Population pharmacokinetic/pharmacodynamic modeling for remimazolam in the induction and maintenance of general anesthesia in healthy subjects and in surgical subjects

Zhou, Jie; Leonowens, Cathrine; Ivaturi, Vijay; Lohmer, Lauren L.; Curd, Laura; Ossig, Joachim; Schippers, Frank; Petersen, Karl‐Uwe; Stoehr, Thomas; Schmith, Virginia D.

doi:10.1016/j.jclinane.2020.109899

Cited by 76 publications

(94 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In case 1, there were no significant changes in MEP signals under general anesthesia using a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/ kg/min. Although the optimal dose of remimazolam during the maintenance phase of general anesthesia is 1 mg/kg/h [13], maintenance dose of remimazolam in this case was lower than previously reported. Remifentanil appears to synergize with the anesthetic effect of remimazolam [13]; thus, using remifentanil in combination with remimazolam enables a reduction in the required amount of remimazolam without interfering with MEP monitoring.…”

Section: Discussioncontrasting

confidence: 64%

“…Although the optimal dose of remimazolam during the maintenance phase of general anesthesia is 1 mg/kg/h [13], maintenance dose of remimazolam in this case was lower than previously reported. Remifentanil appears to synergize with the anesthetic effect of remimazolam [13]; thus, using remifentanil in combination with remimazolam enables a reduction in the required amount of remimazolam without interfering with MEP monitoring. In case 2, increasing the dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals.…”

Section: Discussioncontrasting

confidence: 64%

See 1 more Smart Citation

Intraoperative responses of motor evoked potentials to the novel intravenous anesthetic remimazolam during spine surgery: a report of two cases

et al. 2020

View full text Add to dashboard Cite

Background Remimazolam is a novel short-acting benzodiazepine characterized by metabolism independent from organ function. We report intraoperative MEP responses of two patients who underwent spine surgery under general anesthesia using remimazolam. Case presentation In case 1, MEP monitoring was successfully performed with the use of a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. In case 2, an increasing dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. In both cases, remimazolam was titrated to maintain the values of entropy electroencephalogram (EEG) monitoring at 40–60. Conclusions General anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring by EEG to assess the optimal dose.

show abstract

Section: Discussioncontrasting

confidence: 64%

Section: Discussioncontrasting

confidence: 64%

Intraoperative responses of motor evoked potentials to the novel intravenous anesthetic remimazolam during spine surgery: a report of two cases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Therefore, V1 was fixed to the value from the pilot model and IIV was only estimated in those subjects that had early sampling. The final model ended up with an IIV on V1 that was 61.7%, which was lower than the value (87%) previously reported for remimazolam in general anesthesia, 3 but still relatively high and consistent with some inability to estimate the true V1.…”

Section: Discussioncontrasting

confidence: 63%

“…This difference between arterial vs. venous concentrations were attempted using a semi‐physiologic model by Wiltshire, 1 but were limited by the low number of simultaneous arterial and venous concentrations early after administration and the assumptions about lung metabolism, which have since been shown to be invalid. For the PopPK model in general anesthesia, 3 differences between arterial and venous concentrations were modeled by assuming different residual errors.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, PopPK utilized a physiologic recirculation model 1 ; these models assumed that a significant portion of the metabolism occurred in the lungs, and later in vitro data suggested that the rate of metabolism by CES‐1 in the lungs is much slower than in the liver 2 . The most recent PopPK and population pharmacokinetic/pharmacodynamic (PopPK/PD 3 ) analysis pooled data across studies in healthy volunteers, 1,4,5 surgical patients, 4,6–8 procedural sedation patients, 9,10 and patients in the intensive care unit 11 . There was high interindividual variability (IIV, 87%) in the volume of the central compartment (V1) likely due to the imprecise calculation of V1 after i.v.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Population Pharmacokinetics of Remimazolam in Procedural Sedation With Nonhomogeneously Mixed Arterial and Venous Concentrations

Zhou¹,

Curd²,

Lohmer³

et al. 2020

Clinical Translational Sci

Self Cite

View full text Add to dashboard Cite

Remimazolam is an ultra-short acting benzodiazepine under development for procedural sedation and general anesthesia. Population pharmacokinetic analysis (PopPK) was conducted for remimazolam with arterial and venous samples previously, but results were limited by arterial-venous concentration differences and inaccurate central volume of distribution (V1) estimates. A new model was developed to describe covariate effects after accounting for arterial-venous differences. Arterial and venous plasma concentration-time data from 11 clinical trials were pooled for PopPK. Data from two constant-rate infusion studies were used to account for venous-to-arterial (VtoA) ratio within residual error and to accurately estimate V1. V1 and VtoA ratio from the pilot model were applied to the full dataset, where the optimal fixed/random effects and covariates were assessed. VtoA ratio was described using a maximum effect (E max) model during infusion and as a constant postdose. V1 was estimated as 4.83 L for a 70 kg subject and interindividual variability (IIV) on V1 could only be estimated in studies with early concentrations. IIV on clearance was low (22.9%). Covariates included effects of sex on clearance (women 10% > men), and race on clearance and steady-state volume of distribution (African Americans 16% < other races). Arterialvenous concentration differences were best described using an E max model during infusion with a constant ratio after infusion, resulting in low residual error (20.7%). There are no clinically relevant dose adjustments needed for any covariates based on pharmacokinetic differences. www.cts-journal.com Remimazolam PopPK in Procedural Sedation Zhou et al.

show abstract

Comparison of Remimazolam and Propofol for Drug‐Induced Sleep Endoscopy: A Randomized Clinical Trial

Zhang

Fang

et al. 2023

Otolaryngol.--head neck surg.

View full text Add to dashboard Cite

ObjectiveTo compare the efficacy and safety of remimazolam with those of propofol for drug‐induced sleep endoscopy (DISE) in patients with obstructive sleep apnea‐hypopnea syndrome (OSAHS).Study DesignA prospective, single‐center, randomized clinical trial.SettingXiangya Hospital of Central South University.MethodsPatients with OSAHS receiving DISE were randomly assigned to either the remimazolam or propofol group. The primary outcome was the incidence of hypoxemia (pulse oxygen saturation [SpO2] < 90%) during DISE. The secondary outcomes were the incidence of severe hypoxemia (SpO2 < 80%), the minimal value of SpO2, sedation success rate (completion of DISE according to the medication regimen), and incidence of events of interest (including injection pain, bradycardia, and decreased respiratory rate).ResultsSixty‐four patients were included in this study. The incidence of hypoxemia was significantly lower in the remimazolam than in the propofol group (25.00% vs 62.50%, respectively; relative risk, 0.40; 95% confidence interval [CI], 0.20‐0.74; p < .01). There was no significant difference in the sedation success rate between the remimazolam and propofol groups (96.88% vs 81.25%, respectively; relative risk, 1.19; 95% CI, 1.01‐1.50; p = .10). The incidence of at least 1 event of interest was lower in the remimazolam than in the propofol group (43.75% vs 96.88%, respectively; relative risk, 0.45; 95% CI, 0.29‐0.63; p < .01).ConclusionRemimazolam can present satisfactory sedative efficacy in DISE, with a lower incidence of hypoxemia and a higher safety profile than propofol.

show abstract

Population pharmacokinetic/pharmacodynamic modeling for remimazolam in the induction and maintenance of general anesthesia in healthy subjects and in surgical subjects

Cited by 76 publications

References 18 publications

Intraoperative responses of motor evoked potentials to the novel intravenous anesthetic remimazolam during spine surgery: a report of two cases

Intraoperative responses of motor evoked potentials to the novel intravenous anesthetic remimazolam during spine surgery: a report of two cases

Population Pharmacokinetics of Remimazolam in Procedural Sedation With Nonhomogeneously Mixed Arterial and Venous Concentrations

Comparison of Remimazolam and Propofol for Drug‐Induced Sleep Endoscopy: A Randomized Clinical Trial

Contact Info

Product

Resources

About