Assessment of explicit and implicit memories during remimazolam anaesthesia using the process dissociation procedure: A prospective cohort study.

BACKGROUND: Memory formation during remimazolam anaesthesia, where a bispectral index (BIS) is sometimes not maintained at less than 60 despite the maximal dose, is worthy of evaluation. OBJECTIVE: Investigate the formation of explicit and implicit memories using the process dissociation procedure during remimazolam anaesthesia at a BIS of 60 to 80. DESIGN: A prospective cohort study. SETTING: A tertiary medical centre in Seoul, South Korea, between March 2022 and July 2022. PATIENTS: One hundred patients undergoing general anaesthesia using remimazolam. INTERVENTIONS: The BIS was maintained at 60 to 80 during anaesthesia induction with remimazolam. Words were spoken to patients via headphones for 15 min. MAIN OUTCOME MEASURE: The primary outcome was the probability of explicit or implicit memory formation as calculated using the original and extended models, within 24 h after word presentation. Conscious recall memory was assessed using a short-structured interview within 1 and 24 h after surgery. Memory formation was inferred to be absent if 0 was included in the 95% confidence interval (CI) of the probability. RESULTS: The main results showed no evidence of explicit or implicit memory. The 95% CI of the probability of explicit memory formation included 0 for both models, -0.01 (-0.04 to 0.02) and -0.04 (-0.10 to 0.01), respectively. The 95% CI of the probability of implicit memory formation did not include 0 when evaluated using the original model, 0.08 (0.06 to 0.10), but included 0 when evaluated using the extended model, 0.00 (-0.03 to 0.03). The modified Brice interview revealed no evidence of awareness. CONCLUSIONS: There was no evidence of explicit or implicit memory formation during remimazolam anaesthesia (BIS 60 to 80). Further research is warranted to establish whether explicit and implicit memories are still absent even in the presence of surgical stimulation. CLINICAL TRIAL REGISTRATION: KCT0006752 ( http://cris.nih.go.kr ).

The expected advantage of administering prophylactic antibiotics using target- concentration controlled infusion: Development of a new pharmacokinetic model of cefazolin.

The aim of this study was to explore the utility of target-concentration controlled infusion (TCI) as a prophylactic antibiotic administration method based on the results of a population pharmacokinetic model of cefazolin. In patients undergoing elective gastric surgery, 2 g of cefazolin was dissolved in 50 mL of saline and administered for 10 min prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefazolin. Population pharmacokinetic analysis was performed using non-linear mixed-effects modelling. To evaluate the effectiveness of the TCI method, stochastic simulation was performed based on the model construction results. In total, 360 total and 360 free plasma concentration measurements from 40 patients were used to characterise the pharmacokinetics of cefazolin. The changes in the total concentration of cefazolin over time were well-explained by the three-compartment mammillary model. Fat-free mass and estimated glomerular filtration rate were significant covariates. The probability of target attainment (PTA) to reach the target 100% fraction of time that the free plasma concentration of cefazolin was maintained above its minimal inhibitory concentration (fT > MIC) at MIC of 4 mg/L was also notably higher in the TCI method (90.7%) than in the standard method (17.0%). When cefazolin is administered by the TCI method, patient-tailored antibiotic dosing may be possible. The potential benefits of administering prophylactic antibiotics by the TCI method were observed. Further research is warranted to confirm the effectiveness of the TCI method.

Development of a new pharmacokinetic model for target-concentration controlled infusion of vancomycin in critically ill patients.

The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions). In total, 197 serum concentration measurements from 22 patients were used to characterise the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

Development of a new pharmacokinetic model for target-concentration controlled infusion of cefoxitin as a prophylactic antibiotic in colorectal surgical patients.

AIMS: There are several limitations to the existing method of administering cefoxitin as a prophylactic antibiotic, and the limitations may be overcome by applying the target-concentration controlled infusion (TCI) method. Population pharmacokinetic parameters are required to administer cefoxitin by the TCI method. The aim of this study was to construct a new pharmacokinetic model of cefoxitin for the TCI method in colorectal surgical patients. METHODS: In patients undergoing colorectal surgery, 2 g of cefoxitin was dissolved in 50 mL of saline and administered for 10 minutes prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefoxitin. Population pharmacokinetic analysis was performed using NONMEM software (ICON Development Solutions, Dublin, Ireland). Additionally, stochastic simulation was used to indirectly evaluate the effectiveness of the two administration methods (standard method vs TCI). RESULTS: In total, 297 plasma concentration measurements from 31 patients were used to characterize the pharmacokinetics of cefoxitin. A three-compartment mammillary model described the pharmacokinetics of cefoxitin. Body weight and creatinine clearance were significant covariates for clearance. The stochastic simulation showed that when compared with the standard method, the TCI method has a significantly higher fraction of time that the free concentration of cefoxitin is maintained above the minimum inhibitory concentration (P < .001). CONCLUSIONS: TCI has the potential to become a new infusion method for patient-tailored dosing in surgical patients. To administer cefoxitin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

Population pharmacokinetic analysis of ropivacaine extended-release from a temperature-responsive hydrogel in rats.

Therapeutic agents with a short half-life need to be administered frequently to achieve sustained and effective concentrations. This could be accomplished using sustained drug delivery technology. PF-72 (TGel Bio, Inc., Seoul, Korea) is a drug delivery system based on a powder obtained from lyophilisation of a reverse thermal hydrogel, which could assist in achieving prolonged pain relief if mixed with an anaesthetic and injected into the incision site following surgery. The pharmacokinetic parameters related to the absorption of the local anaesthetic ropivacaine delivered using this hydrogel were quantified. Ten rats were divided into two groups (n = 5 each), and equal doses (4 mg/kg) of different formulations were subcutaneously injected into the abdomen. The experimental group received PF-72 mixed with 0.75% ropivacaine, and the control group received 0.75% ropivacaine. Blood was collected at specific times to measure the plasma concentration of ropivacaine. Population pharmacokinetic analysis was performed using NONMEM VII level 4 (ICON Development Solutions, Dublin, Ireland). The one-compartment absorption model, which combines zero-order absorption and first-order absorption, was used to describe the change in ropivacaine plasma concentration over time. The type of formulation was a significant covariate for zero-order absorption duration (experimental group, 92.9 min; control group, 60.5 min). The addition of PF-72 to 0.75% ropivacaine increased the duration of absorption into the blood, suggesting a longer lasting effect of the analgesic injected into the surgical wound.

Do epoch lengths of hypnotic depth indicators affect estimated of blood-brain equilibration rate constants of propofol?

This study aimed to investigate the effect of epoch length of hypnotic depth indicators on the blood-brain equilibration rate constant (ke0) estimates of propofol. Propofol was administered by zero-order infusion (1.5, 3.0, 6, and 12 mg·kg-1·h-1) for one hour in 63 healthy volunteers. The ke0 of propofol was estimated using an effect-compartment model linking pharmacokinetics and pharmacodynamics, in which response variables were electroencephalographic approximate entropy (ApEn) or bispectral index (BIS) (n = 32 each for propofol infusion rates of 6 and 12 mg·kg-1·h-1). Epoch lengths of ApEn were 2, 10, 30, and 60 seconds (s). The correlations between plasma propofol concentrations (Cp) and BIS and ApEn 2, 10, 30, and 60 s were determined, as was the Ce associated with 50% probability of unconsciousness (Ce50,LOC). The pharmacokinetics of propofol were well described by a three-compartment model. The correlation coefficient between Cp and ApEn 2, 10, 30, and 60 s were -0.64, -0.54, -0.39, and -0.26, respectively, whereas correlation coefficient between Cp and BIS was -0.74. The blood-brain equilibration half-life based on the ke0 estimates for ApEn at 2, 10, 30, 60 s and BIS were 4.31, 3.96, 5.78. 6.54, 5.09 min, respectively, whereas the Ce50,LOC for ApEn at 2, 10, 30, 60 s and BIS were 1.55, 1.47, 1.28, 1.04, and 1.55 µg·ml-1, respectively. Since ke0, which determines the onset of drug action, varies according to the epoch length, it is necessary to consider the epoch length together when estimating ke0.

Evaluation of Surgical Pleth Index and Analgesia Nociception Index as surrogate pain measures in conscious postoperative patients: an observational study.

We evaluated the performance of the Surgical Plethysmographic Index (SPI) and the Analgesia Nociception Index (ANI) as surrogate pain measures and determined their respective cut-off values for detecting pain in conscious postoperative patients. In total, 192 patients after elective surgery were enrolled. Baseline SPI and ANI data were acquired for 10 min in the operating room prior to surgery when the patients rated their pain as 0 on the numerical rating scale (NRS). Upon arrival in the post-anaesthesia care unit (PACU) after surgery, SPI and ANI data were recorded for 10 min. The means of the recorded data at OR and PACU were defined as the values representing baseline and postoperative pain, respectively. SPI and ANI data obtained from 189 patients were analysed, who were anesthetized with propofol (n = 149) or sevoflurane (n = 40). Remifentanil was continuously infused intraoperatively in all patients. The values of SPI and ANI were significantly different in conscious patients without (NRS = 0) and with pain (NRS > 0). The areas under the receiver operating curves for SPI and ANI were 0.73 (P < 0.0001) and 0.67 (P < 0.0001), respectively. The cut-off values for SPI and ANI in predicting postoperative pain were 44 (sensitivity: 84%, specificity: 53%) and 63 (sensitivity: 52%, specificity: 82%), respectively, which are different from those suggested by their respective manufacturers for use in intraoperative state under general anaesthesia. The cut-off values of SPI and ANI for detecting pain were similar regardless of the type of anesthesia.

Pharmacodynamic Analysis of the Influence of Propofol on Left Ventricular Long-Axis Systolic Performance in Cardiac Surgical Patients.

BACKGROUND: Propofol induced a decline in the left ventricular (LV) systolic performance in non-cardiac surgery. We tested the hypothesis that propofol decreased the LV contractile function by dose dependent manner in cardiac surgery patients. METHODS: Anesthesia was maintained with target-controlled infusions of propofol and remifentanil in cardiac surgery patients. With a fixed effect-site concentration (Ce) of remifentanil (20 ng/mL) after sternotomy, the Ce of propofol was adjusted to maintain a Bispectral index of 40-60 (Ce1). Mitral annular Doppler tissue image tracings and other echocardiographic variables, including end-diastolic and end-systolic volumes, stroke volume, and mitral inflow pulse wave Doppler profile at Ce1, were recorded using transesophageal echocardiography. Echocardiographic recordings were repeated after the Ce-values of propofol were doubled and tripled at 10-minute intervals (defined as Ce2 and Ce3, respectively). Serial changes in echocardiographic variables for each Ce of propofol were assessed using generalized linear mixed effect modeling. The pharmacodynamic relationship between the Ce of propofol and peak systolic mitral annular velocity (Sm) was analyzed by logistic regression using non-linear mixed effect modeling (NONMEM). RESULTS: Means of Ce1, Ce2, and Ce3 were 0.8, 1.6, and 2.4 µg/mL, respectively, and their means of Sm (95% confidence interval) were 9.7 (9.3-10.2), 8.7 (8.2-9.1), and 7.5 cm/sec (7.0-8.0), respectively (P < 0.01). Ce values of propofol and Sm showed a significant inter-correlation and predictability (intercept, 10.8; slope-1.0 in generalized mixed linear modeling; P < 0.01). Ce values producing 10% and 20% decline of Sm with 50%-probability were 1.4 and 2.1 µ/mL, respectively. CONCLUSION: Propofol reduces LV systolic long-axis performance in a dose-dependent manner. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01826149.

The Influence of Propofol and Sevoflurane on Acute Kidney Injury After Colorectal Surgery: A Retrospective Cohort Study.

BACKGROUND: Acute kidney injury (AKI) is a primary cause of morbidity and mortality after major abdominal surgery; however, little is known about the effect of anesthetics on the development of AKI after colorectal surgery. The objective of this study was to compare the effects of anesthesia with propofol and sevoflurane on postoperative AKI after colorectal surgery. METHODS: For this study, we reviewed the electronic medical records of 4320 patients who underwent colorectal surgeries between January 2008 and December 2011. The influence of propofol and sevoflurane on the development of postoperative AKI and short-term outcomes was assessed by multivariable analysis, and the effect of the anesthetic agent on overall mortality was analyzed by a Cox proportional hazard model with propensity score matching method. RESULTS: Overall, the incidence of AKI was 9.6% by Acute Kidney Injury Network (AKIN) criteria and 5.8% by risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria. The incidence of AKI incidence was greater in patients receiving sevoflurane than those receiving propofol (142 [11.2%] vs 272 [8.9%], P = 0.02 by AKIN criteria, 94 [7.4%] vs 157 [5.1%], P = 0.004 by RIFLE criteria). Multivariate logistic regression and propensity score matching results indicated that, when compared with propofol, sevoflurane anesthesia may be associated with the development of postoperative AKI (odds ratio [OR], 1.29; P = 0.03; and OR, 1.44; P = 0.02 by AKIN and RIFLE criteria, and OR, 1.41; P = 0.04 by RIFLE criteria, respectively). We found no relationship between sevoflurane and overall mortality. CONCLUSIONS: Compared with anesthesia with propofol, anesthesia with sevoflurane may be associated with a modest increase in the incidence of AKI when RIFLE but not AKIN criteria are used. Thus, the clinical meaning of these results is uncertain. Further work is needed to clarify the relevance of such an association.

The Antiallodynic Effects of Nefopam Are Mediated by the Adenosine Triphosphate-Sensitive Potassium Channel in a Neuropathic Pain Model.

BACKGROUND: Nefopam hydrochloride is a centrally acting compound that induces antinociceptive and antihyperalgesic properties in neuropathic pain models. Previous reports have shown that activation of adenosine triphosphate (ATP)-sensitive and calcium-activated potassium (KATP and KCa2+) channels has antiallodynic effects in neuropathic pain. In the present study, we evaluated the relationship between potassium channels and nefopam to determine whether the antiallodynic effects of nefopam are mediated by potassium channels in a neuropathic pain model. METHODS: Mechanical allodynia was induced by spinal nerve ligation (SNL) in rats, and the paw withdrawal threshold (PWT) was evaluated by the use of von Frey filaments. Nefopam was administered intraperitoneally before or after SNL. We assessed the relationship between nefopam and intrathecal injection of the KCa2+ channel antagonists apamin and charybdotoxin, and the KATP channel blocker glibenclamide to assess their abilities to reverse the antiallodynic effects of nefopam. In addition, we evaluated whether the KATP channel opener pinacidil had antiallodynic effects and promoted the antiallodynic effects of nefopam. RESULTS: Administration of nefopam before and after SNL induced significant antiallodynic effects (P < .01, respectively), which were significantly reduced by glibenclamide (P < .01). Pinacidil improved the antiallodynic effects of nefopam (P < .01); however, apamin and charybdotoxin had little effects on the antiallodynic properties of nefopam. CONCLUSIONS: The antiallodynic effects of nefopam are increased by a KATP channel agonist and reversed by a KATP channel antagonist. These data suggest that the KATP channel is involved in the antiallodynic effects of nefopam in a neuropathic pain model.

Comparison of the analgesic effect of patient-controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery.

Oxycodone is a µ-opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient-controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 µg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient-controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%-75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4-83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4-103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient-controlled oxycodone provides similar effects for pain relief compared to patient-controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery.

High Left Ventricular Filling Pressure on Doppler Echocardiography Is Associated With Graft Failure and Overall Mortality Following Kidney Transplantation.

OBJECTIVE: Although E/e´ is prognostic of mortality in patients with end-stage renal disease (ESED), little is known about the prognostic implications of E/e´ following kidney transplant (KT). The objective of this study was to evaluate whether an elevated E/e´ is associated with graft function, postoperative hemodialysis, and overall mortality in end-stage renal disease patients following KT. DESIGN: A retrospective observational study. SETTING: Tertiary teaching hospital. PARTICIPANTS: In total, 1,045 patients underwent KT at the authors' hospital between January 2006 and December 2013. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided into groups with an E/e´<15 or≥15, as assessed by preoperative echocardiography (median time from preoperative assessment of echocardiography to surgery: 37 days [IQR: 16-68 days]). Of 1,045 patients, 821 patients (78.6%) had an E/e´<15, and 224 patients (21.4%) had an E/e´≥15. Multivariate analysis indicated that age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04, p = 0.001), diabetes mellitus (OR: 2.7; CI: 1.94-3.83, p<0.001), ß-blocker (OR: 1.4; CI: 1.03-1.95, p = 0.034), left atrial dimension (OR: 1.07; CI: 1.04-1.11, p<0.001), and left ventricular mass index (OR: 1.02; CI: 1.01-1.03, p<0.001) are predictive of E/e´≥15. After adjustment using inverse probability of treatment weighting, E/e´≥15 also was associated independently with postoperative hemodialysis (OR: 2.0; 95% CI: 1.5-2.6, p<0.001), graft failure (OR: 1.7; 95% CI: 1.4-2.2; p<0.001), and overall mortality (hazard ratio [HR]: 3.2; 95% CI: 2.1-4.8, p<0.001). CONCLUSIONS: Preoperative E/e´ is a prognostic indicator of overall mortality in ESRD patients undergoing KT.

Hypoalbuminemia Within Two Postoperative Days Is an Independent Risk Factor for Acute Kidney Injury Following Living Donor Liver Transplantation: A Propensity Score Analysis of 998 Consecutive Patients.

OBJECTIVE: Acute kidney injury is a known major complication of liver transplantation. Previous reports have shown that hypoalbuminemia is associated with an increased risk of acute kidney injury. However, little is known about the relationship between the early postoperative albumin level and acute kidney injury after living donor liver transplantation. The aim of this study was to identify the influence of the postoperative albumin level on acute kidney injury prevalence after living donor liver transplantation. DESIGN: A retrospective analysis. SETTING: A tertiary care university hospital. PATIENTS: Nine hundred and ninety-eighty patients underwent living donor liver transplantation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We divided the enrolled patients into two groups: group 1 included patients whose postoperative albumin level was less than 3.0 g/dL (n = 522), and group 2 included patients with an albumin level greater than or equal to 3.0 g/dL (n = 476). The prevalence of acute kidney injury, major adverse cardiac events, hospital stay, ICU stay, 30-day mortality, and overall mortality was analyzed using inverse probability of treatment weighting and propensity-score matching (n = 249 pairs) analysis. The prevalence of acute kidney injury was higher in group 1 defined by both Acute Kidney Injury Network (after adjusting for inverse probability of treatment weighting [n = 364; 69.7%] and propensity-score matching [n = 152; 61.0%]) and Risk, Injury, Failure, Loss, and End-stage kidney disease criteria (after adjusting for inverse probability of treatment weighting [n = 419; 80.3%] and propensity-score matching [n = 190; 76.3%]). The overall mortality was higher in group 1 after adjusting for inverse probability of treatment weighting (n = 61; 11.7%) and propensity-score matching (n = 23; 9.2%). The hospital (p < 0.001) and ICU (p = 0.006) stays were significantly prolonged in group 1. Acute kidney injury was associated with ICU stay by the Acute Kidney Injury Network criteria (p = 0.034), and overall mortality was correlated with acute kidney injury by the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria (p = 0.014). CONCLUSIONS: Early postoperative hypoalbuminemia is an independent risk factor for acute kidney injury, and postoperative acute kidney injury is related to postoperative ICU stay and overall mortality after living donor liver transplantation.

Dosing Strategy of Ramosetron to Prevent Postoperative Nausea and Vomiting and Development of Prediction Models Using Data Obtained From Randomized Controlled Trials: A Comparative Study.

PURPOSE: The study aimed to compare the postoperative nausea and vomiting (PONV) preventive effect of repeated administration of ramosetron with the standard treatment group and compare models to predict the incidence of PONV using machine-learning techniques. METHODS: A total of 261 patients scheduled for breast surgery were analyzed to evaluate the effectiveness of repeated intravenous administration of ramosetron. All patients were administered 0.3 mg ramosetron just before the end of surgery. For the repeated dose of ramosetron group, an additional dose of 0.3 mg was administered at 4, 22, and 46 hours after the end of the surgery. Postoperative nausea, vomiting, and retching were evaluated using the Rhodes Index of Nausea, Vomiting, and Retching at 6, 24, and 48 hours postoperatively. Previously published randomized controlled data were combined with the data of this study to create a new dataset of 1390 patients, and machine-learning-based PONV prediction models (classification tree, random forest, extreme gradient boosting, and neural network) was constructed and compared with the Apfel model. FINDINGS: Fifty patients (38.5%) and 60 patients (45.8%) reported nausea, vomiting, or retching 48 hours postoperatively in the standard and repeated-dose groups, respectively (P = 0.317, χ2 test). Median sensitivity, specificity, and accuracy of the Apfel model analyzed using the training set were 0.815, 0.344, and 0.495, respectively. IMPLICATIONS: The repeated administration of ramosetron did not reduce the incidence of PONV. The Apfel model had high sensitivity, however, its specificity and accuracy were lower than that in machine-learning-based models.

Frequency and characteristics of patients with bispectral index values of 60 or higher during the induction and maintenance of general anesthesia with remimazolam.

In Korea, the approved anesthetic regimen of remimazolam starts with 6 mg/kg/h or 12 mg/kg/h until loss of consciousness, followed by maintenance at 1-2 mg/kg/h. Some patients receiving remimazolam for general anesthesia experience occasional difficulty maintaining bispectral index (BIS) value ˂ 60. This retrospective study aimed to analyze the data from patients undergoing elective surgery under remimazolam based-general anesthesia to determine the frequency and physical characteristics of patients with BIS values ˂ 60. The criterion was established for patients with a poorly maintained BIS value < 60. The frequency and physical characteristics of patients who satisfied this criterion were investigated through their medical records. The modified Brice interview was conducted within 24 h after surgery. Among the 1500 patients included in the analysis, 61 (4.1%) met the criteria for BIS ˂ 60. Based on the modified Brice interview, none of the patients with poorly maintained BIS ˂ 60 complained of intraoperative awareness based on the modified Brice interview or exhibit specific physical characteristics. These patients accounted for less than 5% of the total population studied. Notably, physical characteristics alone are insufficient to predict such patients before surgery.

Effect-site concentration of remimazolam at loss and recovery of responsiveness during general anesthesia: a simulation study.

BACKGROUND: The objective of this study was to investigate the effect-site concentration (Ce) of remimazolam at loss of response (LOR) and recovery of response (ROR) in patients underwent general anesthesia using simulation. In addition, the relationships between patient's factors and simulated Ce at LOR and ROR were examined. METHODS: The medical records of 81 patients who underwent elective surgery under general anesthesia using remimazolam with simulation of Ce between August 4, 2021 and October 12, 2021, were retrospectively reviewed. Remimazolam was administered as an induction dose of 6 or 12 mg/kg/h until the patient became unresponsive, followed by 0.3-2 mg/kg/ h to maintain BIS values below 60. Simultaneously, simulations of manual infusion mode were performed using Asan Pump software and the Ce of remimazolam was simulated using the Schüttler model. Whenever infusion rate of remimazolam was manually changed, the simulated Ce was confirmed almost simultaneously. LOR and ROR, defined as unresponsive and eye-opening to verbal commands, respectively, were recorded in the Asan Pump program. RESULTS: The median (1Q, 3Q) simulated Ce at LOR and ROR were 0.7 (0.5, 0.9) and 0.3 (0.2, 0.4) µg/ml, respectively. LOR was achieved in 1.9 min after remimazolam infusion with cumulative doses of 0.3 mg/kg. There was a significant relationship between age and simulated Ce at ROR (Ce at ROR = -0.0043 × age + 0.57, r = 0.30, P = 0.014). CONCLUSIONS: For optimal dosage adjustment, simulating Ce while administering remimazolam with a weight-based dose during anesthesia is helpful. Elderly patients may recover from anesthesia at lower Ce of remimazolam.

Association of Preoperative Prognostic Nutritional Index and Postoperative Acute Kidney Injury in Patients with Colorectal Cancer Surgery.

The prognostic nutritional index (PNI) has been reported to be associated with postoperative complications and prognosis in cancer surgery. However, few studies have evaluated the association between preoperative PNI and postoperative acute kidney injury (AKI) in colorectal cancer patients. This study evaluated association of preoperative PNI and postoperative AKI in patients who underwent colorectal cancer surgery. This study retrospectively analyzed 3543 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into four groups by the quartile of PNI: Q1 (≤43.79), Q2 (43.79-47.79), Q3 (47.79-51.62), and Q4 (≥51.62). Multivariate regression analysis was performed to assess the risk factors for AKI and 1-year mortality. AKI was defined according to Kidney Disease Improving Global Outcomes classification (KDIGO) criteria. Additionally, we assessed surgical outcomes such as hospital stay, ICU admission, and postoperative complications. The incidence of postoperative AKI tended to increase in the Q1 group (13.4%, 9.2%, 9.4%, 8.8%). In the multivariate analysis, high preoperative PNI was significantly associated with low risk of postoperative AKI (adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93-0.99, p = 0.003) and low 1-year mortality (OR: 0.92, 95% CI: 0.86-0.98, p = 0.011). Male sex, body mass index, diabetes mellitus, and hypertension were risk factors for AKI. The Q1 (≤43.79) group had poor surgical outcomes, such as postoperative AKI (OR: 1.52, 95% CI: 1.18-1.95, p = 0.001), higher rates of ICU admission (OR: 3.13, 95% CI: 1.82-5.39, p < 0.001) and higher overall mortality (OR: 3.81, 95% CI: 1.86-7.79, p < 0.001). In conclusion, low preoperative PNI levels, especially in the Q1 (≤43.79), were significantly associated with postoperative AKI and surgical outcomes, such as hospital stay, postoperative ICU admission, and mortality.

Comparison of the Effects of Laparoscopic and Open Surgery on Postoperative Acute Kidney Injury in Patients with Colorectal Cancer: Propensity Score Analysis.

Postoperative acute kidney injury (AKI) is a serious complication that increases patient morbidity and mortality. However, few studies have evaluated the effect of laparoscopic surgery on postoperative AKI. This study compared the incidence of postoperative AKI between laparoscopic and open surgery in patients with colorectal cancer. This study retrospectively analyzed 3637 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into laparoscopic (n = 987) and open (n = 2650) surgery groups. We performed multivariable regression analysis to assess the risk factors for AKI and propensity score matching analysis to compare the incidence of AKI between the two groups. We also assessed postoperative intensive care unit (ICU) admission, complications, hospital stay, and 1-year mortality. We observed no significant differences in the incidence of postoperative AKI between the two groups before (8.8% vs. 9.1%, p = 0.406) and after (8.8% vs. 7.7%, p = 0.406) matching. Laparoscopic surgery was not associated with AKI even after adjusting for intraoperative variables (adjusted odds ratio (OR): 1.17, 95% confidence interval (CI): 0.84-1.62, p = 0.355). Body mass index, diabetes mellitus, hypertension, and albumin were risk factors for AKI. ICU admission (0.6% vs. 2.5%, p = 0.001), complications (0.2% vs. 1.5%, p = 0.002), hospital stay (6.89 days vs. 8.61 days, p < 0.001), and 1-year mortality (0.1% vs. 0.9%, p = 0.021) were significantly better in the laparoscopic than in the open group. The incidence of postoperative AKI did not differ significantly between laparoscopic and open surgery. However, considering its better surgical outcomes, laparoscopic surgery may be recommended for patients with colorectal cancer.

Performance of the Surgical Pleth Index and Analgesia Nociception Index in Healthy Volunteers and Parturients.

Various commercially available nociception devices have been developed to quantify intraoperative pain. The Surgical Pleth Index (SPI) and Analgesia Nociception Index (ANI) are among the analgesic indices that have been widely used for the evaluation of surgical patients. This study aimed to evaluate the clinical performance of the SPI and ANI in conscious healthy volunteers and parturients. Ten healthy volunteers and 10 parturients participated in this study. An algometer was used to induce bone pain in the volunteers until they rated their pain as five on the numerical rating scale (NRS); this procedure was repeated during the administration of remifentanil or normal saline. The study comprised two periods, and the volunteers were infused with different solutions in each period: normal saline during one period and remifentanil during the other in a randomized order. The parturients' SPI and ANI data were collected for 2 min when they rated their pain levels as 0, 5, and 7 on the NRS, respectively. Both the SPI and ANI values differed significantly between NRS 0 and NRS 5 (P < 0.001) in the volunteers, irrespective of the solution administered (remifentanil or normal saline). At NRS 5, the SPI showed similar values, irrespective of remifentanil administration, while the ANI showed significantly lower values on remifentanil administration (P = 0.028). The SPI and ANI values at NRS 5 and NRS 7 did not differ significantly in the parturients (P = 0.101 for SPI, P = 0.687 for ANI). Thus, the SPI and ANI were effective indices for detecting pain in healthy volunteers and parturients.