Abstract
Purpose
The oculocardiac reflex (OCR) is a frequent and potentially hazardous complication during pediatric strabismus surgery. Achieving hemodynamic stability while ensuring rapid recovery is critical in day-case anesthesia. This study aimed to evaluate the efficacy of a sub-anesthetic dose of esketamine in reducing the incidence of OCR in children undergoing day-case strabismus surgery under total intravenous anesthesia (TIVA).
Patients and Methods
This prospective, randomized, double-blind, placebo-controlled trial enrolled 204 children (aged 2–12 years, ASA I–II) scheduled for elective strabismus surgery. Patients were randomized (1:1) to receive either intravenous esketamine (0.2 mg/kg) or an equal volume of normal saline following laryngeal mask airway insertion. All patients received standardized TIVA with propofol and remifentanil. The primary outcome was the overall incidence of OCR (defined as a heart rate decrease >20% from baseline or arrhythmia upon muscle traction). Secondary outcomes included OCR incidence during three distinct surgical stages: Stage I (conjunctival incision), Stage II (active muscle mobilization and dissection), and Stage III (static sustained muscle traction), as well as severe OCR (<50 bpm), and postoperative recovery quality.
Results
The overall incidence of OCR was significantly lower in the esketamine group compared to the control group (38.2% vs 70.6%; P < 0.05). Heart rates dynamics varied by stage, with the highest OCR incidence occurring during Stage II (37.3% vs 70.6%; P <0.05) compared to Stage III (1.0% vs 6.9%; P =0.071) in both groups. Heart rates in the esketamine group were significantly higher during conjunctival incision (Stage I) and muscle dissection (Stage II) (P < 0.001). For both groups, Stage II was associated with the highest incidence of OCR. Although the incidence of severe OCR was lower in the esketamine group (2.9% vs 8.8%), the difference was not statistically significant. There were no significant differences between groups regarding postoperative nausea and vomiting, emergence agitation, or time to discharge.
Conclusion
A single sub-anesthetic dose of esketamine (0.2 mg/kg) effectively reduces the incidence of OCR and enhances hemodynamic stability in children undergoing day-case strabismus surgery. This regimen provides a safe prophylactic strategy without compromising recovery quality or increasing postoperative adverse events.
Keywords: esketamine, oculocardiac reflex, pediatric strabismus surgery, total intravenous anesthesia, day-case surgery
Introduction
Pediatric strabismus is a prevalent ocular pathology, with a global incidence ranging from 2% to 8%.1,2 Surgery intervention is frequently indicated to restore ocular alignment and prevent irreversible complications, such as amblyopia and the loss of stereopsis.3,4 However, strabismus surgery is uniquely associated with a high incidence of the oculocardiac reflex (OCR), occurring in up to 96.6% of cases—a rate significantly higher than that observed in other ophthalmic procedures.5–7 The OCR is a trigeminal-vagal reflex arch characterized by bradycardia, arrhythmias, or, in extreme cases, asystole. Clinical evidence suggests that the reflex is primarily elicited by mechanical stimulation of the extraocular muscles. Specifically, the phases of muscle sheath dissection and the subsequent traction applied to the muscle tendons are the most critical triggers. The magnitude of this hemodynamic response is often dependent on the intensity of the stimulus and the specific surgical maneuvers involved, making intraoperative management particularly challenging.8–10 This reflex poses a substantial intraoperative hemodynamic risk, particularly in the burgeoning field of pediatric ambulatory surgery. In these settings, anesthesia management must balance the dual requirements of maintaining hemodynamic stability against the OCR while ensuring rapid emergence and minimal postoperative side effects to facilitate timely discharge.7
Esketamine, the S(+) enantiomer of ketamine, has emerged as a promising pharmacological adjunct in pediatric anesthesia. It exhibits a twofold higher affinity for the N-methyl-D-aspartate (NMDA) receptor compared to the racemic mixture.11–13
This increased potency allows for effective sedation and analgesia at lower clinical doses, resulting in a more favorable recovery profile suitable for ambulatory surgery.14 Beyond its established benefits in reducing preoperative anxiety and postoperative emergence agitation,15,16 esketamine provides potent analgesia with minimal respiratory depression.17,18 Crucially, esketamine exerts sympathomimetic effects by inhibiting reuptake catecholamines. This action induces a modest increase in heart rate and systemic vascular resistance, which may physiologically antagonize the vagal hypertonicity induced by mechanical traction and muscle dissection.
Despite the theoretical advantages of esketamine’s hemodynamic profile, robust clinical evidence regarding its efficacy in preventing the OCR during pediatric strabismus surgery remains scare. Therefore, this study aims to evaluate the impact of a sub-anesthetic dose of esketamine (0.2 mg/kg), administered as part of a total intravenous anesthesia regimen, on the incidence and severity of the OCR in children. We hypothesize that esketamine will significantly reduce the occurrence of the OCR, thereby enhancing the safety and stability of anesthesia management in this vulnerable population.
Methods
Study Design
This prospective, randomized, double-blind clinical trial was conducted in the pediatric strabismus day-surgery ward at Beijing Tongren Hospital, Capital Medical University, between December 20, 2024, and June 28, 2025. The study protocol was approved by the Institutional Review Board of Beijing Tongren Hospital (approval number: TREC2024-KY095), and was prospectively registered with the Chinese Clinical Trial Registry (ChiCTR2400094053). This study adhered to Declaration of Helsinki principles. Written informed consent was obtained from the parents or legal guardians of all participating children prior to enrollment.
Participants
Patients were eligible for inclusion if they met the following criteria: (1) scheduled for elective strabismus correction surgery; (2) American Society of Anesthesiologists (ASA) physical status I or II; (3) aged 2 to 12 years; and (4) planned to receive general anesthesia via a laryngeal mask airway (LMA).
Patients were excluded if they had: (1) a history of antiepileptic therapy or current use of medications known to affect electrocardiograms; (2) developmental or mental retardation; (3) known allergies to general anesthetics; or (4) guardians who refused to participate. Enrolled patients were subsequently withdrawn from the analysis (dropout criteria) if they: (1) experienced LMA ventilation failure requiring conversion to endotracheal intubation; (2) had missing or incomplete intraoperative monitoring records; or (3) voluntarily requested to withdraw from the study at any point.
Randomization and Blinding
Eligible patients were randomly assigned in a 1:1 ratio to either the esketamine group or the control group. Randomization was performed using a computer-generated random number sequence. To ensure allocation concealment, the group assignments were enclosed in sequentially numbered, opaque, sealed envelopes, which were securely held by an independent anesthesia technician. The randomization sequence generation and intervention allocation were conducted by an independent researcher who was not involved in clinical anesthesia, data collection, or statistical analysis. Strict double-blinding was maintained throughout the study: the anesthesiologists administering the medications, the personnel collecting intraoperative data, and the postoperative outcome assessors were all fully blinded to the treatment allocation.
Anesthesia Protocol and Management
All patients received standardized general anesthesia. Upon arrival in the operating room, intravenous access was established. Standard monitoring included electrocardiography (ECG), pulse oximetry (SpO2), non-invasive blood pressure (NIBP), and Bispectral Index (BIS) monitoring. After venous access was confirmed and vital signs were stable, anesthesia induction commenced.
Prior to induction, intravenous atropine (0.01 mg/kg) was administered to inhibit glandular secretions. This was followed sequentially by intravenous dexamethasone (0.1 mg/kg), sufentanil (0.1 µg/kg), propofol (2–3 mg/kg), and mivacurium (0.15 mg/kg). After induction, once the eyelash reflex was absent and muscle relaxation was confirmed, the attending anesthesiologist inserted a suitably sized flexible laryngeal mask airway (LMA) and confirmed its correct placement via capnography and bilateral auscultation.
Anesthesia was maintained in both groups with continuous intravenous infusions of remifentanil (0.1–0.2 µg/kg/min) and propofol (6–10 mg/kg/h), with infusion rates adjusted to maintain BIS values between 40 and 50. All patients received volume-controlled ventilation (respiratory rate 14–18 breaths/min, tidal volume 6–8 mL/kg), maintaining end-tidal carbon dioxide (ETCO2) between 35–45 mmHg.
Baseline characteristics, including age, height, weight, sex, American Society of Anesthesiologists (ASA) physical status, underlying comorbidities, type of extraocular muscle involved, anesthesia duration, and surgical duration, were recorded.
Interventions
Following LMA insertion and confirmation of adequate ventilation, patients were assigned to receive either esketamine or an equal volume of saline, according to their group allocation. The study medications were prepared by a designated pharmacist, who performed unblinding based on group allocation and labeled the syringes uniformly to maintain blinding of the clinical staff. Patients in the esketamine group received intravenous esketamine (0.2 mg/kg), while the control group received an equivalent volume of 0.9% normal saline, both administered intravenously. Intraoperative hemodynamic parameters such as heart rate, non-invasive arterial blood pressure, and pulse oximetry were continuously monitored and documented.
Surgical Procedure
Following induction of general anesthesia, a 0.5mL subconjunctival block of 2% lidocaine was administered. The surgical approach was determined by the target muscle: a limbal of fornix-based conjunctival incision was performed to exposure the surgical field (Stage I). The Tenon’s capsule and peribulbar fascia were then meticulously dissected to isolate the muscle form surrounding connective tissues (Stage II). The muscle was secured with 6–0 absorbable locking sutures ate the insertion, disinserted, and reattached to the sclera at the targeted position via scleral fixation. The conjunctiva was closed with 8–0 absorbable sutures. To minimize variability, a 2-minute stabilization period was observed between manipulations of different muscles, and all procedures were performed by a consistent team of three senior ophthalmologists, each possessing over ten years of clinical experience, to minimize inter-operator variability and ensure technical consistency.
Management of OCR
Before the start of surgery, the surgeon performed a subconjunctival block with 2% lidocaine. During surgery, the medical staff closely monitored heart rate dynamics for the occurrence of OCR. Baseline heart rate was defined as the average of three consecutive readings recorded after the induction of anesthesia and laryngeal mask airway insertion, once vital signs had stabilized and prior to surgical manipulation. OCR was defined as a sudden decrease in heart rate exceeding 20% from baseline or the presence of any arrhythmia upon traction of the extraocular muscles. Upon detection of OCR, the intervention strategy was stratified by the degree of heart rate reduction. If the heart rate decreased by less than 20%, no specific intervention was made, but close observation continued. If the heart rate decreased by 20–50% and remained relatively stable without other overt clinical symptoms, immediate action was similarly withheld, though monitoring frequency was increased. However, if the heart rate decreased by 20–50% and progressed, or if it decreased by more than 50% (constituting severe bradycardia, defined as a heart rate <50 bpm during extraocular muscle traction), surgical stimulation was immediately paused. Concurrently, anesthetic depth was swiftly increased by adjusting anesthetic agent doses to mitigate excessive vagal stimulation. If bradycardia persisted after relieving surgical stimulation, intravenous atropine (0.01 mg/kg) was administered to normalize heart rate, and the number of atropine administrations and surgical pauses due to OCR were meticulously recorded.
Postoperative Care
At the end of surgery, all anesthetic infusions were discontinued, and patients were allowed to recover spontaneous breathing. The LMA was removed when stable spontaneous breathing resumed, defined as a tidal volume of at least 5 mL/kg and a respiratory rate exceeding 7 breaths/min. Patients were then transferred to the Post-anesthesia Care Unit (PACU). Patients remained in the PACU for a minimum of 30 minutes, where vital signs were continuously monitored until they met PACU discharge criteria. Upon emergence, agitation was assessed using the Pediatric Anesthesia Emergence Delirium (PAED) scale, with a score ≥10 indicating agitation. Medical staff used verbal communication, behavioral guidance, or toys to alleviate postoperative anxiety. Post-discharge, patients and their guardians were contacted for follow-up regarding intraoperative awareness or any adverse events.
Outcome Measures
The primary outcome of this study was the overall incidence of OCR during surgery. OCR was defined as a sudden decrease in heart rate exceeding 20% from baseline or the presence of any arrhythmia upon traction of the extraocular muscles.9 Secondary outcomes included the incidence of OCR during specific surgical stages, namely Stage I (conjunctival incision), Stage II (active muscle mobilization, including hooking and extraocular muscle dissection), and Stage III (static sustained extraocular muscle traction), to assess the impact of different surgical maneuvers on OCR. Other secondary outcomes comprised the incidence of severe OCR, which was defined as a heart rate less than 50 bpm during extraocular muscle traction (including both dissection and traction phases). Also recorded were the number of atropine administrations necessitated by OCR, the number of surgical pauses due to OCR, the incidence of postoperative nausea and vomiting (PONV), and the incidence of postoperative agitation. Postoperative agitation was assessed using the PAED, with a score of 10 or higher indicating agitation.
Sample Size Calculation
As described in our previous published protocol,19 the sample size was calculated based on preliminary study data showing an overall OCR incidence of approximately 70%, and hypothesizing a 20% reduction with esketamine, a sample size of 91 patients per group was required to achieve 80% power at a two-sided alpha level of 0.05. Accounting for a 10% dropout rate, a total of 204 patients (102 per group) were planned for enrollment.
Statistical Analysis
Statistical analyses were performed using SPSS 23.0. Normality of data distribution was assessed using the Shapiro–Wilk test, and homogeneity of variances using Levene’s test. Continuous data with normal distribution were presented as mean ± standard deviation (SD) and compared using independent samples t-tests. Non-normally distributed continuous data were presented as median [interquartile range (IQR)] and compared using Mann–Whitney U-tests. Categorical data were presented as counts and percentages (n, %) and compared using chi-square tests or Fisher’s exact tests. Ordinal data were compared using rank-sum tests. A two-sided P-value < 0.05 was considered statistically significant.
Results
A total of 220 pediatric patients were screened. Of these, 16 patients were excluded (10 for guardian refusal, 6 for temporary surgery cancellation). Consequently, 204 eligible patients were enrolled and randomly assigned to the esketamine group (n=102) or the control group (n=102).
Baseline demographic (age, sex, height, weight, ASA physical status) and clinical characteristics (anesthesia and surgical duration, baseline hemodynamics, PACU stay time, and surgical specifics) were well-balanced between groups (all P > 0.05; Table 1). The proportion of extraocular muscles involved in OCR did not differ significantly between the two groups (P > 0.05). Similarly, the number of patients undergoing surgery on two extraocular muscles showed no statistically significant difference between groups (P > 0.05).
Table 1.
Baseline Characteristics of the Participants
| Esketamine Group (n=102) | Control Group (n=102) | P-value | |
|---|---|---|---|
| Sex, female (n, %) | 54 (52.9) | 53 (52.0) | 0.889 |
| Age (years) | 6 (5,8) | 6 (5,8) | 0.456 |
| Height (cm) | 125.5 ± 14.9 | 127.8 ± 15.0 | 0.288 |
| Weight (kg) | 23 (20,34) | 25 (20,34) | 0.227 |
| ASA Physical Status, I/II (n) | 95/7 | 93/9 | 0.602 |
| Baseline hemodynamics | |||
| Heart rate (bpm) | 83 (77,93) | 88 (80,98) | 0.241 |
| Systolic blood pressure (mmHg) | 96 (84,102) | 99 (88,107) | 0.273 |
| Diastolic blood pressure (mmHg) | 45 (38,49) | 45 (39,51) | 0.820 |
| Mean arterial pressure (mmHg) | 71 (62,77) | 65 (58,73) | 0.791 |
| Clinical characteristics | |||
| Anesthesia duration (min) | 35 (30, 40) | 35 (30, 40) | 0.418 |
| Surgical duration (min) | 18 (15, 24) | 20 (15, 25) | 0.558 |
| PACU stay time (min) | 35.3±1.6 | 36.3±1.7 | 0.197 |
| Surgical specifics | |||
| Number of muscles, (n, %) | 0.548 | ||
| 1 muscle | 9 (8.8) | 9 (8.8) | |
| 2 muscles | 66 (64.7) | 68 (66.7) | |
| 3 muscles | 22 (21.6) | 16 (15.7) | |
| >3 muscles | 5 (4.9) | 9 (8.8) | |
| Distribution of extraocular muscles (n, %) | 0.431 | ||
| Medial rectus | 94 (41.4) | 86 (37.4) | |
| Lateral rectus | 111 (48.9) | 126 (54.8) | |
| Oblique muscles Two-muscle surgery (n, %) |
22 (9.7) 66 (64.7) |
18 (7.8) 68 (66.7) |
0.768 |
Notes: Data are presented as mean ± standard deviation (SD), median (Q1, Q3), or number (%), as appropriate.
Abbreviations: ASA, American Society of Anesthesiologists; PACU, post-anesthesia care unit.
The primary and secondary outcomes are summarized in Table 2. The overall incidence of OCR was significantly lower in the esketamine group (38.2%, 39/102) compared to the control group (70.6%, 72/102) (P < 0.05). No statistically significant difference was observed in the incidence of severe OCR (esketamine group: 2.9% vs control group:8.8%)(P =0.074). For both groups, the highest incidence of OCR occurred during Stage II (extraocular muscle dissection) compared to Stage I (conjunctival incision) and Stage III (sustained extraocular muscle traction) (all P < 0.05). Notably, no OCR occurred during Stage I in either group (P > 0.05). The incidence of surgical pauses due to OCR was significantly lower in the esketamine group (5.9%, 6/102) than in the control group (17.6%, 18/102) (P < 0.05). Atropine use for OCR, postoperative nausea and vomiting, and postoperative agitation showed no significant differences between groups (all P > 0.05). Heart rates in the esketamine group were significantly higher than in the control group during both Stage I (P < 0.001) and Stage II (P < 0.001). No statistically significant difference in heart rate was observed between the two groups during Stage III (P > 0.05).
Table 2.
Primary and Secondary Outcomes
| Esketamine Group (n=102) | Control Group (n=102) | P-value | |
|---|---|---|---|
| Primary outcome | |||
| Overall OCR incidence (n, %) | 39 (38.2) | 72 (70.6) | <0.001 |
| Secondary outcomes | |||
| Severe OCR incidence (n, %) | 3 (2.9) | 9 (8.8) | 0.074 |
| Phase I OCR incidence (n, %) | 0 (0) | 0 (0) | 1.000 |
| Phase II OCR incidence (n, %)) | 38 (37.3) | 72 (70.6) | <0.001 |
| Phase III OCR incidence (n, %) | 1 (1.0) | 7 (6.9) | 0.071 |
| Phase I heart rate (bpm) Phase II heart rate (bpm) Phase III heart rate (bpm) |
94 (87,102) 86 (74,97) 93 (83,101) |
87 (81,100) 77 (65,90) 90 (82,104) |
<0.001 <0.001 0.523 |
| Atropine administration (n, %) | 2 (2.0) | 8 (7.8) | 0.052 |
| Temporary suspension of surgery (n, %) | 6 (5.9) | 18 (17.6) | 0.009 |
| Postoperative nausea and vomiting (n, %) | 0 (0) | 0 (0) | 1.000 |
| Postoperative agitation (n, %) | 7 (6.9) | 5 (4.5) | 0.052 |
Notes: Data are presented as median (Q1, Q3), or number (%), as appropriate.
Abbreviation: OCR, oculocardiac reflex.
A sub-analysis (esketamine: n=66; control: n=68) on patients undergoing surgery on two extraocular muscles showed that the OCR incidence for both the first and second operated extraocular muscles was significantly lower in the esketamine group compared to the control group (both P < 0.05; Figure 1).
Figure 1.
OCR incidence by order of extraocular muscle operation. Incidence of OCR (%) for the first- and second-operated extraocular muscles in the Esketamine and Control groups. Within-group comparisons between first and second muscles were not statistically significant.
Figure 2 illustrated oculocardiac reflex (OCR) incidence across different extraocular muscle types. In both groups, OCR incidence was markedly higher in medial rectus and oblique muscles compared to lateral rectus muscles, with oblique muscles showing the highest incidence overall (all P < 0.001). Specifically, in the esketamine group, the incidence were 14.4% (16/111) for the lateral rectus, 31.9% (30/94) for the medial rectus, and 54.5% (12/22) for the oblique muscles. In the control group, the incidences were 33.3% (42/126) for the lateral rectus, 54.7% (47/86) for the medial rectus, and 72.2% (13/18) for the oblique muscles. The esketamine group demonstrated a significantly lower OCR incidence across all muscle types compared to the control group (all P < 0.05).
Figure 2.
OCR incidence across different extraocular muscle types. OCR incidence was higher in medial rectus and oblique muscles than in lateral rectus muscles, with oblique muscles showing the highest incidence (all P < 0.001). The esketamine group had significantly lower OCR incidence than the control group for all muscles (all P < 0.05).
Discussion
In this randomized, double-blind, placebo-controlled trial, low-dose esketamine (0.2 mg/kg) in the context of total intravenous anesthesia (TIVA) significantly reduced the overall incidence of oculocardiac reflex (OCR) in children undergoing strabismus surgery with laryngeal mask airway anesthesia. This finding addresses a critical challenge in pediatric ophthalmic anesthesia by enhancing intraoperative cardiac stability without increasing severe OCR or key postoperative adverse events.
Previous studies have evaluated several strategies to reduce OCR during pediatric strabismus surgery, including anticholinergic premedication, modification of anesthetic technique, and use of ketamine. While prophylactic atropine or glycopyrrolate can decrease the incidence or severity of OCR, they often lead to inconsistent results side effects like tachycardia, which limits their routine use in children.20 Adjustments in anesthetic regents or increasing the depth of anesthesia have also explored, but these approaches often result in delayed recovery an increased respiratory risks, making them less suitable for day-case surgery.7,21–25 Although ketamine has been shown to decrease the incidence of OCR,22,26 earlier trials were often limited by small sample sizes and higher doses that could cause psychomimetic effects and slow postoperative emergence. In our study, a low dose of esketamine within a TIVA protocol significantly reduced the overall OCR incidence from 70.6% in the control group to 38.2% in the esketamine group. This reduction is clinically important because of the unique physiological characteristics of children. Unlike adults, children have a less compliant myocardium and a relatively fixed stroke volume, making their cardiac output almost entirely dependent on heart rate. Therefore, a sudden drop in heart rate caused by OCR is not just a minor vital sign change, but a direct threat to systemic perfusion and oxygen delivery.9,27 By effectively lowering the incidence of OCR without prolonging recovery or increasing agitation, esketamine provides a safer hemodynamic profile for children undergoing ambulatory surgery.
Our results showed that heart rates in the esketamine group were significantly higher than those in the control group during Stage I and Stage II. This is consistent with the sympathomimetic properties of esketamine, which enhances endogenous catecholamines release and maintains a more robust hemodynamic baseline.28 This higher baseline likely provides a physiological buffer that prevents the heart rate from dropping below the diagnostic threshold for OCR during initial surgical maneuvers. Interestingly, both groups experienced the highest incidence of OCR during Stage II rather than Stage III (static sustained traction). This finding aligns with observations by Kim et al29 and may be explained by the “fatigue response” of OCR. As muscle manipulation continues, the depletion of cholinergic neurotransmitters may weaken the reflex, leading to a lower incidence during the later traction phase. Meanwhile, from our anesthesia-recording perspective, Stage II served as a broad active mobilization phase encompassing the initial hooking and dynamic maneuvers, which likely provide a more potent stimulus than the subsequent static traction. This categorization of surgical stages may explain the differences between our findings and historical data,30 which often define traction as a single, all-encompassing event. Furthermore, while the incidence of severe OCR was lower in the esketamine group (2.9% vs 8.8%), the difference did not reach statistical significance. This lack of significance may be due to our sample size, which was powered to detect differences in the overall incidence of OCR rather than severe episodes. This suggests that esketamine functions primarily as a prophylactic agent by elevating the physiological threshold for the reflex, rather than as a therapeutic intervention to reverse intense parasympathetic activation. Consequently, while esketamine improves baseline stability, conventional maneuvers—such as pausing surgical stimulation or administering atropine—remain essential for managing severe bradycardia.
Analysis of two-muscle procedures showed no significant difference in OCR incidence between the first and second muscles operated on. This suggests that the surgical sequence did not modulate the reflex, a finding that contrasts with retrospective data from Ha et al, proposing a counter-regulatory attenuation effect. However, our results align with evidence from Stump et al,31 which demonstrated that OCR remains stable and reproducible across sequential muscle stimulations. The absence of a sequence effect in our cohort likely reflects the standardized TIVA protocol and prospective design, which ensured consistent anesthetic depth and minimized the autonomic fluctuations.7,21
Consistent with previous reports,9,32,33 we observed a higher OCR incidence in the medial rectus and oblique muscles compared to the lateral rectus, with the oblique muscles carrying the highest risk. This susceptibility likely relates to anatomical location and the required traction force. The medial rectus is relatively superficial and appears more prone to eliciting OCR during direct traction, whereas the deeper oblique muscles often require greater and multidirectional traction for adequate surgical exposure.34 Given that OCR incidence is proportional to the magnitude of traction applied, the intense, multi-directional pull necessitated by the oblique muscles’ anatomy likely enhances the activation of the reflex arc.8,34 These anatomical factors identify the oblique and medial rectus as critical risk factors, necessitating heightened vigilance during their manipulation.
In our study, we chose a propofol-remifentanil TIVA regimen to optimize perioperative safety and recovery quality. This approach avoids the risk of malignant hyperthermia associated with volatile agents35 and minimizes the emergence agitation frequently triggered by sevoflurane in children.36 Furthermore, propofol-based anesthesia is well-documented for improving emergence quality,37 while remifentanil provides potent analgesia without delaying discharge due to its rapid metabolism.38
This study has several limitations. First, the intensity and duration of extraocular muscle traction were not strictly standardized. Although all surgeries followed a uniform protocol, individual variations in surgical technique may have influenced the occurrence of OCR. Future studies should incorporate mechanical tensiometers to quantify the magnitude of extraocular muscle traction. Furthermore, active collaboration with strabismus surgeons as co-investigators would ensure a more nuanced standardization of surgical maneuvers, such as differentiating between dynamic engagement and static tension. Second, we evaluated only a single sub-anesthetic dose of esketamine (0.2 mg/kg); therefore, the optimal dose-response relationship for OCR prevention remains to be determined. Finally, as a single-center study, the generalizability of our findings should be further validated. Larger, multi-center trials are warranted to confirm these results and explore a broader range of esketamine dosages. Third, our study focused on the categorical incidence of OCR rather than the absolute heart rate values, which limits the quantitative assessment of the reflex’s depth.
Conclusion
In conclusion, a single low dose of esketamine (0.2 mg/kg) significantly reduces the incidence of the oculocardiac reflex in children undergoing day-case strabismus surgery under total intravenous anesthesia. This regimen enhances intraoperative hemodynamic stability without delaying recovery or increasing the risk of postoperative agitation. Our findings suggest that low-dose esketamine is a safe and effective pharmacological strategy for improving perioperative care in pediatric ophthalmic anesthesia.
Acknowledgments
The authors thank all the staffs at the Department of Operation Room of Beijing Tongren Hospital, Capital Medical University, Beijing, China, for their help in this study.
Funding Statement
This work was supported by the Beijing Hospital Authority’s Ascent Plan (No. DFL20220203).
Data Sharing Statement
The raw data supporting the conclusions of this article will be available by the authors without undue reservation. After the article is published, readers can contact the corresponding author to obtain data by email.
Disclosure
The authors report no conflicts of interest in this work.
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