Effect of Airway Devices on Emergence Delirium in Pediatric Strabismus Surgery

Introduction

Emergence delirium (ED) was first reported in the 1960s [1] as a disturbance in a child’s awareness, environmental disorientation, cognitive impairment, and hypersensitivity to stimuli that occur immediately following general anesthesia. Emergence agitation includes ED and other factors [2]. ED is defined as “a disturbance in a child’s awareness or attention to his/her environment with disorientation and perceptual alterations including hypersensitivity to stimuli and hyperactive motor behavior in the immediate post anesthesia period” [3]. Emergence agitation and ED can lead to falls or self-injury in patients, making it a critical concern for parents and medical staff [4].

Several factors contribute to the increased incidence of ED, including age, male sex, type of surgery, emergency operation, use of inhalational anesthetics with low blood-gas partition coefficients, long duration of surgery, anticholinergics, premedication with benzodiazepines, voiding urgency, postoperative pain, and the presence of invasive devices [5]. Strabismus, one of the most common ocular conditions in children, is frequently associated with ED following strabismus surgery [6]. In most cases, ED resolves within 30 min without treatment; however, severe cases can require pharmacological intervention [7].

Various tools are available for determining the presence of ED, with the pediatric anesthesia emergence delirium (PAED) scale being the most widely used. This scale correlates directly with the severity of ED [8].

In previous studies, using a laryngeal mask airway (LMA) and deep removal decreased postoperative ED, compared with using an endotracheal tube (ETT) and awake extubation after pediatric sevoflurane anesthesia [9]. However, no reports have compared using LMA and ETT when awake. We hypothesized that the LMA would allow for less invasive tracheal intubation than the ETT, thus reducing postoperative pain. Therefore, this study aimed to compare the effects of an ETT and a LMA on ED in 73 children undergoing surgery for strabismus.

Material and Methods

ETHICAL APPROVAL:

The study received approval from the Institutional Review Board and was registered in the Clinical Research Trials Registry Platform (registration number: KCT0008293). Patients and their guardians were given a detailed explanation of the entire study, including possible adverse effects, the types of information obtained, the storage method and period of personal information, and the deletion of information. They were also told that they could stop the study at any time they wanted. Written informed consent was obtained from children who understood the study details and their parents.

STUDY DESIGN:

This prospective, randomized, double-blinded, controlled study was conducted at the Department of Anesthesia and Pain Medicine, Pusan National University Hospital, Korea, for 6 months beginning in January 2021.

PARTICIPANTS:

Seventy-three children aged 3 to 9 years with American Society of Anesthesiology physical status I, who were scheduled for strabismus surgery, were enrolled in this study. Patients with sensitivity to ketorolac or fentanyl, anxiety disorders, upper respiratory infections within 6 weeks, neurological impairments, developmental retardation, psychiatric disorders, cardiovascular diseases, renal diseases, or genetic disorders were excluded.

PARTICIPANTS GROUPING:

Participants were randomly assigned to 1 of 2 groups using computer-generated random numbers. Group L received an intubation using LMA, while group E received an intubation using ETT.

INTERVENTION:

All cases were 1-day surgeries. A 24-gauge catheter was inserted into a peripheral vein in the morning, and all surgeries were performed in the morning. No premedication was administered, and the children were accompanied by their parents before falling asleep. Standard hemodynamic monitoring systems were applied upon the patients’ arrival in the operating room. Anesthesia induction involved administering 2.5 mg/kg propofol and 0.5 mg/kg rocuronium, followed by maintenance with sevoflurane, which was adjusted based on vital signs. After the patients fell asleep, the patients in group L were intubated using LMA (LMA Supreme Airway, Teleflex Medical, Athlone Co, Westmeath, Ireland). The size of LMA depends on the child’s weight: size 1.5 for children weighing 5–10 kg, size 2 for children weighing 10–20 kg, and size 2.5 for children weighing 20–30 kg. After opening the mouth, the gel-covered LMA was gently pushed along the tongue with the second and third fingers. At this time, the LMA was pushed as gently as possible, so that no resistance was felt. The patients in group E were intubated using a laryngoscope and ETT (Shiley oral tracheal tube, Covidien, Mansfield, MA, USA) after opening the mouth as wide as possible. The size of ETT depends on the child’s age, calculated as (age in years/4) +3. After intubation, end-tidal carbon dioxide partial pressure was maintained between 30 and 35 mm Hg. A single anesthesiologist performed all anesthetic procedures. At the end of the surgery, sevoflurane was discontinued, and the patients received 0.5 mg/kg ketorolac, 6 mcg/kg ramosetron, 0.1 mg/kg pyridostigmine, and 0.02 mg/kg glycopyrrolate. After extubation, the children were transferred to the post-anesthesia care unit (PACU), where parents were permitted to stay. If a patient reported severe pain (Face, Legs, Activity, Cry, Consolability [FLACC] scale >4) for more than 15 min, 1 mcg/kg fentanyl was administered. If severe ED (PAED scale >12) persisted for over 20 min, 1 mg/kg propofol was given. Patients remained in the PACU until their Aldrete score exceeded 8.

ASSESSMENT:

The primary endpoint was the incidence of ED upon arrival at the PACU. ED was defined as a PAED scale score exceeding 10 [10]. PAED consists of the following 5 items: (1) the child makes eye contact with the caregiver; (2) the child’s actions are purposeful; (3) the child is aware of his/her surroundings; (4) the child is restless; and (5) the child is inconsolable. Items 1, 2, and 3 are reverse-scored as follows: 4=not at all; 3=just a little; 2=quite a bit; 1=very much; and 0=extremely. Items 4 and 5 are scored as follows: 0=not at all; 1=just a little; 2=quite a bit; 3=very much; and 4=extremely. The scores of each item were summed to obtain a total PAED scale score [8]. The PAED scale score was recorded every 5 min for 30 min.

Secondary endpoints were intubation time required to connect the ventilator after securing the ETT tube or LMA and completing tracheal intubation, vital signs monitored for 5 min after intubation, extubation time from cessation of the inhalation agent to extubation, crying time from the cessation of the inhalation agent to crying, anesthesia and operation times, complications, airway responses after intubation, FLACC scales every 5 min in the PACU, PACU stay duration, and incidence of nausea and vomiting.

The FLACC scale is scored in a range of 0 to 10 points, with 0 representing no pain. The scale has 5 criteria, which are each assigned a score or 0, 1 or 2: (1) face: 0=no expression, 1=occasional grimace or frown, withdrawn, uninterested, 2=frequent to constant quivering chin, clenched jaw; (2) legs: 0=normal position or relaxed, 1=uneasy, restless, tense, 2=kicking, or legs drawn up; (3) activity: 0=lying quietly, normal position, moves easily, 1=squirming, shifting, back and forth, tense, 2=arched, rigid or jerking; (4) cry: 0=no cry, 1=moans or whimpers, 2=crying steadily, screams or sobs; (5) consolability: 0=content, relaxed, 1=reassured by occasional touching, hugging or being talked to, distractible, 2=difficult to console or comfort.

Airway responses after intubation were categorized into 4 grades: (1) no gagging, coughing, or laryngospasm; (2) mild gagging, coughing, or laryngospasm; (3) moderate gagging, coughing, or laryngospasm; and (4) severe gagging, coughing, or laryngospasm. Extubation criteria included open eyes, a grimaced face, an end-tidal sevoflurane concentration <0.2%, oxygen saturation >97%, and adequate tidal volume.

STATISTICAL ANALYSIS:

The sample size was predetermined using a z test in G*Power and selected based on the following parameters: tails=2, effect size d=0.678, α error probability=0.05, power (1-β error probability)=0.8, and allocation ratio N2/N1=1. ED was defined as a PAED score >10, based on a previous study reporting a 67.9% incidence of ED [11]. Assuming a 50% reduction in ED incidence, 36 patients were included in each group.

The Shapiro-Wilk method was used for normality tests. Demographic data, intubation information and complications were analyzed using independent t test, Mann-Whitney U test, and chi-square analysis. The incidence of ED was analyzed using chi-square analysis. PAED and FLACC scales were analyzed using repeated-measures analysis of variance (ANOVA). Spearman correlation analysis was used for finding a correlation between PAED and FLACC scale scores. Continuous data were described as mean±standard deviation or median±interquartile range, and categorical data as numbers (percentages). Statistical significance was set at P<0.05. All statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS) software (version 21.0; IBM Corp, Armonk, NY, USA).

Results

DEMOGRAPHIC DATA:

Seventy-four patients were initially enrolled in this study. One patient discontinued surgery before admission, leaving 73 patients, who were randomized into groups L and E. No significant differences in age, weight, height, Mallampati score, anesthesia time, and operation time were observed between the groups (Table 1).

ANESTHETIC DATA:

Intubation times were 11.11±4.60 s in group E and 6.20±2.05 s in group L (P=0.00). PACU stay duration was shorter in group L than in group E (28.27±11.45 min vs 21.92±8.62 min, P=0.02). No significant differences in airway response, extubation time, crying time, anesthesia-related complications, and administration of drugs were observed between the groups (Table 2).

THE TREND OF PAED SCALE AND FLACC SCORE IN PACU:

Repeated-measures ANOVA revealed significant differences in the PAED scale and FLACC scores between the groups (P =0.016 and 0.041, respectively). The PAED scale score was significantly higher in group E at 0, 5, 10, 20, and 25 min after surgery (P=0.062, 0.029, 0.019, 0.007, and 0.028, respectively; Figure 1A). The FLACC score was also higher in group E at 20, 25, and 30 min after surgery (P=0.016, 0.029, and 0.026, respectively; Figure 1B). Spearman correlation analysis showed a strong positive correlation (values 0.888) between the FLACC and PAED scales; therefore, these 2 scales were found to be highly correlated (P=0.00).

INCIDENCE OF ED:

ED was present if the PAED scale score was ≥10. The chi-square test revealed that the ED frequency at 5, 10, and 15 min after surgery was lower in group L than in group E (P=0.024, 0.008, and 0.025, respectively; Table 3). Spearman correlation analysis showed a weak negative correlation (values=−0.5) between age and the incidence of ED (P=0.00).

Discussion

In our study, intubation time and PACU stay time were shorter in group L than in group E, and there were no differences in awakening time or anesthesia-related complications. PAED and FLACC scales were generally lower in group L than in group E. Postoperative ED can be linked to various factors, including the effects of anesthesia, surgical stress, and preexisting patient vulnerabilities [5]. We tried to unify other factors that could affect ED. We did not use preoperative drugs that could increase preoperative tension, and the presence of parents, securing of preoperative venous access, and anesthesia were the same in both groups. We used propofol for induction and sevoflurane for maintenance in both groups. Young age and postoperative pain increases the incidence of ED. Preschool-aged patients showed higher incidence rates of ED, as the surgery was more complex and invasive, regardless of preoperative anxiety [4]. Furthermore, younger children in this age group tend to experience poorer sleep quality before surgery, which increases the likelihood of ED [12]. In the present study, there was also a negative correlation between age and ED.

ED was initially associated with the medications used during anesthesia. The use of inhalation agents, such as sevoflurane, commonly used in pediatric strabismus surgery, has been associated with ED [13,14]. A study found that after strabismus surgery, propofol reduced the incidence of ED by reducing postoperative pain [15,16]. Dexmedetomidine was as effective in lowering ED as total intravenous anesthesia, even under inhalation anesthesia [17]. Anesthesia induction using a mask without an intravenous route, such as volatile induction and maintenance anesthesia, is known to increase ED regardless of postoperative pain [18]. We speculated that anesthesia induction through a mask, rather than the rapid intravenous induction, may have heightened the child’s preoperative anxiety. Therefore, we chose to induce general anesthesia via a venous route. If a patient experienced severe ED for more than 20 min, we administered propofol, as it alleviates ED without extending PACU stay duration. Of the 73 patients, 6 exhibited PAED symptoms lasting more than 20 min, and we administered small doses of propofol, without any adverse effects.

All patients in this study were allowed to sleep comfortably at home the night preceding surgery before arriving at the hospital. To reduce preoperative anxiety, we provided the children with detailed explanations about the anesthesia process and the operating room during the preoperative visit. Additionally, we allowed the children to bring personal belongings that provided comfort, and ensured 1 parent remained present until the child fell asleep. Furthermore, we ensured that an intravenous line was established before entering the operating room, and an intravenous anesthetic was administered to facilitate rapid sleep onset. Anticholinergic drugs administered preoperatively can also increase ED; therefore, we avoided premedication. Since these drugs are often administered to prevent bradycardia during strabismus surgery, they may have contributed to the incidence of ED [5].

Discomfort due to pain can increase ED after surgery [4,5]. In children, pain can lead to restlessness, which can further exacerbate ED. Therefore, we focused on evaluating pain in the pediatric patients. Several tools, such as the visual analog scale or numeric rating scale, are commonly used to measure patient pain intensity. However, when the degree of pain cannot be directly assessed in children, pain is typically scored based on the observer’s judgment. Somaini et al suggested that indicators such as no eye contact and no awareness of the surroundings signaled ED, while abnormal facial expressions, crying, and inconsolability indicated acute pain [19]. Several validated tools are used to measure pain in children, including the Children’s Hospital of Eastern Ontario Pain Scale, Wong-Baker FACES Pain Rating Scale, and FLACC scale, which are known to be more effective than other methods [20]. Notably, the FLACC scale includes an item that evaluates consolability [21]. Total intravenous anesthesia using propofol and remifentanil has been shown to reduce the incidence of ED and postoperative pain [15]. Pain is a well-known factor that increases postoperative delirium, and opioids such as remifentanil, fentanyl, hydromorphone, nalbuphine, and remimazolam have been reported to mitigate ED [22–25]. These opioids also reduced postoperative pain scores, except remimazolam. Additionally, meperidine, paracetamol, propofol, ketamine, fentanyl, and preoperative analgesia were effective in reducing the incidence of ED by managing postoperative pain [26]. In this study, the FLACC scale was consistent with the severity of pain, and pain scores were generally higher in group E. Sore throat and sympathetic nerve stimulation resulting from invasive intubation are presumed to increase ED. Furthermore, our results showed a strong positive correlation between the FLACC and PAED scores.

In a previous study, Lee et al found that LMA and deep removal decreased postoperative ED, compared with ETT and awake extubation. In their study, they could not clearly determine whether it was LMA or deep removal that reduced ED, because they used different extubation timing as well as different instruments for tracheal intubation [9]. However, in our experiment, we showed that LMA reduced ED, by unifying the awakening timing. LMA is used as a method to maintain the open airway without passing through the vocal cord, while ETT passes through the vocal cords (Figure 2). LMA showed less time and fewer number of attempts than did ETT in neonates [27]. The experiments demonstrated that using LMA provided no advantage over the group that did not receive muscle relaxants; however, we administered a small dose of rocuronium for the surgeon’s convenience during strabismus surgery [28]. General anesthesia using LMA was found to reduce airway-related complications and hospital stays, compared with the ETT group [29]. The success rate of one-time implantation in the LMA group was significantly higher than that in the ETT group; however, there were no significant differences in bronchospasm, sore throat, mucosal injury, nausea and vomiting, and reflux aspiration [30]. In our study, the time required for tracheal intubation was shorter in group L, and there was no significant difference in adverse effects. A meta-analysis showed that LMA reduced the incidence of cough, postoperative sore throat, and vomiting, but had no advantage in the incidence of bronchospasm and laryngospasm [31]. In our study, airway-related complications did not differ significantly between the 2 groups, and no difference in the failure rates was observed. This might be because all tracheal intubations were performed by an experienced anesthesiologist, and muscle relaxants were used in all patients. While Farazmehr et al found that LMA placement sometimes induced sore throats [32], their study did not compare LMA with ETT. In our study, when judged through FLACC scale, it could be inferred that group L had less pain than did group E. Kang et al also found that the highest pain scores at 1 h postoperatively and on postoperative day 1 were lower in the LMA group than in the ETT group after laparoscopic cholecystectomy [33].

Before the present study, our medical institution primarily used ETT for general anesthesia during strabismus surgery. The reason was that the surgery involves the eye, and the narrow surgical area could result in the surgeon or assistant inadvertently pressing or touching the LMA with their hands during surgery, causing leaks. However, based on the findings of this study, the trend in our hospital has changed, as we have learned that less invasive tracheal intubation methods, such as LMA, can reduce PAED by decreasing pain in children after surgery. Additionally, surgical assistants have gradually learned how to perform the procedure without touching the LMA.

There are some limitations to our study. The above experiment included only patients with a Mallampati score of 1 or 2; therefore, the results can differ in difficult intubation cases. Also, since the intubation was performed by a very skilled and well-trained anesthesiologist, there is concern that the intubation time could vary from person to person. The learning curves of LMA and ETT can be different, so there can be errors in the interpretation of the results of intubation time and attempt.

Conclusions

LMA is thought to be a more useful intubation method than ETT in pediatric strabismus surgery, as it reduces postoperative pain and PACU stay.