Comparison of the efficacy of supraglottic airway devices in low-risk adult patients: a network meta-analysis and systematic review

Numerous supraglottic airway device (SADs) have been designed for adults; however, their relative efficacy, indicated by parameters such as adequacy of sealing, ease of application, and postinsertion complications, remains unclear. We conducted a systematic review and network meta-analysis to evaluate the efficacy of various SADs. We searched electronic databases for randomized controlled trials comparing at least two types of SADs published before December 2019. The primary outcomes were oropharyngeal leak pressure (OLP), risk of first-attempt insertion failure, and postoperative sore throat rate (POST). We included 108 studies (n = 10,645) comparing 17 types of SAD. The Proseal laryngeal mask airway (LMA), the I-gel supraglottic airway, the Supreme LMA, the Streamlined Liner of the Pharynx Airway, the SoftSeal, the Cobra Perilaryngeal Airway, the Air-Q, the Laryngeal Tube, the Laryngeal Tube Suction II, the Laryngeal Tube Suction Disposable, AuraGain, and Protector had significantly higher OLP (mean difference ranging from 3.98 to 9.18 cmH2O) compared with that of a classic LMA (C-LMA). The Protector exhibited the highest OLP and was ranked first. All SADs had a similar likelihood of first-attempt insertion failure and POST compared with the C-LMA. Our findings indicate that the Protector may be the best SAD because it has the highest OLP. Systematic review registration PROSPERO: CRD42017065273.


Results
presents a flow chart of the trial selection process in 108 eligible randomized controlled trials met our inclusion criteria. Figures 2, 3 and 4 illustrate the network of included studies on the OLP, risk of first-attempt insertion failure, and POST. Table 1 summarizes the characteristics of the 17 types of SADs included in this  www.nature.com/scientificreports/ study, and Supplementary Table S1 summarizes the clinical and methodological characteristics and the main outcomes of each trial.
Oropharyngeal leak pressure (OLP). OLP data were obtained of 7784 adult patients in 75 trials, including 17 types of SADs. The pooled estimates of differences in OLP in the network meta-analysis are displayed in the upper triangle of Table 2, whereas the lower triangle of Table 2 presented the results of traditional pairwise meta-analyses. The Protector laryngeal mask airway (Protector) and Ambu AuraGain Disposable Laryngeal Mask (AuraGain) achieved the greatest highest and most improved OLP compared with that of the C-LMA, with mean differences (95% confidence interval) of 9.18 (5.60, 12.75) and 7.65 (3.63,11.67) cmH 2 O, respectively. The Proseal laryngeal mask airway (P-LMA), I-gel Supraglottic Airway (I-gel), Supreme laryngeal mask airway (S-LMA) and Streamlined Liner of the Pharynx Airway (SLIPA) had significantly higher OLP than that of the C-LMA, with mean differences ranging from 3.98 to 6.72 cmH 2 O. The Portex Soft Seal Laryngeal Mask (SoftSeal), Air-Q Masked Laryngeal Airway (Air-Q), and Cobra Perilaryngeal Airway (Cobra) also achieved higher OLP than did the C-LMA, with mean differences ranging from 4.55 to 6.72 cmH 2 Table S2), whereas the U-LMA and C-LMA had the lowest SUCRA values.  Table 3. The lower triangle in Table 3 presents the results of traditional pairwise meta-analyses. The risk of first-attempt insertion failure of each of the SADs was comparable to that of the C-LMA. The S-LMA and Ambu-O had significantly lower risks of first-attempt insertion failure than that of the P-LMA. The S-LMA also achieved a significantly lower risk than that of the I-gel. The P-LMA, Cobra and LTS achieved significantly higher risks than that of the U-LMA. The Cobra and LTS demonstrated significantly higher risks than that of the S-LMA. In terms of SUCRA values, the Ambu-O and S-LMA were ranked the highest, the AuraGain was ranked fifth and the Protector, was ranked seventh (Supplementary Table S4).
Postoperative sore throat rate (POST) within 24 h and other secondary efficacy-related outcomes. Data on POST were obtained for 4125 adult patients in 37 trials, with 16 types of SADs. POST-related data on the Air-Q were unavailable. POST ranged from 0 to 50%. The results of the network meta-analysis are presented in the upper triangle of Table 4; none of the SAD exhibited a significant difference compared with the C-LMA. The S-LMA and Cobra had significantly higher POSTs than that of the AuraGain. The Cobra also attained a significantly higher POST than that of the Ambu-O. The lower triangle of Table 4 presents the results of the traditional pairwise analysis. The SADs with the highest ranking and lowest POST were the AuraGain and Cobra (Supplementary Table S7). The results regarding the overall insertion failure rate during induction, poor function after successful insertion, device failure during maintenance, hypoxia, and aspiration are presented in Supplementary Tables S10 to S14. Because the evidence on these outcomes is limited and includes many zero events, a network meta-analysis was considered infeasible.
Meta-regression of the effect of using the neuromuscular blocking agents on OLP, risk of first-attempt insertion failure and POST, and effect of positive pressure ventilation on POST. Assessment of the transitivity assumption was performed for the use of neuromuscular blocking agents (NMBAs) (Supplementary Fig. S4). Meta-regression analysis revealed that using NMBAs was negatively associated with the risk of first-attempt insertion failure, and positively associated with OLP, but not associated Table 2. Results for oropharyngeal leak pressure from network meta-analysis. The device in column one is the index device and that in row one is the comparator. The upper triangle is the results of the network meta-analysis, and the lower triangle is the results of the traditional pairwise meta-analysis. The device in the row one minus the device in column one equals the mean difference, which unit is cmH 2 O. Bold and underscored means significance. The significance means the confidence interval not containing the "0".

Discussion
Compared with the C-LMA, many SADs achieved a significantly higher OLP, with a mean difference ranging from 3.98 to 9.18 cmH 2 O. The Protector achieved the highest OLP and ranked the best among the SADs. All SAD exhibited similar risks of first-attempt insertion failure, and not significant differences in POST compared with those of the C-LMA. Evidences on other secondary efficacy-related outcomes was limited due to extremely low incidence rates. Although the Protector achieved the highest OLP, its risk of first-attempt insertion failure and POST were similar to those of the C-LMA. The Protector had the highest OLP, followed by AuraGain, relatively newly developed SAD. The high OLP of the Protector may be attributable to the fact that it is made of medical grade silicone. Moreover, its curve airway tube and inflatable cuff may allow it to better conforms to the anatomical contours of an individual's hypopharynx 10 . Other SADs also attained better OLP than that of the C-LMA, and this finding is consistent with that of a recent network meta-analysis of SADs for pediatric patients, which indicated that the I-gel, Cobra and P-LMA achieved 3.4 to 4.6 cmH 2 O higher OLP than that of the C-LMA 11 . Our results also revealed substantial differences in the efficacy of the SADs: this could not be observed in previous meta-analyses that pooled various SADs into one group 4-6 . In addition, some of the studies included in these meta-analyses used nonstandard methods of measuring OLP or did not clearly describe their measurement method. By contrast, our network meta-analysis evaluated these SADs separately and only included randomized controlled trials that measured OLP through plateau pressure measurement, thereby providing more accurate estimates.
Our results revealed that all SADs exhibited similar risks of first-attempt insertion failure to that of the C-LMA, consistent with the results of a previous network meta-analysis on pediatric patients 11 . Unlike previous studies 6 , we did not use the criterion of "ease of insertion" because it is a highly subjective, operator-dependent assessment; therefore, we used first-attempt insertion failure instead.
Our analysis indicated that all SADs had a POST comparable to that of the C-LMA in contrast to the results of previous meta-analyses 4,5,12,13 . This discrepancy may be because other meta-analyses have pooled data on patients who had received laparoscopic surgery and those from crossover studies when estimating the POST. We excluded Table 4. Results for postoperative sore throat rate from network meta-analysis and pairwise meta-analysis. The device in column one is the index device and that in row one is the comparator. The device in the column one is divided by the device in the row one equals risk ratio, which did not have unit. Bold and underscored means significance. The significance means the confidence interval not containing the "1"  www.nature.com/scientificreports/ crossover studies account for the carry-over effect. Moreover, patients receiving laparoscopic surgery were also excluded due to the higher OLP required, which would result in a greater risk of perilaryngeal tissue trauma.
Our results also demonstrated that adjunctive NMBAs had a significant effect. However, NMBAs exerted a significant effects on the risk of first-attempt insertion failure and OLP, which disagree with the findings of a previous network meta-analysis in which an NMBA was found to have no significant effects on OLP, the POST, or the risk of first-attempt insertion failure 11 .
Our study has several strengths. Rather than grouping various SADs into one group, we assessed the efficacy of each SAD individually and compares them within the same evidence base. Assessment of both OLP and the risk of first-attempt insertion failure according to SUCRA ranking may provide more complete information on SADs, which can help in selecting the appropriate SAD. This network meta-analysis also enabled us to compare therapies indirectly when no head-to-head trial had been performed and obtain more precise effect estimates by jointly assessing direct and indirect comparisons 8 . Furthermore, we also analysed major and efficacy-associated outcomes. The results of our analysis also provide updated evidence, with implications for using SADs in lowrisk adult patients.
This study had some limitation. First, the data in our network meta-analysis were mostly derived from low risk, elective, nonobese patients with a low risk of aspiration. Second, some of our efficacy-related outcomes were reported by a limited number of studies with zero events, thereby resulting in greater uncertainty in our assessment of these outcomes. Third, some of the included studies did not report on NMBA use with SADs, affecting the strength of the meta-regression results on NMBA effects. Fourth, we performed a grey literature search but did not identify additional relevant studies that met our inclusion criteria. Fifth, many anesthetic agents have been developed, and anesthetic strategies have changed over the last 30 years since the C-LMA was developed. We included 108 studies in our network meta-analysis, and this large number of studies may have diluted the impact of the different anesthetic agents within our comparisons. Sixth, the number of patients in our network meta-analysis who were treated with the relatively newer SADs, such as the AuraGain, was much lower than number of patients treated with other SADs, such as the P-LMA or I-gel. A lower number of patients yields a wider confidence interval. More studies are therefore required to confirm the efficacy of these new devices.
In conclusion, SADs including the Proseal LMA, I-gel, Supreme LMA, Streamlined Liner of the Pharynx Airway, SoftSeal, Cobra Perilaryngeal Airway, Air-Q, Laryngeal Tube, and Laryngeal Tube Suction II (LTS-II), Laryngeal Tube Suction Disposable (LTS-D), Protector, and AuraGain, achieve significantly higher OLP and similar risks of first-attempt insertion failure compared with those of the C-LMA. Our data indicate that the Protector may be the best SAD because it achieves the highest OLP and a similar risks of first-attempt insertion failure and similar POST to those of C-LMA.

Methods
Data source and search strategy. The protocol for this network meta-analysis was registered with PROSPERO (number: CRD42017065273). We searched the EMBASE, Cochrane Central Register of Controlled Trials, and PubMed databases from their inception to December 2019 for randomized controlled trials that compared at least two types of SADs. We applied no language restrictions and performed a manual literature search.
We searched for additional studies in the reference lists of all identified publications, including relevant metaanalyses and systematic reviews. We used the following keywords: I-gel, ProSeal LMA (P-LMA), Classic LMA

Study selection.
We included randomized controlled trials on patients, who received elective surgeries under general anesthesia and had an indication for SAD insertion with an American Society of Anesthesiologists (ASA) score of I to III, body mass index (BMI) < 40, and age > 18 years. The SADs identified in the literature included the C-LMA, I-gel, P-LMA, S-LMA, Ambu-O, U-LMA, SLIPA, Solus, SoftSeal, Air-Q, Cobra, LT, LTS-II, LTS-D, LTS, AuraGain, and Protector. We used the C-LMA as the reference because it was the first SAD 14 . The included trials compared at least two SADs and reported one of the following primary or secondary outcomes. The primary outcomes were OLP, the risk of first-attempt insertion failure, and POST within 24 h. The secondary outcomes were overall insertion failure rate, successful insertion but with poor function, device failure during maintenance, aspiration and hypoxia. When OLP was assessed at several time points, we extracted the data recorded immediately after SAD insertion. When OLP was assessed in different head positions, we extracted the data recorded in the neutral head position. The overall insertion failure rate was measured during induction. Successful insertion but with poor function was defined as the SAD need for reinsertion, reposition, manipulation, or failure during intubation following successful insertion. Device failure during maintenance was defined as the need to change to another airway device due to laryngospasm or a hiccup, SAD of a different size was then used in case of poor sealing pressure and the SAD was inserted if necessary during maintenance. Hypoxia was regarded as any episode of hypoxia, hypoxemia or desaturation. The POST was evaluated simply in terms of the record of sore throat within 24 h of surgery. We excluded crossover studies in our analysis of the POST because the causative device could not be ascertained. When analyzing device failure, we excluded studies in which the www.nature.com/scientificreports/ SAD was not used for intraoperative airway management. We excluded studies in which OLP, rate of device failure during maintenance, hypoxia, aspiration, and POST were measured during laparoscopic surgery because the condition of such surgeries may affect these parameters. However, the OLP measured before the laparoscopic condition in the trials was still extracted in our meta-analysis. Higher OLP may be required for adequate sealing during laparoscopic surgery 15 , resulting in increased risks of device failure, hypoxia, and aspiration 16 . Laparoscopic position than in a supine position 17 , leading to a higher risk of ischemic injury at the oropharyngeal mucosa 18 . Therefore, we excluded trials that measured the POST after laparoscopic surgery. In addition, we extracted studies that measured OLP according to plateau pressure. To measure OLP, the expiratory valve of the circle system is closed at a fixed gas flow and the airway pressure is recorded.
The following studies were excluded: (1) duplicate publications; (2) animal or manikin experimental studies; (3) studies with unclear patient conditions (i.e., no clear definition of BMI or ASA); (4) studies in which the size of the selected SAD was not specified ( or in which clinicians did not follow the manufacturers' instructions; (5) studies with a lack of outcome data; (6) studies with unclear descriptions of outcome measurements; (7) studies involving patients with a higher aspiration risk, such as pregnant patients, patients with a history of gastroesophageal reflux, and those with an insufficient fasting time; and (8) studies of patients undergoing emergency surgery.
Data extraction and quality assessment. Two investigators (CJ Lai and YC Yeh) independently screened all titles and abstracts and evaluated relevant articles. If a study was deemed eligible by any reviewer, then it was included for full-text review. The two investigators then independently assessed the full texts of the studies, and any disagreement was resolved through consensus among the members of the study team. These two investigators extracted and entered information regarding the following aspects into an electronic database: study design, patient characteristics, interventions, comparisons and outcomes (OLP, the risk of first-attempt insertion failure, POST, insertion failure during induction, device failure during maintenance, poor device function after successful insertion, aspiration, and hypoxia). When the relevant information on design or outcomes was unclear, we contacted the original authors for clarifications. The two investigators also independently evaluated the methodological quality of eligible trials by using the Cochrane Collaboration's tool for assessing the risk of bias 19 . Disagreements in the evaluation were resolved through consultation with another investigator (YKT). The kappa statistic was used to evaluate the interrater agreement 20 . www.nature.com/scientificreports/