

Data were measured and recorded by an intern who was not aware of group allocation to ensure a double-blind study. Adjuvants administered to each group were prepared by an anesthesiologist and patients were intubated by a resident in endotracheal.

Ethical consideration

All patients were informed about the study objectives and signed the informed consent form. Moreover, the study protocol is approved by ethical committee of medical university by code IR.ARAKMU.REC. 1400.202 and it is registered in Iranian Registry of Clinical Center by clinical trial code of IRCT20141209020258N172.

Statistical analysis

Data analysis was subsequently being carried out by the SPSS (release 22, SPSS Inc., Chicago, IL, USA) with a significance level of 0.05 in which a Chi-square was used for between-group comparisons. Moreover, repeated-measure ANOVA was applied to assess the differences in dependent variables over time and then to compare the differences between the two groups.

Results

The randomized, double-blind, clinical trial enrolled 76 patients under general anesthesia with endotracheal intubation who were admitted to the hospital, and then were stratified into two groups receiving lidocaine-remifentanil intravenous infusion and gargle, comprising of 40 (52.6%) male and 36 (47.4%) female, with minimum and maximum ages of 31 and 56, respectively, mean age of 40.47 ± 6.29 years, and mean body mass index of 22.92 ± 1.79 kg/m². The study revealed no statistically significant intergroup difference in terms of oxygen saturation percentage, mean blood pressure, mean heart rate, and duration of surgery (P > 0.05) and both groups were not significant different regarding age, gender, and body mass index [Table 1].

Table 1: Intergroup comparison of the mean and standard deviation of sore throat

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As shown in [Table 2], a statistically significant intergroup difference was observed in pain in recovery time to 8^th h. After operation between two groups (P < 0.001) but at 12 and 24 h. After surgery there was no difference between two groups. In addition, pain score was less in the intravenous infusion group [Chart 1]. The intergroup difference was found in the score at other times (P > 0.05).

Table 2: Intergroup comparison of the mean and standard deviation of sore throat severity

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Based on study results and according to Chi-square test [Table 3], there was no significant difference between two groups regarding the incidence of hoarseness in all times after operation (P > 0.05). The incidence of hoarseness did not increase significantly after operation to 24 h after operation (P > 0.05). Moreover, there was no any cough occurrence in each patient in two groups. Therefore, two groups were similar regarding to the incidence of cough in all times after operation (P > 0.05). In addition, oral acetaminophen treatment for reduction of pain score was similar in both groups and did not observed a statistically significant difference (P = 0.568).

Table 3: Intergroup comparison of frequency (percentage) of the incidence of hoarseness

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Discussion

Our results showed that pain score in recovery and eight postoperative hours was lower in intravenous infusion group in compare to the gargling, whereas the intergroup difference was not observed at other times. Overall, pain score was lower in the intravenous infusion group during recovery and eight postoperative hours, but two techniques showed no difference in sore throat, cough, and hoarseness.

As shown by one study on the effect of high-dose remifentanil on postoperative sore throat, they found that the incidence of sore throat was higher in the low-dose remifentanil group, concluding that a relatively high-dose intraoperative remifentanil increases postoperative sore throat in patients undergoing orthopedic surgery under general anesthesia.^[22] While our study demonstrated no difference found in sore throat, cough, and hoarseness between the two methods, the intravenous infusion group had lower pain score during recovery and eight postoperative hours. Kim et al. compared the efficacy of dexmedetomidine and remifentanil on hemodynamic changes during recovery and airway reflex and suggested that they had a similar effect in preventing cough and the first can better manage hemodynamic changes than remifentanil,^[23] while our present analysis on pain showed statistically lower pain in the intravenous infusion group during recovery and eight postoperative hours and no difference between both methods in the symptoms including sore throat, cough, and hoarseness.

Another study comparing the effect of intravenous lidocaine on airway responses during endotracheal extubation and concluded that the effect of intravenous and intratracheal lidocaine administration was found almost the same for bucking, cough, and emergence time at the end of general anesthesia.^[24] Our trial also showed a lower pain score in the intravenous infusion group during recovery and eight postoperative hours. Our two techniques had no difference in terms of sore throat, cough, and hoarseness. Dhanger et al.'s study comparing the efficacy of gargling with lidocaine and ketamine on relieving sore throat after classical laryngeal mask airway insertion pointed out that gargling with lidocaine would more effectively result in relieving postoperative sore throat.^[25]

The present clinical trial supported that pain score was found lower in the intravenous infusion group during recovery and eight postoperative hours, whereas we did not observe any intergroup difference in terms of our three events including sore throat, cough, and hoarseness.

As aforementioned, postoperative sore throat and cough are generally believed to be among the most common postoperative complications and some cases occasionally consider it as unpleasant and harmful as pain, postoperative nausea, and vomiting.^[1],[7] Postoperative sore throat is found to be more common in patients under general anesthesia with endotracheal intubation; however, this may occur even in those under general anesthesia without intubation or with supraglottic airway devices. The literature describes its various causes like the presence of endotracheal tube in situ, the use of inappropriately large endotracheal tubes, performing multiple and rough suctions at the beginning or end of anesthesia, the presence of endotracheal tube and light anesthesia, and patient bucking on the endotracheal tube. Furthermore, general anesthesia using the cool and dry anesthetic gas can be a major cause of postoperative sore throat and cough.^[1],[9],[15]

Postoperative sore throat is known to be a feeling of discomfort and many patients being asked about the complication a few hours after surgery frequently report a feeling of dryness and pain in the throat and pharynx, while many patients even point out that sore throat is more of an annoyance than other pains or complications such as postoperative nausea and vomiting. Thus, specific measures are needed to alleviate and control it, while a range of methods are used, such as the use of drugs that suppress and blunt the throat and laryngeal reflexes, like Intravenously administered opioids^[19] and topical anesthesia including lidocaine, by for instance, spraying or gargling in the throat or injecting into the cuff, and the combined with the use of local anesthetics as adjuvants with other drugs, like opioids or anti-inflammatory medications including corticosteroids.^[9],[17] All of the methods for controlling and alleviating excitatory airway reflexes can suppress reflexes such as coughing and raise the threshold for tolerance to pain (e.g., administration of opioids) or cause numbness in the throat.^[13],[26]

Although water absorption is reduced by lidocaine effect on ion transport, the anesthetic can decrease goblet cell secretion by suppressing neural pathways. The different methods of administering lidocaine appear to affect the outcome results.^[7],[11] as confirmed by Yang study addressing the efficacy of intravenous lidocaine on reducing cough.^[7] Remifentanil is commonly administered as an adjunct to general anesthesia and prevents increased airway response and detrimental hemodynamic changes, as emphasized in preceding studies.^[22],[23] Chen et al. suggested that remifentanil can decrease the number of coughs during endotracheal extubation, but the anesthetic does not alter recovery from anesthesia.^[27]

Conclusion

Drawing on the present clinical trial outcomes showing a reduction in sore throat in the group receiving an intravenous infusion of intervention drugs versus the gargle group during recovery and 8 h after surgery, although intravenous infusion of lidocaine is relatively superior to the other, it is necessary to have a larger sample size to make a definite conclusion.

Acknowledgment

The present article is part of the research results of a dissertation in general medicine, with the ethics code of IR.ARAKMU.REC.1400.202 and clinical trial code of IRCT20141209020258N172. Our thanks go to the Valiasr Hospital's clinical research council for its assistance and guidance. Special thanks are also extended to the research deputy of Arak University of Medical Sciences for the assistance and support.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

The permission was taken from the Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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