Kenji Shigemi

Background/Objectives: Under general anesthesia, maintaining patients’ blood pressure (BP) is important to prevent organ ischemia. When bleeding occurs, it is sometimes difficult to increase BP with boluses of fluids or transfusions, and vasoconstrictors must be administered. This study investigated circulatory dynamic changes in patients who bled during surgery and were administered phenylephrine, particularly left ventricular end-diastolic volume (EDV), effective arterial elastance (Ea), and left ventricular end-systolic elastance (Ees), calculating each value from the left ventricular–arterial coupling (Ees/Ea). Methods: We calculated Ees/Ea using electrocardiograms, arterial pressure waveforms, and phonocardiograms using an esophageal stethoscope. We investigated the changes in patients’ EDV, Ea, and Ees during two periods: phenylephrine administration and after BP elevation. Results: The seven participants comprised three men and four women. Between the two periods, linear mixed-model analysis revealed that mean arterial pressure (MAP), Ea, and Ees significantly increased over time (MAP; β = 8.7, p < 0.01, Ea; β = 0.22, p < 0.05, Ees; β = 0.73, p < 0.05), while no significant changes were observed in other parameters such as heart rate and EDV. Conventional parameters demonstrated that stroke volume variation significantly decreased (β = −2.0, p = 0.01), systemic vascular resistance index significantly increased (β = 200, p < 0.01), while no significant change was observed in cardiac index (β = −0.03, p = 0.7). In patients administered phenylephrine due to BP decrease from bleeding, significant changes in afterload and cardiac contractility occurred without changes in preload. Conclusions: Our noninvasive method for calculating EDV, Ea, and Ees can be valuable for monitoring hemodynamics under anesthesia.

Background/Objectives: This study aimed to develop and evaluate an automated fluid infusion management system for preventing hypotension during general anesthesia. Methods: This study was a single-blind, randomized, non-inferiority, clinical trial. Seventy-nine patients undergoing surgery under general anesthesia were randomly assigned to either an automatic group or a manual group. In the automatic group, the infusion rate was automatically adjusted based on stroke volume (SV) and effective arterial elastance (Ea), whereas in the manual group, the attending anesthesiologist manually adjusted the infusion rate according to the Enhanced Recovery After Surgery (ERAS) protocol. The primary endpoint was the proportion of time during anesthesia that mean arterial pressure (Pm) was maintained at ≥65 mmHg. Secondary endpoints included the proportion of time the estimated stroke volume index (esSVI) was below the threshold, total fluid volume administered, total phenylephrine dose, urine output, blood loss, and average estimated stroke volume variation (esSVV). Results: The results demonstrated non-inferiority of the automatic group to the manual group in maintaining Pm ≥ 65 mmHg (automatic group: 82.0 ± 12.7%, manual group: 79.9 ± 15.7%; difference [automatic group−manual group]: 2.0 percentage points; one-sided 97.5% CI lower limit: −4.7%; non-inferiority margin: −5%). There were no significant differences between the groups in total fluid volume, phenylephrine dose, urine output, or blood loss. No severe adverse events or device-related adverse events were observed. Conclusions: The automated system maintained intraoperative blood pressure safely and effectively.

Maintaining respiratory system compliance (Crs) is a clue for lung recruitment strategies during surgery; however, patients’ baseline Crs values have not been adequately addressed. We studied the association of low Crs at the induction of anesthesia (iCrs) with limited intraoperative respiratory management. We conducted a secondary analysis of retrospective study of consecutive surgical patients on ventilators between 2019 and 2020. The intra- and postoperative respiratory-related parameters were compared between the low iCrs group (2O, n = 1392) or the other group (n = 4176). The age was older and both the duration of surgery and the duration of anesthesia were shorter in the low iCrs group than in the other groups. Unexpectedly, the low iCrs group was associated with a smaller decrease in hourly changes in Crs (−1.4% [−11.3% to 11.2%] vs −13.0% [−21.3% to −5.3%], P < .001). Despite the smaller decrease in Crs, the low iCrs group showed a higher incidence of > 3 days of postoperative oxygen therapy (adjusted OR 1.60 (1.29–1.97), P < .001) and > 3 days of mechanical ventilation following surgery (adjusted OR, 1.55 (1.02–2.36), P = .039) than the other group. The significances in postoperative therapies were exaggerated in emergency surgery. The low iCrs patients showed a smaller decline in hourly changes in Crs and longer postoperative respiratory supports. Not only the decrease in Crs during surgery but also the initial Crs value warrant the intra- and postoperative respiratory management.

Background/Objectives: No study has simulated rocuronium (Rb) effect-site concentrations (Ce_Rb) using real-time data—such as Rb concentrations, train-of-four (TOF) count (TOFC), and TOF ratio (TOFR)—under mechanical Rb administration. Therefore, we aimed to investigate post-operative recurarization and changes in the Ce_Rb after sugammadex (SGX) administration under conditions where Rb dosing was strictly administered using an automated delivery system for total intravenous anesthesia. Methods: This non-interventional, retrospective, observational study included 74 patients from an existing clinical trial who met the study criteria. Rb was automatically administered during surgery to maintain a TOFC of 1. SGX (2 mg/kg) was manually administered post-surgery, and the time until the TOFR reached ≥0.9 (if the time exceeded 3 min, 0.5 mg/kg SGX was added every minute). The results were analyzed using a pharmacokinetic (PK)–pharmacodynamic (PD) simulation model of the Rb-SGX complex. Results: The average total dose of administered SGX was 2.2 ± 0.4 mg/kg (mean ± standard deviation). The time from SGX administration till the TOFR reached ≥0.9 was 2.9 ± 1.1 min. Furthermore, Ce_Rb at recovery (Ce_r) was 0.3 ± 0.2 μg/mL. Notably, no cases showed post-operative recurarization within 24 h of surgery. PK–PD model simulations revealed that Ce_Rb increased again after reaching the lowest Ce_Rb in 72 cases, although no increase was recorded beyond Ce_r, suggesting no numerical risk of recurarization. Conclusions: Our results show that if TOFC of 1 is strictly maintained intraoperatively and SGX is administered till the TOFR reaches ≥0.9, post-operative recurarization does not occur.

Objectives: The purpose of this study was to compare left ventricular end-diastolic volume (EDV), derived from left ventricular arterial coupling (Ees/Ea), and mean arterial blood pressure. Both of these methods of measuring EDV require some invasive procedure. However, the method of measuring EDV approximate is less invasive than the EDV coupling measuring method. This is because EDV approximate only requires arterial pressure waveform as an invasive procedure. Methods: This study included 14 patients with normal cardiac function who underwent general anesthesia. The point when blood pressure stabilized after the induction of anesthesia was taken as a baseline according to the study protocol. At the point when systolic arterial blood pressure fell 10% or more from the baseline blood pressure, 300 mL of colloid solution was administered over 15 min. EDV approximate and EDV coupling were calculated for each of the 14 patients at three points during the course of anesthetic. Each value was obtained by calculating a 5 min average. The timing of these three points was 5 min before, 5 min during, and 5 min after infusion loading. Results: The total number of comparable points was 42; 3 points were taken from each of the 14 participants. Both EDV approximate and EDV coupling increased through the infusion load testing. Scatter plots were prepared, and regression lines were calculated from the obtained values. A high correlation was shown between EDV approximate and EDV coupling (R² = 0.96, p < 0.05). Conclusions: In patients with good cardiac function, EDV approximate can be substituted for EDV coupling, suggesting the possibility that EDV can be continuously and less invasively calculated under the situation of general anesthesia.

We developed a system to adjust the rate of a continuous rocuronium (Rb) infusion to achieve 3 ≤ %T1 ≤ 10 with a closed-loop control. Samples were collected from 15 patients, and Rb blood concentrations were measured at the following time points: (1) when %T1 recovered to 3% or more after the initial Rb infusion; (2) when %T1 stabilized within the target range; (3) at the cessation of the Rb infusion; (4) 5 min after the sugammadex administration. The predicted Rb blood concentration at each time point was calculated and recorded using the pharmacokinetic parameters of Wierda et al. At time points (1), (2), and (3), the predicted blood concentrations were in good agreement with the measured values, but after the administration of sugammadex, the blood concentrations were higher than the predicted values because the Rb distributed in the tissues migrated into the blood. From the above, it was confirmed that the predicted blood concentration of Rb can be a good indicator for the automatic Rb administration control.

Background: We previously developed an automated total intravenous anesthesia control system that uses new closed-loop system algorithms to administer propofol, remifentanil, and rocuronium based on the bispectral index and train-of-four data. We recently improved this automated control system by adding a safety mechanism and using a modified monitoring device. Methods: Patients scheduled for elective surgery were randomly assigned to closed-loop feedback control (automatic group) or the manual administration of propofol, remifentanil, and rocuronium (manual group). The proportion of time during which the proper management of three-agent anesthesia was maintained during surgery was determined as the primary endpoint. Results: The proportion of time during which the three components of sedation, analgesia, and muscle relaxation were adequately controlled was 87.21 ± 12.79% in the automatic group, which was non-inferior to the proportion of 65.19 ± 20.16% in the manual group (p < 0.001). Adverse events during the operative or postoperative observation periods were significantly less frequent in the automatic group (54 patients, 90.0%) than in the manual group (60 patients, 100.0%; p = 0.027). Conclusion: Our three-agent automated control system, which features an improved muscle relaxation monitor and safety mechanism added to the basic control algorithms, maintained sedation, analgesia, and muscle relaxation appropriately in a manner non-inferior to anesthesiologists without compromising safety.

Background: Left ventricular-arterial coupling is assessed as the ratio of left ventricular end-systolic elastance (Ees) to arterial elastance (Ea). Previous studies have introduced non-invasive estimations of Ees/Ea. It requires only four variables, namely pre-ejection period, ejection time, end-systolic pressure and diastolic pressure. The aims of the present study were to clarify the reference values of Ees/Ea estimated using the noninvasive technique, and to investigate the effects of age and gender on Ees/Ea in healthy subjects. Methods: This retrospective study utilized data from healthy, 30-79 year old subjects. We recorded electrocardiogram, phonocardiogram, and brachial arterial pulse waves simultaneously using the vascular screening system, and used the observed variables to calculate Ees/Ea. We separated subjects into five groups according to their age and compared Ees/Ea among the different age groups. Results: The study included 2114 males and 2292 females. Ees/Ea ranged from 1.87 to 2.04 in males, and 1.97 to 2.32 in females. We observed no age-related differences in Ees/Ea in males (p=0.10), and significant differences in females (pConclusions: We clarified the reference values of Ees/Ea in healthy subjects. The effect of age on Ees/Ea is different in males and females, although Ees/Ea is maintained within a relatively narrow range in all subjects.

Ejection fraction (EF), which is assessed using ultrasonography, is a standard parameter for evaluating cardiac function in clinical cardiology and for cardiovascular management during general anesthesia. However, it is impossible to continuously and non-invasively assess EF using ultrasonography. The aim of our study was to develop a method for estimating EF non-invasively using the left ventricular arterial coupling ratio (Ees/Ea). Ees/Ea was estimated non-invasively using the parameters pre-ejection period (PEP), ejection time (ET), end-systolic pressure (Pes) and diastolic pressure (Pad), which were calculated from a vascular screening system, VeSera 1000/1500 (Fukuda Denshi Co., Ltd., Tokyo, Japan). Then, left ventricular efficiency (Eff) as a pump, defined as the ratio of external work (EW) to myocardial oxygen consumption, which strongly correlates with the pressure-volume area (PVA), was calculated by a new formula using Ees/Ea, and was used to approximate EF (EFeff). Simultaneously, we measured EF using transthoracic echocardiography (EFecho), and compared it with EFeff. The study included 44 healthy adults (36 males, 8 females), in whom mean EFecho was 66 ± 5% and EFeff was 57 ± 9%. We found a positive correlation between EFecho and EFeff (R² = 0.219, p < 0.05) on Bland-Altman analysis, with limits of agreement of – 7.5 to 24.4%, and percentage error of 24%. The results suggest that EF can be measured non-invasively using left ventricular arterial coupling.

Background: Analgesic and sedative agents interact with each other, and their relationship is explained in a curve convex below. In the automated control anesthesia system based on this relationship that we developed, the dose of analgesic is adjusted with the necessary remifentanil concentration, determined with propofol-remifentanil interactions, as an estimated maximal individual concentration (esMIC). With the system, a study in patients under anesthesia management by an anesthesiologist was conducted to compare the effect-site concentration (ESC) of remifentanil administered at the anesthesiologist’s discretion and the esMIC calculated with drug-drug interactions for their relationship and to assess whether the analgesic dose administered based on esMIC is appropriate. Methodology: In the present study involving 20 patients, anesthesiologists changed the propofol (P) infusion rate and remifentanil (R) infusion rate to maintain BIS value of 45. The estimated target-effect-site concentration of propofol for maintaining BIS 45 and the ESC of remifentanil (ESC_R) based on the model by Minto et al. were calculated. Moreover, with these data sets, the isodynamic curve of ESC of propofol (ESC_P) for maintaining BIS 45 (Y) and ESC_R (X) was determined to be an equilateral hyperbola (Y = c/(X-a) + b). With the ESC_R at which even raising ESC_R would result in small decreases in ESC_P considered the esMIC, the ESC_R at the point at which the slope of this curve is apos;1 (neutral point) and at the point of the curve where the y-component deviation of the asymptote (y = b) is 20% (esMIC₂₀) calculated every 6 sec. The ESC_R at the time point of an adequate analgesic state as deemed by the anesthesiologist after anesthesia had been started for 15 min was compared with the esMIC₂₀ determined by objective calculations. Results: The ESC_R and esMIC were 11.9 ± 2.4 and 11.6 ± 2.0 ng/ml, respectively. Moreover, the median ESC_R and esMIC in the patients showed a very good correlation (correlation coefficient R² = 0.88, p < 0.01). Conclusion: The necessary analgesic concentrations estimated with drug-drug interactions did not contradict those determined at anesthesiologists’ discretion and are considered to assure a reasonable analgesic state. Key words: Analgesia; Sedation; Remifentanil; Effect-Site Concentrations Citation: Matsuki Y, Nagata O, Shigemi K. Good correlation between necessary remifentanil concentrations in individual patients determined from sedative-analgesic interactions using pharmacokinetic simulations and the remifentanil concentrations used at anesthesiologists’ discretion. Anaesth. pain intensive care 2023;27(5):491−494;  DOI: 10.35975/apic.v27i5.2300 Received: April 04, 2023; Reviewed: May 13, 2023; Accepted: June 16, 2023