Hypotension after general anaesthesia induction using remimazolam or propofol in geriatric patients undergoing sevoflurane anaesthesia with remifentanil: a single-centre, double-blind, randomised controlled trial.

BACKGROUND: The occurrence of hypotension after induction of general anaesthesia is common in geriatric patients, and should be prevented to minimise perioperative complications. Compared with propofol, remimazolam potentially has a lower incidence of hypotension. This study aimed to compare the incidence of hypotension after general anaesthesia induction with remimazolam or propofol in geriatric patients. METHODS: This single-centre, double-blind, randomised trial enrolled 90 patients aged ≥80 yr who received general anaesthesia for scheduled surgery. Patients were randomised to receive remimazolam (12 mg kg-1 h-1) or propofol (0.025 mg kg-1 s-1) for anaesthesia induction, with remifentanil and sevoflurane. The presence or absence of hypertension on the ward served as the stratification factor. The incidence of hypotension after the induction of general anaesthesia, defined as a noninvasive mean arterial pressure of <65 mm Hg measured every minute from initiation of drug administration to 3 min after tracheal intubation, was the primary outcome. Subgroup analysis was performed for the primary outcome using preoperative ward hypertension, clinical frailty scale, Charlson Comorbidity Index, and age. RESULTS: Three subjects were excluded before drug administration, and 87 subjects were included in the analysis. The incidence of hypotension was 72.1% (31/43) and 72.7% (32/44) with remimazolam or propofol, respectively. No statistically significant differences (adjusted odds ratio, 0.96; 95% confidence interval, 0.37-2.46; P=0.93) were observed between groups. Subgroup analysis revealed no significant differences between groups. CONCLUSIONS: Compared with propofol, remimazolam did not reduce the incidence of hypotension after general anaesthesia induction in patients aged ≥80 yr. CLINICAL TRIAL REGISTRATION: UMIN000042587.

What are standard monitoring devices for anesthesia in future?

Monitoring the patient's physiological functions is critical in clinical anesthesia. The latest version of the Japanese Society of Anesthesiologists' Guidelines for Safe Anesthesia Monitoring, revised in 2019, covers various factors, including electroencephalogram monitoring, oxygenation, ventilation, circulation, and muscle relaxation. However, with recent advances in monitoring technologies, the information provided has become more detailed, requiring practitioners to update their knowledge. At a symposium organized by the Journal of Anesthesia in 2023, experts across five fields discussed their respective topics: anesthesiologists need to interpret not only the values displayed on processed electroencephalogram monitors but also raw electroencephalogram data in the foreseeable future. In addition to the traditional concern of preventing hypoxemia, monitoring for potential hyperoxemia and the effects of mechanical ventilation itself will become increasingly important. The importance of using AI analytics to predict hypotension, assess nociception, and evaluate microcirculation may increase. With the recent increase in the availability of neuromuscular monitoring devices in Japan, it is important for anesthesiologists to become thoroughly familiar with the features of each device to ensure its effective use. There is a growing desire to develop and introduce a well-organized, integrated "single screen" monitor.

Remimazolam anesthesia in pediatric patients undergoing cardiac catheterization for congenital heart disease: a retrospective observational study.

BACKGROUND: Benzodiazepines are used in pediatric patients with congenital heart disease (CHD) because of their mild hemodynamic depressant effects. A novel short-acting benzodiazepine, remimazolam, is expected to be suitable for these patients. We examined the characteristics of remimazolam anesthesia in pediatric patients with CHD undergoing cardiac catheterization. METHODS: This single-center retrospective study included pediatric patients undergoing cardiac catheterization for CHD. The primary outcome was the remimazolam dose for loss of consciousness. Secondary outcomes included the mean maintenance remimazolam dose, recovery time from anesthesia, predicted remimazolam concentration at emergence, decrease in blood pressure and heart rate, vasopressor administration during anesthesia, electroencephalogram index (bispectral index: BIS or patient state index: PSI), and life-threatening adverse events. RESULTS: Thirty-nine patients, aged 2 months to 16 years, were included. Thirty-three patients received a median [interquartile] midazolam dose of 0.10 [0.10-0.10] mg.kg-1 in the pre-anesthesia room. The remimazolam dose for loss of consciousness was 0.34 [0.26-0.45] mg.kg-1. The mean maintenance dose was 1.0 [0.8-1.4] mg.kg-1.h-1. The recovery time was 15 [12-17] min. The predicted remimazolam concentration at emergence was 0.4-1.2 µg.ml-1 in 3-6-year-old patients. Blood pressure and heart rate decreased by 30% in 15 and 6 patients, respectively. Vasopressors were administered as a bolus in 8 patients. The BIS or PSI did not fall ≤ 60 or ≤ 50, respectively, in 51% of patients before tracheal intubation. No life-threatening adverse events were reported. CONCLUSIONS: Remimazolam is a good alternative anesthetic agent for pediatric patients undergoing cardiac catheterization for CHD.

Remimazolam: its clinical pharmacology and evolving role in anesthesia and sedation practice.

PURPOSE OF REVIEW: Remimazolam is a novel benzodiazepine anesthetic/sedative, designed as a rapidly metabolized carboxylic acid. Since its recent launch, the role of remimazolam in modern anesthesia and sedation practice is still evolving. This review aims to outline the clinical pharmacology and clinical utility of remimazolam to elucidate its potential advantages and limitations. RECENT FINDINGS: Remimazolam is "short-acting" but not ultra-short-acting compared with propofol based on context-sensitive decrement times. But compared to propofol, the availability of the benzodiazepine antagonist, flumazenil, is considered an advantage, particularly in certain emergency situations such as in patients with difficult airways. However, because flumazenil is shorter acting than remimazolam when remimazolam accumulates or is present in a high concentration, the reappearance of remimazolam sedation may occur after the initial reversal of anesthesia/sedation from flumazenil administration. Although it is beneficial that remimazolam causes less respiratory depression and hypotension than propofol, serious respiratory depression and hypotension can still occur. Remimazolam administration causes minimal or no pain on injection. Remimazolam is associated with less postoperative nausea and vomiting than inhaled anesthetics, but propofol is clearly superior in this regard. The anesthetic/sedative effects may be prolonged by severe hepatic impairment; remimazolam tolerance can occur in long-term benzodiazepine users. SUMMARY: Remimazolam may be beneficial to use in procedural sedation and general anesthesia for patients with difficult airways or hemodynamic instability. Further clinical studies with remimazolam are warranted to identify the potential benefits in other settings and patient populations.

Equilibration rate constant, ke0, to determine effect-site concentration for the Masui remimazolam population pharmacokinetic model in general anesthesia patients.

Effect-site concentration is widely used to determine drug dosage in anesthesia practice. To obtain effect-site concentration, a pharmacokinetic model with a corresponding equilibration rate constant between plasma and effect-site, ke0, is necessary. Remimazolam, a novel short-acting benzodiazepine, has been approved as anesthetic/sedative. Recently, a remimazolam pharmacokinetic model has been published using a large dataset including wide range of subject characteristics (416 males and 246 females, age 18-93 years, total body weight 34-149 kg, height 133-204 cm, body mass index 14-61 kg m-2, ASA physical status: I-IV, and Asian, White, American African, and 2 other races). This Masui model can be applicable to various patients, but a pharmacodynamic model including ke0 was not developed simultaneously. A previous article has indicated that the time to peak effect of drug after its bolus should be used to determine ke0 for a pharmacokinetic model without simultaneous development of corresponding pharmacodynamic model. The ke0 value can be calculated using numerical analysis but not algebraic solution. We provide the detail method of the numerical analysis and a tool to have ke0 value easily for the Masui remimazolam PK model. Additionally, we provide a multiple regression model to have ke0 value for the PK model.

A population pharmacokinetic model of remimazolam for general anesthesia and consideration of remimazolam dose in clinical practice.

BACKGROUND: Remimazolam besylate is a novel short-acting benzodiazepine. An appropriate pharmacokinetic model of remimazolam is desirable in anesthesia practice. The aim of the study was to develop a pharmacokinetic model using plasma samples from patients anesthetized with remimazolam. Influence of patient characteristics, context-sensitive decrement-times, and dose regimens were also examined. METHODS: Data were obtained from four trials on patients, and seven trials on healthy volunteers. The characteristics of 416 male and 246 female subjects were as follows: age, 18-93 years; body weight, 34-149 kg; and American Society of Anesthesiologists physical status (ASA-PS), I-IV. 2231 arterial and 3200 venous samples were used for the final model. The equilibration rate constant between arterial plasma and effect-site was estimated using the concept of time to peak effect. The final model was used to generate context-sensitive decrement times and dose regimens for general anesthesia. RESULTS: A three-compartment model plus virtual venous compartment with allometric scaling of adjusted body weight (ABW), age, sex, and ASA-PS as covariates were selected as the final model. Elimination clearance was lower in males, and in subjects with higher ABW and ASA-PS scores. Approximately 10% or 20% higher dose rate was necessary in females than in males or ASA-PS I/II than III/IV patient. The context-sensitive half-time for effect-site concentration in a 55-year-old, 70-kg, 170-cm male or female ASA-PS I/II patient after > 6-h infusion was 16.7 or 15.9 min. CONCLUSION: Remimazolam pharmacokinetic model for general anesthesia was successfully developed. ABW, ASA-PS, and sex has a considerable impact on the remimazolam concentration.

Propofol suppresses the His-ventricular conduction in paediatric patients.

WHAT IS KNOWN AND OBJECTIVE: Propofol is the most commonly used intravenous anaesthetic worldwide and is considered to be safe for all ages. However, there have been some reports that propofol induces severe atrioventricular (AV) blocks in humans and some studies demonstrated that propofol suppressed the cardiac conduction system in animals. A precise mechanism by which the block is induced has not been elucidated yet in humans. The objective of this study was to investigate the effects of propofol on the cardiac conduction system and the cardiac autonomic nervous balance in children. METHODS: We enrolled 23 paediatric patients (age: 6-15 years; males: 16, females: 7) who were scheduled to undergo radiofrequency catheter ablation (RFCA) under general anaesthesia. Anaesthesia was induced with 2 mg/kg propofol and 0.5 µg/kg/min remifentanil, and tracheal intubation was performed with the aid of 1 mg/kg rocuronium. Anaesthesia was maintained with 5-7 mg/kg/h propofol and 0.2 µg/kg/min remifentanil during the RFCA. After the completion of the RFCA, anaesthesia was further maintained with 5 mg/kg/h propofol and 0.2 µg/kg/min remifentanil for at least 10 min (LC: low propofol concentration state), followed by the injection of 2 mg/kg propofol and the infusion of 10 mg/kg/h propofol for 10 min (HC: high propofol concentration state). The sinus node recovery time (SNRT), sinoatrial conduction time (SACT), atrial-His (AH) interval and the His-ventricular (HV) interval were measured at the end of both the LC and HC. Cardiac autonomic regulation was simultaneously assessed based on heart rate variability. RESULTS AND DISCUSSION: Propofol significantly suppressed intrinsic cardiac HV conduction, but did not affect the SNRT, SACT or the AH interval. As HV blocks, which occur below the His bundle, are often life-threatening, the HV conduction delay may be a cause of severe AV blocks induced by propofol. Propofol directly suppressed parasympathetic nerve activity, and sympathetic nerve activity was also suppressed. WHAT IS NEW AND CONCLUSION: These results indicate that propofol suppresses the HV conduction and might help to elucidate the mechanism by which propofol causes lethal AV blocks.

Pharmacokinetics and effects on clinical and physiological parameters following a single bolus dose of propofol in common marmosets (Callithrix jacchus).

The objectives of this study were (a) to establish a population pharmacokinetic model and (b) to investigate the clinical and physiological effects of a single bolus dose of propofol in common marmosets. In Study 1, pharmacokinetic analysis was performed in six marmosets under sevoflurane anaesthesia. 8 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Blood samples were collected 2, 5, 15, 30, 60, 90, 120 or 180 min after starting propofol administration. Plasma concentration was measured, and population pharmacokinetic modelling was performed. A two-compartment model was selected as the final model. The population pharmacokinetic parameters were as follows: V1  = 1.14 L, V2  = 77.6 L, CL1  = 0.00182 L/min, CL2  = 0.0461 L/min. In Study 2, clinical and physiological parameters were assessed and recorded every 2 min after 12 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Immobilization was sustained for 5 min following propofol administration without apparent bradycardia. While combination of propofol and sevoflurane caused apnoea in Study 1, apnoea was not observed following single administration of propofol in Study 2. These data provide bases for further investigation on intravenous anaesthesia using propofol in common marmosets.

Interpretation of laboratory tests for prevention of the SARS-CoV-2 transmission.

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medical providers should take care to prevent the transmission of SARS-CoV-2 in hospitals including super-spreading. Understanding super-spreading would be useful to reduce future transmission. Some publications have shown clusters of SARS-CoV-2 such as at choir practice and in hospitals. Aerosol can be considered as a primary transmission route. As SARS-CoV-2 stability in aerosol is similar to SARS-CoV-1 with the higher reproductive number of SARS-CoV-2 than SARS-CoV-1, another factor causes rapidly spread-out, e.g. a higher discharge ratio from infected people or a higher viral intake ratio to human body. A basic research suggests higher infectivity of SARS-CoV-2 in the nose than the peripheral lung. Universal masking would be important to prevent the exposure of SARS-CoV-2 droplet to uninfected people. To detect SARS-CoV-2 infection, laboratory tests such as reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays are applied. Although sensitivity and specificity are provided for the ability of the test, positive or negative prediction values are useful to indicate the possiblity of infection or non-infection in clinical practice. We have to realize that the positive and negative prediction values depend on the sensitivity, specificity, and infection probability of the patient.

Clinical characteristics of cancer-associated myositis complicated by interstitial lung disease: a large-scale multicentre cohort study.

OBJECTIVE: To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. RESULTS: CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation-associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). CONCLUSION: Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.

Individual pharmacometric analysis for sugammadex reversal and re-administration of neuromuscular blockade.

Sugammadex is an innovative reversal agent for neuromuscular blockade (NMB) induced by rocuronium. Although there is a case that re-paralysis is necessary after sugammadex administration, limited reports can be found on the sugammadex dosage for reversal from profound paralysis after induction and immediate re-paralysis following such reversal in detail. We experienced a case in which NMB reversal was required in a short period after paralysis for induction due to the discovery of anisocoria. We successfully re-induced general anesthesia with tracheal intubation soon after. To examine the validity of the dosing, we performed a pharmacometric analysis. A pharmacokinetic-pharmacodynamic model was developed for the patient based on a published pharmacokinetic-pharmacodynamic model for rocuronium and sugammadex. The developed model appropriately describes the train of four ratio observed. In this case, the dose of approximately 8 mg/kg sugammadex but not the conventional dose of 16 mg/kg would be enough for immediate reversal after induction. For the re-paralysis 30 min after NMB reversal, not 1.4 mg/kg but 2.2 mg/kg rocuronium was an adequate dose. Taking individual differences including given dose and time intervals in consideration, NMB monitoring should be used to determine the necessary dose of rocuronium and sugammadex in such situations.

Suspected propofol infusion syndrome during normal targeted propofol concentration.

To this day, the pathophysiology and risk factors of propofol infusion syndrome (PRIS) remain unknown. Moreover, there is no widely accepted definition of PRIS, even though it is a potentially fatal condition. While many suspected cases of PRIS have been reported in both pediatric and adult populations, the actual propofol plasma concentration (Cp) has never been clarified. In this clinical report, we described the first suspected PRIS case in which the propofol Cp was measured 25 min after 226 min of propofol infusion (7.2 µg/mL), which was 12 times higher than the predicted value (0.6 µg/mL). In the presented case, we observed gradually progressive uncontrollable hypercapnia and tachycardia, followed by severe lactic acidosis during surgical anesthesia based on the target-controlled infusion of propofol. Levels of liver enzymes were slightly elevated which suggests little or no liver damage though propofol is mainly metabolized by the liver. Meanwhile, renal impairment, a common secondary feature of PRIS, occurred concomitantly when hypercapnia and metabolic acidosis were manifested. In this case, low or delayed propofol clearance might have been a triggering factor causing severe lactic acidosis.

Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients.

OBJECTIVE: To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ⩾16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. RESULTS: JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ⩾60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ⩾1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). CONCLUSION: We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality.

Clinical Utility of Intraoperative Motor-Evoked Potential Monitoring to Prevent Postoperative Spinal Cord Injury in Thoracic and Thoracoabdominal Aneurysm Repair: An Audit of the Japanese Association of Spinal Cord Protection in Aortic Surgery Database.

BACKGROUND: Spinal cord ischemic injury is the most devastating sequela of descending and thoracoabdominal aortic surgery. Motor-evoked potentials (MEPs) have been used to intraoperatively assess motor tract function, but it remains unclear whether MEP monitoring can decrease the incidence of postoperative motor deficits. Therefore, we reviewed multicenter medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open surgery and endovascular repair) to assess the association of MEP monitoring with postoperative motor deficits. METHODS: Patients included in the study underwent descending or thoracoabdominal aortic repair at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery between 2000 and 2013. Using multivariable mixed-effects logistic regression analysis, we investigated whether intraoperative MEP monitoring was associated with postoperative motor deficits at discharge after open and endovascular aortic repair. RESULTS: We reviewed data from 1214 patients (open surgery, 601 [49.5%]; endovascular repair, 613 [50.5%]). MEP monitoring was performed in 631 patients and not performed in the remaining 583 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. Multivariable logistic regression analysis revealed that postoperative motor deficits at discharge did not have a significant association with MEP monitoring (adjusted odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69-1.88; P = .624), but with other factors: history of neural deficits (adjusted OR, 6.08; 95% CI, 3.10-11.91; P < .001), spinal drainage (adjusted OR, 2.14; 95% CI, 1.32-3.47; P = .002), and endovascular procedure (adjusted OR, 0.45; 95% CI, 0.27-0.76; P = .003). The sensitivity and specificity of MEP <25% of control value for motor deficits at discharge were 37.8% (95% CI, 26.5%-49.5%) and 95.5% (95% CI, 94.7%-96.4%), respectively. CONCLUSIONS: MEP monitoring was not significantly associated with motor deficits at discharge.

Rocuronium pharmacodynamic models for published five pharmacokinetic models: age and sex are covariates in pharmacodynamic models.

PURPOSE: Equilibration rate constant is necessary to calculate effect-site concentration, which is useful to control drug effect. We developed pharmacodynamic models for published five compartmental pharmacokinetic models published by Wierda, Szenohradszky, Cooper, Alvarez-Gomez, and McCoy. METHODS: We used 3848 train-of-four ratios from 15 male and nine female patients (21-76 years; 44-93 kg body weight; 148-181 cm height; and 17.3-29.8 kg/m2 body mass index) as pharmacodynamic measures, which were collected at the start of 0.6 mg/kg rocuronium administration until the end of the surgery. Effect compartment was assumed to be connected to central compartment of the pharmacokinetic model with equilibration rate constant (ke0). Sigmoid Emax model was fitted to describe the relationship between train-of-four ratio and effect-site concentration. Age, sex, and body mass index were assessed as possible covariates of the following model parameters: ke0, effect-site concentration for half of maximum effect, and the steepness of the effect-site concentration versus effect relationship. RESULTS: The duration of neuromuscular monitoring was 69 (37-129) [median (range)] min. All pharmacodynamic models included age and three included sex as significant covariates. Ke0 values ranged between 0.0820 and 0.247 depending on the pharmacokinetic model. The time-courses of the effect-site concentration were similar among the pharmacodynamic models for Wierda, Cooper, and Alvarez-Gomez pharmacokinetic models, which were lower than that for the Szenohradszky pharmacokinetic model. CONCLUSION: Each pharmacodynamic model with the corresponding pharmacokinetic model can be described the time course of rocuronium effect appropriately. The required effect-site concentration of rocuronium for a pharmacodynamic effect was depending on the applied models.

Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

BACKGROUND: The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. OBJECTIVE: The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. DESIGN: Randomised, single-blinded study. SETTING: A secondary hospital from October 2013 to July 2014. PATIENTS: In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. INTERVENTION: Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. MAIN OUTCOME MEASURES: Arterial plasma rocuronium concentrations. RESULTS: Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 µg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. CONCLUSION: Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. TRIAL REGISTRATION: Umin identifier: UMIN000011981.

Influence of maternal remifentanil concentration on fetal-to-maternal ratio in pregnant ewes.

PURPOSE: Maternal remifentanil infusion is used for minimally invasive fetal surgery or ex-utero intrapartum treatment. The fetal-to-maternal (F/M) ratio of remifentanil concentration at various dosing regimens is useful to manage remifentanil effects. The aim of this study was to investigate the F/M ratio of remifentanil at various concentrations. METHODS: Five pregnant ewes received continuous remifentanil infusion under propofol anesthesia. The remifentanil infusion rate was increased by 0.4 µg/kg/min every 15 min. The response to tail clamping in fetuses was assessed immediately before the change of infusion rate. Arterial remifentanil concentrations in the mother and fetus were determined at each tail clamp. After observing a loss of response to tail clamping, remifentanil infusion was terminated and the concentrations were assessed. RESULTS: The median remifentanil maximum infusion rate and maternal concentration were 3.0 µg/kg/min (range 2.4-3.6) and 21.6 (range 18.0-29.9) ng/mL, respectively. During continuous infusion, the F/M ratio was 0.15 (0.07-0.17), and the slope of the linear regression for the F/M ratio versus infusion rate in each individual was -0.001 ± 0.012/µg kg min (P = 0.876 vs hypothetical value of 0). The F/M ratio at the first sampling point in the elimination phase [0.33 (0.07-0.65)] was higher (P = 0.033) than at the last sampling point during continuous infusion [0.15 (0.06-0.17)]. CONCLUSION: The F/M ratio was constant at a steady state regardless of the remifentanil concentration up to 29.9 ng/mL, and increased in the elimination phase in pregnant ewes.