A pharmacodynamic analysis of factors affecting recovery from anesthesia with propofol-remifentanil target controlled infusion.
ABSTRACT: AIM: To examine individual patient's demographic parameters and clinical variables related to return of consciousness (ROC) and the pharmacodynamic relationship between propofol effect-site concentration (C(e)) and ROC from propofol-remifentanil anesthesia. METHODS: Ninety-four patients received propofol-remifentanil anesthesia using the effect-site target-controlled infusion (TCI) system. All clinical events were noted, and variables possibly related to propofol C(e) at ROC were examined using linear correlation analyses. Pharmacodynamic modeling incorporating covariates was performed using NONMEM (Nonlinear Mixed Effects Modeling) VII software. RESULTS: The C(e) values of propofol at loss of consciousness (LOC) and ROC were 4.4±1.1 μg/mL and 1.1±0.3 μg/mL, respectively. Age was negatively correlated with propofol C(e) at ROC (r=-0.48, P<0.01). Including age as a covariate in C(e50) (the effect-site concentration associated with 50% probability of return of consciousness) and λ (the steepness of the concentration-versus-response relationship) significantly improved the performance of the basic model based on the likelihood ratio test, with a significant decrease in the minimum value of the objective function. The C(e50) in 25-, 50-, and 75-year-old patients was predicted to be 1.38, 1.06, and 0.74 μg/mL, respectively. The λ in 25-, 50-, and 75-year-old patients was predicted to be 12.23, 8.70, and 5.18, respectively. CONCLUSION: Age significantly affects the relationship between propofol C(e) and ROC, and pharmacodynamic modeling including age could lead to better predictions of ROC during emergence from propofol-remifentanil anesthesia.
Project description:Propofol is a rapid, efficient hypnotic agent with antiemetic effects. However, a high dosage is related to hemodynamic abnormalities such as hypotension and bradycardia. Pretreatment with remifentanil can decrease injection pain and stabilize hemodynamics during the induction period. Remifentanil or midazolam in combination with propofol can provide synergistic or additive effects during anesthesia induction. However, the hypnotic doses of propofol required in patients who receive pretreatment with remifentanil or midazolam remain unclear.Patients aged 20 to 50 years who were scheduled to undergo surgery under general anesthesia were enrolled in this study. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in Group P (Propofol) received only propofol for loss of consciousness, those in Group PR (Propofol-Remifentanil) received remifentanil prior to propofol, and those in Group PMR (Propofol-Midazolam-Remifentanil) received remifentanil and midazolam prior to propofol. After propofol administration, loss of both the eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method.A total of 124 patients were initially enrolled. Of these, 4 were excluded, and the remaining 120 patients were randomized to each (n?=?40) of the 3 groups. The 95% effective dose of propofol for loss of consciousness was 1.74?, 1.38, and 0.92?mg/kg in Groups P, PR, and PMR, respectively. Blood pressure decreased at 2?minutes after propofol administration in all the groups. However, compared with Group P, Groups PR and PMR exhibited a significant decrease in blood pressure.The effective dose of propofol for loss of consciousness could be decreased by 21% and 47% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in blood pressure was greater with pretreatment than sole propofol use. These findings suggest that the combination of remifentanil with or without midazolam may have no benefit on hemodynamic stability during induction using propofol.NCT02536690 (clinicaltrials.gov).
Project description:BACKGROUND:Older people are more vulnerable to hemodynamic instability caused by propofol due to their decreased initial distribution volume and increased sensitivity to propofol. Midazolam or remifentanil can often be coadministered because of their synergistic or additive effects with propofol as well as amnesic properties and the blockade of sympathetic stimulation. However, no study has confirmed the appropriate dose of propofol for loss of consciousness in aged patients when administered with other drugs, including opioids or benzodiazepines. METHODS:Patients >65 years scheduled for general anesthesia were enrolled. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in group P (propofol) received only propofol for loss of consciousness, those in group PR (propofol-remifentanil) received remifentanil before propofol, and those in group PMR (propofol-midazolam-remifentanil) received remifentanil and midazolam before propofol. After propofol administration, loss of both eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method. RESULTS:In total, 120 patients were randomized into the 3 groups (n = 40). The 95% effective dose of propofol for loss of consciousness was 1.13, 0.87, and 0.72 mg/kg in groups P, PR, and PMR, respectively. The mean blood pressure (MBP) in group PMR was more significantly decreased before propofol injection (P = .041) as well as 2 minutes (P = .005) and 3 minutes after propofol administration (P<.001), compared with group P, but there were no intergroup differences at other time points. CONCLUSIONS:The effective dose of propofol for loss of consciousness in elderly patients could be decreased by 23% and 36% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in MBP was greater with remifentanil and midazolam pretreatment than with propofol alone. These findings suggest that pretreatment with midazolam for propofol infusions with remifentanil in elderly patients should be cautiously used, due to hemodynamic instability during induction.
Project description:We hypothesized that the addition of dexmedetomidine in a clinically relevant dose to propofol-remifentanil anesthesia regimen does not exert an adverse effect on motor-evoked potentials (MEP) and somatosensory-evoked potentials (SSEP) in adult patients undergoing thoracic spinal cord tumor resection.Seventy-one adult patients were randomized into three groups. Propofol group (n = 25): propofol-remifentanil regimenand the dosage was adjusted to maintain the bispectral index (BIS) between 40 and 50. DP adjusted group (n = 23): Dexmedetomidine (0.5 μg/kg loading dose infused over 10 min followed by a constant infusion of 0.5 μg/kg/h) was added to the propofol-remifentanil regimen and propofol was adjusted to maintain BIS between 40 and 50. DP unadjusted group (n = 23): Dexmedetomidine (administer as DP adjusted group) was added to the propofol-remifentanil regimen and propofol was not adjusted. All patients received MEP, SSEP and BIS monitoring.There were no significant changes in the amplitude and latency of MEP and SSEP among different groups (P > 0.05). The estimated propofol plasma concentration in DP adjusted group (2.7 ± 0.3 μg/ml) was significantly lower than in propofol group (3.1 ± 0.2 μg/ml) and DP unadjusted group (3.1 ± 0.2 μg/ml) (P = 0.000). BIS in DP unadjusted group (35 ± 5) was significantly lower than in propofol group (44 ± 3) (P = 0.000).The addition of dexmedetomidine to propofol-remifentanil regimen does not exert an adverse effect on MEP and SSEP monitoring in adult patients undergoing thoracic spinal cord tumor resection.The study was registered with the Chinese Clinical Trial Registry on January 31st, 2014. The reference number was ChiCTR-TRC-14004229.
Project description:Propofol is associated with pain during injection, which is stressful to patients. The present study was designed to investigate the analgesic effect of pretreatment with remifentanil and esmolol in minimizing propofol injection pain, compared with placebo.In a randomized, double-blind, prospective trial, 120 patients, scheduled for elective dental surgery under general anesthesia, were randomized to 1 of the 4 treatment arms (n = 30 each) receiving normal saline, remifentanil 0.35 μg/kg, esmolol 0.5 mg/kg, and 1 mg/kg before administration of propofol. During injection of 1% propofol 0.5 mg/kg, pain was evaluated by a 4-point score (0 = none, 1 = mild, 2 = moderate, 3 = severe). Any adverse effects such as hypotension and bradycardia were recorded during the perioperative periods.In all, 120 patients completed this study. There were no significant differences in terms of demographic data. The incidence of pain on injection of propofol was 11 (36.7%) with remifentanil 0.35 μg/kg, 12 (40%) with esmolol 0.5 mg/kg, and 11 (36.7%) with esmolol 1 mg/kg, compared with 25 (83.3%) with normal saline (respectively, P < 0.05). There were no significant differences in the incidence of pain between groups with remifentanil 0.35 μg/kg, and esmolol 0.5 mg/kg and 1 mg/kg. There were no emergence reactions such as hypotension and bradycardia in all groups.Pretreatment with esmolol 0.5 mg/kg and 1 mg/kg and remifentanil 0.35 μg/kg equally decreased pain during propofol injection.
Project description:We conducted a prospective, randomized, multicenter study to evaluate the differences in the blocking effect of different doses of rocuronium between sevoflurane- or propofol-remifentanil anesthesia in an Asian population.A total of 368 ASA I-II patients was enrolled. Anesthesia was induced with 2.0 mg/kg propofol and 0.1 μg/kg/min remifentanil (TIVA) or 5.0 vol.% sevoflurane with 0.1 μg/kg/min remifentanil (SEVO). Tracheal intubation was facilitated at 180 s after the administration of rocuronium at 0.3, 0.6, or 0.9 mg/kg and then intubation condition was evaluated. The time to maximum block and recovery profile were monitored by TOF stimulation of the ulnar nerve and by recording the adductor pollicis response using acceleromyography.The numbers of patients with clinically acceptable intubation conditions were 41, 82, and 97 % (TIVA) and 34, 85, and 90 % (SEVO) at each dose of rocuronium, respectively. There were no significant differences in the time to maximum block between groups at each rocuronium dose. There were significant differences in the recovery to a train-of-four ratio of 90 % between the groups: 42.7 (19.5), 74.8 (29.9), and 118.4 (35.1) min (TIVA) and 66.5 (39.3), 110.2 (43.5), and 144.4 (57.5) min (SEVO) at 0.3, 0.6, and 0.9 mg/kg, respectively (P < 0.001).There are no significant differences in intubation conditions between propofol-remifentanil and sevoflurane-remifentanil anesthesia at the same dose of rocuronium. The type of anesthetic does not significantly influence the time to maximum block by rocuronium. Rocuronium at a dose of 0.9 mg/kg should be used for better intubation conditions with both anesthesia regimens in an Asian population.UMIN-CTR Clinical Trial ( http://www.umin.ac.jp/ctr/index.htm ; UMIN#000007289 ; date of registration 14(th) February 2012).
Project description:Growth hormone (GH) secretion is regulated by various hormones or neurotransmitters, including gamma-aminobutyric acid. The aim of this study was to determine the propofol requirement in patients with GH-secreting pituitary tumors undergoing transsphenoidal surgery. General anesthesia was induced in 60 patients with GH-secreting tumors (GH group, n = 30) or nonfunctioning pituitary tumors (NF group, n = 30) using an effect-site target-controlled intravenous propofol infusion. The effect-site concentrations were recorded at both a loss of consciousness and a bispectral index (BIS) of 40, along with the effect-site concentration after extubation, during emergence from the anesthesia. The effect-site concentration of propofol was higher in the GH group than in the NF group at a loss of consciousness and a BIS of 40 (4.09 ± 0.81 vs. 3.58 ± 0.67, p = 0.009 and 6.23 ± 1.29 vs. 5.50 ± 1.13, p = 0.025, respectively) and immediately after extubation (1.60 ± 0.27 vs. 1.40 ± 0.41, p = 0.046). The total doses of propofol and remifentanil during anesthesia were comparable between the groups (127.56 ± 29.25 vs. 108.64 ± 43.16 µg/kg/min, p = 0.052 and 6.67 ± 2.89 vs. 7.05 ± 1.96 µg/kg/h, p = 0.550, respectively). The propofol requirement for the induction of a loss of consciousness and the achievement of a BIS of 40 is increased during the induction of general anesthesia in patients with GH-secreting tumors.
Project description: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 ?g/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 ?/mL, respectively. CONCLUSION:Propofol reduces LV systolic long-axis performance in a dose-dependent manner. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01826149.
Project description:The performance of a new monitor for the depth of anesthesia (DOA), the Depth of Anesthesia Index (Ai) based on sample entropy (SampEn), 95% spectral edge frequency (95%SEF), and burst suppression ratio (BSR) was evaluated compared to Bispectral Index (BIS) during total intravenous anesthesia (TIVA). 144 patients in six medical centers were enrolled. General anesthesia was induced with stepwise-increased target-controlled infusion (TCI) of propofol until loss of consciousness (LOC). During surgery propofol was titrated according to BIS. Both Ai and BIS were recorded. Primary outcomes: the limits of agreement between Ai and BIS were -17.68 and 16.49, which were, respectively, -30.0% and 28.0% of the mean value of BIS. Secondary outcomes: prediction probability (Pk) of BIS and Ai was 0.943 and 0.935 (p=0.102) during LOC and 0.928 and 0.918 (p=0.037) during recovery of consciousness (ROC). And the values of BIS and Ai were 68.19 and 66.44 at 50%LOC, and 76.65 and 78.60 at 50%ROC. A decrease or an increase of Ai was significantly greater than that of BIS when consciousness changes (during LOC: -9.13±10.20 versus -5.83±9.63, p<0.001; during ROC: 10.88±11.51 versus 5.32±7.53, p<0.001). The conclusion is that Ai has similar characteristic of BIS as a DOA monitor and revealed the advantage of SampEn for indicating conscious level. This trial is registered at Chinese Clinical Trial Registry with ChiCTR-IOR-16009471.
Project description:BACKGROUND:Vitrectomy under general anesthesia is considered as a candidate for ambulatory surgery. An anesthetic method with high quality of postoperative recovery should be selected for successful ambulatory surgery. We thus compared quality of postoperative recovery on the day of vitrectomy using the Quality of Recovery (QoR)-40 questionnaire between propofol total intravenous anesthesia (propofol group) and desflurane inhalation anesthesia (desflurane group) as the 2 representative anesthetic methods. METHODS:Eighty-four patients (20-80 years old) undergoing elective vitrectomy under general anesthesia were randomized into 2 groups. The propofol group received propofol and remifentanil using effect-site target-controlled infusion (TCI), and the desflurane group received desflurane inhalation and remifentanil using effect-site TCI. We assessed quality of recovery at 6?hours after surgery through interviews using the QoR-40 questionnaire. We also collected data related to recovery and complications during emergence and recovery period. RESULTS:The median of QoR-40 score on the day of surgery was significantly higher in the propofol group than that in the desflurane group (181.0 vs 169.5, respectively; P?=?.033). In particular, propofol group had significantly higher scores for physical comfort and physical independence dimensions. The amount of remifentanil administered was significantly higher, and the emergence time was significantly longer in propofol group. However, there were no significant differences in other complications between the 2 groups. CONCLUSIONS:Propofol total intravenous anesthesia provided significantly better quality of recovery on the day of surgery than desflurane inhalation anesthesia.
Project description:BACKGROUND:Phase lag entropy (PLE) is a novel anesthetic depth indicator that uses four-channel electroencephalography (EEG) to measure the temporal pattern diversity in the phase relationship of frequency signals in the brain. The purpose of the study was to evaluate the anesthetic depth monitoring using PLE and to evaluate the correlation between PLE and bispectral index (BIS) values during propofol anesthesia. METHODS:In thirty-five adult patients undergoing elective surgery, anesthesia was induced with propofol using target-controlled infusion (the Schneider model). We recorded the PLE value, raw EEG, BIS value, and hemodynamic data when the target effect-site concentration (Ce) of propofol reached 2, 3, 4, 5, and 6??g/ml before intubation and 6, 5, 4, 3, 2??g/ml after intubation and injection of muscle relaxant. We analyzed whether PLE and raw EEG data from the PLE monitor reflected the anesthetic depth as the Ce of propofol changed, and whether PLE values were comparable to BIS values. RESULTS:PLE values were inversely correlated to changes in propofol Ce (propofol Ce from 0 to 6.0??g/ml, r2?=?-?0.83; propofol Ce from 6.0 to 2.0??g/ml, r2?=?-?0.46). In the spectral analysis of EEG acquired from the PLE monitor, the persistence spectrogram revealed a wide distribution of power at loss of consciousness (LOC) and recovery of consciousness (ROC), with a narrow distribution during unconsciousness. The power spectrogram showed the typical pattern seen in propofol anesthesia with slow alpha frequency band oscillation. The PLE value demonstrated a strong correlation with the BIS value during the change in propofol Ce from 0 to 6.0??g/ml (r2?=?0.84). PLE and BIS values were similar at LOC (62.3 vs. 61.8) (P?>?0.05), but PLE values were smaller than BIS values at ROC (64.4 vs 75.7) (P?<?0.05). CONCLUSIONS:The PLE value is a useful anesthetic depth indicator, similar to the BIS value, during propofol anesthesia. Spectral analysis of EEG acquired from the PLE monitor demonstrated the typical patterns seen in propofol anesthesia. TRIAL REGISTRATION:This clinical trial was retrospectively registered at ClinicalTrials.gov at October 2017 (NCT03299621).