Risk Factors for Emergence Agitation in the Postanesthesia Care Unit: A Propensity Score-Matched Analysis.

Sevoflurane is a volatile anesthetic agent with low pungency, non-irritating odor, and low blood/gas partition coefficient that makes it an attractive alternative to halothane. However, a high incidence of emergence agitation (EA) has been reported in pediatric patients after sevoflurane anesthesia. The underlying mechanism of sevoflurane-induced EA remains unclear. Rapid recovery of consciousness (emergence) from sevoflurane anesthesia has been proposed as one possible mechanism. We, therefore, hypothesized that sedatives such as midazolam may counteract sevoflurane's rapid emergence and thus reduce the incidence and the severity of sevoflurane-induced EA. A prospective, controlled, single-blinded study was carried out in 88 ASA class I or II pediatric patients scheduled for elective outpatient surgery. Patients were assigned to receive either midazolam (oral midazolam, 0.2 mg/kg as anesthetic premedication) or saline (oral normal saline as premedication) before the conduct of anesthesia. When separation from parents was due its process was watched and evaluated. Induction of anesthesia and maintenance of anesthesia were uniform in both groups. Induction of anesthesia was made possible with 8% sevoflurane and N2O in 50% O2. Intubation was performed straight without the aid of muscle relaxant and the ventilator was set to maintain normocapnia. Anesthesia was maintained with 3% sevoflurane and N2O in 50% O2 until the surgery was over. All matters of relevant time periods were recorded (induction, surgical procedure, extubation and transportation). In the post-anesthesia care unit (PACU), adverse events, the incidence and the severity of EA, analgesic requirement, duration of PACU stay, and parental as well as PACU nurses' satisfaction were evaluated. A significant lower incidence and less severity of EA were noted in patients premedicated with midazolam. Less postoperaive analgesia was required in patients who had received midazolam. Although midazolam-premedicated patients remained sedated after sevoflurane anesthesia, the duration of the PACU stay was not significantly different from that of saline-treated patients. Both parents and PACU nurses were more satisfied with midazolam as premedication. No solid evidence showed that there was close correlation between the process of separation from parents and the occurrence of EA. Premedication with oral midazolam is safe, convenient and effective in decreasing the occurrence of sevoflurane-induced EA. It does not delay discharge from PACU and is suitable for outpatient surgery.

Emergence agitation after sevoflurane anaesthesia in children

Taking care of surgical with temporary mental dysfunction is one of the biggest challenges for the anesthesiologist in the recovery room. This temporary mental dysfunction presents with two different faces: one is emergence agitation (EA) in pediatric and the other is delirium in geriatric patients. EA is the clinical condition of pediatric who are suffering from temporary mental dysfunction after general anesthesia. It is a transient dysfunction of the brain. However, it is essential to differentiate EA from the similar condition of agitation due to insufficient pain control in the recovery room. The clinical presentations of EA and agitation due to pain are so similar in presentation that differentiation of the two conditions is very difficult in pediatric patients. Furthermore, the sedation caused by anesthetic drugs is another contributing factor to the onset and degree of EA. Sedation resulting from anesthetic drugs can mask or delay the onset of EA. If we wish to study the effect of a test drug on EA in pediatric in the recovery room, it is necessary to prove that there are no differences in the degree of agitation resulting from insufficient pain control and sedation from residual anesthetics between the control and experimental group. If this is not done, it would be very difficult to interpret the results in relation to EA in the experimental group. Particularly, if the test drug has significant greater sedative effect compared to the control drug, it would be impossible to calculate how much the test drug had contributed to the onset and degree of EA, reflected in the EA scores, in the children. In the case of agitation due to incomplete pain control, regional anesthesia or use of the same amount of pain-killer would provide proof of the same degree of pain in the pediatric in the recovery room. In addition, the sedation score would be a better parameter to use to demonstrate the same degree of sedation in the two groups. A recent paper studied EA in pediatric in the recovery room. The title of the article is A comparison of postoperative emergence agitation between sevoflurane and thiopental anesthesia induction in pediatric patients (Korean J Anesthesiol 2015 Aug; 68(4): 373-378). In terms of the two factors mentioned above, some questions arise regarding the results of this paper. Although the author discussed his rationale for using the different EA scales, a four-point agitation scale at 5 minutes and the Pediatric Anesthesia Emergence Delirium scale at 20 minutes, it would be impossible for the author to rule out the possibility of overestimation of the number of children receiving low scores for EA in the thiopental group. That is to say, the sedation from the residual effect of the thiopental was regarded as no EA at 5 minutes in the experimental group in the recovery room. If sedation scores were measured in both groups, the effect of sedation would be ruled out from the EA. Additionally, the results would be improved if the data on the pain-killer used in the recovery room was mentioned in the paper. In conclusion, an elaborate study design to rule out the effects of sedation and pain on EA in the recovery room would assist in the generation of improved results in the paper.

To evaluate risk factors associated with emergence agitation (EA) in pediatrics after general anesthesia. A prospective cohort study was conducted in 268 pediatric patients aged 2-9 years, who received general anesthesia for various operative procedures in our hospital between January 2008 and October 2011. The incidence of EA was assessed. Difficult parental-separation behavior, pharmacologic and non-pharmacologic interventions, and adverse events were also recorded. Univariate and multivariate analysis were used to determine the factors associated with EA. A p-value of less than 0.05 was considered significant. One hundred and sixteen children (43.3%) had EA, with an average duration of 9.1 ± 6.6 minutes. EA associated with adverse events occurred in 35 agitated children (30.2%). From univariate analysis, factors associated with EA were difficult parental-separation behavior, preschool age (2 - 5 years), and general anesthesia with sevoflurane. However, difficult parental-separation behavior, and preschool age were the only factors significantly associated with EA in the multiple Logistic regression analysis with OR = 3.091 (95%CI: 1.688, 5.465, P < 0.01) and OR = 1.965 (95%CI: 1.112, 3.318, P = 0.024), respectively. The present study indicated that the incidence of EA was high in PACU. Preschool children and difficult parental-separation behavior were the predictive factors of emergence agitation.

Sevoflurane is an inhalational anesthetic used widely as a pediatric or outpatient anesthesia due to its excellent hemodynamic stability and low blood solubility, which allows rapid induction and emergence from general anesthesia, as well as control of the depth of anesthesia. However, when sevoflurane is used alone it is associated with a higher incidence of emergence agitation in children. The rapid removal of residual anesthetics due to low blood solubility of sevoflurane has been suggested to cause emergence agitation in some patients [1,2]. In addition, a variety of other explanations have been proposed for the etiology of emergence agitation. These include the lack of a young child's ability to adapt to sudden changes due to an unfamiliar environment after awakening, immature neurological development, anxiety from being separated from their parents, increased pain sensation and sympathetic hyperactivation [2,3]. Emergence agitation is characterized by self-limiting aggressive agitation that develops in the early phase of awakening from anesthesia at the end of surgery. Emergence agitation can be dangerous to patients, particularly to young children. Patients suffering from emergence agitation may harm themselves and dislodge drains or catheters, which affects the results of surgery. They may inflict a bodily injury on their care-givers or cause a paranoiac accident, which makes the management and monitoring of patients at the post anesthesia care unit difficult [4]. There have been many attempts to reduce the incidence of emergence agitation but the etiology and preventive treatments of emergence agitation are still unclear. Some studies have reported that midazolam which acts on its target effect site GABAA, reduces emergence agitation [5,6], and its antagonist, flumazenil reverses this effect [7]. However, the mechanism is still not clear, and it is not known whether sevoflurane and midazolam interact at the GABAA receptor level. Most GABAA receptors consist of two α subunits, two β subunits and a γ subunit. The γ2 subunits of GABAA receptor exist as a long type (γ2L) and a short type (γ2S), generated by alternative splicing of RNA. The most common pattern for GABAA receptor is α1β2γ2 type, which accounts for 43% of all GABAA receptors [8]. This implies that the diversity of the subtype variants and the distribution of GABAA receptors may affect the anesthetics from subject to subject. In this edition of the Korean journal of anesthesiology, Eom et al. [9] postulated that alternative splicing of the γ2 subunit is related to emergence agitation on the basis of characteristics of midazolam, sevoflurane and γ2 subunit. Sevoflurane binds to GABAA receptor, benzodiazepine-like midazolam prevents emergence agitation and also binds to α and γ subunit of GABAA receptor, and alternative splicing of γ2 subunit is different based on the age of the patient. Whole-cell patch clamp to the α1β2γ2L and α1β2γ2S GABAA receptors expressed in human embryonic kidney 293 cells with midazolam and/or sevoflurane was performed. The concentration-response relationships were recorded for midazolam and sevoflurane. They showed that the concentration-response relationships for midazolam and sevoflurane were dose-dependent with no differences between the α1β2γ2L and α1β2γ2S subtypes. It was concluded that the difference in the γ2 subunit cannot explain the emergence agitation of sevoflurane in children in vitro. These finding suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the γ2 subunit and concentration of both drugs. Their effort to reveal the mechanism of emergence agitation induced by sevoflurane anesthesia could be a major step towards studying the basic mechanisms of the anesthetic agent. Further study to reveal the mechanism of emergence agitation is expected.

Eficácia de dexmedetomidina para o surgimento de agitação em lactentes submetidos à palatoplastia: estudo clínico randomizado

Effectiveness of dexmedetomidine for emergence agitation in infants undergoing palatoplasty: a randomized controlled trial

Sevoflurane is widely used in pediatric anesthesia. However, a high incidence of emergence agitation (EA) after general anesthesia with sevoflurane has been reported and pain has been regarded as a significant contributing factor. The objective of this prospective randomized, placebo-controlled trial was to determine whether infraorbital nerve block reduces EA in children undergoing repair of cleft lip after sevoflurane. In this randomized, placebo-controlled trial, we enrolled 110 children (5 months to 6 years of age), who were scheduled for cleft lip surgery, and randomized them to the following two groups: Group S and Group B, where 1.5 ml saline (Group S) or 1.5 ml 0.25% bupivacaine (Group B) were administered in the infraorbital foramen. Emergence behavior was assessed in the postanesthesia care unit using the Pediatric Anesthesia Emergence Delirium (PAED) scale and a 5-point scale described by Cole. Pain was evaluated using the Children and Infants Postoperative Pain Scale (CHIPPS). One-hundred children (n = 50 per group) completed the study. The endtidal concentration of sevoflurane in Group B was lower than that in Group S. The incidence of EA was 16% in Group B and 42% in Group S (P = 0.008). The PAED scale score in Group B (mean [95% CI] 9 [8-12]) was lower than that in Group S (11.5 [9.8-15]). The duration of EA in Group B was shorter than that in Group S. CHIPPS score in postanesthetic care unit were lower in Group B (mean [95% CI] 3 [2-3.3]) compared with that in Group S (5 [4-6]). In children undergoing cleft lip repair surgery, infraorbital nerve block at the beginning of surgery significantly decreased the incidence of EA and the duration of EA, and provided satisfactory postoperative analgesia without delaying the time to extubation with sevoflurane anesthesia.

Objective To determine the risk factors for emergence agitation (EA) during the recovery period after general anesthesia.Methods One thousand and thirty-four patients of both sexes aged 18-89 yr undergoing general anesthesia were divided into EA group and non-EA group.EA occurring during recovery from general anesthesia was assessed by using Riker sedation-agitation scale.Age,sex,complication,education,medical history,ASA physical status,type and duration of anesthesia and operation,volume of blood loss,fluid replacement,urine volume,duration of stay in PACU,number of drainage tubes and so forth were recorded.Multivariate logistic regression was used to analyze the risk factors for the occurrence of EA.Results Thirty-six patients developed EA during recovery from anesthesia.The incidence of EA was 3.5 ％.Logistic regression indicated that high risk operation,premedication with diazepam,induction of anesthesia without midazolom and fluid replacement during operation were the risk factors for EA (P ＜ 0.05).Conclusion High-risk operation,premedication with diazepam,induction of anesthesia without midazolom and fluid replacement during operation are the risk factors for EA during recovery from general anesthesia. Key words: Anesthesia, general; Anesthesia recovery period; DYSPHORIA; Risk factor; Postoperative complication

Emergence agitation (EA), defined as restlessness, disorientation, excitation, and/or inconsolable crying, is a common phenomenon during early recovery from general anesthesia. In this study, we aimed to determine the (1) EA incidence after rhinoplasty operations in adults; (2) the effects of ketamine administered at sub-anesthetic doses just 20min before the end of the surgery in rhinoplasty operations on agitation level, postoperative pain, side effects, and complications; and (3) to determine the risk factors for EA in adults after rhinoplasty. Totally 140 patients scheduled to undergo elective rhinoplasty were enrolled in this prospective study. Patients were equally and randomly divided into two groups: saline group (control group) (n=70) and ketamine group (n=70). Twenty minutes before surgery completion, 1ml saline was administered via the intravenous (i.v.) route to the saline group, while 0.5mg/kg ketamine was administered via i.v. patients in the ketamine group. The emergence agitation level of the patients was evaluated using the Richmond Agitation-Sedation Scale just after extubation and in the post-anesthesia care unit (PACU). For postoperative pain evaluation, the Numerical Rating Scale (NRS) was scored (from 0 to 10) every 10min until the patients were discharged from PACU. EA incidence in the control group was as high as 54.3%, while in the ketamine group it was 8.6% just after extubation (p<0.001). In the PACU, EA incidence was 28.6% in the control group, while none of the patients had EA in the PACU in the ketamine group (p<0.001). Male gender, severe pain (NRS≥5), and smoking were defined as significant risk factors for EA both after extubation and during follow-ups in the PACU (p<0.001). Emergence agitation after rhinoplasty is a common complication, likely disturbing operative outcomes in adults. Ketamine at sub-anesthetic doses is highly effective in preventing EA. Further, larger-scale prospective studies are warranted to determine preventive measures for EA development in rhinoplasty. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

BackgroundThis study aims to define the incidence and risk factors of both emergence agitation and hypoactive emergence in adult patients and substance-dependent patients following general anesthesia to elaborate on the risk factors and precise management of them. MethodsThe study recruited 1,136 adult patients who received elective surgeries under general anesthesia for this prospective observational study. Inadequate emergence was determined according to the Richmond Agitation-Sedation Scale (RASS). Emergence agitation was defined as a RASS ≥ +1 point, and hypoactive emergence was defined as a RASS ≤ –2 points. Subgroup analyses were then conducted on patients with substance dependence.ResultsInadequate emergence in the post-anesthesia care unit (PACU) occurred in 20.3% of patients, including 13.9% with emergence agitation and 6.4% with hypoactive emergence. Ninety-five patients had a history of substance dependence. Compared to divorced patients, never-married and presently married patients, who underwent gynecological and thoracic surgeries, had a lower risk of agitation. Neurologic disorders, intraoperative blood loss, intraoperative morphine, and PACU analgesic drug administration were associated with increased agitation risk. Hypertension and psychological disorders, intraoperative opioids, and PACU Foley catheter fixation were associated with increased hypoactive emergence risk. Substance-dependent patients had higher risk for agitation (21.1%, P = 0.019) and hypoactive emergence (10.5%, P = 0.044). ConclusionsInadequate emergence in PACU following general anesthesia is a significant problem correlated with several perioperative factors. Patients with a history of substance dependence appear to be more at risk of inadequate emergence than the general population.

The effect of topical tetracaine eye drops on emergence behavior and pain relief after strabismus surgery

Background Emergence agitation (EA) can occur following recovery from general anesthesia. The patient may exhibit aggressive behavior, disorientation, agitation, and restlessness. If untreated, this complication may result in significant morbidity. EA has been poorly investigated in patients undergoing laparoscopic sleeve gastrectomy. Aim The aim was to assess the efficacy of perioperative dexmedetomidine infusion on EA and quality of recovery after elective laparoscopic sleeve gastrectomy in morbidly obese adult patients. Materials and methods A total of 60 patients undergoing laparoscopic sleeve gastrectomy were randomized into two groups (30 patients each). The dexmedetomidine group (group D, N=30) received dexmedetomidine infusion, whereas the control group (group C, N=30) received normal saline in the same volume and rate as placebo. Propofol, fentanyl, and atracurium were used for induction of anesthesia, and isoflurane was used for maintenance of anesthesia. Postoperative hemodynamic variables, postoperative pain, the need for ‘rescue’ analgesics and antiemetics, and the incidence of agitation were recorded up to 2 h postoperatively. Pain was evaluated using the visual analog scale score in the postanesthesia care unit on arrival, at 5 min, and then every 15 min for 120 min. EA was evaluated at the same time intervals by Richmond agitation-sedation scale (RASS). Pethidine 50 mg intravenously was given for pain (if pain score >4) or severe agitation (RASS score >+1). Results No patients in group D experienced postoperative EA during the second hour postoperatively (RASS ˂1). On the contrary, RASS scores of patients in group C were 2 (2–3) on arrival to postanesthesia care unit and greater than +1 during the remaining time up to 2 h postoperatively, indicating postoperative EA. In group C, 25 (92.5%) patients required rescue analgesia compared with only five (18.5%) patients in group D. Hemodynamic parameters were stable in group D. Conclusion Dexmedetomidine infusion during laparoscopic sleeve gastrectomy for morbidly obese patients is beneficial and effective in preventing postoperative pain and postoperative EA.

Background: Sevoflurane is widely used to ambulatory pediatric anesthesia. But, sevoflurane is associated with a high incidence of emergence agitation in children. In this study, we examined the effect of single intravenous lidocaine prior to extubation on emergence agitation and cough in children undergoing adenotonsillectomy. Methods: All patients received a standardized anesthetic regimen with 23% sevoflurane in 50% O2/N2O after anesthetic induction with intravenous glycopyrrolate 0.004 mg/kg, thiopental 5 mg/kg and vecuronium 0.1 mg/kg. In a double-blinded trial, 120 children (39 years) were randomly assigned to receive normal saline 0.1 ml/kg (Group C), 1% lidocaine 1 mg/kg (Group L1) or 2% lidocaine 2 mg/kg (Group L2), at 1 min after beginning of spontaneous respiration. After extubation, the sedation score and the incidence of agitation and cough were recorded. Results: The incidence of agitation and cough in Group L1 and L2 were significantly less than Group C (P ＜ 0.05). At 5 min after arrival at postanesthetic care unit (PACU), more patients in Group L1 and L2 were in deeper sedation (the sedation score ≥ 2) than Group C. More patients in Group L1 were in deeper sedation than Group L2 and C at 10 min after arrival at PACU. Conclusions: We conclude that intravenous lidocaine prior to extubation reduces emergence agitation and cough after sevoflurane anesthesia in children undergoing adenotonsillectomy.

Background: Management of emergence agitation (EA) following tonsillectomy with or without adenoidectomy under general anaesthesia in children has been a major challenge for anaesthesiologists.Several medications have been investigated in an attempt to reduce the occurrence and severity of EA. Objectives: The purpose of this study is to determine the effect of premedication with intravenousmidazolam and ketamine on EA following tonsillectomy with or without adenoidectomy under generalanaesthesia in children. Study design: Randomised clinical study. Methods: Sixty children of both sex, American Society of Anaesthesiologists (ASA) physical status I &amp; IIage 5 to 12 years scheduled to undergo elective tonsillectomy with or without adenoidectomy were randomlyassigned into two groups. Patients in group K (n=30) received premedication of intravenous ketamine0.25 mg/kg body weight in 5 ml total volume and in group M (n=30) received premedication 0.1 mg/kgbody weight intravenous midazolam in 5 ml total volume. After completion of surgery patients weretransferred to recovery. Incidences and severity of EA(Paediatric Anaesthesia Emergence Delirium Scale),pain score (Wong-Baker FACES Pain scale) and postoperative nausea and vomiting (PONV) were assessedat admission in the recovery (T0) and in the post anaesthesia care unit (PACU) at 5 min (T5), at 15 min(T15) and at 30 min (T30). Results: Incidences of EA in Group K remained significantly lower than Group M at admission to therecovery and in the PACU at 5 min and 15 min (P&lt;0.05). Severity of EA was significantly lower patientsin Group K than Group M at admission in recovery and in PACU at 5 minute and 15 minute (P&lt;0.05).There were no significant differences in pain scores between two groups. Regarding PONV there was nosignificant difference between two groups. Conclusion: Premedication with ketamine was more effective than midazolam in the prevention of EAfollowing tonsillectomy with or without adenoidectomy in pediatric patients under general anaesthesia. JBSA 2020; 33(2): 55-61