Lidocaine for preventing postoperative sore throat
Abstract
Background
Sore throat is a common side‐effect of general anaesthesia and is reported by between 30% and 70% of patients after tracheal intubation. The likelihood of a sore throat varies with the type, diameter, and cuff pressure of the endotracheal tube used. If intubation is essential, it may be helpful to give drugs prophylactically to alleviate postoperative sore throat. Local anaesthetics and steroids have been used for this purpose. This review was originally published in 2009 and was updated in 2015.
Objectives
The objective of this review was to evaluate the efficacy and any harm caused by topical and systemic lidocaine used prophylactically to prevent postoperative sore throat in adults undergoing general anaesthesia with endotracheal intubation.
Search methods
We searched CENTRAL (The Cochrane Library 2013, Issue 9), MEDLINE (January 1966 to October 2013), and EMBASE (1980 to October 2013). We also contacted manufacturers and researchers in the field. The original search was undertaken in June 2007. We reran the search in February 2015 and found four studies of interest. We will deal with those studies when we next update the review.
Selection criteria
We included randomized controlled trials (RCTs) of topical and systemic prophylactic lidocaine therapy versus control (using air or saline) that reported on the risk and severity of postoperative sore throat as an outcome.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information, such as the risk of any adverse effects.
Main results
We included 19 studies involving 1940 participants in this updated review. Of those 1940 participants, 952 received topical or systemic lidocaine therapy and 795 were allocated to the control groups. Topical and systemic lidocaine therapy appeared to reduce the risk of postoperative sore throat (16 studies, 1774 participants, risk ratio (RR) was 0.64 (95% confidence interval (CI) 0.48 to 0.85), the quality of the evidence was low), although when only high‐quality trials were included (eight studies, 814 participants) the effect was no longer significant (RR 0.71, 95% CI 0.47 to 1.09). Lidocaine given systemically in two studies (320 participants) did not reveal evidence of an effect (RR 0.44, 95% CI 0.19 to 1.05 ). The severity of sore throat as measured on a visual‐analogue scale (VAS) was reduced by lidocaine therapy (six trials, 611 participants, (mean difference (MD) ‐10.80, 95% CI ‐14.63 to ‐6.98). The adverse effects of lidocaine were not reported in these studies, though toxicity is generally rare.
Authors' conclusions
In our revised systematic review, although the results of included studies show generally positive results, they should be interpreted carefully. The effect size of lidocaine appeared to be affected by study quality; drug concentration; route of administration; management of cuff pressure during anaesthesia; the included population; and the type of outcome measured.
PICOs
Plain language summary
Lidocaine for prevention of a sore throat following an operation under general anaesthetic
Review question
We reviewed the evidence of the effect of lidocaine for preventing a sore throat in people following an operation under general anaesthetic. (General anaesthetics are medicines used to send people asleep. They can be given via an intravenous line (IV) into the person's veins, via a mask, or via an endotracheal tube placed through the mouth past the larynx (voicebox) into the trachea. In this review the anaesthetic was given via an endotracheal tube.)
Background
Sore throat is a common side‐effect of having a general anaesthetic. It is usually caused by the endotracheal tube that is inserted through a person's mouth, placed in the airway, to keep their airway open and make sure that person is breathing properly. People sometimes buck and cough when the tube is inserted in their airway and even if they do not, the presence of the tube during the operation can give them a sore throat. It may be possible to use drugs, such as the local anaesthetic lidocaine, to prevent postoperative sore throat. (A local anaesthetic prevents a person feeling pain. It is given to one specific area rather than the whole body.)
Study characteristics
The evidence is current to October 2013. We included 19 randomized controlled trials (1940 participants) in this updated review. (We reran the search in February 2015 and found four studies of interest. We will deal with those studies when we next update the review.) Lidocaine was either put into the cuff (the cuff makes sure that the tube stays in place), sprayed onto the person's vocal cords, or used as a gel smeared on the end of the tube.
Key results
The summarized results of the included studies showed positive results. However, the interpretation of the results should be judged carefully. Though the possible adverse effects of using lidocaine were not reported in the included studies, there are a few case reports about lidocaine toxicity, although this is very rare.
Quality of evidence
For lidocaine therapy versus control, the quality of the evidence for risk of sore throat was low (according to Grading of Recommendations Assessment, Development and Evaluation (GRADE)). This is because most of the trials did not describe how allocation was concealed and the results of the risk of sore throat were inconsistent, the quality of the evidence of the severity of sore throat , measured by the visual‐analogue scale, was moderate (according to GRADE).
Authors' conclusions
Summary of findings
| lidocaine versus control (air/saline) for preventing postoperative sore throat | ||||||
| Patient or population: patients presenting with postoperative sore throat | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Lidocaine versus control (air/saline) | |||||
| Risk of sore throat 12 hours to 30 hours after the operation | Study population | RR 0.64 | 1744 | ⊕⊕⊝⊝ | ||
| 306 per 1000 | 196 per 1000 | |||||
| Moderate | ||||||
| 300 per 1000 | 192 per 1000 | |||||
| Severity of sore throat 12 hours to 30 hours after the operation | The mean visual‐analogue scale of severity of sore throat in the intervention groups was | 611 | ⊕⊕⊕⊝ | |||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| We downgraded the quality of evidence for the reasons below. 1. Allocation concealment was not described in most studies and there was inconsistency of results of risk of sore throat. 2. Allocation concealment was not described in most studies. | ||||||
Background
Description of the condition
Sore throat is a frequent side‐effect of general anaesthesia and is reported by between 30% and 70% of patients after tracheal intubation (Combes 2001; Herlevsen 1992; Navarro 1997; Xu 2012). This means more than 0.51 million to 1.2 million patients might experience postoperative sore throat per year in Japan (Ministry of Health, Labor and Welfare 2012) The aetiology of sore throat is thought to involve mucosal erosion caused by the cuff of the endotracheal tube (Combes 2001; Xu 2012), trauma from intubation, and mucosal dehydration (Navarro 1997; Stout 1987). Mucosal erosion may be caused by the patient bucking or coughing, or friction between the tracheal mucosa and the endotracheal tube during general anaesthesia. Whilst medical staff may concentrate on avoiding problems during surgery, patients will only be aware of postoperative complications. These complications can affect their satisfaction with treatment (Estebe 2002; Macario 1999). The prevalence of postoperative sore throat varies with the diameter and the type of endotracheal tube used (Mandoe 1992), which patients do not know about. The cuff pressure may also influence the prevalence and severity of postoperative sore throat. Use of a laryngeal mask airway is known to reduce the risk of sore throat and can be a good alternative for some types of surgery where tracheal intubation is not essential (Brimacombe 1995; Joshi 1997). If tracheal intubation is required then prophylactic use of drugs may help to alleviate postoperative sore throat. Local anaesthetics and steroids have been used for this purpose (Ayoub 1998; Goddard 1967; Herlevsen 1992; Navarro 1997). These studies showed the effectiveness of such interventions. To reduce heterogeneity, we selected only lidocaine therapy in this review. Steroids and non‐steroidal anti‐inflammatory drugs may be considered in future systematic reviews. This review was originally published in 2009 (Tanaka 2009); and updated in 2015.
Description of the intervention
The interventions used in the studies were lidocaine in the cuff of the endotracheal tube, aerolized lidocaine, intravenous lidocaine, and lidocaine gel on the endotracheal tube. The doses of lidocaine used were: 2% lidocaine in the cuff of the endotracheal tube; 4% spray (aerolized lidocaine); 4% lidocaine gel.
How the intervention might work
Patients bucking and coughing at intubation are the main causes of injury to the tracheal mucosa. Lidocaine in the cuff of the endotracheal tube has a pharmacological action during the operation. By preventing these complications lidocaine is effective in reducing sore throat even after its pharmacological action has worn off; the local anaesthetic effect of lidocaine on the upper airway lasts from 20 minutes to 30 minutes. The strong stimulation of laryngoscopy or moving the tube may excite sensory C fibres and produce secondary neuroplasticity, associated with postoperative sore throat and cough. Lidocaine prevents this excitement of sensory C fibres (Chang 1999). Therefore, another possible mechanism for preventing postoperative sore throat is to use lidocaine to suppress excitation of airway sensory C fibres and the release of sensory neuropeptides such as tachykinins that produce bronchoconstriction (Sloway 1991). Lidocaine is also thought to be useful in reducing injury to the tracheal mucosa during extubation.
Why it is important to do this review
This is an update of a Cochrane review first published in 2009 (Tanaka 2009). The risk of postoperative sore throat is high (30% to 70%) following surgery under general anaesthesia. There are preventive methods for this common and sometimes severe condition; in such cases lidocaine is commonly used. Technological advances in surgery have meant safer anaesthesia with the use of airway management tools including video laryngoscopes and supraglottic airway devices, perioperative assessment by transoesophageal echocardiography (during non‐cardiac and cardiac surgery), and new anaesthetic agents and muscle relaxants such as remifentanil and rocuronium bromide. Nowadays, the emphasis is on the quality of a patient's postoperative recovery (Murphy 2011); and sore throat is known to affect a patient's perception of the anaesthesia (Estebe 2002). Many randomized controlled studies have been undertaken examining lidocaine for preventing postoperative sore throat; however, there are controversies about the effects of this lidocaine therapy and, therefore, conducting a systematic review and meta‐analysis is important.
Objectives
The objective of this review was to assess the efficacy and any detrimental effects of topical and systemic lidocaine used prophylactically to prevent postoperative sore throat in adults undergoing endotracheal intubation during general anaesthesia.
Methods
Criteria for considering studies for this review
Types of studies
We included randomized controlled trials (RCTs) of topical and systemic prophylactic lidocaine therapy to prevent postoperative sore throat. All methods of randomization were acceptable and the differences in the study quality were taken into account in the analysis. Factors such as the type of endotracheal tube; number of intubation attempts; method of anaesthesia; type of surgery; cuff pressure during anaesthesia; and the time of evaluation of sore throat after the operation would have strongly affected the rates of sore throat and would be clearly described in the relevant studies.
We included all the results of the RCTs that were of interest and excluded observational studies.
Types of participants
We included trials that investigated topical and systemic lidocaine therapy to prevent postoperative sore throat in adults.
We excluded children because different anaesthetic techniques may be used from adults, and children cannot always report postoperative sore throat in the same way. .
Types of interventions
We included the use of various concentrations of lidocaine in the cuff of the endotracheal tube, aerolized lidocaine, intravenous lidocaine, and lidocaine gel on the endotracheal tube. The doses were 2% lidocaine in the cuff of the endotracheal tube; 4% aerolized lidocaine spray; and 4% lidocaine gel.
Types of outcome measures
We monitored the risk and severity of sore throat at 12 hours to 30 hours after the operation. On occasions patients are unable to correctly assess sore throat because of a residual effect of the general anaesthesia.
Primary outcomes
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Risk of sore throat 12 hours to 30 hours after the operation.
Secondary outcomes
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Severity of postoperative sore throat at 12 hours to 30 hours after the operation, assessed on a visual‐analogue scale (VAS) (0 to 100 mm).
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Risk of adverse effect due to lidocaine; occurrence of lidocaine toxicosis such as allergic reaction, unconsciousness, convulsion, coma, respiratory arrest, and cardiovascular system depression.
Search methods for identification of studies
We searched for studies and presented the results according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011); and PRISMA statement (Moher 2009).
Electronic searches
In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE (1966 to October 2013); and EMBASE (1980 to October 2013). We identified RCTs using the search strategies found in Appendix 1 (MEDLINE Silver Platter); Appendix 2 (EMBASE Silver Platter); Appendix 3 (CENTRAL). The original search was undertaken in June 2007 (Tanaka 2009). We combined the search strategy with the Cochrane highly sensitive search strategy detailed in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
We reran the search in February 2015. We will deal with any studies of interest when we next update the review.
Searching other resources
We identified additional articles from the searches named above. Furthermore, we contacted relevant pharmaceutical companies and asked them to provide information on both published and unpublished trials.
Data collection and analysis
Selection of studies
We were not blinded to study authors, institutions, published journals, or study results. Two authors (in a combination from YT or MN or YS or YTs) independently evaluated the titles and abstracts of trials identified in the literature search. We resolved disagreements through discussion. If this method was not successful, a third author (TN) evaluated the disputed study and decided on its eligibility.
Data extraction and management
We recorded the information on participants, methods, interventions, outcomes, and adverse events using a modified Cochrane Anaesthesia Review Group (CARG) data extraction sheet. We recorded dichotomous outcomes as the number of participants with the outcome event and the number of participants in the treatment group. If the dichotomous outcome was expressed as a proportion, we converted the data into the original fraction. For continuous data (such as measures on a visual‐analogue scale (VAS)), we extracted the mean value and standard deviation (SD) for each group. Two authors (YT, MN, YS or YTs) independently extracted data from the included studies. We resolved disagreements by consulting with a third author (TN).
Assessment of risk of bias in included studies
We used the criteria described in the Cochrane Handbook for Systematic Reviews of Interventions to describe the quality of trials researched (Higgins 2011). Two review authors independently assessed risk of bias of the selected studies (YT and YT for the original review and for the update). We resolved any differences of opinion by discussion and consensus and finally by discussion with a third author (TN). To assess any risk of bias we focused on the following dimensions as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
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Adequate sequence generation (such as computer‐generated random numbers and random number tables; inadequate approaches included the use of alternation, case record numbers, birth dates or days of the week or no description of methods of randomization).
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Adequate measures to conceal allocation. Concealment was deemed adequate where randomization was centralized or pharmacy‐controlled, or where the following were used: serially numbered containers, on‐site computer‐based systems where assignment is unreadable until after allocation, other methods with robust methods to prevent foreknowledge of the allocation sequence to clinicians and participants.
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Blinding was deemed adequate if blinding was applied (whether the participant, care provider or outcome assessors).
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Incomplete outcome data addressed; high risk: the number of missing data was large enough to produce significant bias. Low risk: the number of missing data was small and did not have a clinically relevant impact on the intervention effect estimate. Unclear: the information could not be obtained for detecting missing data.
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Freedom from selective reporting: this was deemed to be adequate if all stated outcomes were reported on and presented. We highlighted any selective outcome reporting.
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Other bias: the study‐specific issues that may raise concerns about the possibility of bias should be considered and judgement should be formulated about them under this domain of the tool.
The risk of bias graph for each trial was made available to assess quality.
Measures of treatment effect
We used risk ratio (RR) as the measure of effect for each dichotomous outcome. The absolute risk reduction (ARR) was used to estimate the number needed to treat for an additional beneficial outcome (NNTB) to prevent one sore throat. We also used the visual analogue scale for continuous data about intensity of postoperative sore throat.
Unit of analysis issues
We managed unit of analysis issues according to theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The unit of analysis was a problem of participants who were individually randomized to the treatment group (intervention or control). Some RCTs selected for this review had multiple interventions. We also described studies with multi‐arm interventions. The SD, sample size, and mean of the combined group was calculated according to the formula described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Dealing with missing data
If too much data was missing (i.e. follow‐up rate was less than 80%), we excluded the study.
Assessment of heterogeneity
We used the I2 statistic to interpret the heterogeneity between included studies (Higgins 2002).
Assessment of reporting biases
A funnel plot using the data for the primary outcome of risk of postoperative sore throat was used to test for publication bias. Asymmetry in the funnel plot indicates the presence of publication bias (Egger 1997). Recently the validity and reliability of these plots has been questioned (Tang 2000; Terrin 2005). We used Harbord's modified test to detect any large publication bias (Habord 2006).
Data synthesis
For I2 less than 30% we used a fixed‐effect model; if I2 was greater than 30% we used a random‐effects model. The fixed‐effect model used the Mantel‐Haenszel method and the random‐effects model the Der Simonian and Laird method. For continuous data, the methods for summarizing results were based on variance.
Subgroup analysis and investigation of heterogeneity
The subgroup analysis involved the different kinds of intervention such as topical, systemic (or both), the description of controlled cuff pressure of endotracheal tube and the alkalinization of lidocaine.
Sensitivity analysis
The sensitivity analysis was done for the quality of the study.
Assessment of quality of evidence using GRADE and selection of outcomes for Summary of findings tables
We assessed the quality of the evidence according to the GRADE system. We included the following patient‐centred outcomes into the 'Summary of findings' table: we exported data from Review Manager to GRADE profiler (GRADEpro version 3.6) in order to create a 'Summary of findings' table.
We included the following outcomes into the 'Summary of findings' table:
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Risk of sore throat 12 hours to 30 hours after the operation
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Visual‐analogue scale of severity of sore throat
Results
Description of studies
Results of the search
We updated our search in October 2013. We reran the search in February 2015. We identified 1322 citations through electronic searching. Of those initial 1322 articles, 39 articles were of interest to us and we obtained full paper copies for review. From those initial 39 full reviewed articles, we included four new trials in this updated review and another four new studies are awaiting classification (Figure 1).
Flow diagram.
Included studies
In total, we included 19 studies (see 'Characteristics of included studies') in this updated review; 18 of the 19 studies reported obtaining informed consent from the participants and had prior ethics committee approval. We recorded the data on the interventions, outcomes, and study characteristics such as participant age and gender, the method of anaesthesia, the kind of endotracheal tube, and the type of surgery for included studies, using a modified version of the Cochrane Anaesthesia Review Group's (CARG) data extraction form.
Types of participants
The eligible participants were 1940 surgical patients who received general anaesthesia and endotracheal intubation. One study did not describe the gender of the participants (Basaranoglu 2004). One study included only female participants (Porter 1999); and the remaining 17 included studies gave the numbers of female and male participants.
Surgical procedure
Altintas 2000 included orthopaedic surgery. This study excluded neck surgery and cases involving massive blood loss.
Bajaj 2004 included surgery of less than three‐hours duration.
Basaranoglu 2004 gave no description regarding the type of surgery.
Estebe 2002 and Estebe 2004 involved lumbar spinal surgery.
Estebe 2005 involved only thyroidectomy surgery.
Hashimoto 1981 included general surgery without thoracic surgery.
Hara 2005 included supine position surgery without neck or oral surgery.
Herlevsen 1992 and Takekawa 2006 included abdominal, gynaecological, urological, and orthopaedic surgery.
Klemola 1988 targeted otolaryngical surgery that did not involve the mouth, pharynx, and larynx.
Navarro 1997 excluded neck and head surgery.
Porter 1999 included gynaecological surgery, but excluded eye, nose, and ear surgery.
Soltani 2002 included only cataract surgery.
Krishnan 2008 included orthopaedic urological general surgery, ear, nose and throat (ENT) or neurosurgical procedures.
Jaicobandram 2009 included any ophthalmic surgery.
Xu 2012 included only participants undergoing thyroid surgery without laryngeal surgery and tracheotomy.
Intervention
Lidocaine was administered via various routes including: in the cuff of the endotracheal tube, as a lubricant on the endotracheal tube, and sprayed on the vocal cords. Ten studies used lidocaine solution in the cuff of the endotracheal tube (Altintas 2000; Bajaj 2004; Estebe 2002; Estebe 2004; Estebe 2005; Jaicobandram 2009; Krishnan 2008; Navarro 1997; Navarro 2012; Porter 1999).
In Basaranoglu 2004 lidocaine jelly and pomade were used as a lubricant on the distal end of the endotracheal tube.
Three studies used lidocaine spray on the pharynx (Hara 2005; Hashimoto 1981; Herlevsen 1992).
In one study both jelly on the end of the endotracheal tube and spray on the larynx were used as the intervention (Klemola 1988).
Two studies used lidocaine administered intravenously (Takekawa 2006; Xu 2012).
Soltani 2002 had multiple interventions such as lidocaine sprayed on the distal end of endotracheal tube (ETT) for group 1; lidocaine sprayed on laryngopharyngeal structures near the inlet of the larynx for group 2; lidocaine jelly lubricated on the distal end and the cuff of the ETT for group 3; lidocaine administered intravenously at the conclusion of surgery for group 4; and lidocaine in the cuff of the ETT for group 5
Contents of cuff
The cuff of the ETT contained either air or saline.
In three studies the cuff was filled with saline in the control group (Altintas 2000; Krishnan 2008; Navarro 2012). In one study, the cuff of the ETT was filled with air (Navarro 2012). Three studies used both saline and air in the control intervention (Bajaj 2004; Jaicobandram 2009; Porter 1999). In six studies the contents of the cuff were not described (Basaranoglu 2004; Hara 2005; Hashimoto 1981; Herlevsen 1992; Soltani 2002; Takekawa 2006); however, it is likely that air was used. In six studies the cuff was filled with air in the control group (Estebe 2002; Estebe 2004; Estebe 2005; Klemola 1988; Navarro 1997; Navarro 2007).
Sample size calculation
Eight studies used sample size calculations in experimental planning to control type one and type two errors (Estebe 2002; Estebe 2004; Estebe 2005; Hara 2005; Herlevsen 1992; Navarro 2007; Takekawa 2006; Krishnan 2008). In the other included studies the sample sizes were 50 to 240 participants.
Excluded studies
Of the initial 1322 articles, 39 were of interest to us and we obtained full paper copies for review. We excluded 16 papers for the following reasons: four studies assessed sore throat immediately after general anaesthesia, which was too early for inclusion in our chosen outcome analysis (Durmus 2001; Huang 1998; Shroff 2009; Yörükoğlu 2006); four studies did not use random allocation of participants (Cox 1996; Fuller 1992; Kori 2009; Maruyama 2004); in five studies the control group was not relevant (el Hakim 1993; Honarmand 2008; Hung 2010; Lee 2011; Sumathi 2007); in Loeser 1980 an endotracheal tube was not used during anaesthesia; in Crerar 2008 the intervention was a larger size intubation tube and the control used smaller sized endotracheal tubes; and we were unable to extract the data from D'Aragon 2013; (see Characteristics of excluded studies).
Awaiting classification
There are four studies awaiting classification (Bousselmi 2014; D'AragonF 2013; Ishida 2014; Zeng 2014). Please see Characteristics of studies awaiting classification table for more information.
Ongoing studies
There are no ongoing studies.
Risk of bias in included studies
Three authors (YT, YT, TN) independently assessed the methodological quality of the included trials. We resolved any discrepancies by discussion. We based the quality assessment on: method of randomization, concealment of treatment allocation, use of blinding or masking, completeness of trial data. If necessary, we sought additional information from trial authors. This information was presented in the 'Risk of bias' tables within the 'Characteristics of included studies'. The funnel plot was presented in Figure 2. The existence of major publication bias was not evident by Harbord's modified test for small‐study effects (the bias; P value = 0.52) (Habord 2006).
Funnel plot of comparison: 1 lidocaine versus control (air/saline), outcome: 1.1 Risk of sore throat 12 hours to 30 hours after the operation.
Allocation
All included studies were described as having random allocation. However, only three included studies described true random allocation i.e. using a random allocation table, or computer‐generated random sequence (Estebe 2005; Hara 2005; Porter 1999). In the remaining 16 studies random allocation was not clearly described (Altintas 2000; Bajaj 2004; Basaranoglu 2004; Estebe 2002; Estebe 2004; Hashimoto 1981; Herlevsen 1992; Jaicobandram 2009; Klemola 1988; Krishnan 2008; Navarro 1997; Navarro 2007; Navarro 2012; Soltani 2002; Takekawa 2006; Xu 2012).
Concealment of random allocation was adequate in two included studies using opaque envelopes (Hara 2005; Herlevsen 1992). In 17 included studies there was no explicit description about concealment of random allocations (Altintas 2000; Bajaj 2004; Basaranoglu 2004; Estebe 2002; Estebe 2004; Estebe 2005; Hashimoto 1981; Jaicobandram 2009; Klemola 1988; Krishnan 2008; Navarro 1997; Navarro 2007; Navarro 2012; Porter 1999; Soltani 2002; Takekawa 2006; Xu 2012).
Blinding
Basaranoglu 2004 had no description of blinding; however, as the participants were anaesthetized, they could be considered to have been blinded. The authors of one study stated that it was double blinded (Porter 1999). In 12 studies there were explicit descriptions of double blinding (Bajaj 2004; Estebe 2002; Estebe 2004; Estebe 2005; Hara 2005; Hashimoto 1981; Herlevsen 1992; Klemola 1988; Krishnan 2008; Navarro 1997; Navarro 2012; Porter 1999). In Xu 2012, the blinding was described as single blinding; however, the participants and assessor were also blinded. In five studies participants and independent outcome assessors were blinded to the intervention received (Altintas 2000; Estebe 2004; Jaicobandram 2009; Navarro 2007; Soltani 2002).
Incomplete outcome data
In seven studies follow up was 100% (Altintas 2000; Bajaj 2004; Basaranoglu 2004; Estebe 2005; Hashimoto 1981; Porter 1999; Takekawa 2006). Analysis included all participants with outcome data.
In eight studies follow‐up was unclear as there was no description or information on drop‐outs (Estebe 2002; Estebe 2004; Jaicobandram 2009; Krishnan 2008; Navarro 1997; Navarro 2007; Navarro 2012; Soltani 2002 ).
In Herlevsen 1992, 96% of participants were followed up. The reason for dropping out was a mistake in the procedure.
In Hara 2005, 93% of participants were followed up. The reasons for dropping out were failure of the intubation procedure and low Ramsey sedation score.
In Klemola 1988 the follow up ratio was 87%. The reasons for dropping out were not described.
Selective reporting
Outcome measures were clearly defined in all included studies. The risk and intensity of postoperative sore throat were the outcomes for this review and were the main outcome of interest for included studies. Three studies reported only intensity of postoperative sore throat (Estebe 2002; Estebe 2004; Estebe 2005). Three studies described both outcomes of risk and intensity of postoperative sore throat (Altintas 2000; Navarro 1997; Xu 2012). Thirteen studies reported only risk of postoperative sore throat (Bajaj 2004; Basaranoglu 2004; Hara 2005; Hashimoto 1981; Herlevsen 1992; Jaicobandram 2009; Klemola 1988; Krishnan 2008; Navarro 2007; Navarro 2012; Porter 1999; Soltani 2002; Takekawa 2006). There were no explicit descriptions about selective reporting or the making of protocols before conducting the studies.
Other potential sources of bias
In two studies, all included participants had hyperreactive airways because of their smoking history (Jaicobandram 2009; Navarro 2012). In two studies, only thyroidectomy participants were included (Estebe 2005; Xu 2012).
Effects of interventions
Risk of sore throat 12 hours to 30 hours after the operation
See Table 1.
| Studies | Intervention | Control | Relative risk (95% CI) | ARR (95% CI) |
| 10% lidocaine to inflate the endotracheal tube (ETT) cuff | Saline to inflate the ETT cuff | 0.20 (0.06 to 0.64) | 0.33 (0.14 to 0.52) | |
| Cuff of ETT inflated with 4% lidocaine | Cuff of ETT inflated with air and saline | 0.39 (0.05 to 2.89) | 0.078 (‐0.04 to 0.20) | |
| 4% lidocaine in cuff of ETTs | air in cuff of ETTs | 0.55 (0.35 to 0.86) | 0.26 (0.08 to 0.45) | |
| Air group: air in cuff of ETT | Lido group: lidocaine in cuff of ETT | 0.20 (0.06, 0.64) | 0.36 (0.14 to 0.58) | |
| 4% lidocaine in cuff of ETTs | Saline to inflate the ETT cuff | 1.15 (0.64 to 2.06) | 0.06 (‐0.2 to 0.18) | |
| Group 1: 10% lidocaine was sprayed (3 puffs) on the distal end of ETT Group 2: the 10% lidocaine was sprayed on laryngopharyngeal structures near the inlet of the larynx through a nozzle connected to the spray device during laryngoscopy Group 3: the distal end of the ETTs and their cuffs were lubricated with 2.5 g of 2% lidocaine jelly Group 4: 1.5 mg/kg of lidocaine IV was administered at the conclusion of surgery Group 5: 7 to 8 ml of 2% lidocaine for 90 minutes before intubation, evacuated before intubation | Group 6: the distal end of ETTs and their cuffs were lubricated with normal saline | 0.57 (0.28 to 1.18) | 0.1 (‐0.05 to 0.25) | |
| Group 1: lidocaine (1 mg/kg) Group 2: lidocaine (1.5 mg/kg) | Control: normal saline | 0.25 (0.09 to 0.68) | 0.3 (0.12 to 0.48) | |
| Group L1: 4% Lidocaine In cuff of endotracheal tube | Group C: Distilled water in cuff of endotracheal tube | 1.05 (0.61, 1.81) | 0.013(‐0.15 to 0.13) | |
| Group L: alkalinized lidocaine in the cuff of endotracheal tube | Air in cuff of tracheal tube, Saline in cuff of endotracheal tube | 0.40 (0.13, 1.25) | 0.18(‐0.03 to 0.34) | |
| ETT intra cuff alkalinized 2% lidocaine (L group) | ETT intra cuff 0.9% saline (S group) | 0.14 (0.01, 2.63) | 0.1(‐0.063 to 0.281) | |
| ETT size 7.0 with lidocaine, ETT size 6.0 with lidocaine. | ETTsize 7.0 with saline; ETT size 6.0 with saline | 0.61 (0.44, 0.86) | 0.183(0.06 to 0.30) |
ARR = absolute risk reduction
ETT = endotracheal tube
Sixteen of the 19 included studies reported risk of postoperative sore throat (Altintas 2000; Bajaj 2004; Basaranoglu 2004; Hara 2005; Hashimoto 1981; Herlevsen 1992; Jaicobandram 2009; Klemola 1988; Krishnan 2008; Navarro 1997; Navarro 2007; Navarro 2012; Porter 1999; Takekawa 2006; Xu 2012; Soltani 2002). A total of 1744 participants were analysed: 952 were allocated to lidocaine therapy and 795 to the control group. The summary preventive effect of lidocaine, expressed as a risk ratio (RR), was 0.64 (95% confidence interval (CI) 0.48 to 0.85) (Analysis 1.1). The number needed to treat for an additional beneficial outcome (NNTB) was 8 (95% CI, 6 to 13).The quality of the evidence for the risk of sore throat 12 hours to 30 hours post‐operatively was low (according to GRADE), since in most included trials allocation concealment was not described and there was inconsistency of results of the risk of sore throat.
Severity of postoperative sore throat (assessed on a 0 to 100 mm visual analogue scale)
See Table 2.
| Studies | Intervention | Control | MD (Random) (95% CI) |
| 10% lidocaine to inflate the ETT cuff | Saline to inflate the ETT cuff | ‐10.20 (‐12.97 to ‐7.43) | |
| Group L: (2% lidocaine in the cuff of the ETT) Group LB: (alkalinized 2% lidocaine in the cuff of the ETT) | Group C (air in cuff of the ETT) | ‐7.5 (‐12.06 to ‐2.94) | |
| Group W: ETT cuff lubricated with sterile water and filled with alkalinized lidocaine Group G: ETT cuff lubricated with water‐soluble gel and filled with alkalinized lidocaine | ETT cuff lubricated with sterile water and filled with air | ‐19.5 (‐24.09 to 14.91) | |
| 8.4% NaHCO3 + 2% lidocaine in cuff of ETT, 1.4% NaHCO3 + 2% lidocaine in cuff of ETT | Air in cuff of ETT | ‐13.5 (‐19.98 to ‐7.02) | |
| 4% lidocaine in the cuff of the ETT | Air in the cuff of the ETT | ‐6.90 (‐17.3 to 3.48) | |
| ETT size 7.0 with lidocaine, ETT size 6.0 with lidocaine | ETT size 7.0 with saline; ETT size 6.0 with saline | ‐7.00 (‐8.44, ‐5.56) |
ETT = endotracheal tube
MD = mean difference
Six trials reported the intensity of postoperative sore throat measured on a visual analogue scale (Altintas 2000; Xu 2012; Navarro 1997; Estebe 2002; Estebe 2004; Estebe 2005). In total, 611 participants were included. Of those 611, 339 participants were allocated to lidocaine therapy and 272 participants to the control group. The summary preventive effect of lidocaine for intensity of postoperative sore throat was a mean difference (MD) of ‐10.80 (95% CI, ‐14.63 to ‐6.98 (Analysis 1.5). The quality of the evidence of intensity of sore throat (VAS) was moderate (according to GRADE)
Sensitivity analysis
The sensitivity analysis was about the quality of studies. The evaluation of the quality of studies was based on the 'Risk of bias' table (Figure 3; Figure 4). There were eight high‐quality studies (Bajaj 2004; Basaranoglu 2004; Hashimoto 1981; Herlevsen 1992; Hara 2005; Navarro 1997; Porter 1999; Takekawa 2006). The summary effect of high‐quality studies, without low‐quality studies, favoured lidocaine therapy (RR 0.71, 95% CI (0.47 to 1.09). However, it was not significant. The summary effect of eight low quality studies favoured lidocaine therapy (RR 0.57, 95% CI 0.37 to 0.86) (Altintas 2000; Jaicobandram 2009; Klemola 1988; Krishnan 2008; Navarro 2007; Navarro 2012; Soltani 2002; Xu 2012).
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Subgroup analyses
The first subgroup analysis considered the method of lidocaine administration. The summary effects of studies of topical lidocaine favoured lidocaine therapy (RR 0.68, 95% CI 0.48 to 0.98) (Altintas 2000; Bajaj 2004; Basaranoglu 2004; Hara 2005; Hashimoto 1981; Herlevsen 1992; Jaicobandram 2009; Klemola 1988; Krishnan 2008; Navarro 1997; Navarro 2007). The summary effect of systemic use of lidocaine favoured lidocaine (RR 0.44, 95% CI 0.19 to 1.05) but was not statistically significant (Takekawa 2006; Xu 2012). Both topical and systemic use of lidocaine favoured lidocaine (RR 0.57, 95% CI 0.28 to 1.18) but was not statistically significant (Soltani 2002).
The second subgroup analysis looked at cuff pressure. Eight studies did not describe controlled cuff pressure (Bajaj 2004; Basaranoglu 2004; Hara 2005; Hashimoto 1981; Jaicobandram 2009; Krishnan 2008; Soltani 2002; Takekawa 2006). The results favoured lidocaine therapy and were statistically significant (RR 0.58, 95% CI 0.41 to 0.83). Eight studies described controlled cuff pressure (Altintas 2000; Herlevsen 1992; Klemola 1988; Navarro 1997; Navarro 2007; Navarro 2012; Porter 1999; Xu 2012). The results showed a trend toward favouring lidocaine therapy but statistically were not significant (RR 0.74, CI 0.50 to 1.09).
The third subgroup analysis reported about alkalinization of lidocaine. In 14 studies alkalinized lidocaine was not used and the summary effect of these studies favoured lidocaine (RR 0.66, 95% CI 0.50 to 0.89) (Altintas 2000; Bajaj 2004; Hara 2005; Hashimoto 1981; Herlevsen 1992; Klemola 1988; Krishnan 2008; Navarro 1997; Navarro 2007; Porter 1999; Soltani 2002; Takekawa 2006; Xu 2012). In two studies alkalinized lidocaine was used and the summary effects were statistically significant (RR 0.34, 95% CI 0.12 to 0.99) (Jaicobandram 2009; Navarro 2012).
Discussion
Summary of main results
The conclusion of this updated systematic review remains the same as the original systematic review (Tanaka 2009): lidocaine given topically and systemically reduces the risk and severity of postoperative sore throat. The risk of postoperative sore throat was reduced significantly (RR 0.64, 95% CI 0.48 to 0.85) after adding four new included studies (Jaicobandram 2009; Krishnan 2008; Navarro 2012; Xu 2012); and correcting the data of one study (Hara 2005). The severity of sore throat on a visual analogue scale (VAS) was also reduced significantly (mean difference (MD) ‐10.80, 95% CI ‐14.63 to ‐6.98). We updated our search strategy from 2007 to 2013 and we found 12 new trials from the updated search strategy. Of those 12 studies we included four new studies which met our inclusion criteria (Jaicobandram 2009; Krishnan 2008; Navarro 2012; Xu 2012). We excluded the remaining eight trials (Crerar 2008; D'Aragon 2013; Honarmand 2008; Hung 2010; Kori 2009; Lee 2011; Sumathi 2007; Shroff 2009). We corrected data input from one study into RevMan 5.3 (Hara 2005). In Tanaka 2009, the previous published version of our review, Hara 2005 favoured lidocaine for reducing the risk of postoperative sore throat (RR 0.56, 95% CI 0.20 to 1.59). We responded to feedback (Feedback 1) and corrected the data, which now favoured the control intervention (RR 1.77, 95% CI 0.63 to 5.00). There were reports about the risk of postoperative sore throat in each of the studies; however we could not find out from the data how many participants were affected by this condition. There were multiple doses of lidocaine so the interpretation of the results may be difficult. Though the possible adverse effects of using lidocaine were not reported in these studies, there were a few case reports about lidocaine toxicoses. They reported it as a very rare incident (Lee M 2011; Menif 2011).
Overall completeness and applicability of evidence
We conducted comprehensive search strategies for finding relevant studies. We included 19 studies and analysed 1940 participants. Therefore, the studies identified might be sufficient to address all of the objectives of our reviews. We identified the relevant participants who underwent surgery under general anaesthesia with endotracheal intubations, testing interventions of topical and systemic lidocaine therapy for preventing postoperative sore throats and outcomes such as risk and intensity of postoperative sore throat. The results of this review are applicable to adults who undergo an operation under general anaesthesia with endotracheal intubations. We excluded children because different anaesthetic techniques may be used from adults, and children cannot always report postoperative sore throat in the same way. The interventions of topical and systemic use of lidocaine investigated all seemed relevant. The outcome 'postoperative sore throat' is a relevant issue for participants in clinical practices.
Quality of the evidence
We included 19 studies involving 1940 participants in the updated review. In all included studies, summary of risk of postoperative sore throat and the intensity of postoperative sore throat showed a statistically positive effect for lidocaine as an intervention (Analysis 1.1; Analysis 1.5). The majority of the trials included were small and many had methodological weaknesses (Figure 3). There was substantial heterogeneity (Analysis 1.1); this might be explained by variations in the control, type of intervention, the surgical procedures and risk of bias. The first subgroup analysis of quality study showed that the combined effect size of a high‐quality score was not statistically significant (Analysis 1.2). That may show that there was an effect of risk of bias. The second subgroup analysis, investigating the route of lidocaine administration, showed that systemic lidocaine, or systemic and topical lidocaine, were not effective statistically for preventing postoperative sore throat (Analysis 1.1). This seems to show that effectiveness of lidocaine varies according to the route of administration. The third subgroup analysis was about the control of cuff pressure. The summary effect of studies with the descriptions of controlled cuff pressure were not statistically significant (Analysis 1.3). That may mean that the controlled cuff pressure changed the effectiveness of lidocaine for preventing postoperative sore throat. According to the GRADE evaluation, the quality of evidence of lidocaine for preventing the risk of postoperative sore throat was low (summary of findings Table for the main comparison).
Potential biases in the review process
We attempted to reduce bias by identifying all relevant studies through a comprehensive systematic search of the literature and using electronic search engines such as EMBASE, MEDLINE and CENTRAL. There was also contact with the authors and pharmaceutical companies for both published and unpublished studies. However in this updated review, unlike the previous review (Tanaka 2009), we did not use Google or Google scholar. We accept that we have possibly overlooked relevant studies and that some publication bias is inevitable and this is indicated by the rather asymmetrical funnel plot (Figure 2); though it was not statistically significant according to Habord's methods (Habord 2006). This is likely to lead to an overestimate of effect size of lidocaine, because positive trials are more likely to be published than negative trials. The criteria for sore throat is not standardized. Therefore, the variation of measurement of sore throat may produce biases.
Agreements and disagreements with other studies or reviews
To our knowledge there is no other systematic review of our research question; therefore, we cannot state that our systematic review agrees or disagrees with other reviews. The conclusion of this review agrees with 11 of the 16 included studies about decreasing the risk of postoperative sore throat. The five studies that disagree may have had their own specific conditions (Hara 2005; Herlevsen 1992; Klemola 1988; Krishnan 2008; Porter 1999). Klemola 1988 pointed out that lidocaine jelly contains impurities which seemed to affect the results. In Porter 1999, all of the included participants were women; an earlier study has shown that late complications are more common in women than in men (Jensen 1982); therefore, the population studied may affect the results. In Herlevsen 1992, larger intubation tubes, size 9.5 inner diameter, were used for men rather than the size 8.5 inner diameter used for women. Thirty‐two participants among the 197 participants were intubated with smaller endotracheal tubes than outlined in the protocol of this study. The prevalence and severity of sore throat after endotracheal intubation were both reduced by using a smaller endotracheal tube in one study (Stout 1987). In one study, the intervention was lidocaine spray on larynx and trachea (Hara 2005). The control was saline spray. The authors stated that the reason for the worsening of postoperative sore throat might be because of the additive in the lidocaine spray. Moreover, in this study 15 participants dropped out during the study period. This might break the condition of 'intention to treat' and create bias. In one study, the intervention was 4% lidocaine in the cuff of the endotracheal tube and the control was saline in the cuff (Krishnan 2008). This study did not show a statistically significant effect of lidocaine. The authors stated that water in the cuff may reduce the risk of sore throat compared with air in the cuff. In a previous positive study, there was air in the cuff of the endotracheal tube (Navarro 1997).
Funnel plot of comparison: 1 lidocaine versus control (air/saline), outcome: 1.1 Risk of sore throat 12 hours to 30 hours after the operation.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Comparison 1 lidocaine versus control (air/saline), Outcome 1 Risk of sore throat 12 hours to 30 hours after the operation.
Comparison 1 lidocaine versus control (air/saline), Outcome 2 Sensitivity analysis.
Comparison 1 lidocaine versus control (air/saline), Outcome 3 Sub group analysis １.
Comparison 1 lidocaine versus control (air/saline), Outcome 4 Sub group Analysis 2.
Comparison 1 lidocaine versus control (air/saline), Outcome 5 Visual‐analogue scale of severity of sore throat.
| lidocaine versus control (air/saline) for preventing postoperative sore throat | ||||||
| Patient or population: patients presenting with postoperative sore throat | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Lidocaine versus control (air/saline) | |||||
| Risk of sore throat 12 hours to 30 hours after the operation | Study population | RR 0.64 | 1744 | ⊕⊕⊝⊝ | ||
| 306 per 1000 | 196 per 1000 | |||||
| Moderate | ||||||
| 300 per 1000 | 192 per 1000 | |||||
| Severity of sore throat 12 hours to 30 hours after the operation | The mean visual‐analogue scale of severity of sore throat in the intervention groups was | 611 | ⊕⊕⊕⊝ | |||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| We downgraded the quality of evidence for the reasons below. 1. Allocation concealment was not described in most studies and there was inconsistency of results of risk of sore throat. 2. Allocation concealment was not described in most studies. | ||||||
| Studies | Intervention | Control | Relative risk (95% CI) | ARR (95% CI) |
| 10% lidocaine to inflate the endotracheal tube (ETT) cuff | Saline to inflate the ETT cuff | 0.20 (0.06 to 0.64) | 0.33 (0.14 to 0.52) | |
| Cuff of ETT inflated with 4% lidocaine | Cuff of ETT inflated with air and saline | 0.39 (0.05 to 2.89) | 0.078 (‐0.04 to 0.20) | |
| 4% lidocaine in cuff of ETTs | air in cuff of ETTs | 0.55 (0.35 to 0.86) | 0.26 (0.08 to 0.45) | |
| Air group: air in cuff of ETT | Lido group: lidocaine in cuff of ETT | 0.20 (0.06, 0.64) | 0.36 (0.14 to 0.58) | |
| 4% lidocaine in cuff of ETTs | Saline to inflate the ETT cuff | 1.15 (0.64 to 2.06) | 0.06 (‐0.2 to 0.18) | |
| Group 1: 10% lidocaine was sprayed (3 puffs) on the distal end of ETT Group 2: the 10% lidocaine was sprayed on laryngopharyngeal structures near the inlet of the larynx through a nozzle connected to the spray device during laryngoscopy Group 3: the distal end of the ETTs and their cuffs were lubricated with 2.5 g of 2% lidocaine jelly Group 4: 1.5 mg/kg of lidocaine IV was administered at the conclusion of surgery Group 5: 7 to 8 ml of 2% lidocaine for 90 minutes before intubation, evacuated before intubation | Group 6: the distal end of ETTs and their cuffs were lubricated with normal saline | 0.57 (0.28 to 1.18) | 0.1 (‐0.05 to 0.25) | |
| Group 1: lidocaine (1 mg/kg) Group 2: lidocaine (1.5 mg/kg) | Control: normal saline | 0.25 (0.09 to 0.68) | 0.3 (0.12 to 0.48) | |
| Group L1: 4% Lidocaine In cuff of endotracheal tube | Group C: Distilled water in cuff of endotracheal tube | 1.05 (0.61, 1.81) | 0.013(‐0.15 to 0.13) | |
| Group L: alkalinized lidocaine in the cuff of endotracheal tube | Air in cuff of tracheal tube, Saline in cuff of endotracheal tube | 0.40 (0.13, 1.25) | 0.18(‐0.03 to 0.34) | |
| ETT intra cuff alkalinized 2% lidocaine (L group) | ETT intra cuff 0.9% saline (S group) | 0.14 (0.01, 2.63) | 0.1(‐0.063 to 0.281) | |
| ETT size 7.0 with lidocaine, ETT size 6.0 with lidocaine. | ETTsize 7.0 with saline; ETT size 6.0 with saline | 0.61 (0.44, 0.86) | 0.183(0.06 to 0.30) | |
| ARR = absolute risk reduction ETT = endotracheal tube | ||||
| Studies | Intervention | Control | MD (Random) (95% CI) |
| 10% lidocaine to inflate the ETT cuff | Saline to inflate the ETT cuff | ‐10.20 (‐12.97 to ‐7.43) | |
| Group L: (2% lidocaine in the cuff of the ETT) Group LB: (alkalinized 2% lidocaine in the cuff of the ETT) | Group C (air in cuff of the ETT) | ‐7.5 (‐12.06 to ‐2.94) | |
| Group W: ETT cuff lubricated with sterile water and filled with alkalinized lidocaine Group G: ETT cuff lubricated with water‐soluble gel and filled with alkalinized lidocaine | ETT cuff lubricated with sterile water and filled with air | ‐19.5 (‐24.09 to 14.91) | |
| 8.4% NaHCO3 + 2% lidocaine in cuff of ETT, 1.4% NaHCO3 + 2% lidocaine in cuff of ETT | Air in cuff of ETT | ‐13.5 (‐19.98 to ‐7.02) | |
| 4% lidocaine in the cuff of the ETT | Air in the cuff of the ETT | ‐6.90 (‐17.3 to 3.48) | |
| ETT size 7.0 with lidocaine, ETT size 6.0 with lidocaine | ETT size 7.0 with saline; ETT size 6.0 with saline | ‐7.00 (‐8.44, ‐5.56) | |
| ETT = endotracheal tube MD = mean difference | |||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Risk of sore throat 12 hours to 30 hours after the operation Show forest plot | 16 | 1744 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.48, 0.85] |
| 1.1 Topical lidocaine | 13 | 1220 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.48, 0.98] |
| 1.2 Systemic lidocaine | 2 | 320 | Risk Ratio (M‐H, Random, 95% CI) | 0.44 [0.19, 1.05] |
| 1.3 Both topical and systemic lidocaine | 1 | 204 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.28, 1.18] |
| 2 Sensitivity analysis Show forest plot | 16 | 1744 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.48, 0.85] |
| 2.1 High quality study | 8 | 814 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.47, 1.09] |
| 2.2 Low quality data | 8 | 930 | Risk Ratio (M‐H, Random, 95% CI) | 0.57 [0.37, 0.86] |
| 3 Sub group analysis １ Show forest plot | 16 | 1744 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.48, 0.85] |
| 3.1 Studies without describing controlled cuff pressure of ETT | 9 | 918 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.40, 0.93] |
| 3.2 Studies with describing controlled cuff pressure of ETT | 7 | 826 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.44, 1.01] |
| 4 Sub group Analysis 2 Show forest plot | 16 | 1744 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.48, 0.85] |
| 4.1 Studies without using alkalinization of lidocaine New Subgroup | 14 | 1622 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.50, 0.89] |
| 4.2 Studies with using alkalinization of lidocaine | 2 | 122 | Risk Ratio (M‐H, Random, 95% CI) | 0.34 [0.12, 0.99] |
| 5 Visual‐analogue scale of severity of sore throat Show forest plot | 6 | 611 | Mean Difference (IV, Random, 95% CI) | ‐10.80 [‐14.63, ‐6.98] |
| 5.1 Studies without using alkalinization of intracuff lidocaine | 3 | 416 | Mean Difference (IV, Random, 95% CI) | ‐8.21 [‐10.75, ‐5.67] |
| 5.2 Studies with using alkalinization of lidocaine | 3 | 195 | Mean Difference (IV, Random, 95% CI) | ‐13.50 [‐21.12, ‐5.87] |
