Laryngeal mask versus intubation on adverse reactions in pediatric retinoblastoma patients

Introduction

Retinoblastoma is one of the most common infantile malignant solid tumors, with a uniform incidence rate of 1 in 15,000–20,000 live births, corresponding to approximately 9,000 new cases annually (1). Although chemotherapy and radiation treatment aim to spare the eye, enucleation (i.e., removal of the entire eyeball) is considered the primary treatment for end-stage ocular diseases (2). For patients with orbital extension of retinoblastoma, clinicians have tended to avoid performing orbital exenteration because of the unfavorable poorer prognosis and facial deformity, and replace it with chemoreduction followed by extended enucleation (3). Enucleation is performed as an outpatient procedure under general anesthesia. Endotracheal intubation (ETT) and laryngeal mask airway (LMA) are often used to manage the airway in such cases. During ETT, a flexible plastic tube, called an endotracheal tube, is inserted into the mouth or nose, and then into the airway to provide positive pressure ventilation. There are multiple techniques available, including visualization of the vocal cords using a laryngoscope or video laryngoscope, direct placement of the endotracheal tube into the trachea via cricothyrotomy, and fiberoptic visualization of the vocal cords via the nasal or oral route. However, ETT has been shown to correlate with coughing, straining, breath-holding, and increased of ocular pressure (4). As an alternative to intubation, LMA are widely used in emergency situations and anesthetic management. Flexible LMA (FLMA) has been developed to prevent interference in the surgical field and is especially useful for operations that are close to the face. LMA permits stable heart rate (HR) variability with fewer cases of perioperative respiratory adverse events, such as sore throat, cough, the incidence of hypoxemia, bronchospasm, and postoperative nausea (5,6). A potential risk of LMA is an incomplete mask seal, which causes air leakage or insufflation of air into the stomach (7). Moreover, disadvantages of the use of LMA include restricted surgical visualization and manipulation of the tonsils.

Previous studies have compared the differences between laryngeal mask intubation and ETT in abdominal surgery, tonsillar surgery, and pediatric strabismus surgery (5,8). To our knowledge, few studies have compared the effect of LMA with ETT on airway management in pediatric enucleation surgery. The main objective of this retrospective analysis was to compare the effects of LMA and ETT on airway management and perioperative adverse reactions in pediatric patients with retinoblastoma undergoing enucleation. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-311/rc).

Methods

Patients

The study protocol was approved by the Ethics Committee of the Peking University People’s Hospital (approval No. 2021PHB269). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. As shown in Figure 1, we retrospectively analyzed the history data of 371 patients with retinoblastoma who were admitted to our hospital during 1^st January 1, 2007, and 31^th December 31, 2020, by searching our electronic medical record database using the key word “retinoblastoma”. The inclusion criteria were as follows: (I) retinoblastoma diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI); (II) aged between 3 and 13 years; and (III) all the information related to the patients’ features available for analysis. The exclusion criteria were as follows: (I) patients with missing clinical data; and (II) those complicated with other ophthalmic diseases (such as injuries). Demographic and clinical information were recorded using an electronic anesthetic documentation system. Based on the aforementioned criteria, 313 patients were excluded and 58 patients were included in the statistical analysis. Based on the type of intubation under general anesthesia, the patients were divided into an ETT group (Group A; n=35) and an LMA group (Group B; n=23). Assessments of baseline respiratory status were included, and no recent respiratory infections were observed.

Figure 1 Flow diagram of the study showing the number of patients at each screening step. The history data of 371 patients were retrieved by searching our electronic medical record database using the key word “retinoblastoma”. Three hundred and thirteen patients were excluded and 58 patients were included into statistical analysis. According to different types of intubations under general anesthesia, the patients were divided into an endotracheal intubation group (Group A; n=35) and a laryngeal mask airway group (Group B; n=23). ASA, American Society of Anesthesiologists; BMI, body mass index; CT, computed tomography; MRI, magnetic resonance imaging; RB, retinoblastoma.

Upon entering the operating room, patients first received standard monitoring. For ETT or LMA, general anesthesia was induced using propofol 2 mg/kg, followed by 4–6% sevoflurane as needed. Placement of the endotracheal tube or LMA was then carried out by experienced anesthesiologists after fentanyl (2 µg/kg) or rocuronium bromide 0.6 mg/kg was administered for smooth induction and anesthesia as needed. Anesthesia was maintained with 2–3% sevoflurane or propofol 3–5 mg/kg/h and remifentanil 0.4–0.6 µg/kg/min as needed. And adjust the remifentanil infusion speed according to intraoperative blood pressure (BP) (if it is 120% higher than basal BP, then we increase the pump injection speed at 0.15 mL/kg/h). Each interval was 3 min; if it was below 80% of basal BP, then we reduced the pump velocity to 0.15 mL/kg/h. When spontaneous breathing was recovered, a tidal volume of 5 mL/kg, respiratory rate <20 beats/min, fingertip oxygen saturation of 95%, patient compliance, temperature of 36 ℃, and ETT or LMA were removed after routine administration of muscle relaxant antagonism (atropine + neostigmine).

Observation indexes

The collected demographic data included patient age, sex, height, weight, and body mass index (BMI). The retrieved clinical data included American Society of Anesthesiologists (ASA) physical status, number of patients using inhaled sevoflurane, number of patients using muscle relaxant (rocuronium bromide), number of patients using retrobulbar block, dose of fentanyl and remifentanyl, duration of operation, duration of anesthesia, and time spent in the hospital from the day of operation to the day of hospital discharge. In addition, HR and mean arterial pressure (MAP) were retrieved when entering the operating room (T₀), before intubation (T₁), at skin incision (T₂), before extubation (T₃), and when leaving the operating room (T₄). Perioperative complications were also collected, including the number of intubation attempts, ocular cardiac reflex, laryngeal spasm after extubation, desaturation, arrhythmia, and oral injuries (teeth, lower lip, tongue, soft tissue, vocal cord, etc.).

Statistical analysis

Statistical software (SPSS 24.0) was used for the data description and analysis. Continuous variables were expressed as mean ± standard deviation. The independent sample t-test was employed for measurement data, and the Chi-squared or Fisher’s exact tests were used for categorical data. Statistical significance was set at P<0.05. Post-hoc power analysis based on this estimated effect size was conducted using G*Power software (version 3.1.9.2, Heinrich Heine University, Düsseldorf, Germany).

Results

Patient characteristics

The history data of 371 patients were retrieved by searching our electronic medical record database using the key word “retinoblastoma”. A total of 313 patients were excluded and 58 patients (25 men and 33 women) were included in the statistical analysis. The mean age was 4.48±2.14 years, and the mean BMI was 17.05±2.65 kg/m². Among the 58 patients included in the analysis, 60.34% (35/58) underwent ETT, and 39.66% (23/58) underwent LMA placement. Based on the type of intubation under general anesthesia, the patients were divided into an ETT group (Group A; n=35) and an LMA group (Group B; n=23). Demographic variables, including age, sex, height, weight, BMI, and ASA status, were all comparable between the two groups (all P>0.05; Table 1). There were also no statistically significant differences in the proportion of patients using rocuronium bromide, the proportion of patients using retrobulbar block, the dose of fentanyl and remifentanyl, the duration of surgery, the duration of anesthesia, or postoperative hospital stay (all P>0.05; Table 1). However, the proportion of patients using inhaled sevoflurane was significantly lower in Group B than in Group A (P=0.007; Table 1). The above results suggest that the two sets of data are comparable between the two groups, and that in patients receiving ETT, more sevoflurane is needed to combat the stress caused by ETT.

Perioperative conditions

To compare the effects of LMA versus ETT on the stability of the perioperative process, we compared the changes in HR and MAP over time relative to baseline. An increase in the HR can be detrimental to patients undergoing enucleation. For this, we compared the HR responses to ETT using a conventional laryngoscope and LMA in patients undergoing enucleation. HR and MAP were retrieved when entering the operating room (T₀), before intubation (T₁), at skin incision (T₂), before extubation (T₃), and when leaving the operating room (T₄). We found that in Group A, the HR value declined during surgery, and in Group B, the index declined and then increased gently after the end of surgery, suggesting that the circulation recovered quickly in Group B (Figure 2). Generally, the HR value in Group A appeared to be lower than that in Group B, indicating less circulation fluctuation from the LMA than ETT. In particular, patients with LMA placement in Group B showed significantly lower HR before skin incision (T₂) than those receiving ETT in Group A (P=0.02). Due to the significant difference in HR at time point T₂ between the two groups, a post hoc power analysis was conducted. The HR data at T₂ were 90±14 bpm for the LMA group (n=23) and 103±20 bpm for the ETT group (n=35). A two-sided independent samples t-test was used to compare the mean differences. To assess the effect size, Cohen’s d was calculated using the pooled standard deviation (SD): pooled SD = √{[(22 × 14²) + (34 × 20²)]/(23 + 35 − 2)} ≈ √(17,912/56) ≈ 17.88. Cohen’s d = (103 − 90)/17.88 ≈ 0.727. Based on this effect size, a post hoc power analysis was performed using G*Power with a two-sided α of 0.05, and sample sizes of 23 and 35. The resulting power was approximately 0.84 (84%), indicating that the study had sufficient statistical power to detect the observed difference in HR between the groups at T₂. These findings suggest that ETT induces a stress response to the sympathetic system, leading to the over-release of catecholamines.

Figure 2 Comparison of clinical indexes between the two groups. (A) HR of the two groups at each time point as indicated. (B) MAP of the two groups at each time point as indicated. T₀: when entering the operating room; T₁: before intubation; T₂: at skin incision; T₃: before extubation; T₄: when leaving the operating room. *, P<0.05. HR, heart rate; MAP, mean arterial pressure.

Perioperative complications

We also analyzed perioperative complications, including the number of intubation attempts, ocular cardiac reflex, laryngeal spasm after extubation, desaturation, arrhythmia, and oral injuries (teeth, lower lip, tongue, soft tissue, vocal cord, etc.). In Group B, one patient (1/23, 4.35%) experienced laryngeal spasm after the removal of the laryngeal mask, and one patient (1/23, 4.35%) experienced a second attempt at LMA insertion due to poor alignment of the laryngeal mask at the first time (Table 2). Moreover, the occurrence of the ocular cardiac reflex in Group B was 43.38%, which was higher than that in Group A (22.86%, P=0.09; Table 2). Obviously, the insufficient depth of anesthesia in Group B led to easier disturbance of the ETT and made it more accessible to the appearance of ocular cardiac reflex. Moreover, no desaturation or arrhythmia was observed in either group.

Discussion

To our knowledge, this is the first report to elucidate the difference between the LMA and ETT in retinoblastoma nucleation surgery. This retrospective study showed that LMA intubation provides more stable perioperative conditions and reduces the use of inhaled anesthetics during the procedure. Based on these findings, LMA intubation is recommended for children undergoing eye enucleation surgery.

Retinoblastoma is a rare type of eye cancer found in children. Although systemic and radiation therapy retain important roles in retinoblastoma management, modern enucleation is employed mainly for advanced intraocular disease with life-threatening features or failed conservative treatment—not as a blanket prophylactic measure (9). The functional anatomy of the airway in children is important for enucleation because the airway changes in size, shape, and position throughout its development from neonate to adult. The cricoid cartilage is the narrowest portion of the larynx. A rapid phase of growth occurs in the first three years of life, and the unique anatomical features in children contribute to the loss of the upper airway space and poor visibility during intubation (10). Although fiberoptic evaluation and high-resolution CT can provide important information, pediatric airway management remains a great challenge (11,12). The LMA and endotracheal tube are classic tools used to manage the airway of children receiving general anesthesia. In a systematic review and meta-analysis of 1,433 patients undergoing laparoscopic surgery, LMA was found to permit more stable perioperative hemodynamic parameters and less stress than ETT (13). For ophthalmic surgery in pediatric patients, the use of an LMA is also beneficial for less fluctuation in intraocular pressure (14). However, ETT has been criticized because it induces undesirable stress responses and hemodynamic alterations due to an elevation in serum cortisol (15). Similarly, in our study, the HR before skin incision was significantly lower in patients with LMA placement than in those receiving ETT, suggesting fewer adverse effects on circulation. The LMA, as a supraglottic ventilation device, has no glottic exposure during intubation and causes no harm to the airway with little cardiovascular stress. Thus, children may have better access to general anesthesia with LMA.

The strong influence of tracheal intubation might interfere with circulation and respiratory systems due to the release of stress hormones, such as endothelin and thromboxane A2, in response to the stimulus (16,17). Compared with LMA, ETT is less effective at the same anesthesia depth; therefore, sevoflurane is commonly used to minimize the stimulus of ETT (18). In our study, 45.71% of the patients received the inhaled anesthetic drug (sevoflurane) when using ETT, while in the LMA group, only 8.70% of the patients received sevoflurane. The administration of sevoflurane can increase the risk of memory impairment. Especially for children who have undergone repeated and long-term general anesthesia, the harmful effects were more susceptible and accumulated (19). LMA intubation is associated with reduced use of inhaled anesthetics in children undergoing eye enucleation surgery, which could have implications for memory function.

Perioperative complications may occur during the process of ETT or LMA placement, such as laryngeal spasm after extubation, ocular cardiac reflex, desaturation, arrhythmia, and oral injuries (teeth, lower lip, tongue, soft tissue, vocal cord, etc.). Laryngospasm is most commonly observed in the post-extubation phase of anaesthesia (20). In most cases, the laryngospasm is self-limiting. However, laryngospasm sometimes persists, and if not appropriately treated, it may result in serious complications that may be life-threatening. In our study, one child experienced laryngospasm (1/58, 1.72%) during general anesthesia as manifested by stridor, which spontaneously returned to normal. Ocular cardiac reflex is another common perioperative complication during enucleation (21). In our study, the occurrence of ocular cardiac reflex was relatively higher in patients receiving LMA than in those receiving ETT, whereas the proportion of patients using retrobulbar block was comparable. For the successful rate of LMA insertion, we witnessed a second attempt at LMA insertion due to poor alignment of the laryngeal mask, and the LMA was successfully reentered after retreating and adjusting the LMA.

We also reviewed the distribution of potential confounders between groups. ASA physical status did not differ significantly (P>0.05), suggesting comparability in baseline health status. However, sevoflurane use was significantly different between groups (P=0.007), indicating a potential confounding effect on cardiovascular responses. As volatile anesthetics can influence cardiovascular parameters. Although the primary focus of our study was the impact of airway device on cardiovascular responses, it is possible that the observed effects were at least partially mediated by differences in anesthetic technique.

Our study included children aged 3 to 13 years. According to World Health Organization (WHO) growth references, BMI-for-age is an appropriate indicator for assessing nutritional status in children and adolescents aged 2 to 19 years (22). In addition, in our study cohort, CT scans were used selectively during the diagnostic workup primarily to assess intraocular calcifications, which can support the diagnosis of RB when clinical findings are equivocal, and when MRI was either not available or contraindicated.

Limitations

It is noteworthy that this study used records that were not specially designed; therefore, the available data may be of poor quality and result in a small sample size. The sample size limits our ability to detect rare complications. The multivariate analysis would be underpowered and potentially misleading. Meanwhile, the objective measurement tools for anesthesia depth and incomplete recording of rare perioperative events such as regurgitation is also lacking. Because LMA intubation cannot be performed on a blinded basis. The potential influence of anesthesiologist preference on airway selection, as well as the retrospective nature of data collection might also have resulted in some bias. The HR might be substantiated by the analysis of the many factors that can affect HR, such as volume status and medications, which might also introduce some bias. Haemodynamic changes are critically related to the anesthetic drugs given before intubation/LMA placement. The retrospective characteristics of this study might also produce some bias. Therefore, it is difficult to identify an appropriately exposed cohort. Further investigation awaits a large multicenter randomized controlled trial.

Conclusions

LMA intubation provides more stable perioperative conditions in children undergoing eye enucleation surgery. LMA intubation does not generate more adverse events than ETT.

Acknowledgments

We thank the surgeons from the Department of Ophthalmology for their sincere cooperation.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-311/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-311/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-311/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-311/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Ethics Committee of the Peking University People’s Hospital (approval No. 2021PHB269).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Leclerc R, Olin J. An Overview of Retinoblastoma and Enucleation in Pediatric Patients. AORN J 2020;111:69-79. [Crossref] [PubMed]
2. Jin M, Tian Z, Xie Y, et al. Diagnosis and treatment of infantile malignant solid tumors in beijing, China: A multicenter 10-year retrospective study. Pediatr Investig 2020;4:178-85. [Crossref] [PubMed]
3. Kaliki S, Vempuluru VS, Mohamed A, et al. Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries. Ophthalmology 2024;131:468-77. [Crossref] [PubMed]
4. Lee JY, Sim WS, Kim ES, et al. Incidence and risk factors of postoperative sore throat after endotracheal intubation in Korean patients. J Int Med Res 2017;45:744-52. [Crossref] [PubMed]
5. Liu X, Cao H, Tan X, et al. Comparison of the Effect of Laryngeal Mask Airway Versus Endotracheal Tube on Airway Management in Pediatric Patients with Tonsillar Hypertrophy. J Perianesth Nurs 2021;36:142-6. [Crossref] [PubMed]
6. Dong W, Zhang W, Er J, et al. Comparison of laryngeal mask airway and endotracheal tube in general anesthesia in children. Exp Ther Med 2023;26:554. [Crossref] [PubMed]
7. Miskovic A, Johnson M, Frost L, et al. A prospective observational cohort study on the incidence of postoperative sore throat in the pediatric population. Paediatr Anaesth 2019;29:1179-85. [Crossref] [PubMed]
8. Shin SY, Kim MJ, Joo J. Oculocardiac reflex and oculorespiratory reflex during strabismus surgery under general anesthesia using the laryngeal mask airway with maintenance of spontaneous respiration: A retrospective study. J Int Med Res 2020;48:300060520945158. [Crossref] [PubMed]
9. Teixeira LF, Macedo CRPD, Fonseca JRF, et al. Intra-arterial Chemotherapy for Retinoblastoma, Outcomes Analysis in 357 Eyes: Thirteen Years of Experience in a Referral Center in Brazil. Ophthalmol Retina 2025;9:798-806. [Crossref] [PubMed]
10. Downard MG, Lee AJ, Heald CJ, et al. A Retrospective Evaluation of Airway Anatomy in Young Children and Implications for One-Lung Ventilation. J Cardiothorac Vasc Anesth 2021;35:1381-7. [Crossref] [PubMed]
11. Elders B, Ciet P, Tiddens H, et al. MRI of the upper airways in children and young adults: the MUSIC study. Thorax 2021;76:44-52. [Crossref] [PubMed]
12. Hsu G, von Ungern-Sternberg BS, Engelhardt T. Pediatric airway management. Curr Opin Anaesthesiol 2021;34:276-83. [Crossref] [PubMed]
13. Kachakayala RK, Bhatia P, Singh S, et al. A comparative study of supraglottic airway devices Baska mask and ProSeal-laryngeal mask airway in short gynaecological procedures. International Journal of Research in Medical Sciences 2020;8:285-9.
14. Gulati M, Mohta M, Ahuja S, et al. Comparison of laryngeal mask airway with tracheal tube for ophthalmic surgery in paediatric patients. Anaesth Intensive Care 2004;32:383-9. [Crossref] [PubMed]
15. Allahyari E, Azimi A, Zarei H, et al. Comparison of endotracheal intubation, laryngeal mask airway, and I-gel in children undergoing strabismus surgery. J Res Med Sci 2021;26:9. [Crossref] [PubMed]
16. Abdi W, Amathieu R, Adhoum A, et al. Sparing the larynx during gynecological laparoscopy: a randomized trial comparing the LMA Supreme™ and the ETT. Acta Anaesthesiologica Scandinavica 2009;54:141-6. [Crossref] [PubMed]
17. Kim EH, Jang YE, Ji SH, et al. Changes in Plasma Glial Fibrillary Acidic Protein in Children Receiving Sevoflurane Anesthesia: A Preliminary Randomized Trial. J Clin Med 2021;10:662. [Crossref] [PubMed]
18. Theodoraki K, Fassoulaki A. Sevoflurane consumption--laryngeal mask vs. tracheal intubation. Eur J Anaesthesiol 2008;25:607-9. [Crossref] [PubMed]
19. Fan XY, Shi G, Zhao P. Neonatal Sevoflurane Exposure Impairs Learning and Memory by the Hypermethylation of Hippocampal Synaptic Genes. Mol Neurobiol 2021;58:895-904. [Crossref] [PubMed]
20. Apai C, Shah R, Tran K, et al. Anesthesia and the Developing Brain: A Review of Sevoflurane-induced Neurotoxicity in Pediatric Populations. Clin Ther 2021;43:762-78. [Crossref] [PubMed]
21. Vézina-Audette R, Steagall PVM, Gianotti G. Prevalence of and covariates associated with the oculocardiac reflex occurring in dogs during enucleation. J Am Vet Med Assoc 2019;255:454-8. [Crossref] [PubMed]
22. A health professional’s guide for using the new WHO growth charts. Paediatr Child Health 2010;15:84-98. [Crossref] [PubMed]