Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study.

OBJECTIVE: To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study. MATERIALS AND METHODS: Fifty-six Sprague-Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.47 µL/g of gadolinium-based contrast agent were injected into the tail vein. Serum levels of blood urea nitrogen, creatinine, cystatin C (Cys C), and malondialdehyde (MDA) were measured. mRNA and protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. RESULTS: Levels of serum creatinine (SCr) were significantly higher in repeated CT contrast agent injection groups than in PC (0.21 ± 0.02 mg/dL for PC; 0.40 ± 0.02, 0.34 ± 0.03, and 0.41 ± 0.10 mg/dL for 2-, 4-, and 24-hour interval groups, respectively; P < 0.001). There was no significant difference in the average Cys C and MDA levels between PC and repeated CT contrast agent injection groups (Cys C, P = 0.256-0.362; MDA, P > 0.99). Additional doses of MR contrast agent did not make significant changes compared to PC in SCr (P > 0.99), Cys C (P = 0.262), and MDA (P = 0.139-0.771) levels. mRNA and protein levels of KIM-1 and NGAL were not significantly different among additional CT or MR contrast agent groups (P > 0.05). CONCLUSION: A sufficient time interval, probably more than 24 hours, between repeated contrast-enhanced CT examinations may be necessary to avoid deterioration in renal function. However, conducting contrast-enhanced MRI on the same day as contrast-enhanced CT may not induce clinically significant kidney injury.

Preoperative Frailty Is an Independent Risk Factor for Postinduction Hypotension in Older Patients Undergoing Noncardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Intraoperative hypotension is a risk factor for perioperative adverse outcomes and is highly prevalent in older patients. Frailty has been associated with hemodynamic instability but its impact on postinduction hypotension is unclear. Therefore, we assessed the association between frailty and postinduction hypotension in older patients. METHODS: We retrospectively evaluated electronic medical records of patients aged ≥65 years who were assessed for preoperative frailty and underwent noncardiac surgery under general anesthesia. Reported Edmonton Frail Scale (REFS) scores were used to stratify patients into a nonfrail (REFS scores 0-5), prefrail (6-7), and frail (8-18) groups. Postinduction hypotension was defined as a mean blood pressure below 65 mmHg or 20% from baseline occurring within the first 20 minutes after anesthesia induction and evaluated using multivariate logistic regression analysis. RESULTS: Independent factors related to postinduction hypotension in our sample (421 patients) were status of frail (REFS score ≥8) compared to nonfrail (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.44-5.18; p = .002), lower baseline mean blood pressure in the operating room (OR, 0.98; 95% CI, 0.96-0.999; p = .034) and at the presurgical center (OR, 0.96; 95% CI, 0.94-0.99; p = .003), and orthopedic (compared to urologic) surgery (OR, 2.22; 95% CI, 1.14-4.30; p = .019). CONCLUSION: Preoperative frail status based on REFS scores is associated with postinduction hypotension. Frailty screening tool for older patients may enhance traditional risk calculators and improve patient selection for noncardiac surgery under general anesthesia.

Delivery of recombinant sestrin2 ameliorates oxidative stress, mitochondrial damage and renal dysfunction in contrast-induced acute kidney injury.

Although the use of iodinated contrast agents is sometimes unavoidable for accurate diagnosis, contrast-induced acute kidney injury (CI-AKI) is a possible complication of its administration. The pathogenesis of CI-AKI has not been fully elucidated, but oxidative stress is thought to be a major factor. Sestrin2 plays an important role in cellular and mitochondrial homeostasis by regulating oxidative stress. In this study, we aimed to investigate whether recombinant adenovirus containing sestrin2 (RS) can attenuate CI-AKI by reducing oxidative stress in a CI-AKI mice model. Our results showed that RS decreases oxidative stress, pro-inflammatory cytokines (TNF-α, IL-1α, IL-1ß and IL-6) and apoptosis (Bax/Bcl2 and cleaved caspase-3) in the CI-AKI model. Additionally, RS alleviated mitochondrial damage, as evidenced by morphological changes, are restored ATP synthesis. Furthermore, RS administration resulted in a decrease in mitochondrial fission marker (Drp1) that was increased in the CI-AKI model, while the mitochondrial fusion marker (Mfn2) increased, indicating a restoration of mitochondrial dynamics. Decreased relative blood volume, as evaluated on computed tomography (CT), significantly increased compared to the CI-AKI group after RS administration. Finally, renal injury markers such as Kim-1, Ngal, IL-18 also decreased and kidney function was preserved with RS. These results suggested that RS can mitigate the deterioration of renal function in CI-AKI model.

Strategy to Reduce Hypercapnia in Robot-Assisted Radical Prostatectomy Using Transcutaneous Carbon Dioxide Monitoring: A Prospective Observational Study.

Purpose: Monitoring end-tidal carbon dioxide partial pressure (PETCO2) is a noninvasive, continuous method, but its accuracy is reduced by prolonged capnoperitoneum and the steep Trendelenburg position in robot-assisted radical prostatectomy (RARP). Transcutaneous carbon dioxide partial pressure (PTCCO2) monitoring, which is not affected by ventilator-perfusion mismatch, has been suggested as a suitable alternative. We compared the agreement of noninvasive measurements with the arterial carbon dioxide partial pressure (PaCO2) over a long period of capnoperitoneum, and investigated its sensitivity and predictive power for detecting hypercapnia. Patients and Methods: The patients who underwent RARP were enrolled in this study prospectively. Intraoperative measurements of PETCO2, PTCCO2, and PaCO2 were analyzed. The primary outcome was the agreement of noninvasive monitoring with PaCO2 during prolonged capnoperitoneum. Bias and precision between noninvasive measurements and PaCO2 were assessed using Bland-Altman analysis. The bias and mean absolute difference were compared using a two-tailed Wilcoxon signed-rank test for pairs. The secondary outcome was the sensitivity and predictive power for detecting hypercapnia. To assess this, the Yates corrected chi-square test and the area under the receiver operating characteristic curve were used. Results: The study analyzed 219 datasets from 46 patients. Compared with PETCO2, PTCCO2 had lower bias, greater precision, and better agreement with PaCO2 throughout the RARP. The mean absolute difference in PETCO2 and PaCO2 was larger than that of PTCCO2 and PaCO2, and continued to exceed the clinically acceptable range of 5 mmHg after 1 hour of capnoperitoneum. The sensitivity during capnoperitoneum and overall predictive power of PTCCO2 for detecting hypercapnia were significantly higher than those of PETCO2, suggesting a greater contribution to ventilator adjustment, to treat hypercapnia. Conclusion: PTCCO2 monitoring measured PaCO2 more accurately than PETCO2 monitoring during RARP requiring prolonged capnoperitoneum and a steep Trendelenburg position. PTCCO2 monitoring also provides more sensitive measurements for ventilator adjustment and detects hypercapnia more effectively than PETCO2 monitoring.

Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure.

Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.

Perineural dexamethasone reduces rebound pain after ropivacaine single injection interscalene block for arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: A single injection interscalene block (ISB) is a common regional analgesic technique in patients undergoing arthroscopic shoulder surgery. However, rebound pain after ISB resolution may reduce its overall benefit. Our primary aim was to assess whether perineural dexamethasone reduces the intensity and incidence of rebound pain in patients undergoing arthroscopic shoulder surgery under general anesthesia combined with a preoperative single injection ISB. METHODS: The patients were randomly assigned to receive single injection ISB using either 0.5% ropivacaine (control) or 0.5% ropivacaine containing 5 mg of dexamethasone. The primary outcomes were the pain score difference before and after ISB resolution, and the incidence of rebound pain. The secondary outcomes were the onset and duration of rebound pain, the presence of sleep disturbances due to postoperative pain, the first time when an analgesic was requested, and pain scores at various predefined time points. RESULTS: Pain increase following ISB resolution was lower in the dexamethasone group compared with the control group (4.5±2.4 and 6.9±2.2, respectively, p<0.001). The incidence of rebound pain was significantly lower in the dexamethasone group compared with the control group (37.1% and 82.9%, respectively, p<0.001). The controls experienced greater sleep disturbance during the postoperative period compared with those who received ISB with perineural dexamethasone. CONCLUSIONS: Perineural dexamethasone added to ISB using ropivacaine led to a much smoother resolution of ISB, reflected in a significantly smaller increase in pain after block resolution, a lower incidence of rebound pain and a lower sleep disturbance during the first postoperative week. TRIAL REGISTRATION NUMBER: Clinical Trial Registry of Korea (KCT0004418).

Quantitative Analysis of Microperfusion in Contrast-Induced Nephropathy Using Contrast-Enhanced Ultrasound: An Animal Study.

OBJECTIVE: To investigate imaging biomarkers of microperfusion in contrast-induced nephropathy (CIN) using contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: The CIN model was fabricated by administering indomethacin (10 mg/kg), L-NAME (15 mg/kg), and iopamidol (10 mL/kg) to Sprague-Dawley rats. After 24 hours, CEUS was performed on CIN (n = 6) and control (n = 6) rats with sulphur hexafluoride microbubbles (SonoVue). From time-intensity curves obtained from the kidney arriving time (AT), acceleration time (AC), time to peak (TTP), and peak enhancement (PE) were measured and compared between the groups. After CEUS, the rats were sacrificed, and cell apoptosis markers were evaluated to confirm the development of CIN. RESULTS: Among CEUS parameters, AT (7.8 ± 1.6 vs. 4.2 ± 0.5 s, p = 0.002), AC (4.7 ± 1.4 vs. 2.0 ± 0.4 s, p = 0.002), and TTP (12.5 ± 2.9 vs. 6.2 ± 0.6 s, p = 0.002) were significantly prolonged in the CIN group compared to controls. PE was significantly higher in the control group than in the CIN group (17.1 ± 1.9 vs. 12.2 ± 2.0 dB, p = 0.004). In kidney tissue, mRNA and protein levels of the apoptotic makers were significantly higher in the CIN group than in the control group (p = 0.003 and p = 0.002). CONCLUSION: CEUS parameters can be used as imaging biomarkers for microperfusion in CIN. In rats with CIN, AT, AC, and TTP were significantly prolonged, while PE was significantly lower compared to controls.

Risk Factors for Perioperative Respiratory Adverse Events in Children with Recent Upper Respiratory Tract Infection: A Single-Center-Based Retrospective Study.

PURPOSE: In pediatric patients, the most common reason for delaying surgical intervention is an upper respiratory tract infection (URI). To date, there has been no consensus regarding the optimal timeframe for deferring surgery in children with URI. We conducted this study to evaluate whether a URI symptom-free period and other risk factors affect the incidence of perioperative respiratory adverse events (RAEs). PATIENTS AND METHODS: The study population included 267 pediatric patients (aged 0 to 13 years) with a recent URI episode who underwent surgery under general anesthesia. Following a retrospective review of medical records, several risk factors including a URI symptom-free period for intra- and postoperative RAEs were analyzed using univariate and multivariate logistic regression analyses. RESULTS: RAEs occurred in 23 of 267 patients (8.6%). Univariate analysis revealed that abnormal preoperative chest images (odds ratio [OR], 7.48; 95% confidence interval [CI], 2.46-22.68, p < 0.001) and emergency operations (OR, 2.84; 95% CI, 1.03-7.81, p = 0.04) were associated with RAEs. Four variables (abnormal preoperative chest images, emergency operations, age under 1 year and symptom-free period of 7-13 days) with a significance of <0.20 in the univariate logistic regression analysis were selected as candidate risk factors for the multivariate model. Among the four variables, abnormalities in preoperative chest images (OR, 7.60; 95% CI, 2.28-25.3, p = 0.001) and a symptom-free period of 7-13 days (OR, 0.13; 95% CI, 0.02-0.88, p = 0.04) were independently associated with RAEs in multivariate logistic regression analysis. CONCLUSION: For pediatric patients who require surgery and have a recent history of URI, procedures should be performed after a URI symptom-free period of at least 1-2 weeks. Confirming the absence of abnormalities in preoperative chest images can reduce the incidence of perioperative RAEs.

The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect.

As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RT-PCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.

Excessive remifentanil during total intravenous anesthesia is associated with increased risk of pain after robotic thyroid surgery.

The widespread use of remifentanil during total intravenous anesthesia (TIVA) has raised concerns about the risk of postoperative remifentanil-associated pain. Although a recent meta-analysis suggests that remifentanil-associated pain is unlikely to occur in patients with TIVA because of the protective effect of co-administered propofol, the evidence is not conclusive. We retrospectively assessed 635 patients who received robotic thyroid surgery under TIVA to evaluate the risk of remifentanil-associated pain. Postoperative pain was evaluated using 11-point numeric rating scale (NRS). Time dependent Cox proportional hazards regression analysis was used to determine the risk factors of treatment-requiring pain (NRS > 4) during the first 48 postoperative hours. Postoperative pain rapidly decreased, and treatment-requiring pain remained in 12.8% (81 out of 635) of patients at 48 hours postoperatively. After adjusting for the time-dependent analgesic consumption, intraoperative use of remifentanil > 0.2 mcg/kg/min was a positive predictor of postoperative pain with a hazard ratio of 1.296 (95% C.I., 1.014-1.656, P = 0.039) during 48 hours after surgery. In conclusion, excessive use of remifentanil during TIVA was associated with increased risk of pain after robotic thyroid surgery. Prospective trials are required to confirm these results and determine whether decreasing remifentanil consumption below the threshold can reduce postoperative pain.

Determination of insertion depth of flexible laryngeal mask airway in pediatric population-A prospective observational study.

STUDY OBJECTIVE: The purpose of this study was to determine the ideal insertion depth of the flexible laryngeal mask airway (FLMA) by elucidating the relationships between insertion depth and patient's age, body weight, height, and other parameters. We also evaluated an insertion technique that uses the change in intracuff pressure for proper positioning of the FLMA in cases where it is difficult to sense resistance during FLMA insertion. DESIGN: This study was a prospective observational study. SETTING: Participants were recruited from the Seoul National University Children's Hospital. PATIENTS: We enrolled 154 children aged ≤15 years with an American Society of Anesthesiologists physical status of I or II who were scheduled for ophthalmic surgery of <2 hours duration under general anesthesia. INTERVENTIONS: After induction of general anesthesia, FLMA insertion was guided by the change in intracuff pressure, measured using a manometer. The FLMA position was assessed using a fiberoptic bronchoscope. MEASUREMENTS: The FLMA insertion depth was measured at the end of each surgical procedure. A multiple linear regression model was then created using age, height, weight, nasal-tragus length, and sternal length. MAIN RESULTS: The FLMA was successfully inserted in the first attempt in 134 patients using continuous monitoring of intracuff pressure. Using multiple linear regression analysis and the Durbin-Watson test, we found that insertion depth was best predicted by height and weight (r2=0.777), and the resulting formula was as follows: insertion depth of FLMA (cm)=7.0+0.04×height (cm)+0.05 ×weight (kg). CONCLUSIONS: The FLMA insertion depth can be calculated using height and weight. Continuous monitoring of intracuff pressure during FLMA insertion is a useful alternative insertion method in cases where resistance is difficult to sense.

Clinical outcomes after unplanned extubation in a surgical intensive care population.

BACKGROUND: Clinical outcome after unplanned extubation (UE) in patients admitted to the surgical intensive care unit (SICU) has not been fully investigated. In this study we assessed in-hospital mortality of patients with UE and determined whether UE is a predictor of in-hospital mortality. Finally, we sought to identify predictors of reintubation after UE in mechanically ventilated patients in the SICU. METHODS: Medical charts of patients (n = 4,407) admitted to the SICU between October 2007 and December 2011 were reviewed retrospectively. RESULTS: Eighty-five episodes of UE occurred in 81 patients. Patients with UE required emergency surgery more frequently and had higher ICU and hospital mortality rates, reintubation rate, and APACHE II scores and longer mechanical ventilation (MV) and ICU stay than patients without UE (P < 0.05 for all associations). Multivariate analysis revealed that reintubation (odds ratio [95 % confidence interval]: 4.14 [2.58-6.67]; P < 0.001), APACHE II scores (1.14 [1.12-1.17]; P < 0.001), emergency surgery (1.73 [1.18-2.53]; P = 0.005), and chronic neurologic disease (2.11 [1.30-3.41]; P = 0.002) were associated with hospital mortality. Reintubation was necessary in 17 patients. On multivariate analysis, a score on the Richmond Agitation-Sedation Scale (RASS, 0.48 [0.31-0.76]; P = 0.001), PaO2/FiO2 ratio (0.99 [0.99-1.00]; P = 0.048), and MV duration before UE (1.46 [1.08-1.98]; P = 0.014) were independently associated with reintubation after UE. CONCLUSIONS: Our results indicated that although patients with UE had high in-hospital mortality, UE was not directly associated with in-hospital mortality. Reintubation, chronic neurologic disease, emergency operation, and higher APACHE II score were related to increased in-hospital mortality. A low RASS score, a low PaO2/FiO2 ratio, and long MV duration before UE were related to reintubation after UE.

Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis.

The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5'-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC50 = 27 microM.