Study of Two Sedative Protocols for Drug-Induced Sleep Endoscopy: Propofol versus Propofol-Remifentanil Combination, Delivered in Target-Controlled Infusion Mode.

Background and Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing pathology with significant clinical consequences, including increased cardiovascular risk and cognitive decline. Continuous positive airway pressure (CPAP) is the gold-standard treatment, but alternative strategies are sometimes needed for patients intolerant to CPAP. Drug-induced sleep endoscopy (DISE) is a key diagnostic tool for assessing upper airway obstruction in OSA patients and subsequently tailoring a surgical approach, with sedation protocols playing a crucial role in its efficacy and results accuracy. This study aimed to investigate the effect of adding remifentanil to a propofol target-controlled infusion (TCI) regimen on the sedation parameters and procedural outcomes of DISE. Materials and Methods: The study was conducted at the Central University and Emergency Military Hospital "Dr. Carol Davila" and Ria Clinic in Bucharest between July 2021 and October 2023. Thirty-one patients were enrolled and randomised into two groups: a propofol group (P group, n= 11) and a remifentanil-propofol group (R-P group, n = 20). DISE was performed using standardised protocols, sedative drugs were administered in TCI mode, and data on sedation levels, respiratory and cardiovascular parameters, and procedural incidents were collected. Results: The addition of remifentanil at 1 ng/mL effect-site concentration significantly reduced the effect-site concentration of propofol required for adequate sedation (3.4 ± 0.7 µg/mL in the P group vs. 2.8 ± 0.6 µg/mL in the R-P group, p = 0.035). The time to achieve adequate sedation was also shorter in the R-P group (7.1 ± 2.5 min vs. 9.5 ± 2.7 min, p = 0.017). The incidence of cough, hypoxemia, and cardiovascular events did not significantly differ between the two groups. Conclusions: Adding remifentanil to a propofol TCI regimen for DISE effectively reduces the required propofol effect-site concentration and shortens sedation time without increasing the risk of adverse events. This combination may enhance the safety and efficiency of DISE, offering a promising alternative for patients undergoing this procedure.

Is target-controlled infusion better than manual controlled infusion during TIVA for elective neurosurgery? Results of a single-centre pilot study.

INTRODUCTION: Maintaining optimal systemic circulatory parameters is essential to ensure adequate cerebral perfusion (CPP) during neurosurgery, especially when autoregulation is impaired. AIM OF STUDY: To compare two types of total intravenous anaesthesia i.e. target controlled infusion (TCI) and manually controlled infusion (MCI) with propofol and remifentanil in terms of their control of cardiovascular parameters during neurosurgical resection of intracranial pathology. MATERIAL AND METHODS: Patients with supratentorial intracranial pathology were selected for the study. Patients in ASA grades III and IV and those with diseases of the circulatory system were excluded. Patients were randomly divided into two equal groups according to the method of general anaesthesia used i.e. TCI or MCI. During the neurosurgery, the values of mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS) and central venous pressure were monitored and recorded at the designated 14 relevant (i.e. critical from the anaesthetist's and neurosurgeon's points of view) measurement points. RESULTS: Fifty patients (25 TCI and 25 MCI) were enrolled in the study. The groups did not differ with respect to sex, age and BMI, operation time or volume of removed lesions. TCI-anaesthetised patients had better MAP stability at the respective time points. CONCLUSIONS: Due to the greater stability of MAP, which has a direct effect on CPP, TCI appears to be the method of choice in anaesthesia for intracranial surgery.

Comparison of the target-controlled infusion and the manual infusion of propofol anesthesia during electroconvulsive therapy: an open-label randomized controlled trial.

BACKGROUND: Target-controlled infusion (TCI) of propofol is a well-established method of procedural sedation and has been used in Japan for anesthesia during electroconvulsive therapy (ECT). However, the usefulness of the TCI of propofol for ECT has yet to be determined. This study aimed to compare the TCI and manual infusion (MI) of propofol anesthesia during ECT. METHODS: A total of forty psychiatric inpatients receiving bitemporal ECT were enrolled in the present study and randomized into the TCI group (N = 20) and the MI group (N = 20). Clinical Global Impression (CGI) and Montreal Cognitive Assessment (MoCA) scores were measured before and after ECT. The clinical outcomes, anesthesia-related variables, and ECT-related variables were compared between the two groups. Generalized estimating equations (GEEs) were used to model the comparison throughout the course of ECT. RESULTS: A total of 36 subjects completed the present study, with 18 subjects in each group. Both the groups didn't significantly differ in the post-ECT changes in CGI and MoCA scores. However, concerning MoCA scores after 6 treatments of ECT, the MI group had improvement while the TCI group had deterioration. Compared with the MI group, the TCI group had higher doses of propofol, and longer procedural and recovery time. The TCI group seemed to have more robust seizures in the early course of ECT but less robust seizures in the later course of ECT compared with the MI group. CONCLUSIONS: The present study does not support the use of TCI of propofol for anesthesia of ECT. TRIAL REGISTRATION: (ClinicalTrials.gov): NCT03863925 . Registered March 5, 2019 - Retrospectively registered.

A Prototype Patient-Maintained Propofol Sedation System Using Target Controlled Infusion for Primary Lower-Limb Arthroplasty.

Each year, many operations in the UK are performed with the patient awake, without the use of general anaesthesia. These include joint replacement procedures, and in order to reduce patient anxiety, the supervising anaesthetist delivers the sedative propofol intravenously using a target-controlled infusion (TCI) device. However, it is clinically challenging to judge the required effect-site concentration of sedative for an individual patient, resulting in patient care issues related to over or under-sedation. To improve the process, patient-maintained propofol sedation (PMPS), where the patient can request an increase in concentration through a hand-held button, has been considered as an alternative. However, due to the proprietary nature of modern TCI pumps, the majority of PMPS research has been conducted using prototypes in research studies. In this work, a PMPS system is presented that effectively converts a standard infusion pump into a TCI device using a laptop with TCI software. Functionally, the system delivers sedation analogous to a modern TCI pump, with the differences in propofol consumption and dosage within the tolerance of clinically approved devices. Therefore, the Medicines and Healthcare products Regulatory Agency (MHRA) has approved the system as a safe alternative to anaesthetist-controlled TCI procedures. It represents a step forward in the consideration of PMPS as a sedation method as viable alternative, allowing further assessment in clinical trials.

To ascertain the plasma concentration of propofol to achieve bispectral index-guided sedation using a target-controlled infusion in patients undergoing elective surgeries under neuraxial anaesthesia.

Background and Aims: Sedation improves patient satisfaction, comfort and acceptance of regional anaesthesia. Propofol using bispectral index (BIS)/target-controlled infusion (TCI) system can be an optimal method of sedation, as it combines objective measurement of sedation using BIS along with maintenance of a steady plasma concentration of propofol with the TCI device. The aim of this study was to ascertain the dose and safety of propofol using BIS/TCI system for sedation in patients undergoing surgeries under neuraxial anaesthesia. Methods: One hundred and seven adult patients, undergoing elective surgical procedures under spinal or combined spinal epidural anaesthesia, were recruited. Propofol infusion was started with TCI at an initial target plasma concentration (Cpt) of 1.2 µg/mL, and after equilibration between Cpt and effect site concentration (Ce), propofol was then adjusted in increments and/or decrements of 0.2 µg/mL in order to maintain a BIS value between 60 and 80. The average time to reach BIS = 80 after starting infusion was 7.32 ± 3.13 minutes. The objective was to calculate mean Cpt value maintaining BIS between 60 and 80 and to observe recovery time and complications. Results: Mean Cpt value was 1.13 ± 0.17 mg/mL with 95% confidence interval (1.10-1.16 µg/mL). In 85% of patients, a BIS value of 60-80 was maintained at Cpt ≤ 1.2 µg/mL. No patient had severe complications requiring stoppage of infusion. Conclusion: Propofol sedation using BIS/TCI system can provide safe and convenient sedation during neuraxial anaesthesia at very low plasma concentration, Cpt ≤ 1.2 µg/mL in majority of patients. There were no periprocedural complications, and recovery was rapid.

Effects of dexmedetomidine as an adjuvant in thoracic paravertebral block on EC50 of propofol for successful laryngeal mask insertion: a randomized controlled trial.

BACKGROUND: Dexmedetomidine as an adjuvant can improve the duration and the quality of thoracic paravertebral block (TPVB); however, its quantitative effect on propofol infusion is unclear. This study aimed to investigate the effect of dexmedetomidine as an adjuvant in TPVB on the medium effective concentration (EC50) of propofol for successful laryngeal mask insertion. METHODS: Sixty breast cancer patients who underwent elective modified radical mastectomy were enrolled and randomized at a 1:1 ratio into control group (Group C, n=30) or dexmedetomidine group (Group D, n=30). Ultrasound-guided T3 paravertebral block was performed before induction of anesthesia. In Group C, 0.5% ropivacaine 0.3 mL/kg was injected into T3 paravertebral space, while subjects in Group D received 0.5% ropivacaine 0.3 mL/kg with dexmedetomidine (1 µg/kg). Propofol target-controlled infusion (TCI) was performed, with an initial target effect-site concentration of 5 µg/mL determined for both groups. The laryngeal mask was inserted once the effect chamber achieved the target concentration. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.5 mg/mL intervals, based on the success of the laryngeal mask insertion. Probit analysis was used to determine the propofol EC50. Mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS) and application of atropine or ephedrine was recorded. Participants, TPVB giver, and data recorder were blinded to group assignment. RESULTS: Propofol EC50 for successful laryngeal mask insertion were statistically significant, with 5.256 µg/mL (95% CI: 4.833, 5.738 µg/mL) in Group C and 3.172 µg/mL (95% CI: 2.701, 3.621 µg/mL) in Group D. Both groups displayed significantly lower MAP and HR, post propofol TCI (P<0.05). However, subjects in Group D exhibited lower MAP and HR levels compared to patients in Group C (P<0.05). Application of atropine (0% vs. 10%) and ephedrine (20.0% vs. 13.3%) were not significantly different between two groups. CONCLUSIONS: Dexmedetomidine, administered as an adjuvant in TPVB, can reduce the TCI concentration of propofol for successful laryngeal mask placement in females. The target concentration of propofol requires adjustment and close monitoring of hemodynamic changes, post induction is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016614.

A Non-invasive Monitoring of Propofol Concentration in Blood by a Virtual Surface Acoustic Wave Sensor Array.

Propofol (2,6-diisopropylphenol) is widely used in total intravenous anesthesia. An unknown drug concentration in blood always leads to some side effects in patients with propofol injection. However, the drug concentration in the blood is hard to be continuously measured since invasive sampling causes a loss of blood at each measurement. Here, we introduced a virtual surface acoustic wave sensor array (VSAWSA) to non-invasively detect the propofol concentration in blood through exhaled gases. Calibration was conducted by a parallel test using gas chromatography and mass spectrometry (GC-MS) with solid-phase micro-extraction (SPME) for preconcentration. The limit of detection of VSAWSA reached 0.15 nmol/L for propofol. Six cases of clinical trials was conducted to compare the exhaled propofol concentrations to the plasma concentrations controlled by target-controlled infusion (TCI). The calibration by GC-MS ensured the feasibility, reliability, and accuracy of the VSAWSA (R = 0.9904, p <0.001). The clinical monitoring data by VSAWSA showed an excellent consistency with TCI.

[Effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients after target-controlled induction].

OBJECTIVE: To observe the clinical effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients who underwent abdominal external hernia surgery at the time of consciousness and pain disappearing by target-controlled infusion (TCI) and bispectral index (BIS). METHODS: Fifty patients who underwent elective abdominal hernia surgery were randomly assigned into an observation group and a control group, 25 cases in each one. In the observation group, 30 minutes before anesthesia induction, Fugugou (Extra), Gan (CO12), Pizhixia (AT4), and Shenmen (TF4) were embedded by auricular needles until the end of surgery, 10 times of counter press each point. In the control group, the same amount of auricular tape was applied until the end of surgery at the same points without stimulation 30 minutes before anesthesia induction. Patients in the two groups were given total intravenous anesthesia, and BIS was monitored by BIS anesthesia depth monitor. Propofol was infused by TCI at a beginning concentration of 1.5µg/L and increased by 0.3µg/L every 30s until the patients lost their consciousness. After that, remifentanil was infused by TCI at a beginning concentration of 2.0µg/L and increased by 0.3µg/L every 30s until the patients had no body reaction to pain stimulation (orbital reflex). Indices were recorded, including mean arterial pressure (MAP), heart rate (HR) and the BIS values, at the time of T0 (entering into the operation room), T1 (losing consciousness) and T2 (pain relief), the plasma and effect site concentrations of propofol at T1, the plasma and effect site concentrations of remifentanil at T2. After surgery we recorded the total amounts of propofol and remifentanil, surgery time and anesthesia time. RESULTS: At T1 and T2, MAP and HR of the observation group were higher than those of the control group (P<0.05, P<0.01). At T1, the plasma and effect site concentrations of propofol in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). At T2, the plasma and effect site concentrations of remifentanil in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). There was no significant difference in BIS values at T1 and T2 between the two groups (bothP>0.05). There was no significant difference in operation time and anesthesia time between the two groups (bothP>0.05). The total amount of remifentanil in the observation group was significantly lower than that in the control group (P<0.01). There was no significant difference in the total amount of propofol between the two groups (P>0.05). CONCLUSIONS: Ear points embedding combined with propofol-remifentanil TCI could reduce the plasma and effect site concentrations of propofol and remifentanil and the total amount of remifentanil in elderly patients with extra-abdominal hernia surgery, and had the effect of assisting sedation and analgesia.

Determination of total and unbound propofol in patients during intensive care sedation by ultrafiltration and LC-MS/MS.

For the quantification of propofol total and unbound drug concentrations a sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. To separate unbound propofol an ultrafiltration step before sample preparation was performed. Both the ultrafiltrate and plasma samples were extracted with solid-phase extraction and substituted with deuterated propofol as an internal standard. Separation was performed by gradient elution using UPLC-like system and analyzed by MS/MS consisting of an electrospray ionization source. To detect low and high concentration levels of propofol two calibration curves were identified and showed linearity within the range of 1-50ng/ml and 50-20000ng/ml. The lower limit of quantification was 1ng/ml. Intra- and interassay precision and accuracy did not exceed ±15%. The method was applied to a clinical study during intensive care treatment of patients after coronary artery bypass grafting.

Evaluation of Plasmatic Concentration of Propofol 2.5µg/ml by TCI using Marsh Modified Model, during oocyte retrieval for IVF in Latin-American women (Venezuelans).

OBJECTIVE: To evaluate efficacy of Propofol at Cp 2.5 µg/ ml administered by Target Controlled Infusion (TCI) using Marsh Modified Model, in pre-medicated with midazolam/ fentanil Latin-American women (Venezuelans) during oocyte retrieval for In Vitro Fertilization. METHODS: Prospective, descriptive study included 72 women, 18-44 years old, ASA I-II, non obese, undergoing oocyte retrieval, pre-medicated with midazolam 0.04 mg/kg and fentanil 2µg/kg and received anesthesia based in Propofol at Cp 2.5µg/ml by Target Controlled Infusion using Marsh Modified Model. Demographic data, propofol doses, duration of procedure and recovery time was registered using descriptive statistic. Anesthesia efficacy was measured by Biespectral Analysis (BIS), Intra-Operative Movements Scale (0 to 5) graded, Postoperative Pain by Visual Analog Scale (VAS) and nausea/vomits incidence. ANOVA and Pearson Chi2 were used with an error of 0.05. RESULTS: Age average was 33.04±6 years old, procedure average time 18.06±8min, Propofol total doses 146.64±53 mgs, Propofol infusion doses average 155.2±3µg/Kg/min. During procedure, 70.8% of patients had no movement, 22.2% movement Grade I and 6.9% Grade II. (Grade I-II movement did not interfere with procedure continuity). 70.8% achieved BIS 40-50 and 93.1% had BIS equal o less than 60. There was a statistic significant correlation between BIS 40-50 and no movements. Recovery post-anesthesia time was 25.2±8 min. 98.6% of patients reported excellent comfort. CONCLUSION: With midazolam/fentanil pre-medication, Propofol at Cp 2.5µg/ml by TCI using Marsh Modified Model showed a 93% of effectiveness during oocyte retrieval in Latin-American women subjected to IVF, allowing an ultra- fast recovery time.

The dexmedetomidine concentration required after remifentanil anesthesia is three-fold higher than that after fentanyl anesthesia or that for general sedation in the ICU.

PURPOSE: The general dexmedetomidine (DEX) concentration required for sedation of intensive care unit patients is considered to be approximately 0.7 ng/mL. However, higher DEX concentrations are considered to be required for sedation and/or pain management after major surgery using remifentanil. We determined the DEX concentration required after major surgery by using a target-controlled infusion (TCI) system for DEX. METHODS: Fourteen patients undergoing surgery for abdominal aortic aneurysms (AAA) were randomly, double-blindly assigned to two groups and underwent fentanyl- or remifentanil-based anesthetic management. DEX TCI was started at the time of closing the peritoneum and continued for 12 hours after stopping propofol administration (M0); DEX TCI was adjusted according to the sedation score and complaints of pain. The doses and concentrations of all anesthetics and postoperative conditions were investigated. RESULTS: Throughout the observation period, the predicted plasma concentration of DEX in the fentanyl group was stable at approximately 0.7 ng/mL. In contrast, the predicted plasma concentration of DEX in the remifentanil group rapidly increased and stabilized at approximately 2 ng/mL. The actual DEX concentration at 540 minutes after M0 showed a similar trend (0.54±0.14 [fentanyl] versus 1.57±0.39 ng/mL [remifentanil]). In the remifentanil group, the dopamine dose required and the duration of intubation decreased, and urine output increased; however, no other outcomes improved. CONCLUSION: The DEX concentration required after AAA surgery with remifentanil was three-fold higher than that required after AAA surgery with fentanyl or the conventional DEX concentration for sedation. High DEX concentration after remifentanil affords some benefits in anesthetic management.