Propofol-remifentanil Anesthesia Research Articles

Impact of desflurane-remifentanil and propofol-remifentanil anesthesia on postoperative recovery assessed by the QoR-40K: a prospective, randomized controlled trial

Impact of desflurane-remifentanil and propofol-remifentanil anesthesia on postoperative recovery assessed by the QoR-40K: a prospective, randomized controlled trial

The arousal effect of sugammadex reversal of neuromuscular blockade differs with anesthetic depth in propofol-remifentanil anesthesia: a randomized controlled trial

Sugammadex reverses neuromuscular blockade by encapsulating steroidal neuromuscular blockers; therefore, it does not pharmacologically affect sedation levels. However, some clinicians avoid using it because of sudden unwanted acting out or patient arousal. Previous studies suggested sugammadex-induced awakening, but frontal muscle contraction after sugammadex administration compromised reliability of results obtained from EEG-based anesthesia depth monitoring tools like bispectral index (BIS). We hypothesized that sugammadex would affect patients’ arousal depending on their baseline levels of sedation. We evaluated arousal signs after sugammadex administration with BIS between 25 − 35 and 45 − 55 under steady-state propofol-remifentanil anesthesia at the end of a surgery (n = 33 in each group). After sugammadex administration, twelve patients with a BIS of 45 − 55 showed clinical signs of awakening but none with a BIS of 25 − 35 (36.4% vs. 0%, P = 0.001). The distribution of the modified observer’s assessment of alertness/sedation scale scores was also significantly different between the two groups (P < 0.001). Changes in the BIS were significantly greater in the BIS 45 − 55 than in the 25 − 35 group (median difference, 7; 95% CI 2 − 19, P = 0.002). Arousal after sugammadex was affected by patient sedation levels, and clinical signs of awakening appeared only in those with BIS 45 − 55. Unwanted arousal of the patient should be considered when using sugammadex under shallow anesthesia.Clinical trial registry number: Clinical Trial Registry of Korea (https://cris.nih.go.kr; Principal investigator: Jieae Kim; Registration number: KCT0006248; Date of first registration: 11/06/2021).

Postoperative Sleep Quality of Insomnia Patients After TIVA Anesthesia: A Prospective Study

PurposeThe purpose of this study is to observe the postoperative sleep quality of insomnia patients undergoing laparoscopic gynecologic oncology surgery after total intravenous anesthesia. DesignProspective study. MethodsWe conducted a prospective, observational study in our hospital. All patients underwent propofol-remifentanil anesthesia without other sedative medications before or during the operation. Pittsburgh Sleep Quality Index (PSQI) scores of the baseline value, night-1 (the first night after surgery), night-3, night-5, and night-30 were observed. FindingsSixty-nine female insomnia patients were allocated based on the results of the PSQI and the diagnostic criteria of insomnia. The PSQI global scores were respectively 6 (5–8), 5 (4–6), 5 (3–6), and 6 (5–7) on night-1, night-3, night-5, and night-30, significantly lower than the baseline 7 (6–8) (P < 0.05). The 5 components (subjective sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction) had significant changes at different postoperative time points (P < 0.05). The daytime dysfunction could also be improved 1 month after the surgery (P < 0.05). In contrast, the variations of sleep disturbance and use of sleep medication had no statistical differences. ConclusionsThe sleep quality of female patients with insomnia was improved on the first night after surgery in the sides of sleep latency and daytime dysfunction, and the improvement could also be obtained 1 month after propofol-remifentanil general anesthesia.

EEG-derived pain threshold index-guided versus standard care during propofol-remifentanil anesthesia: A randomized controlled trial

PurposeThe pain threshold index (PTI), a novel index of nociception based on spontaneous EEG wavelet analysis, has been reported to provide reliable accuracy for predicting postoperative pain and hemodynamic reactivity. The present study is aimed to investigate whether PTI-guided analgesia reduces the pain intensity and rate of remedial analgesia in the post-anesthesia care unit (PACU). MethodsA total of 122 females undergoing elective gynecologic surgeries had been randomized to receive either PTI-guided analgesia (PTI group) or standard clinical care (control group). Remifentanil administration in the PTI group was guided by PTI to maintain the value between 40 and 65, while that in the control group was guided by hemodynamic changes. The primary outcome was remedial analgesia rate in the PACU. The postoperative pain scores, intraoperative remifentanil requirements, opioid-related adverse events and perioperative serum stress hormone concentrations between the two groups were also compared. FindingsIt was found that 23 of 58 patients (40%) in the control group and 8 of 58 patients (14%) in the PTI group needed remedial analgesia. The relative risk of receiving remedial analgesia was 2.88 (95% CI, 1.40–5.89, P = 0.002) in the control group. Sufentanil consumption in the PACU (μg) was lower in the PTI group (P = 0.002) than in the control group. Remifentanil and propofol consumption, opioid-related adverse events between these two groups were comparable. ImplicationsPTI-guided analgesia during gynaecologic operations resulted in 25.87% less remedial analgesia. However, studies with different PTI thresholds and larger, more diverse populations should be conducted to further demonstrate the clinical effectiveness of PTI.

Effect of sevoflurane-remifentanil and propofol-remifentanil anesthesia on glycocalyx shedding during deep inferior epigastric perforator flap breast reconstruction: a prospective randomized, controlled trial.

The endothelial glycocalyx (EG) is an important structure that regulates vascular homeostasis. Deep inferior epigastric perforator (DIEP) flap is expected to cause substantial EG breakdown owing to the long procedural duration and ischemia- reperfusion injury. This prospective, randomized, controlled study aimed to compare syndecan-1 levels during sevoflurane-remifentanil and propofol-remifentanil anesthesia in patients who underwent DIEP flap breast reconstruction. Fifty-one patients were randomized to either sevoflurane (n = 26) or propofol (n = 25) groups. Anesthesia was maintained with remifentanil in combination with either sevoflurane or propofol. The primary endpoint was the concentration of serum syndecan-1 measured at 1 h after surgery. Fifty patients (98.0%) completed the study. Patients in the propofol group had significantly lower levels of syndecan-1 than patients in the sevoflurane group at 1 h after operation (23.8 ± 1.6 vs. 30.9 ± 1.7 ng/ml, respectively; Bonferroni corrected P = 0.012). There were no significant differences between groups in postoperative complications. The postoperative hospital stay was 8.4 ± 2.5 days in the sevoflurane group and 7.4 ± 1.0 days in the propofol group (P = 0.077). Propofol-remifentanil anesthesia resulted in lesser increases in syndecan-1 levels compared to increases with sevoflurane-remifentanil anesthesia in patients who underwent DIEP flap reconstruction. Our results suggest that propofol-remifentanil anesthesia shows protective effects against EG damage during DIEP flap breast reconstruction in contrast to sevoflurane-remifentanil anesthesia.

Cerebral Tissue Oxygen Saturation Correlates with Emergence from Propofol-Remifentanil Anesthesia: An Observational Cohort Study.

Anesthesia emergence is accompanied by changes in cerebral circulation. It is unknown whether cerebral tissue oxygen saturation (SctO2) could be an indicator of emergence. Changes in SctO2, bispectral index (BIS), mean arterial pressure (MAP), and heart rate (HR) were evaluated during the emergence from propofol-remifentanil anesthesia. At the time of cessation of anesthetic delivery, SctO2, BIS, MAP, and HR values were recorded as baseline. The changes of these parameters from the baseline were recorded as Δ SctO2, Δ BIS, Δ MAP, and Δ HR. The behavioral signs (body movement, coughing, or eye opening) and response to commands (indicating regaining of consciousness) were used to define emergence states. Prediction probability (Pk) was used to examine the accuracy of SctO2, BIS, MAP, and HR as indicators of emergence. SctO2 showed an abrupt and distinctive increase when appearing behavioral signs. BIS, MAP, and HR, also increased but with a large inter-individual variability. Pk value of Δ SctO2 was 0.97 to predict the appearance behavioral signs from 2 min before that, which was much higher than the Pk values of Δ BIS (0.81), Δ MAP (0.71) and Δ HR (0.87). The regaining of consciousness was associated with a further increase in the SctO2 value.

Effect of Electroencephalography Spectral Edge Frequency (SEF) and Patient State Index (PSI)-Guided Propofol-Remifentanil Anesthesia on Delirium After Laparoscopic Surgery: The eMODIPOD Randomized Controlled Trial.

The effect of SedLine electroencephalography (EEG)-guided anesthetic care on postoperative delirium (POD) has not been studied. This single-center randomized EEG Monitoring tO Decrease the Incidence of Post-Operative Delirium (eMODIPOD) trial involved 1560 patients aged 50 years or above undergoing laparoscopic surgery. Propofol-remifentanil anesthesia was guided either by SedLine (EEG-guided care, n=779) or not (usual care, n=781). The goal of EEG-guided care was to maintain spectral edge frequency between 10 and 15 and patient state index (PSI) between 25 and 50. The primary outcome was the incidence of POD on postoperative days 1 to 5. The secondary outcomes included emergence delirium, composite moderate-to-severe complications, length of hospital stay, intensive care unit admission, 30-day hospital readmission and all-cause mortality, and intraoperative awareness. Of the 1560 randomized patients, 1545 were included in the modified intention-to-treat analysis. The median propofol administered for anesthesia maintenance was 900 mg and 1000 mg in the EEG-guided and usual care groups, respectively (P=0.21). POD occurred in 1.0% (8/771) and 1.2% (9/774) of patients in the EEG-guided and usual care groups, respectively (risk ratio: 0.89; 95% confidence interval: 0.35-2.30). There were no between-group differences in all secondary outcome measures. Emergence delirium occurred in 11.8% (91/771) and 13.2% (102/774) of the EEG-guided care and usual care groups, respectively (risk ratio: 0.90; 95% confidence interval: 0.69-1.17; P=0.41). Three patients from each group reported intraoperative awareness. Compared with usual care, SedLine spectral edge frequency-guided and patient state index-guided propofol-remifentanil anesthetic care neither alters anesthetic delivery nor decreases the unexpected low incidence of POD in relatively young Chinese patients undergoing laparoscopic surgery.

Forehead Regional Oxygen Saturation (rSO2)-Related Ear-Level Arterial Pressure and Lower Thigh rSO2 in the Steep Trendelenburg Position with CO2 Pneumoperitoneum and the Beach Chair Position.

IntroductionRegional oxygen saturation (rSO2) reflects tissue perfusion. This observational study aimed to examine the change in the forehead and lower thigh rSO2 associated with intraoperative posture, anesthesia regimen, or mean arterial pressure (mAP) at heart and external auditory meatus (ear) levels.MethodsPatients undergoing robot-assisted laparoscopic radical prostatectomy in the Trendelenburg position at 30° with pneumoperitoneum (TPP) or arthroscopic shoulder surgery in the beach chair position at 70° (BCP) under desflurane-remifentanil (D/R) or propofol-remifentanil (P/R) anesthesia were examined. Bilateral forehead and lower thigh rSO2 values and mean radial artery pressure were measured simultaneously at heart and ear levels.ResultsIn TPP, there were no differences under anesthesia regimens in the forehead or lower thigh rSO2change, although one patient with an absolute lower thigh rSO2 of ≤50% in the lithotomy position complained of transient limb pain. No correlation was observed between rSO2 and mAP. In BCP, forehead rSO2 decreased and lower thigh rSO2 increased under either of the anesthesia regimens. The coefficient of correlation between forehead rSO2 andheart-level and ear-level mAP was 0.341 and 0.236, respectively.ConclusionsThere were no differences under anesthesia regimens in the changes of forehead rSO2 and lower thigh rSO2. In TPP, significant changes in forehead rSO2 and lower thigh rSO2 were not observed. Monitoring lower thigh rSO2 might be useful for preventing lower extremity pain. In BCP, forehead rSO2 decreased and lower thigh rSO2 increased from the supine position to the BCP. To prevent brain damage, anesthesiologists should pay attention to heart- and ear-level mAP.

Sevoflurane-Remifentanil Versus Propofol-Remifentanil Anesthesia During Noncardiac Surgery for Patients with Coronary Artery Disease - A Prospective Study Between 2016 and 2017 at a Single Center.

BackgroundVolatile anesthesia possesses cardioprotective properties, and it is widely used in patients undergoing coronary artery bypass surgery, but no randomized controlled trials (RCTs) are available on the use of sevoflurane-remifentanil versus propofol-remifentanil anesthesia for patients with coronary artery disease (CAD) during noncardiac surgery. This study was designed to compare the 2 different types of general anesthesia in patients with CAD undergoing noncardiac surgery at a single center.Material/MethodsPatients with CAD undergoing noncardiac surgery were enrolled in an RCT conducted between March 2016 and December 2017. The participants were randomized to receive either sevoflurane-remifentanil or propofol-remifentanil anesthesia. The primary endpoint was occurrence of in-hospital cardiovascular events. The secondary endpoints included delirium, postoperative nausea and vomiting (PONV), Intensive Care Unit (ICU) length of stay (LOS), in-hospital morbidity and mortality, and hospital LOS.ResultsA total of 164 participants completed the study (sevoflurane: 81; propofol: 83). The occurrence of in-hospital cardiovascular events did not differ between the 2 groups (42.6% vs 39.4%, P=0.86). The occurrence of delirium did not differ between the 2 groups after the operation. PONV had a higher frequency after sevoflurane anesthesia at 48 h compared with propofol. In-hospital morbidity and mortality, ICU LOS, and hospital LOS were similar between the 2 groups (all P>0.05). At 30 days after surgery, no between-group differences in cardiac morbidity and mortality were observed.ConclusionsIn this study, anesthesia using sevoflurane-remifentanil did not provide additional postoperative cardioprotection in comparison with propofol-remifentanil in patients with CAD undergoing noncardiac surgery.

Comparison of remifentanil concentrations with and without dexmedetomidine for the prevention of emergence cough after nasal surgery: a randomized double-blinded trial

BackgroundPreventing emergence cough after nasal surgery is critical. Emergence cough can provoke immediate postoperative bleeding, which leads to upper airway obstruction. In the present study, we compared the effect-site concentration (Ce) of remifentanil to prevent emergence cough after propofol anesthesia for nasal surgery when remifentanil was or was not combined with dexmedetomidine.MethodsForty-seven patients with propofol-remifentanil anesthesia for nasal surgery were randomly assigned to a dexmedetomidine group (Group D, n = 23) or a saline group (Group S, n = 24). Group D and Group S were infused with dexmedetomidine (0.5 μg/kg) and saline, respectively, for 10 min before the completion of surgery. A predetermined Ce of remifentanil was infused until extubation. Remifentanil Ce to prevent cough in 50 and 95% of patients (EC50 and EC95) was estimated using modified Dixon’s up-and-down method and isotonic regression. Hemodynamic and recovery parameters were recorded.ResultsThe EC50 of remifentanil Ce was significantly lower in Group D than in Group S (2.15 ± 0.40 ng/mL vs. 2.66 ± 0.36 ng/mL, p = 0.023). The EC95 (95% CI) of remifentanil Ce was also significantly lower in Group D [2.75 (2.67–2.78) ng/mL] than in Group S [3.16 (3.06–3.18) ng/mL]. Emergence and recovery variables did not differ between the two groups.ConclusionThe remifentanil EC50 to prevent cough after propofol-remifentanil anesthesia was significantly lower (approximately 19%) when a combination of remifentanil and 0.5 μg/kg dexmedetomidine was used than when remifentanil infusion alone was used in patients undergoing nasal surgery. Therefore, the Ce of remifentanil may be adjusted to prevent emergence cough when used in combination with dexmedetomidine.Trial registrationClinicalTrials.gov (NCT03622502, August 9, 2018).

Effects of Propofol and Propofol-Remifentanil Combinations on Haemodynamics, Seizure Duration and Recovery during Electroconvulsive Therapy.

ObjectiveThis study aimed to evaluate the effects of adding different doses of remifentanil to propofol treatment compared with propofol alone with regard to parameters, including the seizure duration, haemodynamic changes and recovery time, in patients undergoing electroconvulsive therapy (ECT).MethodsThis study was designed as a self-controlled, prospective, double-blind investigation of 17 patients between the ages of 20 and 65 years who had planned treatment with ECT at a psychiatric clinic. Group P (propofol) was administered 10 mL of normal saline after 0.5 mg kg−1 intravenous (IV) bolus of propofol. Group R I (propofol plus remifentanil-1) was administered 1.5 μg kg−1 of remifentanil, and group R II (propofol plus remifentanil-2) was given 2 μg kg−1 of remifentanil after 0.5 mg kg−1 IV bolus of propofol. The haemodynamic variables after seizure and the seizure duration were recorded. Time to return to spontaneous respiration, eye opening and achieving Aldrete score >9 were recorded.ResultsThe electroencephalography seizure duration was significantly longer in groups R I (34.7±13 s) and R II (34.9±12) than in group P (24±7.5). Motor seizure duration was longer in groups R I (29.70±12.8) and R II (28.1±10) than in group P (21±7.3). The amount of total propofol was 121±21 mg in group P, 69.4±2 mg in group R I and 67±17 mg in group R II. Times to eye opening, following simple commands, and achieving Aldrete score >9 were significantly shorter in groups R I and R II than in group P.ConclusionECT is a safe and effective treatment for patients with psychiatric disorders. Propofol-remifentanil anaesthesia prolongs the seizure duration and shortens the recovery time, suggesting that this combination may particularly be well suited for use in this patient group.

Comparison of Pupillometry With Surgical Pleth Index Monitoring on Perioperative Opioid Consumption and Nociception During Propofol-Remifentanil Anesthesia: A Prospective Randomized Controlled Trial.

Intraoperative monitoring with pupillometry has shown promising results for nociception/antinociception balance monitoring. However, its benefits in clinical practice remain unproven. The aim of this study was to evaluate the efficacy of intraoperative pupillometry monitoring on intraoperative opioid consumption and postoperative pain compared to surgical pleth index (SPI), another widely investigated monitoring. American Society of Anesthesiologists (ASA) I-II patients scheduled for elective laparoscopic cholecystectomy were included. This prospective, parallel-arm, single-center study was conducted in 2 steps. First, we evaluated the feasibility of using pupillometry and SPI monitoring compared with conventional hemodynamic monitoring. Next, a parallel-arm, double-blind randomized study compared the peak postoperative pain measured with numerical rating scale (NRS) from 0 (no pain) to 10 (extreme pain) as a primary outcome between pupillometry (pupillometry group, n = 43) and SPI monitoring (SPI group, n = 43) using Mann-Whitney U test. Secondary outcomes included intraoperative remifentanil consumption, postoperative opioid responsiveness (a decrease in NRS by ≥1 after fentanyl administrations), number of analgesic administrations, and opioid-related complications. In the preliminary study (n = 50), remifentanil consumption was less under pupillometry monitoring compared to SPI monitoring, and peak postoperative pain was lower under pupillometry compared to conventional monitoring. In the main study (n = 86), peak postoperative pain and intraoperative remifentanil consumption were lower in the pupillometry group (median [first to third quartile], 5 [4-6]; mean ± standard deviation [SD], 0.078 ± 0.019 μg·kg·minute) compared to the SPI group (7 [5-8] and 0.0130 ± 0.051 μg·kg·minute; P < .001), with the median difference in peak postoperative pain of -1 and its 95% confidence interval between -2 and -0.5. The pupillometry group had better responsiveness to fentanyl (84.6% vs 61.0%; P = .005) and lower number of analgesic administrations (2 [1-2] vs 2 [1-3]; P = .048) compared to the SPI group. Intraoperative pupillometry monitoring reduced intraoperative remifentanil consumption and postoperative pain. It may be an alternative option for intraoperative opioid control under general anesthesia in adult patients.

Effects of anesthetics on post-operative 3-month neuroendocrine function after endoscopic transsphenoidal non-functional pituitary adenoma surgery.

Anesthetic techniques can affect perioperative neuroendocrine function. The objective of this study was to compare 3-month post-operative neuroendocrine functional outcomes between sevoflurane and propofol anesthesia in patients undergoing endoscopic transsphenoidal surgery (ETS) for removal of non-functional pituitary adenomas (NFPAs) retrospectively. Among 356 patients who underwent ETS for removal of NFPAs under sevoflurane-remifentanil anesthesia (sevoflurane group, n=103) or propofol-remifentanil anesthesia (propofol group, n=253), 92 patients in each group were selected and their 3-month post-operative neuroendocrine functional outcomes (primary outcome measure) were compared after propensity score matching. Overall changes in post-operative 3-month neuroendocrine function compared to pre-operative baseline did not differ between the sevoflurane and propofol groups (worsened: 32.6% vs 29.3%, persistently decreased: 9.8% vs 12.0%, improved: 12.0% vs 20.7%, normalized: 9.8% vs 12.0%, persistently normal: 18.5% vs 19.6%; P=.400). The incidence of pituitary hormone deficiency at 3 months post-operatively did not differ between the sevoflurane and propofol groups (adrenocorticotropic hormone deficiency: 18.5% vs 17.4%, P = 1.000; thyroid-stimulating hormone deficiency: 10.9% vs 3.3%, P=.081; gonadotropin deficiency: 54.3% vs 48.9%, P=.555; growth hormone deficiency: 45.7% vs 48.9%, P=.768; panhypopituitarism: 1.1% vs 1.1%, P=1.000). In patients undergoing ETS for removal of NFPAs, the effects of both sevoflurane-remifentanil and propofol-remifentanil anesthetic techniques on post-operative 3-month neuroendocrine functional outcomes were similar, suggesting that propofol and sevoflurane can be freely used in such patients in terms of post-operative intermediate-term neuroendocrine functional outcome.

Sevoflurane versus PRopofol combined with Remifentanil anesthesia Impact on postoperative Neurologic function in supratentorial Gliomas (SPRING): protocol for a randomized controlled trial

BackgroundPatients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens.MethodsThis is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer’s assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense.DiscussionThis randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients’ recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population.Trial registrationThe study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177). Principle investigator: Nan Lin (email address: linnan127@gmail.com) and Ruquan Han (email address: hanrq666@aliyun.com) Date of Registration: September 8th, 2016. Country of recruitment: China.

Effect of ketamine on the NeuroSENSE WAVCNS during propofol anesthesia; a randomized feasibility trial.

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAVCNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAVCNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg-1 initial bolus, 10 mcg kg-1 min-1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg-1 remifentanil over 30 s, then 1.5 mg kg-1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAVCNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAVCNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAVCNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAVCNS. This effect should be considered when using the WAVCNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945.

Adaptive drug interaction model to predict depth of anesthesia in the operating room

The availability of accurate models for predicting the drug effect in patients undergoing general anesthesia is an important factor in producing a personalized drug infusion. These models should consider different clinical factors to provide realistic predictions. This paper proposes a new methodology for modeling the depth of hypnosis (DOH) during anesthesia. The model, which is based on a pharmacokinetic–pharmacodynamic structure, explicitly takes into account the interaction between the hypnotic and opioid drugs delivered during surgery. Patients undergoing general surgery with intravenous propofol–remifentanil anesthesia were considered. The bispectral index (BIS) was used for monitoring the DOH. In contrast with previous research, the uniqueness of this study lies in the proposal of an adaptive model to deal simultaneously with the variabilities in the clinical response of the patients, the drug interactions, and the variable time delay introduced by the BIS monitor. The proposed method was validated using data from 17 patients undergoing general anesthesia. Successful results were obtained for predicting the evolution of BIS during the induction and maintenance phases of propofol–remifentanil anesthesia. Specifically, the convenience of an adaptive model that included all the factors likely to affect the anesthetic process was demonstrated. The proposed methodology can be used for the development of new models to be employed in model predictive control strategies for closed-loop anesthesia.

Influence of an "Electroencephalogram-Based" Monitor Choice on the Delay Between the Predicted Propofol Effect-Site Concentration and the Measured Drug Effect.

Clinicians can optimize propofol titration by using 2 sources of pharmacodynamic (PD) information: the predicted effect-site concentration for propofol (Ceprop) and the electroencephalographically (EEG) measured drug effect. Relation between these sources should be time independent, that is, perfectly synchronized. In reality, various issues corrupt time independency, leading to asynchrony or, in other words, hysteresis. This asynchrony can lead to conflicting information, making effective drug dosing challenging. In this study, we tried to quantify and minimize the hysteresis between the Ceprop (calculated using the Schnider model for propofol) and EEG measured drug effect, using nonlinear mixed-effects modeling (NONMEM). Further, we measured the influence of EEG-based monitor choice, namely Bispectral index (BIS) versus qCON index (qCON) monitor, on propofol PD hysteresis. We analyzed the PD data from 165 patients undergoing propofol-remifentanil anesthesia for outpatient surgery. Drugs were administered using target-controlled infusion (TCI) pumps. Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and qCON monitor values. We quantified the models' misspecification due to hysteresis, on an individual level, using the root mean squared errors (RMSEs). Subsequently, we optimized the PD models' predictions by adding a lag term to both models (lag-time PD models) and quantified the optimization using the RMSE. There is a counterclockwise hysteresis between Ceprop and BIS/qCON values. Not accounting for this hysteresis results in a direct PD model with an effect-site concentration which produces 50% of the maximal drug effect (Ce50) of 6.24 and 8.62 µg/mL and RMSE (median and interquartile range [IQR]) of 9.38 (7.92-11.23) and 8.41(7.04-10.2) for BIS and qCON, respectively. Adding a modeled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models' prediction, resulting in similar Ce50 (3.66 and 3.62 µg/mL for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49-9.90) and 6.56 (5.28-8.57) for BIS and qCON. There is a significant "Ceprop versus EEG measured drug effect" hysteresis. Not accounting for it leads to conflicting PD information and false high Ce50 for propofol in both monitors. Adding a lag term improved the PD model performance, improved the "pump-monitor" synchrony, and made the estimates of Ce50 for propofol more realistic and less monitor dependent.

Photoplethysmography-derived approximate entropy and sample entropy as measures of analgesia depth during propofol-remifentanil anesthesia.

The ability to monitor the physiological effect of the analgesic agent is of interest in clinical practice. Nonstationary changes would appear in photoplethysmography (PPG) during the analgesics-driven transition to analgesia. The present work studied the properties of nonlinear methods including approximate entropy (ApEn) and sample entropy (SampEn) derived from PPG responding to a nociceptive stimulus under various opioid concentrations. Forty patients with ASA I or II were randomized to receive one of the four possible remifentanil effect-compartment target concentrations (Ceremi) of 0, 1, 3, and 5ng·ml-1 and a propofol effect-compartment target-controlled infusion to maintain the state entropy (SE) at 50 ± 10. Laryngeal mask airway (LMA) insertion was applied as a standard noxious stimulation. To optimize the performance of ApEn and SampEn, different coefficients were carefully evaluated. The monotonicity of ApEn and SampEn changing from low Ceremi to high Ceremi was assessed with prediction probabilities (PK). The result showed that low Ceremi (0 and 1ng·ml-1) could be differentiated from high Ceremi (3 and 5ng·ml-1) by ApEn and SampEn. Depending on the coefficient employed in algorithm: ApEn with k = 0.15 yielded the largest PK value (0.875) whereas SampEn gained its largest PK of 0.867 with k = 0.2. Thus, PPG-based ApEn and SampEn with appropriate k values have the potential to offer good quantification of analgesia depth under general anesthesia.

P4580The effect of anesthetic techniques on cardiac troponin-T after non-cardiac surgery

Abstract Background The effects of anesthetics on cardiac protection and clinical outcomes have shown conflicting results in patients undergoing non-cardiac surgery. Unlike cardiac surgeries in which cardio-protective effects of anesthetic techniques have been reported, it lacks evidence and reproducibility in non-cardiac surgery. A current generation high-sensitivity cardiac troponin (hs-cTnI) is known to detect perioperative myocardial injury in non-cardiac surgery which is closely related to clinical outcomes. In this study, we hypothesized that balanced anesthesia using both remifentanil and volatile agents is the most effective in reducing postoperative myocardial injury, and compared the incidence of postoperative myocardial injury among different types of general anesthesia. Methods We analyzed the data of 3555 patients who underwent general anesthesia for non-cardiac surgery in our hospital between February 2010 and December 2016. In all patients, hs-cTnI was detected in preoperative period and postoperative period within 48 hours. Major exclusion criteria was troponin elevation before surgery. Patients were stratified into three groups; 661 patients who were received propofol-remifentanil total intravenous anesthesia (TIVA group), 1279 patients who were received volatile anesthesia without remifentanil (Volatile group) and 1622 patients who were received volatile anesthesia with remifentanil (Balanced group). The Primary outcome was troponin elevation [hs-cTnI≥0.04 ng/mL] within post-operative within 48 hours, and the incidence of postoperative complications such as postoperative acute kidney injury, new-onset atrial fibrillation and in-hospital mortality were also compared. Results The occurrence of myocaridial injury were significant difference between three groups. The occurrence of myocardial injury was significantly lower in the Balanced group than in Volatile group after adjustment (Odds ratio (OR) = 0.727; 95% confidence interval (CI) = 0.59–0.89; P-value = 0.002). Balanced group and TIVA group showed comparable results in risk of postoperative troponin elevation after adjustment (OR 1.131; 95% CI 0.96–1.33; P-value = 0.133). The incidence of troponin elevation was significantly higher in Volatile group than TIVA group after adjustment (OR 1.6; 95% CI 0.52–0.96; P-value = 0.005). The incidence of AKI was significantly lower in Balanced group than Volatile group after adjustment (OR 0.637; 95% CI 0.49–0.81; P-value &lt;0.001). Conclusion The remifentanil combination during general anesthesia may be associated with myocardial protection effect in patients undergoing non-cardiac surgery. Whether this impact leads to adverse long-term outcome remains unclear, and requires further investigation.

Photoplethysmography Response to Laryngeal Mask Airway Insertion during Propofol-Remifentanil Anethesia.

The present study was aimed to evaluate the abilities of photoplethysmography (PPG)-derived parameters, including sample entropy of PPG (SampEn), amplitude of PPG (PPGA), pulse beat interval (PBI) and diastolic interval (DI) extracted by nonlinear or linear methods, to monitor the balance between nociception and antinociception. 26 ASA I or II patients were randomized into one of the three groups to receive a remifentanil effect-compartment target controlled infusion (Ceremi) of 1, 3 and 5 ng/ml and an effect-compartment target controlled propofol infusion (Ceprop) to keep the state entropy (SE) at 50 (40~60). Laryngeal mask airway (LMA) insertion was applied as a noxious stimulus. The percentage of change in SampEn (△SampEn, AUC=0.896), PBI (△PBI, AUC=0.896) and DI (ΔDI, AUC=0.972), but not in PPGA (△PPGA, AUC=0.667), were statistically excellent in discriminating low Ceremi (1 ng/ml) from higher Ceremi (3 and 5 ng/ml). Additionally, the prediction probabilities (Pk) values of △SampEn, ΔPBI and ΔDI were high as well with 0.795, 0.754 and 0.813 for discriminating Ceremi. These results demonstrated that nonlinear and linear parameters of SampEn, PBI and DI had strong dependency on Ceremi in response to LMA insertion and could provide nociceptive information during propofol-remifentanil anesthesia. This indicated that PPG-derived parameters were potential to develop the clinical assessment of nociception-antinociception balance under general anesthesia.