Effect of Remimazolam on the Incidence of Intraoperative Hypothermia Compared with Inhalation Anesthetics in Patients Undergoing Endoscopic Nasal Surgery: A Prospective Randomized Controlled Trial.

BACKGROUND: Remimazolam is an ultrashort-acting benzodiazepine that is increasingly used for its efficacy in anesthesia induction and maintenance. However, limited research has explored its impact on intraoperative hypothermia compared to that of traditional inhalation anesthetics. This study aimed to compare the incidence of hypothermia during endoscopic nasal surgery when using remimazolam for maintenance anesthesia versus using inhalation anesthetics. METHODS: This prospective study included 70 patients who underwent endoscopic nasal surgery under general anesthesia. The patients were randomly assigned to one of two groups: the inhalation anesthetic (IA) group (n=35), in which desflurane and nitrous oxide were administered, and the remimazolam (R) group (n=35), in which remimazolam and remifentanil were administered for anesthesia maintenance. The primary outcome was the incidence of intraoperative hypothermia, defined as an esophageal temperature below 36 °C during anesthesia. RESULTS: The incidence of intraoperative hypothermia was significantly higher in the R group than in the IA group (P = 0.014). Furthermore, the temperature at the end of the surgery was significantly lower in the R group than in the IA group (P = 0.006). Additionally, the use of warming devices after surgery was more frequent in the R group than in the IA group (P = 0.047). CONCLUSIONS: These findings suggest that the use of remimazolam for maintenance anesthesia during endoscopic nasal surgery increases the risk of intraoperative hypothermia compared to the use of inhalation anesthetics. This highlights the importance of temperature monitoring in patients receiving remimazolam to minimize the adverse outcomes associated with hypothermia during surgery.

The First Case of a Korean Patient with a Mutation-Confirmed Tumor Necrosis Factor Receptor-Associated Periodic Syndrome.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS, OMIM: #142680) is a rare autoinflammatory disease (AID) with recurrent febrile episodes. To our knowledge, we report herein the first case of a patient with TRAPS in South Korea whose symptoms included fever, arthralgia, abdominal pain, rash, myalgia, cough, and lymphadenopathy. A pathogenic de novo mutation, c.175T>C (p.Cys59Arg), in the tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) gene, was confirmed by gene sequencing. The patient has been with tocilizumab (an interleukin-6 inhibitor); tocilizumab administration every other week has completely alleviated the patient's symptoms. Our report further expands the clinical spectrum of patients with TRAPS and reaffirms the use of tocilizumab as a viable alternative treatment option for those patients who are unsatisfactorily responsive to other commonly used biologics, such as canakinumab, anakinra, infliximab, and etanercept. Furthermore, our report may aid in increasing awareness about the existence of mutation-confirmed TRAPS in South Korea in addition to emphasizing the importance of actively pursuing genetic testing to correctly diagnose rare AID.

Airway leakage due to malpositioning of esophageal temperature probe during robot-assisted radical prostatectomy: a case report.

Measuring patients' core body temperature during surgery is essential and commonly performed with an esophageal temperature probe. The probe must be placed in the lower third of the esophagus for accurate measurement. In this case report, we describe our experience of discovering an inadvertently malpositioned esophageal temperature probe in the right inferior lobar bronchus, which led to ventilation-related problems in a patient undergoing prostate surgery.

The effect of combining prewarming with intraoperative phenylephrine infusion on the prevention of hypothermia in patients undergoing urological surgery: a prospective, randomized, and controlled trial.

Background: Hypothermia is common in patients undergoing urological surgery; however, no single preventative modality is completely effective. This study evaluated the effects of combining prewarming with intraoperative phenylephrine infusion for the prevention of hypothermia in patients undergoing urological surgery. Methods: This prospective study enrolled 58 patients scheduled for urological surgery under general anesthesia. The patients were randomized into two groups (n = 29). Patients in the experimental (prewarming and phenylephrine infusion) group (PP group) received prewarming for 20 min and intraoperative phenylephrine infusion, whereas those in the control group (C group) received no active prewarming with only intermittent administration of vasoactive agents. The patient's sublingual temperatures before and after anesthesia and nasopharyngeal temperature during anesthesia were recorded as core temperatures. Results: The incidence of intraoperative hypothermia was higher in the C group than in the PP group (57.7% [15/26] vs. 23.1% [6/26], P = 0.01). The severity of intraoperative hypothermia was higher in the C group than in the PP group (P = 0.004). The nasopharyngeal temperature at the end of surgery was lower in the C group than in the PP group (35.8 ± 0.6°C vs. 36.3 ± 0.4°C, P = 0.002). The trend of core temperature decline during the first hour after anesthesia induction differed between the two groups (P = 0.003; its decline was more gradual in the PP group). Conclusions: The combination of prewarming for 20 min and intraoperative phenylephrine infusion reduced the incidence and severity of intraoperative hypothermia and modified the trend of decreasing core temperatures in patients undergoing urological surgery.

Comparison of the effects of intraoperative remifentanil and sufentanil infusion on postoperative pain management in robotic gynecological surgery: a retrospective cohort study.

BACKGROUND: Remifentanil and sufentanil are potent short-acting synthetic opioid analgesics. The administration of remifentanil has been associated with the incidence of opioid-induced hyperalgesia. Opioid-induced hyperalgesia may be alleviated when opioids, such as morphine, are switched to sufentanil. Therefore, this retrospective observational study aimed to compare the effects of remifentanil and sufentanil on postoperative pain in patients undergoing robotic gynecological surgery. METHODS: We retrospectively analyzed the electronic medical records of patients who underwent elective robotic gynecological surgery between January 2016 and February 2021. The patients were classified into sufentanil (n = 159) or remifentanil (n = 359) groups according to the opioids administered continuously during anesthesia. The primary outcome assessed in this study was the postoperative pain score measured using the numeric rating scale (NRS). The secondary outcomes assessed included the recovery time (from discontinuation of opioid infusion to extubation) and frequency of rescue analgesic administration in the post-anesthesia care unit (PACU). RESULTS: The recovery time did not differ significantly between the two groups. The NRS score for pain (median [1Q, 3Q]) in the PACU was significantly lower in the sufentanil group than in the remifentanil group (2 [2, 3] vs. 4 [3, 7], P < 0.001). The frequency of rescue analgesic administration in the PACU was 6.3% and 35.4% in the sufentanil and remifentanil groups, respectively (P < 0.001). CONCLUSIONS: Sufentanil, as an adjunct to sevoflurane anesthesia is more advantageous than remifentanil in terms of postoperative pain control during robotic gynecological surgery.

Spontaneous pneumothorax after shoulder arthroscopy under general anesthesia: a case report.

A woman in her early 70s presented with a right fifth rib fracture along with left scapular body and glenoid fractures resulting from a traffic accident. She had no history of lung disease. The patient underwent multi-incisional video-guided arthroscopic fracture reduction and screw fixation in the right lateral decubitus position under general anesthesia, and surgery was followed by chest tube insertion. Left-sided pneumothorax was found during routine postoperative radiography despite the absence of relevant symptoms or signs such as hypoxia, chest pain, or respiratory difficulty. We herein report this unusual case with a brief literature review.

Clinical efficacy of short-term prewarming in elderly and adult patients: A prospective observational study.

Background: Short-term prewarming effectively reduces intraoperative hypothermia in adult patients. However, few data exist regarding its efficacy in elderly patients. Elderly people have a reduced ability to regulate their body temperature, which affects the efficacy of prewarming. This study aimed to compare the clinical efficacy of short-term pre-warming in elderly patients with that in adult patients. Methods: We enrolled 25 adult (20-50 years) and 25 elderly (> 65 years) patients scheduled for ureteroscopic stone surgery under general anaesthesia. All patients received preanaesthetic forced-air warming for 20 min. The core temperature was measured using an infrared tympanic thermometer during awakening and nasopharyngeal thermistors during anaesthesia. Incidence and severity of intraoperative hypothermia (< 36°C) was compared. Postoperative shivering and number of patients requiring active warming in the post-anaesthesia care unit were also assessed. Results: Intraoperative hypothermia was more frequent in elderly than in adult patients (58.3% vs. 12.0%; relative risk 2.6; 95% confidence interval 1.5 to 4.6; effect size h = 1.010; p = 0.001). The severity of intraoperative hypothermia showed a significant intergroup difference (p = 0.002). Postoperative shivering was more frequent in elderly than in adult patients (33.3% vs. 8.0%, p = 0.037). A greater number of elderly patients in the post-anaesthesia care unit required active warming (33.3% vs. 8.0%, p = 0.037). Conclusions: The effects of short-term prewarming on the prevention of hypothermia and maintenance of perioperative normothermia are not the same in the elderly and adult patients.

Risk Factors for Postoperative Hypothermia in Patients Undergoing Robot-Assisted Gynecological Surgery: A Retrospective Cohort Study.

Since postoperative hypothermia increases the morbidity and mortality rates of surgery, identifying its risk factors is an important part of perioperative management. Considering the increasing demand for robot-assisted surgery and other characteristics of conventional laparoscopic surgery, identifying the risk factors for hypothermia in robot-assisted surgery is necessary. However, this has not yet been clearly established. This study aimed to identify the risk factors and incidence rate of postoperative hypothermia in patients undergoing robot-assisted gynecological surgery. In total, 516 patients aged ≥ 19 years undergoing robot-assisted gynecological surgery at a single university hospital between January 2018 and November 2020 were retrospectively analyzed. Postoperative hypothermia was defined as 36.0°C or lower body temperature at the end of the surgery, and multivariate logistic regression analysis was performed to identify the risk factors for postoperative hypothermia. Among the 516 patients, the incidence rate of postoperative hypothermia was 28.1% in 145 patients. The independent risk factors for postoperative hypothermia included body mass index ≤ 22.9 kg/m2, baseline heart rate ≤ 73 rate/min, baseline body temperature ≤ 36.8°C, use of intraoperative nicardipine, and amount of administered intravenous fluid larger than 800 mL. Therefore, to prevent hypothermia in patients undergoing robot-assisted gynecological surgery, these risk factors must be considered.

Prewarming for Prevention of Hypothermia in Older Patients Undergoing Hand Surgery Under Brachial Plexus Block.

BACKGROUND: Older patients are more vulnerable to inadvertent perioperative hypothermia. Prewarming contributes to the prevention of inadvertent perioperative hypothermia in patients under general or neuraxial anesthesia. However, the effects of brachial plexus block (BPB) on thermoregulation and the efficacy of prewarming in the prevention of hypothermia in older patients undergoing surgery with BPB remain unclear. This study evaluated the effects of BPB on thermoregulation and the efficacy of prewarming during BPB in older patients. METHODS: Patients aged ≥65 years were randomly allocated to receive either standard preoperative insulation (control group, n=20) or preanesthetic forced-air warming for 20 minutes before BPB (prewarming group, n=20). During the perioperative period, tympanic temperatures were measured. Thermal comfort scores and shivering grades were also obtained. RESULTS: The tympanic temperatures at the end of surgery did not differ between the groups (36.9°C±0.5°C and 37.0°C±0.4°C in the control and prewarming groups, respectively; p=0.252). The maximum temperature change was significantly lower in the prewarming group compared to the control group (0.36°C±0.4°C and 0.65°C±0.3°C, respectively; p=0.013). The hypothermia incidence and severity, thermal comfort scores, and shivering grades did not differ between the groups. CONCLUSION: Regardless of the application of prewarming, BPB did not cause a clinically significant impairment of thermoregulation. Moreover, the efficacy of prewarming appeared to be low; thus, it may not be routinely required in patients undergoing orthopedic hand surgery under BPB.

Comparison of the effects of dexmedetomidine and propofol on hypothermia in patients under spinal anesthesia: a prospective, randomized, and controlled trial.

Background: Redistribution hypothermia caused by vasodilation during anesthesia is the primary cause of perioperative hypothermia. Propofol exerts a dose-dependent vasodilatory effect, whereas dexmedetomidine induces peripheral vasoconstriction at high plasma concentrations. This study compared the effects of dexmedetomidine and propofol on core temperature in patients undergoing surgery under spinal anesthesia. Methods: This prospective study included 40 patients (aged 19-70 years) with American Society of Anesthesiologists Physical Status class I-III who underwent elective orthopedic lower-limb surgery under spinal anesthesia. Patients were randomly allocated to a dexmedetomidine or propofol group (n = 20 per group). After induction of spinal anesthesia, patients received dexmedetomidine (loading dose: 1 µg/kg over 10 min; maintenance dose: 0.2-0.7 µg/kg/h) or propofol (loading dose: 75 µg/kg over 10 min; maintenance dose: 12.5-75 µg/kg/min). The doses of sedatives were titrated to maintain moderate sedation. During the perioperative period, tympanic temperatures, thermal comfort score, and shivering grade were recorded. Results: Core temperature at the end of surgery did not differ significantly between the groups (36.4 ± 0.4 and 36.1 ± 0.7°C in the dexmedetomidine and propofol groups, respectively; P = 0.118). The lowest perioperative temperature, incidence and severity of perioperative hypothermia, thermal comfort score, and shivering grade did not differ significantly between the groups (all P > 0.05). Conclusions: In patients undergoing spinal anesthesia with moderate sedation, the effect of dexmedetomidine on patients' core temperature was similar to that of propofol.

Double-Stranded RNA Enhances Matrix Metalloproteinase-1 and -13 Expressions through TLR3-Dependent Activation of Transglutaminase 2 in Dermal Fibroblasts.

UV-irradiation induces the secretion of double-stranded RNA (dsRNA) derived from damaged noncoding RNAs in keratinocytes, which enhance the expression of matrix metalloproteinases (MMP) in non-irradiated dermal fibroblasts, leading to dysregulation of extracellular matrix homeostasis. However, the signaling pathway responsible for dsRNA-induced MMP expression has not been fully understood. Transglutaminase 2 (TG2) is an enzyme that modifies substrate proteins by incorporating polyamine or crosslinking of proteins, thereby regulating their functions. In this study, we showed that TG2 mediates dsRNA-induced MMP-1 expression through NF-κB activation. Treatment of poly(I:C), a synthetic dsRNA analogue binding to toll-like receptor 3 (TLR3), generates ROS, which in turn activates TG2 in dermal fibroblast. Subsequently, TG2 activity enhances translocation of p65 into the nucleus, where it augments transcription of MMP. We confirmed these results by assessing the level of MMP expression in Tlr3-/-, TG2-knockdowned and Tgm2-/- dermal fibroblasts after poly(I:C)-treatment. Moreover, treatment with quercetin showed dose-dependent suppression of poly(I:C)-induced MMP expression. Furthermore, ex vivo cultured skin from Tgm2-/- mice exhibited a significantly reduced level of MMP mRNA compared with those from wild-type mice. Our results indicate that TG2 is a critical regulator in dsRNA-induced MMP expression, providing a new target and molecular basis for antioxidant therapy in preventing collagen degradation.

Effects of chlorpheniramine on emergence agitation after general anesthesia for ureteroscopic stone surgery: a retrospective cohort study.

BACKGROUND: The presence of a urinary catheter, postoperative pain, and postoperative nausea and vomiting are risk factors for emergence agitation (EA). Antimuscarinic agents are primary agents used in the prevention and treatment of urinary catheter-related bladder discomfort. Chlorpheniramine has antimuscarinic, antinociceptive, and antiemetic effects. This retrospective study investigated the role of chlorpheniramine in EA prevention following ureteroscopic stone surgery. METHODS: Of 110 adult patients who underwent ureteroscopic stone surgery under general anesthesia between January and December 2019, the medical records of 93 patients were analyzed retrospectively. The patients were divided into control (n = 52) and chlorpheniramine (n = 41) groups according to the receipt of intravenous chlorpheniramine before the induction of anesthesia. The incidence and severity of EA were compared between the groups as primary and secondary endpoints, respectively. The effects of chlorpheniramine on the requirement for inhalation anesthetic (desflurane) during surgery, changes in mean blood pressure and heart rate during emergence, and adverse events were also compared. RESULTS: The incidence (21.2% in the control group, 24.4% in the chlorpheniramine group) and severity of EA did not differ between groups. The intraoperative requirement for desflurane, changes in mean blood pressure and heart rate during emergence, and adverse events were also similar between groups. CONCLUSIONS: Chlorpheniramine was not associated with a decrease in EA incidence or severity in patients who underwent ureteroscopic stone surgery.

Effects of dexamethasone on catheter-related bladder discomfort and emergence agitation: a prospective, randomized, controlled trial.

BACKGROUND: Catheter-related bladder discomfort (CRBD) is common in patients with a urinary catheter and is a risk factor for emergence agitation (EA). The mainstay of CRBD management is anticholinergics. Dexamethasone inhibits acetylcholine release. This study aimed to evaluate the effects of dexamethasone on postoperative CRBD and EA. METHODS: In this prospective study, 90 patients undergoing urological surgery requiring urinary catheterization were allocated randomly to one of two groups (each n = 45). Before induction of anesthesia, the dexamethasone group received 10 mg (2 ml) of dexamethasone intravenously, while the control group received 2 ml of saline in the same manner. The incidence and severity of CRBD were assessed 0, 1, 2, and 6 h after the patient arrived in the post-anesthesia care unit (PACU) as the primary outcomes. The incidence and severity of EA were also compared during emergence and recovery from anesthesia as secondary outcomes. RESULTS: The incidences of CRBD in the control group and dexamethasone group at 0, 1, 2, and 6 h postoperatively were 28.9% and 15.6%, 55.6% and 55.6%, 57.8% and 46.7%, and 53.3% and 51.1%, respectively. The incidence and severity of CRBD assessed at 0, 1, 2, and 6 h postoperatively did not show intergroup differences. The incidence and severity of EA in the operating room and PACU also showed no difference between the groups. CONCLUSIONS: Dexamethasone (10 mg) administered before induction of anesthesia did not further reduce the incidence or severity of CRBD or EA in patients undergoing urological surgery.

Transglutaminase 2 mediates UVB-induced matrix metalloproteinase-1 expression by inhibiting nuclear p65 degradation in dermal fibroblasts.

Matrix metalloproteinases (MMPs) play a key role in tissue remodelling by cleaving extracellular matrix (ECM) components. In the skin, UV irradiation increases expression of MMPs that causes dysregulation of ECM homeostasis in dermis, leading to acceleration of skin aging. However, the mediator(s) that links UV irradiation to the upregulation of MMPs have not been fully defined. Previously, we showed that UVB irradiation activated transglutaminase 2 (TG2) in keratinocytes, eliciting an inflammatory response by activating NF-κB signalling. In this study, we reported the role of TG2 in mediating the UVB-induced expression of MMP-1. In human dermal fibroblasts, UVB irradiation enhanced the expression and activity of TG2, which in turn promotes the expression of MMP-1. Analyses of MMP-1 promoter showed that activation of the NF-κB signalling pathway, rather than AP-1, was responsible for the TG2-mediated upregulation of MMP-1. Moreover, Western blot analysis revealed that TG2 increased the activity of NF-κB by inhibiting degradation of p65 in the nucleus. Furthermore, ex vivo skin from TG2-knockout mice exhibited significantly reduced levels of MMP-1 compared to that from wild-type mice. These results indicate that TG2 functions as a mediator for the UVB-induced expression of MMP-1 in dermal fibroblasts, providing a new target for preventing skin photodamage.

Effects of neuromuscular blocking agents on the clinical performance of i-gel® and surgical condition in elderly patients undergoing hand surgery: a prospective randomized controlled trial.

Background: The effects of neuromuscular blocking agents on the clinical performance of supraglottic airway devices and surgical condition in elderly patients undergoing hand surgery have not been established. We evaluated the effects of rocuronium on the clinical performance of an i-gel® supraglottic device and surgical condition in elderly patients undergoing orthopedic hand surgery. Methods: Patients aged 65-85 years were randomized to receive either rocuronium (rocuronium group) or saline (control group). We compared the rates of successful insertion of the i-gel on the first attempt as a primary outcome and also assessed the adequacy of i-gel maintenance during controlled ventilation, anesthetic requirement, surgical condition, and recovery time. Results: The rates of successful insertion of the i-gel on a first attempt were 93.1% in the rocuronium group versus 82.1% in the control group (P = 0.423). Peak inspiratory pressure (PIP) was lower in the rocuronium group than in the control group (15.2 vs. 17.9 cmH2O, respectively, P = 0.028). Spontaneous breathing was less common in the rocuronium group (24.1% vs. 57.1%, respectively, P = 0.011). The requirement of additional fentanyl to suppress spontaneous breathing or patient movement was less in the rocuronium group than in the control group (24.1% vs. 50.0%, respectively, P = 0.043). Surgical condition did not differ between the two groups. Recovery time was shorter in the rocuronium group than in the control group (8.4 vs. 9.9 min, respectively, P = 0.030). Conclusions: Rocuronium did not enhance the success rate of inserting the i-gel® or the surgical condition in elderly patients. However, using rocuronium reduced PIP, the frequency of spontaneous breathing, the requirement for additional fentanyl and patients' recovery time.

Effects of Chlorpheniramine Maleate on Catheter-Related Bladder Discomfort in Patients Undergoing Ureteroscopic Stone Removal: A Randomized Double-Blind Study.

Catheter-related bladder discomfort (CRBD) associated with intraoperative urinary catheterization is a distressing symptom during recovery from anesthesia. Anticholinergics have been used to manage CRBD. Chlorpheniramine maleate (CPM) is a first-generation antihistamine, which also has anticholinergic effects. This study was undertaken to evaluate the efficacy of CPM in preventing CRBD. Seventy-six adults (19-65 years old) with American Society of Anesthesiologists physical status I, II, or III of either sex, undergoing elective ureteroscopic stone removal under general anesthesia were randomized into one of two groups (each n = 38). Group C (control) received a placebo, and group CPM received 8 mg of intravenous CPM before the induction of anesthesia. CRBD was assessed upon arrival in the post-anesthetic care unit at 0, 1, 2, and 6 h. The severity of CRBD was graded as none, mild, moderate, and severe. Tramadol was administered when the severity of CRBD was more than moderate. The incidence rate and overall severity of CRBD did not differ between the groups at any of the time points (р > 0.05). The incidence of moderate CRBD was higher in group C than in group CPM only at 0 h (26.3% vs. 5.3%, р = 0.025). However, fewer patients in the CPM group required rescue tramadol to relieve CRBD after surgery (31.6% vs. 60.5%, р = 0.011). CPM administration before the induction of anesthesia had little effect on the incidence and severity of CRBD after surgery, but it reduced the administration of tramadol required to control CRBD postoperatively.

Keratinocyte transglutaminase 2 promotes CCR6+ γδT-cell recruitment by upregulating CCL20 in psoriatic inflammation.

Keratinocyte-derived cytokines and chemokines amplify psoriatic inflammation by recruiting IL-17-producing CCR6+ γδT-cells and neutrophils. The expression of these cytokines and chemokines mainly depends on NF-κB activity; however, the pathway that activates NF-κB in response to triggering factors is poorly defined. Here, we show that transglutaminase 2 (TG2), previously reported to elicit a TH17 response by increasing IL-6 expression in a mouse model of lung fibrosis, mediates the upregulation of cytokines and chemokines by activating NF-κB in imiquimod (IMQ)-treated keratinocytes. TG2-deficient mice exhibited reduced psoriatic inflammation in skin treated with IMQ but showed systemic immune responses similar to wild-type mice. Experiments in bone marrow (BM) chimeric mice revealed that TG2 is responsible for promoting psoriatic inflammation in non-BM-derived cells. In keratinocytes, IMQ treatment activated TG2, which in turn activated NF-κB signaling, leading to the upregulation of IL-6, CCL20, and CXCL8 and increased leukocyte migration, in vitro. Consequently, TG2-deficient mice showed markedly decreased CCR6+ γδT-cell and neutrophil infiltration in IMQ-treated skin. Moreover, TG2 levels were higher in psoriatic skin than in normal skin and correlated with IL-6, CXCL8, and CCL20 levels. Therefore, these results indicate that keratinocyte TG2 acts as a critical mediator in the amplification of psoriatic inflammation.

Emergence agitation: current knowledge and unresolved questions.

Emergence agitation (EA), also referred to as emergence delirium, can have clinically significant consequences. The mechanism of EA remains unclear. The proposed risk factors of EA include 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. If preoperative or intraoperative objective monitoring could predict the occurrence of agitation during emergence, this would help to reduce its adverse consequences. Several tools are available for assessing EA. However, there are no standardized clinical research practice guidelines and its incidence varies considerably with the assessment tool or definition used. Total intravenous anesthesia, propofol, µ-opioid agonists, N-methyl-D-aspartate receptor antagonists, nefopam, α2-adrenoreceptor agonists, regional analgesia, multimodal analgesia, parent-present induction, and preoperative education for surgery may help in preventing of EA. However, it is difficult to identify patients at high risk and apply preventive measures in various clinical situations. The risk factors and outcomes of preventive strategies vary with the methodologies of studies and patients assessed.This review discusses important outcomes of research on EA and directions for future research.