Effect of a repeated verbal reminder of orientation on emergence agitation after general anaesthesia for minimally invasive abdominal surgery: a randomised controlled trial.

BACKGROUND: An orientation strategy providing repeated verbal reminders of time, place, and person has been widely used for the non-pharmacological management of delirium. We hypothesised that using this strategy could reduce emergence agitation and improve recovery profiles. METHODS: This prospective observer-blinded RCT included male and female patients aged 18-70 yr undergoing minimally invasive abdominal surgery. During emergence from general anaesthesia, subjects in the orientation group (n=57) were provided a repeated reminder, including orientation: '(Patient's name), you are now recovering from general anaesthesia after surgery at Seoul National University Hospital, open your eyes!' via noise-cancelling headphones, whereas those in the control group (n=57) only heard their name: '(Patient's name), open your eyes!'. The primary outcome was the incidence of emergence agitation (Riker sedation agitation scale [SAS] ≥5). The incidence of dangerous agitation (SAS=7), maximal SAS score in the operating room, and recovery profile until 24 h postoperatively were evaluated as secondary outcomes. RESULTS: The incidence of emergence agitation in the operating room was significantly lower in the orientation group than in the control group (16/57 [28.1%] vs 38/57 [66.7%]; relative risk [95% confidence interval], 0.5 [0.3-0.7]; P<0.001). The incidence of dangerous agitation (0 [0.0%] vs 10 [17.5%], P=0.001) and the median maximal SAS score (4 [4-5] vs 5 [4-6], P<0.001) were also lower in the orientation group. Secondary outcomes, other than agitation-related variables, were comparable between the two groups. CONCLUSIONS: Repeated verbal stimulation of orientation may serve as a simple and easily applicable strategy to reduce emergence agitation after general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT05105178.

High peak inspiratory pressure may be associated with intraoperative coughing during neurosurgery under general anesthesia without neuromuscular blockade: a retrospective study.

BACKGROUND: The endotracheal cuff pressure depends on the airway pressure during positive-pressure ventilation. A high endotracheal cuff pressure may be related to intraoperative coughing, which can be detrimental during neurosurgery. We investigated the incidence of intraoperative coughing and its association with peak inspiratory pressure (PIP) during neurosurgery under general anesthesia without neuromuscular blockade. METHODS: This retrospective study divided 1656 neurosurgical patients who underwent total intravenous anesthesia without additional neuromuscular blockade after tracheal intubation into high (PIP > 21.6 cmH2O, n = 318) and low (PIP ≤ 21.6 cmH2O, n = 1338) PIP groups. After propensity score matching, 206 patients were selected in each group. Demographic, preoperative, surgical, and anesthetic data were collected retrospectively from electronic medical records and continuous ventilator, infusion pump, and bispectral index data from a data registry. RESULTS: Intraoperative coughing occurred in 30 (1.8%) patients, including 9 (0.5%) during the main surgical procedure. Intraoperative coughing was more frequent in the high PIP group than in the low PIP group before (14/318 [4.4%] vs. 16/1338 [1.2%], P < 0.001) and after (13/206 [6.3%] vs. 1/206 [0.5%], P = 0.003) propensity score matching. In multivariable logistic regression analysis after propensity score matching, a high PIP (odds ratio [95% confidence interval] 14.22 [1.81-111.73], P = 0.012), tidal volume divided by predicted body weight (mL/kg, 1.36 [1.09-1.69], P = 0.006), and surgical duration (min, 1.01 [1.00-1.01], P = 0.025) predicted intraoperative coughing. CONCLUSION: The incidence of intraoperative coughing was 1.8% in neurosurgical patients undergoing general anesthesia without neuromuscular blockade and might be associated with a high PIP.

Perioperative Respiratory-Adverse Events Following General Anesthesia Among Pediatric Patients After COVID-19.

BACKGROUND: The perianesthetic morbidity, mortality risk and anesthesia-associated risk after preoperative coronavirus disease 2019 (COVID-19) omicron variant in pediatric patients have not been fully demonstrated. We examined the association between preoperative COVID-19 omicron diagnosis and the incidence of overall perioperative adverse events in pediatric patients who received general anesthesia. METHODS: This retrospective study included patients aged < 18 years who received general anesthesia between February 1 and June 10, 2022, in a single tertiary pediatric hospital. They were divided into two groups; patients in a COVID-19 group were matched to patients in a non-COVID-19 group during the omicron-predominant period in Korea. Data on patient characteristics, anesthesia records, post-anesthesia records, COVID-19-related history, symptoms, and mortality were collected. The primary outcomes were the overall perioperative adverse events, including perioperative respiratory adverse events (PRAEs), escalation of care, and mortality. RESULTS: In total, 992 patients were included in the data analysis (n = 496, COVID-19; n = 496, non-COVID-19) after matching. The overall incidence of perioperative adverse events was significantly higher in the COVID-19 group than in the non-COVID-19 group (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.89-1.94). The difference was significant for PRAEs (OR, 2.00; 95% CI, 1.96-2.02) but not in escalation of care or mortality. The most pronounced difference between the two groups was observed in instances of high peak inspiratory pressure ≥ 25 cmH2O during the intraoperative period (OR, 11.0; 95% CI, 10.5-11.4). Compared with the non-COVID-19 group, the risk of overall perioperative adverse events was higher in the COVID-19 group diagnosed 0-2 weeks before anesthesia (OR, 6.5; 95% CI, 2.1-20.4) or symptomatic on the anesthesia day (OR, 6.4; 95% CI, 3.30-12.4). CONCLUSION: Pediatric patients with the preoperative COVID-19 omicron variant had increased risk of PRAEs. Patients within 2 weeks after COVID-19 or those with symptoms had a higher risk of PRAEs.

Association between intraoperative body temperature and postoperative delirium: A retrospective observational study.

STUDY OBJECTIVE: The effect of perioperative body temperature derangement on postoperative delirium remains unclear. This study aimed to evaluate the association between intraoperative body temperature and postoperative delirium in patients having noncardiac surgery. DESIGN: Single-center retrospective observational study. SETTING: Tertiary university hospital. PATIENT: Adult patients who had major noncardiac surgery under general anesthesia for at least two hours between 2019 and 2021. INTERVENTIONS: Patients were classified into three groups according to their intraoperative time-weighted average body temperature: severe hypothermia (<35.0 °C), mild hypothermia (35.0 °C-36.0 °C), and normothermia (≥36.0 °C) groups. MEASUREMENTS: The primary outcome was the risk of delirium occurring within seven days after surgery, which was compared using logistic regression analysis. A multivariable procedure was performed adjusting for potential confounders including demographics, history of hypertension, diabetes, atrial fibrillation or flutter, myocardial infarction, congestive heart failure, and stroke or transient ischemic attack, preoperative use of antidepressants and statins, preoperative sodium imbalance, high-risk surgery, emergency surgery, duration of surgery, and red blood cell transfusion. Cox regression analysis was also performed using the same covariates. MAIN RESULTS: Among 27,674 patients analyzed, 5.5% experienced postoperative delirium. The incidence rates of delirium were 6.2% (63/388) in the severe hypothermia group, 6.4% (756/11779) in the mild hypothermia group, and 4.6% (712/15507) in the normothermia group. Compared with the normothermia group, the risk of delirium was significantly higher in the severe hypothermia (adjusted odds ratio, 1.43; 95% confidence interval, 1.04-1.97) and mild hypothermia (1.15; 1.02-1.28) groups. The mild hypothermia group also had a significantly increased risk of cumulative development of delirium than the normothermia group (adjusted hazard ratio 1.14; 95% confidence interval, 1.03-1.26). CONCLUSIONS: Intraoperative hypothermia (even mild hypothermia) was significantly associated with an increased risk of postoperative delirium.

Continuous versus intermittent infusion of human antithrombin III concentrate in the immediate postoperative period after liver transplantation.

Antithrombin-III (AT-III) concentrates have been used in the immediate postoperative period after liver transplantation to prevent critical thrombosis. We aimed to investigate a more appropriate method for AT-III concentrate administration to maintain plasma AT-III activity level within the target range. In this randomized controlled trial, 130 adult patients undergoing living-donor liver transplantation were randomized to either the intermittent group or continuous group. In the intermittent group, 500 international units (IU) of AT-III concentrate were administered after liver transplantation and repeated every 6 h for 72 h. In the continuous group, 3000 IU of AT-III were continuously infused for 71 h after a loading dose of 2000 IU over 1 h. Plasma AT-III activity level was measured at 12, 24, 48, 72, and 84 h from the first AT-III administration. The primary outcome was the target (80%-120%) attainment rate at 72 h. Target attainment rates at other timepoints and associated complications were collected as secondary outcomes. A total of 107 patients were included in the analysis. The target attainment rates at 72 h post-dose were 30% and 62% in the intermittent group and continuous group, respectively (p = 0.003). Compared to the intermittent group, patients in the continuous group reached the target level more rapidly (12 vs. 24 h, median time, p < 0.001) and were more likely to remain in the target range until 84 h. For maintaining the target plasma AT-III activity level after living-donor liver transplantation, continuous infusion of AT-III seemed to be more appropriate compared to the conventional intermittent infusion regimen.

Pulmonary artery catheter monitoring versus arterial waveform-based monitoring during liver transplantation: a retrospective cohort study.

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47-1.56), p = 0.229; EAD: 0.99 (0.38-1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).

Vasoconstriction potency induced by aminoamide local anesthetics correlates with lipid solubility.

Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED(50)) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED(50)) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED(50) in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r(2) = 0.9563; P < 0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

Hospital case-volume and mortality after lung cancer surgery: A population-based retrospective cohort study.

OBJECTIVES: Recent advances in lung cancer treatment warrants reassessment of the volume-outcome association in lung cancer surgery. This study reassessed the relationship between surgical case-volume and both in-hospital and long-term mortality after lung cancer surgery using a current database to reflect recent advances. MATERIALS AND METHODS: Using the database of the National Health Insurance Service in Korea, data of all adult patients who underwent lung cancer surgery in Korea between 2005 and 2019 were obtained. Hospitals were categorized by the annual number of lung cancer surgeries. Risk-adjusted in-hospital and 1, 3, 5-year mortality after surgery were assessed. RESULTS: A total of 84,194 lung cancer surgeries were performed in 163 centers during the study period. High-volume centers were defined as > 200 cases/year, medium-volume centers as 60-200 cases/year, and low-volume centers as < 60 cases/year. After adjustment, in-hospital mortality was significantly lower in high-volume centers (1.03%) compared to medium-volume centers (2.06%, adjusted odds ratio [OR], 1.43; 95% confidence interval [CI], 1.23-1.65; P < 0.001), and low-volume centers (3.08%, OR, 1.32; 95% CI, 1.16-1.51; P < 0.001). Long-term mortality was also significantly lower in high-volume centers compared to the other groups. CONCLUSION: High-volume centers showed lower in-hospital and long-term mortality compared to centers with less case-volume.

Effect of pre-operative carbohydrate loading on aspiration risk evaluated with ultrasonography in type 2 diabetes patients: a prospective observational pilot study.

Owing to concerns about delayed gastric emptying or hyperglycemia, evidence is lacking regarding whether pre-operative carbohydrate loading can be routinely administered to patients with type 2 diabetes. The objective of this study was to determine the aspiration risk and gastric volume after pre-operative carbohydrate loading in patients with type 2 diabetes. A prospective, single-center, observational cohort study. The study was conducted at a tertiary teaching hospital in Seoul, Korea, from May 2020 to May 2021. Patients (n = 49) with type 2 diabetes underwent elective noncardiac surgery. All patients were administered carbohydrate loading two hours before surgery. Once in the operating room, they underwent gastric ultrasonography to determine gastric volume. The anesthesiologists monitored the patients' glucose concentrations during and after surgery. The primary outcome was the predicted risk of aspiration. The secondary outcomes were gastric volume, antral grade, satisfaction score, and perioperative glucose profile. Forty-nine patients were analyzed. All patients had a low risk of aspiration after carbohydrate loading, as follows: 33 (67.3%) patients classified as antral grade 0 and 16 (32.7%) patients classified as antral grade 1. The median time from carbohydrate drink ingestion to ultrasound examination was 120 min (IQR 115-139). After carbohydrate loading, the median gastric volume in the right-lateral position after carbohydrate loading was 2.64 ml (IQR 0.00-32.05). The mean glucose concentrations (SD) were 134 (24) mg/dl, 159 (37) mg/dl, 150 (32) mg/dl, and 165 (36) mg/dl at baseline, after induction, 30 min after surgery, and in the post anesthesia care unit, respectively. The median satisfaction score of the patients was 5 (IQR 4-5). Pre-operative carbohydrate loading may be feasible for patients with type 2 diabetes and without complications.Trial registration: ClinicalTrials.gov (NCT04456166). Registered on 2 July 2020.

Allogeneic renal graft rejection in a rat model: in vivo MR imaging of the homing trait of macrophages.

PURPOSE: To evaluate the feasibility of MR imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to aid diagnosis of graft rejection in kidney transplantation. MATERIALS AND METHODS: This study was approved by the institution's committee on animal research. Eighteen male Lewis rats received a kidney transplant; 12 had an F344 rat donor and six had a Lewis rat donor. Peritoneal macrophages were harvested from thioglycollate-treated Lewis rats, cultured, and labeled with SPIO. After resuspension of macrophages in a concentration of 1 x 10(7) cells per milliliter of Hanks balanced salt solution, 5 x 10(6) of SPIO-labeled macrophages was administered through the tail vein 2 or 5 days after transplantation in each group. The transplanted kidneys were imaged on a 4.7-T MR imager 24 hours after macrophage administration. The Wilcoxon signed rank test was performed for evaluating the differences between the relative signal intensity (SI) before and after SPIO-labeled macrophage administration. RESULTS: A low-SI zone was predominantly noted in the medulla of the transplanted kidneys, and the relative SI decreased significantly from 1.40 to 0.53 (P < .001) in the allogeneic transplants following SPIO-labeled macrophage administration 5 days after the allogeneic transplantation. In the syngeneic group, the lower-SI zone was not noted in the grafts. At histopathologic examination, the lower-SI zone corresponded to the distribution of the SPIO-labeled macrophages. CONCLUSION: This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored in the allograft rejection model on in vivo MR images.

In vivo MR evaluation of the effect of the CCR2 antagonist on macrophage migration.

The CCR2 antagonist is a receptor antagonist for monocyte chemoattractant protein-1 and is known to be a potential anti-inflammatory therapeutic agent. Recently used optimized labeling techniques for superparamagnetic iron oxide, macrophage homing, and recruitment toward the infection site can be observed on in vivo MRI. This study details the effect of the CCR2 antagonist on the macrophage migration and the feasibility of in vivo MRI for assessing the inhibition of chemotactic activity by the CCR2 antagonist. On binding assay, the CCR2 antagonist inhibits the binding affinity of monocyte chemoattractant protein-1 to CCR2. Increased expression of messenger ribonucleic acid (mRNA) and expression of CCR2 and CD11b on the cellular surface, as induced by monocyte chemoattractant protein-1, was shown, and the effect of monocyte chemoattractant protein-1 on CCR2 and CD11b was restricted by the CCR2 antagonist. In a migration test using the transwell system, macrophages treated with the CCR2 antagonist showed significantly decreased chemotactic migration compared to that of wild-type macrophages. MR images of infected left calf muscles in 12 mice were obtained 24 h after administration of macrophages labeled with superparamagnetic iron oxide. MRI successfully demonstrated the effect of the CCR2 antagonist on the directional migration of macrophages.

Graft rejection in the xenogeneic transplantation of mice: diagnosis with in vivo MR imaging using the homing trait of macrophages.

BACKGROUND: To evaluate the feasibility of magnetic resonance (MR) imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to diagnose graft rejection in xenogeneic transplantation. METHODS: We transplanted the trachea of SD rat (xenogeneic) or C3H/HeN mouse (syngeneic) into the left thighs of six male C3H/HeN mice. The SPIO-labeled macrophage was administered through the tail vein 2 days (acute) or 14 days (chronic) after transplantation in each group. The left thighs of the mice were imaged on a 4.7-T MR scanner 24 h after macrophage administration. We evaluated the extent and pattern of the susceptibility effect (macrophage distribution) and compared them in the two groups. The MR findings were then correlated with the histopathologic results. We also measured in both groups the monocyte chemoattractant protein (MCP)-1 level before and 2 days, 2 weeks, and 4 weeks after transplantation. RESULTS: The band-shaped lower signal intensity (SI) zone was noted around the graft in the acute and chronic phases of xenogeneic group and in the acute phase of syngeneic group, but it was not noted in the chronic phase of syngeneic transplantation. The lower SI zone corresponded to the distribution of SPIO-labeled macrophages on histopathological analyses. On histologic examination, the severe inflammation developed around the xenogeneic graft, but only slightly around the syngeneic graft. MCP-1 was elevated 2 days after transplantation in both groups, but then gradually decreased in the syngeneic group; in xenogenic group, the MCP-1 value decreased by week 2 but then increased by week 4. CONCLUSIONS: This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored on MR imaging and is correlated with the MCP-1 level and the histopathologic findings of the xenograft rejection.

Pace of macrophage recruitment during different stages of soft tissue infection: semi-quantitative evaluation by in vivo magnetic resonance imaging.

We describe the pace of recruitment of iron-oxide-labeled macrophages to the site of different stages of infection by in vivo magnetic resonance (MR) imaging. Peritoneal macrophages were labeled with superparamagnetic iron oxide ex vivo and administered through the tail vein 6 (acute) or 48 (subacute) h after bacterial inoculation. The legs of the mice were imaged sequentially on a 4.7-T MR unit before and 3, 6, 12, 18, 24, 48 and 72 h after macrophage administration. The band-shaped lower signal intensity zone around the abscess on T2*-weighted GRE images became more obvious due to recruited macrophages up until 24 h after injection in the subacute and 48 h after injection in the acute group, indicating that the relative SI of the abscess wall decreased more rapidly and the pace of recruitment of macrophages was faster in the subacute than in the acute group. Chemokine antibody arrays of mouse sera detected increased concentration of granulocyte-colony-stimulating factor and tissue inhibitor of metalloproteinase-1 beginning at 12 h and increased interleukin-13 at 18 h. Monocyte chemoattractant protein-1 and macrophage-colony-stimulating factor began to increase at 96 h after infection. This difference in pace of recruitment may result from the release of chemokines.

Survivin inhibits anti-growth effect of p53 activated by aurora B.

Genomic instability and apoptosis evasion are hallmarks of cancer, but the molecular mechanisms governing these processes remain elusive. Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors. Notably, exogenous introduction of the aurora B in human BJ cells was shown to decrease cell growth and increase the senescence-associated beta-galactosidase activity by activation of p53 tumor suppressor. However, aurora B overexpression failed to inhibit cell proliferation in BJ and U87MG cells transduced with dominant-negative p53 as well as in p53(-/-) mouse astrocytes. Aurora B was shown to increase centrosome amplification in the p53(-/-) astrocytes. Survivin was shown to induce anchorage-independent growth and inhibit anti-proliferation and drug-sensitive apoptosis caused by aurora B. Overexpression of both survivin and aurora B further accelerated the proliferation of BJ cells. Taken together, the present study indicates that survivin should accelerate tumorigenesis by inhibiting the anti-proliferative effect of p53 tumor suppressor that is activated by aurora B in normal and glioblastoma cells containing intact p53.