Emergence delirium (ED) is defined in pediatric anesthesia as reduced awareness or disorientation to their surroundings and perceptual disturbances, including hypersensitivity to stimuli and hyperactive motor behavior during the period of anesthesia.
[ 1 ] Several adverse events have been associated with ED and expose patients to life-threatening situations, including falls that may cause injury, disruption of surgical sites, and detachment of medical equipment. [ 2 ]
Preoperative anxiety is one of the risk factors for ED.
[ 1 , 3 , 4 ] Identifying risk factors for preoperative anxiety is essential since the routine use of pharmacologic and behavioral interventions has its advantages and disadvantages. Therefore, predicting children at risk for developing extreme anxiety and distress before surgery may help guide optimization of the limited resource. One of the methods to prevent and identify the occurrence of ED is by assessing the child’s behavior before surgery or anesthesia.
There are several instruments to assess the child’s behavior before undertaking general anesthesia. Over the past decade, the modified Yale preoperative anxiety scale (mYPAS) has become the instrument of choice for assessing preoperative anxiety. This scale determines a child’s level of anxiety by evaluating a range of behaviors ranging from calm to very agitated. The mYPAS scale is best to use before induction of anesthesia.
[ 5-8 ] A newer and simpler measuring tool, pediatric anesthesia behavior (PAB), was developed by Beringer et al. [ 9 ] This score relies on observations of children undergoing anesthesia induction. It categorizes children based on their behavior before induction into three groups: happy, sad, and angry. A strong correlation was found between the PAB and mYPAS and the PAB with the PAED score. The PAB score has also been identified as a predictor for ED in one study. [ 3 ] However, no study has assessed the correlation between these anxiety scores (PAB and mYPAS) with postoperative ED in children. Therefore, this study aimed to evaluate the impact of preoperative anxiety on the occurrence of ED and the degree of correlation between these two anxiety scores to postoperative ED. S
ubjects and M ethods
The study was conducted after approval from the institutional research ethics committee (registry number KE/FK/0349/EC/2020 dated on 30 March 2020). The study complies with the Helsinki Declaration 2013. All legal guardians of the subjects involved in this study provided written informed consent before inclusion.
We assessed pediatric patients between the ages of 2 and 12 years with American Society of Anesthesiology (ASA) physical status I and II, who were scheduled for elective surgery under general anesthesia between July and September 2020 in our hospital. A minimum sample size of as many as 99 patients was based on the following assumptions: (1) expected value of the (Cox-Snell) R-squared the model: 0.5, (2) number of candidate predictor parameters: 8 (mYPAS: 5, PAB:3), (3) level of shrinkage desired at validation: 0.9, (4) overall outcome proportion (for a prognostic model) or overall prevalence: 20%, (5) C-statistic reported in an existing prediction model study: 0.900.
[ 10 ]
Written informed consent was sought from the parents. Patients diagnosed with mental retardation, history of antipsychotic medication, psychotic disorders, central nervous system disorders, and postoperative continuous opioid medication were excluded from the study. The drop-out criteria were: patients with unplanned admission to pediatric intensive care unit (PICU), patients’ family withdrawal from the study, or patients who had cardiorespiratory emergency events before the complete data could be retrieved.
Patients’ characteristics, including age, gender, body mass index (BMI), ASA physical status, premedication drugs, intraoperative data (type of induction, maintenance of anesthesia, type of surgery), and postoperative analgesics, were recorded.
All children were scored with PAB and mYPAS during arrival in the induction room. No children were accompanied by their parents when the PAB and mYPAS scores were calculated because the presence of their parents may interfere with the measurement.
[ 11 ] We designed a comfortable, stress-free environment to minimize the anxiety of the children, such as speaking with the children or letting the child hold their favorite toy. The PAB score rates children’s status as 1–3: “1” = happy, “2” = sad, and “3” = angry. [ 9 ] The mYPAS consists of 27 items divided into five categories: activity, vocalizations, emotional expressivity, state of arousal, and use of parent; an mYPAS score >30 was considered anxiety. [ 5 , 8 ] The items and scoring of mYPAS were described elsewhere. [ 8 ] The incidence of ED was assessed 10 minutes after the children arrived at the post-anesthetic care unit (PACU) or recovery room (RR) using the pediatric anesthesia emergence delirium (PAED) scale. [ 2 ] ED occurrence was defined as a PAED score of ≥12 with “no eye contact” and “no awareness of surroundings” symptoms. [ 10 ]
Two investigators (senior anesthesiologists) observed all children. Inter-observer reliability was analyzed using the interclass correlation coefficient (ICC) test for numerical data and the Kappa test for categorical data. Both instruments were evaluated for ease of use through three aspects: simple sentences, short time of application, and easy assessment of the patient’s condition.
All data were analyzed using IBM Statistical Package for Social Sciences (SPSS) (version 25.0 SPSS Inc., Chicago, Illinois). The demographic data, premedication, anesthesia induction, anesthesia maintenance, postoperative analgesia, and the type of surgery were calculated using the chi-square test.
P-value <0.05 was considered significant. We measured discrimination by calculating the area under the curve (AUC) of the model’s receiver operating characteristic (ROC) curve. Curve analyses were performed to determine a cut-off value for high-risk patients who would experience ED after general anesthesia. The optimal cut-off point was identified using the Youden index J (sensitivity + specificity − 1). From the cut-off point, we calculated the odds ratio of developing ED. R
One hundred and four patients were enrolled in this study. However, four subjects dropped out because of admission to the PICU due to the deterioration of their condition [
Figure 1]. A total of 100 patients were included and analyzed. The mean age of patients was 6.6 ± 3.4 years, mean BMI was 17.1 ± 4.1 [ Table 1]. Most subjects had midazolam as premedication (74%), sevoflurane for induction (60.6%), sevoflurane as inhalation agent for maintenance of anesthesia (55%) [ Table 2], and underwent eye surgery (20%) [ Table 1]. Paracetamol was the most widely used postoperative analgesia (84%) [ Table 2]. Figure 1::
The sample selectionHundred patients were analyzed after four patients dropped out due to the deterioration of condition (admitted to PICU)
Patients’ related variables that may influence emergence delirium
Pharmacologic variables that may influence emergence delirium
The inter-observer measurement analysis found that mYPAS was in almost perfect agreement with an ICC value of 0.83 (>0.80), whereas PAB was acceptable with a kappa value = 0.62 (>0.60). The inter-observer measurement analysis for delirium assessment (PAED score) was also good, with a kappa value = 0.74 (>0.70). These results suggested minimal inter-observer bias in assessing mYPAS, PAB, and the incidence of ED.
The PAB was easier to use than mYPAS (
P < 0.05) based on 99 observations; it is easier in terms of sentences in 65 observations (65.7%, P < 0.001), faster completion in 66 observations (66.7%, P < 0.001), and easier application in 66 observations (66.7%, P < 0.001).
ED developed in 33% of patients. In patients, who developed ED, the majority were male (60.6%) patients, were in ASA II (57.6%) [
Table 1], received midazolam premedication (74%), sevoflurane as induction (55%), sevoflurane as maintenance of anesthesia, and paracetamol for postoperative analgesia (81.8%), but the variations were not statistically significant. Post hoc analysis demonstrated the type of induction using a combination of inhalational agent (sevoflurane) and intravenous agent instigated significantly lower occurrence of ED ( P = 0.016) [ Table 2]. The ED group had a significantly higher mYPAS score, but there were no statistical differences in the ED occurrence between the PAB score of 2 (sad) and 3 (angry) [ Table 3]. Table 3::
mYPAS and PAB score that may influence emergence delirium
The mYPAS exhibited a remarkable discriminatory performance with an AUC of 0.76 (0.65–0.86) [
Figure 2]. The optimal mYPAS score cut-off point for correlation to ED, calculated with the Youden Index, was 29 (sensitivity and specificity: 78.8% and 73.1%, respectively). Multivariable analysis demonstrated that mYPAS ≥29 increased the risk for ED by 11-fold (odds ratio [OR] 11.7; P < 0.001), whereas the type of induction of anesthesia was not an influencing factor [ Table 4]. The PAB score could not predict the occurrence of ED. Figure 2::
ROC curve of mYPAS for EDThe discrimination of the mYPAS is good with AUC (95% CI) 0.76 (0.65–0.86) for the prediction of the emergence delirium (ED)
Multivariable logistic regression for the independent variable
This study confirms that preoperative anxiety is the risk factor for ED and the patients with mYPAS ≥29 were 11.7 times more prone to ED than those with a lower score. This study proved that mYPAS is a useful tool to identify the risk of ED as reported in Weldon
et al. [ 12 ] The ability of the PAB score to identify the risk of ED was not established in this study.
In this study, ED was reported in 33 patients (33%), which was lower than that in the previous study where the incidence was 55% from 88 participants.
[ 1 ] Other report described the incidence of ED bas between 25% and 80%. [ 13 , 14 ] The mean age of participants who experienced ED was 5.78 ± 3.37 years and non-ED was 6.89 ± 3.5 years (not statistically significant). Kain et al. [ 14 ] reported that children aged 1-5 years had more preoperative anxiety and were associated with more postoperative behavior maladaptation.
Midazolam was the premedication in this study, but the incidence of ED did not vary between the ones who were premedicated and not. Midazolam has a controversial effect on ED incidence and this study has not presented a consistent preventive role.
[ 14 ]
There were differences in the incidence of ED between patients induced with an inhalational agent (sevoflurane), intravenous, and combination from the post-hoc analysis. However, the difference became insignificant after the multivariable analysis was conducted. Maintenance of anesthesia did not instigate the occurrence of ED in this study. Rashad and Soud
[ 15 ] assessed children undergoing elective hypospadias surgery who had caudal block anesthesia and found that the incidence of ED escalated from 20% at five minutes after RR admission to 40% at 30 minutes. These findings were in contrast to Cole et al. [ 16 ] who reported brief behavioral changes in the RR with a progressive reduction through time. The distinct assessment scales for the ED and use of additional drugs might account for the diverse ED incidence between studies.
Numerous preoperative variables, including age, ethnicity, socio-economic background, temperament, previous hospitalization, and anxiety levels, were associated with ED in other studies. Moreover, duration and type of procedure might be considered prominent factors for ED.
[ 1 , 3 , 4 , 17 ] but they were not proven in this study.
Patients with ED had notably higher mYPAS and fewer “happy” patients (PAB score: 1). The association between preoperative anxiety with emergence agitation has been discussed.
[ 16 , 17 ] However, conflicting results have been reported. [ 18 , 19 ] Children who showed signs of preoperative anxiety are at a greater risk of delirium and other maladaptive changes after surgery. [ 16 ] Further studies showed that the temperament of children who were more emotional, more impulsive, and less able to adapt socially or environment are risk factors for ED. [ 20 ]
The mYPAS score had good discrimination for ED detection with an AUC of 0.76 (0.65–0.86) [
Figure 2]. The optimal cut-off point of mYPAS for identification of the ED is 29 [ Table 3]. Multivariable analysis demonstrated that mYPAS 29 had an OR of 11.7, meaning an increased risk by 11-fold compared to patients with a lower score. Patients with ED have a higher mYPAS score ( P < 0.001), and there was a different proportion of ED in each score of PAB ( P < 0.001) [ Table 4].
et al. [ 17 ] found that every increment of 10 points in the child’s state anxiety score (mYPAS) would increase the odds of having marked symptoms of ED by 10%. Children with marked emergence status had an odds ratio of 1.43 compared to children with no signs of ED on having new-onset postoperative maladaptive behavior. [ 16 ] The weakness of the mYPAS is that it is impracticable in busy operating room settings.
Observers’ subjectivity may affect the performance of the PAB score. We also found that the PAB score had poorer reliability than mYPAS for anxiety assessment. In contrast with this study, Beringer
et al. [ 9 ] reported that PAB scores identified anxiety in children during induction of anesthesia and had a significant association with the mYPAS and the induction compliance checklist score, with a Spearman’s rank correlation coefficient of 0.672 ( P < 0.001) and 0.765 ( P < 0.001), respectively. The PAB score was slightly correlated with the PAED score ( P = 0.031) and the post-hospitalization behavior questionnaire ( P = 0.034). A higher score of PAB was correlated with increased ED in PACU and the development of post-hospitalization behavior changes.
Currently, there is no risk scoring to predict ED events in pediatric patients. A systematic review by Petre
et al. [ 21 ] reported only one study detailing the development and validation of a risk score on ED and showed good discrimination for the development and validation phase with AUC of 0.84 (95% confidence interval [CI]: 0.74–0.94) and 0.81 (95% CI: 0.72–0.89), respectively. [ 3 , 21 ] The PAB score was included as a variable in the emergence agitation risk scale (EARS) to predict ED in pediatrics. The score was “4” for screaming/shouting (angry) and “2” for tearful and withdrawal (sad) but compliant with induction. The EARS score ranged from 1 to 23, with the cut-off point for ED being 11. [ 3 ]
This study possessed some limitations: possible confounding variables such as surgical procedure, surgical technique, premedication, anesthetic induction and maintenance, and postoperative pain management were not controlled. We also did not evaluate specific factors that may potentially be independent variables for ED, such as patients’ and parents’ personalities, as well as the interaction between patient, parent, and healthcare provider.
[ 4 ] C
Preoperative anxiety is associated with ED. The mYPAS has a better correlation with postoperative ED than the PAB score.
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Conflicts of interest
There are no conflicts of interest.
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