Laryngeal mask versus endotracheal intubation for pre-hospital emergency airway management: a meta-analysis of randomized manikin and human studies

Background Pre-hospital emergency airway management plays an important role in pre-hospital care. Laryngeal masks are increasingly employed for the airway management of pre-hospital critical patients and have achieved promising results. Although several randomized controlled trials have reported benefits, the efficacy of laryngeal masks in pre-hospital emergency airway management compared to endotracheal intubation have not been systematically reviewed. Methods Electronic databases (PubMed, Cochrane Library, Embase, Scopus and CNKI) were searched up to April 2019 for related randomized studies. Outcome indicators were overall intubation success rates, success rates of the initial intubation, insertion time, ventilation efficiency rates, SpO2 rise time and blood gas index. Two investigators selected the trials, extracted the data according to inclusion and exclusion criteria, and assessed the quality of the literature according to the Jada score. The meta-analysis was performed using stata14.0 software. Results We included 9 randomized manikin studies and 31 human studies. Meta-analysis of the manikin studies showed that the overall intubation success rates of the laryngeal mask group [RR=1.10, 95% CI (1.02, 1.18), P<0.05] and the success rates of first intubation [RR=1.25, 95% CI (1.01, 1.55), P <0.05] were significantly higher than the endotracheal intubation group. The insertion time of the laryngeal mask group was also significantly shorter [SMD = -1.53, 95% CI (-1.88, -1.17), P <0.05]. In human studies, excluding the success rates of first intubation and insertion time, the laryngeal mask was superior to endotracheal intubation and improved the patients’ blood gas index and shortened the SpO2 rise time. All the results were statistically significant. Conclusions Compared to endotracheal intubation, laryngeal masks could quickly and effectively improve in . for laryngeal significantly shorter. These results indicate that the laryngeal mask had improved success rates


Introduction
Pre-hospital emergency airway management is crucial in pre-hospital care and is associated with the outcomes of critical patients. Effective airway management avoids systematic hypoxia and ensures organ oxygenation to reduce mortality rates and extend the time for further medical treatments of pre-hospital critical patients. Although tracheal intubation is regarded as an effective method to maintain pulmonary ventilation, it requires a skilled operator, precise placement and rapid responses (within 20 s), reducing its success rates. In particular, the success rates of tracheal intubation by nonclinical emergency personnel are generally low. In addition, tracheal intubation leads to laryngeal edema, airway injury, and other complications. Hence, clinicians do not support tracheal intubation due to concerns over its safety and effectiveness [1].
The laryngeal mask is a novel supraglottic ventilation device that was designed based on the anatomical structure of the human pharynx, which achieves good ventilation levels without intubation. The mask can effectively reduce iatrogenic infections and pharyngeal compression injury, limiting the disruption of pharyngeal hemodynamics [2][3]. Recent studies reported a high efficacy of ventilation therapy when the laryngeal mask was applied to pre-hospital emergency patients.
However, the majority of these studies had small sample sizes and did not adequately evaluate laryngeal mask efficacy. Hence, the effectiveness and safety of its application in pre-hospital emergency patients remains controversial [4][5]. In this study, we included randomized manikin and human studies to compare the ventilation effects of laryngeal masks and endotracheal intubation in pre-hospital emergencies, so as to provide reference for clinical practice.

Methods
This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to report [6].
success rate of the initial intubation and insertion time.

Quality assessment
The Jada scale was used to evaluate randomized research methods, blind methods, a loss of follow-up and withdrawal. The score was 0 to 5, ≤ 2 points were classified as low-quality studies, and ≥ 3 points were classified as high-quality studies. An independent quality assessment of the included literature was performed by two individuals and conducted and checked. Studies with inconsistent evaluations were identified through discussions and confirmed by a third reviewer.

Data Analysis
Stata 14.0 statistical software was used for meta-analysis. Continuous variables were expressed as mean standard differences (m ± SD / SMD) due to non-uniform units. If an article provided only the median and interquartile range (IQR), SD values were calculated according to the Cochrane manual equation: SD = IQR/1.35 [7]. Dichotomous variables were expressed as a risk ratio (RR). The 95% feasible interval (CI) was calculated for both effect sizes. Heterogeneity analysis was performed using Chi-square (x2) tests. When P < 0.05 and I2 > 50%, heterogeneity existed between the studies. If no heterogeneity was observed, the fixed effect model was used. In other cases, the random effects model was employed. Subgroup analysis was conducted to explore the source of heterogeneity, such as environment and participant identity. Descriptive analysis was used if the sources of heterogeneity were not identified. Sensitivity analysis was performed through altering the effect model. Publication bias was assessed using funnel plots and Egger's tests to determine reliability. If bias existed, metatrim methods were performed.

Study characteristics and quality assessment
According to the search strategy, a total of 996 related articles were retrieved. A total of 292 articles were excluded after duplicates were removed and 673 articles were initially included. After reading titles, abstracts and full texts, 667 articles were excluded, of which 35 were reviews. A total of 14 reports, 532 non-pre-hospital emergency studies, 40 that did not use laryngeal masks, 36 with nonrandomized data and 7 with insufficient data were excluded. Finally, 9 randomized studies [8-16] on manikins and 31 randomized studies [17-47] on humans were included. In the manikin studies, the participants included medical students, paramedics, anesthesiologists, EMT, nurses, intensive care and emergency physicians. The human studies included cases of cardiac arrest, respiratory failure, coma and other critical illnesses. Flow diagrams for the literature selection are shown in Figure 1. The study characteristics are shown in Tables 1-2.

Success rates of first intubation
A total of 4 randomized studies [8,11,13,16] reported the success rates of the initial intubation.
There was statistical heterogeneity (P = 0.000, I2 = 73.2%) so a random effects model was used. The result showed that the success rates of the initial intubation of the laryngeal mask group were significantly higher than those of the endotracheal intubation group [RR=1.25, 95% CI (1.01, 1.55), P<0.001] ( Figure 3).

Subgroup analysis
Due to the existence of heterogeneity, we performed subgroup analysis on the initial success rates of the first insertion and insertion time. As shown in Table 3, we failed to identify any source of heterogeneity in insertion times across the human studies.

Sensitivity analysis and publication bias
The results of sensitivity analysis and publication bias are shown in Table 4. Funnel plots of manikin and human studies are shown in Figures 9-10, respectively. Sensitive analysis suggested that all the results were stable. Egger's tests showed the presence of publication bias in the ventilation efficiency rates and insertion times of human studies, but metatrim suggested that the bias had no influence on the final results.

Discussion
To our knowledge, this is the first systematic review and meta-analysis to compare the clinical effects of laryngeal masks and endotracheal intubation from manikins and humans for pre-hospital emergencies. Our study showed that for both manikin and human studies, the overall effects of the laryngeal mask ventilation were superior to endotracheal intubation. Sensitivity analysis and publication bias tests also suggested that the results were stable and reliable.
Laryngeal masks have unique advantages for clinical applications, including ease of use and the ability to rapidly maintain the airways. Even when the position of the laryngeal mask was not ideal, it can maintain airway patency [48]. A secondly advantage is that no laryngoscopes are needed.
Compared to endotracheal intubation, it is easy for beginners to insert the laryngeal mask and the success rates are relatively high [49]. Thirdly, the laryngeal mask is used as a supraglottic ventilation device, which has the advantage of establishing the airways for autonomous ventilation and ventilation control, thus avoiding mucosal damage in the trachea. Ventilation management through endotracheal intubation is not satisfactory. Cobas et al [50] reported that the failure rates of nonanesthesiologists for endotracheal intubation can be as high as 31%. Even with experienced clinicians, the misalignment rates were as high as 17.4. %, of which the esophageal insertion rates were 6.7% [51]. This can be fatal for comatose patients.
Our meta-analysis showed that the success rates of first-pass intubation in the laryngeal mask group were significantly higher than the control group, and the time taken for laryngeal mask placement was significantly shorter. These results indicate that the laryngeal mask had improved success rates for first-pass intubation. Unlike blind tracheal tube placement, the use of a laryngeal mask does not involve glottis exposure, is easy to operate, and easy to master. Furthermore, its shorter placement times are beneficial to the early recovery of the patient's ventilator function. Hypoxia in the brain tissue for more than 5 minutes can lead to irreversible brain damage; thus, establishing airway ventilation as early as possible is key to successful cardiopulmonary resuscitation. Brimacombe et al [52] reported that medical staff without experience in laryngeal mask placements were more likely to insert laryngeal masks with shorter insertion times, which was similar to our subgroup analysis. The Laryngeal mask ventilation also improved the blood gas index, leading to higher levels of PaO 2 and SpO 2 and shorter SpO 2 rise times, which are important to ensure good patient prognosis.
The included manikin studies were randomized crossover trials, and the risk of bias was primarily in the blinding method, which could not be implemented. Due to the small sample size, we performed Egger's tests. The results showed that the small sample effect did not influence the final data outcomes. Moreover, specific information of the human studies was unknown due to random grouping.
The study had some limitations. First, the quality of the evidence in the included studies was weak.
Secondly, the sources of heterogeneity for the comparison of first intubation success rates and insertion times were not clearly identified. Thirdly, we failed to study the different methods of laryngeal masks and endotracheal intubation. Moreover, the update of the laryngeal mask was rapid with standard types, intubable types, esophageal drainage types and no cuff types. The application of these different laryngeal masks in pre-hospital emergencies also requires further exploration. Finally, the included data were inadequate, so specific subgroup analysis regarding the participants identity in the overall intubation success rate was not conducted.

Conclusions
In summary, laryngeal masks could quickly and effectively improve patient ventilation compared to endotracheal intubation. Laryngeal masks are therefore a more effective ventilation device and should be employed in pre-hospital emergencies. Further high-quality randomized controlled trials are now required to further demonstrate the reliability of our conclusions.

Ethics approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Availability of data and materials
All data generated or analyzed during this study are included in this published article.

Competing interests
There is no competing interests for publication of this paper.

Funding
This study was supported by the 12th Five-year medical science research foundation of PLA (CWS14J068).      Forest plot of overall intubation success rates in the manikin studies Forest plot of success rates of the initial intubation in the manikin studies Forest plot of the ventilation efficiency rates in the human studies Figure 6 Forest plot of the overall intubation success rate and success rate of the initial intubation in the human studies  Funnel plots of overall intubation success rates (A), success rates of initial intubation (B) and insertion times (C) in the manikin studies.

Figure 10
Funnel plots of ventilation efficiency rates (A), success rates of initial intubation (B) and insertion times (C) in the human studies.

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