Target-controlled Infusion Pump Research Articles

Effect of remifentanil on three effect-site concentrations of propofol and their relationship during electroencephalography at loss of response, at maximum alpha power, and at onset of burst suppression: a prospective randomized trial.

The effect-site concentration (Ce) at loss of response (Ce-LOR) to propofol closely correlates both with Ce as electroencephalographic alpha power becomes highest (Ce-alpha) and with Ce at onset of burst suppression (BS) (Ce-OBS), when no opioids are administered. Co-administration of opioids dose-dependently decreases Ce-LOR. We investigated the influence of remifentanil on the relationship between these three Ces. After receiving approval from our local ethical committee, with written informed consent, we enrolled 90 participants (ASA-PS I or II) who were scheduled for elective surgery. Participants were randomly assigned to three groups: constant remifentanil Ce 0ng/ml (Remi_0); 1ng/mL (Remi_1); and 2ng/mL (Remi_2). We recorded both raw EEG and EEG-derived parameters on a computer. After reaching remifentanil equilibrium, we administered propofol using a target-controlled infusion pump such that propofol Ce increased to about 0.3μg/mL/min. After determining Ce-LOR, we administered 0.6mg/kg of rocuronium and started mask ventilation. The study protocol ended after observation of BS. Three participants were excluded. Ce-LOR in each group (Remi_0, Remi_1, Remi_2) was 2.00 ± 0.58μg/mL, 1.43 ± 0.49μg/mL, and 1.37 ± 0.42μg/mL. Ce-alpha was 2.91 ± 0.63μg/mL, 2.30 ± 0.41μg/mL, and 2.12 ± 0.39μg/mL. Ce-OBS was 3.80 ± 0.69μg/mL, 3.25 ± 0.68μg/mL, and 2.90 ± 0.57μg/mL. In three other instances, Ce was decreased by remifentanil. Generalized linear model analysis revealed that remifentanil had no influence on the relationship between the three Ces. During propofol anesthesia, even low concentrations of remifentanil shifted concentration-related electroencephalographic changes.

Effects of adding low-dose esketamine to sufentanil and propofol sedation during cervical conization: a single-centre, randomized controlled trial

BackgroundCervical conization is a brief but painful procedure that can be performed under sufficient sedation with propofol and opioids. However, this sedation approach comes with a high risk of sedation-related adverse events (SRAEs). Esketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, causes less cardiorespiratory depression than opioids. The aim of this study was to assess the efficacy and safety of adding a low dose of esketamine to propofol and sufentanil sedation as an opioid-reduced regimen.MethodsA total of 122 consecutive patients with ASA I-II, body mass index < 30, and STOP-BANG score < 3 who underwent cervical conization were enrolled and randomly divided into Group S and Group ES. Using a closed-loop target-controlled infusion (TCI) pump with a target bispectral index (BIS) value of 60 ± 5, patients in Group S were sedated with 0.2 mcg·kg-1 sufentanil and propofol, while patients in Group ES were sedated with 0.15 mg·kg-1 esketamine, 0.1 mcg·kg-1 sufentanil and propofol. The primary outcome was the incidence and severity of SRAEs, while the secondary outcomes included effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, and patient and gynaecologist satisfaction.ResultsData from 120 patients were analysed. The incidence of composite SRAEs was significantly higher in Group S than in Group ES (85.0% vs. 56.7%, P < 0.05). Furthermore, the severity of SRAEs was higher in Group S than in Group ES (P < 0.001). There were no significant differences in the effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, or patient and gynaecologist satisfaction between the two groups.ConclusionAdding low-dose esketamine to propofol and sufentanil sedation reduces the incidence and severity of SRAEs in patients undergoing cervical conization, with equal sedation efficacy, recovery quality, and no additional psychomimetic side effects.Trial registrationChiCTR2000040457, 28/11/2020.

Target-controlled infusion: A comparative, prospective, observational study of the conventional TCI pump and the novel smartphone-based application iTIVA.

Empirically adjusted, standard drug doses fail to address interindividual pharmacokinetic and pharmacodynamics variability. Target-controlled infusion (TCI) delivers drugs in calibrated boluses to achieve and maintain a selected target plateau drug level (plasma or effect site). Interactive total intravenous anesthesia (iTIVA™) smartphone software simulates TCI and employs 31 established pharmacokinetic models for 11 different intravenous agents and is coupled with standard volumetric infusion pumps for administering TCI. This prospective, observational, study investigates the degree of agreement between iTIVA and a conventional TCI pump (CTP) for the volume of propofol infused using the Schnider pharmacokinetic model in adult patients of either sex undergoing oncosurgery lasting 1-3 h under total intravenous anesthesia. Bland-Altman analysis of 124 data pairs from 30 patients provided bias, precision, and limits of agreement between the volumes infused by CTP and iTIVA (V-CTP and V-iTIVA) during specific identical time periods. Spearman's rho and Kendall's tau rank correlation coefficients provided the degree of association between V-CTP and V-iTIVA. Spearman's rho and Kendall's tau were 0.996 and 0.964, respectively. Bias or the mean of differences was -0.02, while the limits of agreement were 0.58 and -0.63, respectively (Bland-Altman plot). The maximum allowed difference of 2 ml was much larger than the 95% confidence intervals for the limits of agreement. The Mountain plot was short tailed (-1.28 to 1.55) and centred over zero (0.01). The volume of propofol infused using TCI pump was similar to that calculated by iTIVA in identical time periods, confirming the clinical applicability of iTIVA.

Does Propofol Effect Site (Brain) Concentration Predicted by Target-Controlled Infusion Correlate with Propofol Measured in the Brain? An Exploratory Study in Neurosurgical Patients

Total intravenous anesthesia with propofol can be administered by target-controlled infusion pumps, which work on the principles of pharmacokinetic modeling. While designing this model, neurosurgical patients were excluded as the surgical site and drug action site remained the same (brain). Whether the predicted set propofol concentration and the actual brain site concentration correlate, especially in neurosurgical patients with impaired blood-brain barrier (BBB), is still unknown. In this study we compared the set propofol effect-site concentration in the target-controlled infusion pump with actual brain concentration measured by sampling the cerebrospinal fluid (CSF). Consecutive adult neurosurgical patients requiring propofol infusion intraoperatively were recruited. Blood and CSF samples were collected simultaneously when patients received propofol infusion at 2 different target effect-site concentrations-2 and 4 ug/mL. To study BBB integrity, CSF-to-blood albumin ratio and imaging findings were compared. The propofol level in the CSF was compared with set concentration using the Wilcoxon signed-rank test. Fifty patients were recruited, and the data were analyzed from 43 patients. There was no correlation between propofol concentration set in TCI and propofol concentration measured in blood and CSF. Though imaging findings were suggestive of BBB disruption in 37/43 patients, the mean (±standard deviation) CSF-to-serum albumin ratio was 0.0028 ± 0.002, suggesting intact BBB integrity (ratio >0.3 was considered as disrupted BBB). CSF propofol level did not correlate with set concentration in spite of acceptable clinical anesthetic effect. Also, the CSF-to-blood albumin measurement did not provide information on the BBB integrity.

Relationship between decrement time and recovery time in pediatric total intravenous anesthesia with propofol and remifentanil.

Propofol target-controlled infusion is now used in many countries for the administration of total intravenous anesthesia (TIVA) and uses population pharmacokinetic data incorporated into the target-controlled infusion pump to administer a dose which will achieve a target concentration selected by the practitioner. Modern target-controlled infusion pumps can include an estimate of how long it will take for the plasma propofol concentration to fall to a value programmed into the pump, once the propofol infusion is stopped. This is known as decrement time. Many users consider decrement time to be equivalent to recovery time for the patient, despite the several assumptions that makes. To determine if the decrement time estimated by the target-controlled infusion pumps at the end of anesthesia could be reliably used to predict recovery time for individual patients. Target-controlled infusion pumps at Birmingham Children's Hospital are programmed with a propofol decrement concentration of 1.5 μg.mL-1 . Patients for a variety of surgical procedures were anesthetised with propofol-remifentanil TIVA. Eye opening was used as a surrogate of recovery time. Data were analyzed using median absolute deviation, Mann-Whitney U test, and linear regression to see if there was any correlation with decrement time and recovery time, total dose of propofol administered, duration of anesthesia and patient age. A total of 55 patients were audited. Median age was 7.2 years (range 0.9-15.9), and median weight was 26 kg (range 8.5-77). Median decrement time was 11.8 min (IQR 8.3-21), while median recovery time was 15 min (IQR 9-20). Recovery time was the same as decrement time in 2% of patients, less than in 40% of patients and more in 58% of patients. Two thirds of patients opened eyes at an estimated plasma propofol concentration between 1.2 and 1.8 μg.mL-1 . The median absolute deviation for the difference between decrement time and recovery time was 5.7 min, from a median of 1 min. Analysis demonstrated there was no statistical correlation between decrement time to 1.5 μg.mL-1 and recovery time, age, total propofol dose administered, or duration of anesthesia, for individual patients. There was variation between decrement time to 1.5 μg.mL-1 and recovery time of over 5 min in nearly half of patients. Decrement time to 1.5 μg.mL-1 must be used with caution when trying to predict recovery time for individual patients following TIVA.

Is Sedation of Choice in Thyroplasty Surgery? A Study on the Effects of Sedatives on Voice Quality

In order to establish the ideal anesthetic protocol in thyroplasty type I surgery, where the intraoperative voice test is used to guide the medialization of the paralyzed fold, we have studied the effects of a sedation with midazolam premedication and adjusted intravenous doses of propofol and remifentanil on voice quality in patients without vocal fold pathology undergoing otorhinolaryngology surgery other than thyroplasty. Prospective cross-sectional study included 40 adult patients. A voice recording was performed when the patient was fully awake and when an appropriate level of conscious sedation was reached. Following premedication with midazolam at anxiolytic doses, remifentanil and propofol were administrated by target controlled infusion pumps (TCI). These results were compared with those obtained in a previous study carried out by the same team using intravenous bolus (IV) according to weight. The recorded voice analysis was performed using the computer program Praat (v.5.3.39) for a sustained vowel. All the parameters obtained from the acoustic analysis of the voice were altered after sedation with target controlled infusion in a statistically significant way. Comparing with bolus intravenous, harmonic and noise ratio (HNR) was the only parameter that decreased less in the TCI group. The state of sedation obtained using midazolam premedication, propofol and remifentanil adjusted intravenous doses alters significantly all the voice parameters, although this alteration is considerably less than the changes produced by the medication administered in bolus IV. According to these results, the sedation and the voice test during thyroplasty surgery would present a series of limitations when it comes to guiding the medialization of the paralyzed vocal fold and therefore it could not be considered as the ideal anesthetic protocol in thyroplasty surgery.

Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD.

The intravenous induction or loading dose in children is commonly prescribed per kilogram. That dose recognizes the linear relationship between volume of distribution and total body weight. Total body weight comprises both fat and fat-free mass. Fat mass influences the volume of distribution and the use of total body weight fails to recognize the impact of fat mass on pharmacokinetics in children. Size metrics alternative to total body mass (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale pharmacokinetic parameters (clearance, volume of distribution) for size. Clearance is the key parameter used to calculate infusion rates or maintenance dosing at steady state. Dosing schedules recognize the curvilinear relationship, described using allometric theory, between clearance and size. Fat mass also has an indirect influence on clearance through both metabolic and renal function that is independent of its effects due to increased body mass. Fat-free mass, lean body mass and ideal body mass are not drug specific and fail to recognize the variable impact of fat mass contributing to body composition in children, both lean and obese. Normal fat mass, used in conjunction with allometry, may prove a useful size metric but computation by clinicians for the individual child is not facile. Dosing is further complicated by the need for multicompartment models to describe intravenous drug pharmacokinetics and the concentration effect relationship, both beneficial and adverse, is often poorly understood. Obesity is also associated with other morbidity that may also influence pharmacokinetics. Dose is best determined using pharmacokinetic-pharmacodynamic (PKPD) models that account for these varied factors. These models, along with covariates (age, weight, body composition), can be incorporated into programmable target-controlled infusion pumps. The use of target-controlled infusion pumps, assuming practitioners have a sound understanding of the PKPD within programs, provide the best available guide to intravenous dose in obese children.

Detection of Motor Cerebral Activity After Median Nerve Stimulation During General Anesthesia (STIM-MOTANA): Protocol for a Prospective Interventional Study.

Accidental awareness during general anesthesia (AAGA) is defined as an unexpected awareness of the patient during general anesthesia. This phenomenon occurs in 1%-2% of high-risk practice patients and can cause physical suffering and psychological after-effects, called posttraumatic stress disorder. In fact, no monitoring techniques are satisfactory enough to effectively prevent AAGA; therefore, new alternatives are needed. Because the first reflex for a patient during an AAGA is to move, but cannot do so because of the neuromuscular blockers, we believe that it is possible to design a brain-computer interface (BCI) based on the detection of movement intention to warn the anesthetist. To do this, we propose to describe and detect the changes in terms of motor cortex oscillations during general anesthesia with propofol, while a median nerve stimulation is performed. We believe that our results could enable the design of a BCI based on median nerve stimulation, which could prevent AAGA. To our knowledge, no published studies have investigated the detection of electroencephalographic (EEG) patterns in relation to peripheral nerve stimulation over the sensorimotor cortex during general anesthesia. The main objective of this study is to describe the changes in terms of event-related desynchronization and event-related synchronization modulations, in the EEG signal over the motor cortex during general anesthesia with propofol while a median nerve stimulation is performed. STIM-MOTANA is an interventional and prospective study conducted with patients scheduled for surgery under general anesthesia, involving EEG measurements and median nerve stimulation at two different times: (1) when the patient is awake before surgery (2) and under general anesthesia. A total of 30 patients will receive surgery under complete intravenous anesthesia with a target-controlled infusion pump of propofol. The changes in event-related desynchronization and event-related synchronization during median nerve stimulation according to the various propofol concentrations for 30 patients will be analyzed. In addition, we will apply 4 different offline machine learning algorithms to detect the median nerve stimulation at the cerebral level. Recruitment began in December 2022. Data collection is expected to conclude in June 2024. STIM-MOTANA will be the first protocol to investigate median nerve stimulation cerebral motor effect during general anesthesia for the detection of intraoperative awareness. Based on strong practical and theoretical scientific reasoning from our previous studies, our innovative median nerve stimulation-based BCI would provide a way to detect intraoperative awareness during general anesthesia. Clinicaltrials.gov NCT05272202; https://clinicaltrials.gov/ct2/show/NCT05272202. PRR1-10.2196/43870.

Safety and efficacy of target controlled infusion administration of propofol and remifentanil for moderate sedation in non-hospital dental practice.

Fearful and anxious patients who find dental treatment intolerable without sedative and analgesic support may benefit from moderate sedation. Target controlled infusion (TCI) pumps are superior to bolus injection in maintaining low plasma and effect-site concentration variability, resulting in stable, steady-state drug concentrations. We evaluated the safety and efficacy of moderate sedation with remifentanil and propofol using TCI pumps in non-hospital dental settings. A prospective chart review was conducted on 101 patients sedated with propofol and remifentanil using TCI pumps. The charts were completed at two oral surgeons and one general dentist's office over 6 months. Hypoxia, hypotension, bradycardia, and over-sedation were considered adverse events and were collected using Tracking and Reporting Outcomes of Procedural Sedation (TROOPS). Furthermore, patient recovery time, sedation length, drug dose, and patient satisfaction questionnaires were used to measure sedation effectiveness. Of the 101 reviewed sedation charts, 54 were of men, and 47 were of women. The mean age of the patients was 40.5 ±18.7 years, and their mean BMI was 25.6 ± 4.4. The patients did not experience hypoxia, bradycardia, and hypotension during the 4694 min of sedation. The average minimum Mean Arterial Pressure (MAP) and heartbeats were 75.1 mmHg and 60.4 bpm, respectively. 98% of patients agreed that the sedation technique met their needs in reducing their anxiety, and 99% agreed that they were satisfied with the sedation 24 hours later. The average sedation time was 46.9 ± 55.6 min, and the average recovery time was 12.4 ± 4.4 min. Remifentanil and propofol had mean initial effect-site concentration doses of 0.96 µ/ml and 1.0 ng/ml respectively. The overall total amount of drug administered was significantly higher in longer sedation procedures compared to shorter ones, while the infusion rate decreased as the procedural stimulus decreased. According to the results of this study, no patients experienced adverse events during sedation, and all patients were kept at a moderate sedation level for a wide range of sedation times and differing procedures. The results showed that TCI pumps are safe and effective for administering propofol and remifentanil for moderate sedation in dentistry.

Recent advancements in total intravenous anaesthesia and anaesthetic pharmacology.

Target-controlled infusion pumps and depth of anaesthesia monitors have made total intravenous anaesthesia (TIVA) easy, safe, and precise. The merits of TIVA were highlighted during the coronavirus disease 2019 (COVID-19) pandemic, confirming its potential further in the post-COVID clinical practice as well. Ciprofol and remimazolam are newer drugs that are being tried with a hope to upgrade the practice of TIVA. While research on safe and effective drugs continues, TIVA is being practised with a combination of drugs and adjuncts to overcome the disadvantages of each and to provide complete and balanced anaesthesia with additional benefits in recovery and pain relief postoperatively. Modulation of TIVA for the special population groups is still under process. Advancement in digital technology with mobile apps has increased the scope of TIVA in day-to-day use. The formulation and update of guidelines can establish a safe and efficient practice of TIVA.

Comparison of 2 effect-site concentrations of remifentanil with midazolam during transrectal ultrasound-guided prostate biopsy under procedural analgesia and sedation: A randomized controlled study.

Until now, target-controlled infusion of remifentanil with midazolam for transrectal ultrasound-guided prostate biopsy has not been described. Here, we investigate 2 effect-site concentrations of remifentanil with intermittent bolus midazolam for transrectal ultrasound-guided prostate biopsy under procedural analgesia and sedation. A prospective, randomized controlled trial including patients who received a transrectal ultrasound-guided prostate biopsy between February 2019 and January 2021 was conducted. Group 1 and Group 2 were respectively administered an initial effect-site concentration of remifentanil of 1.0 ng/mL and 2.0 ng/mL by a target-controlled infusion pump with Minto model. In both groups, maintenance of the effect-site concentration of remifentanil was adjusted upward and downward by 0.5 ng/mL to keep patient comfort with acceptable pain (remaining moveless), and mean arterial pressure and heart rate within baseline levels ± 30%, and using intermittent bolus midazolam to keep the Observer's Assessment of Alertness/Sedation scale between 2 and 4. The primary outcome was to determine which effect-site concentration of remifentanil provide adequate patient comfort with acceptable pain (remaining moveless) during the procedure. A total of 40 patients in Group 1 and 40 patients in Group 2 were eligible for analysis. Most parameters were insignificantly different between Group 1 and Group 2, except Group 1 having higher peripheral oxygen saturation while probe insertion compared with Group 2. Group 2 patients had less intraoperative movements affecting the procedure (2 vs 18; P < .001), and less total times of target-controlled infusion pump adjustment (0 [0-1] vs 1 [0-3], P < .001) compared with group 1. However, group 1 patients had less apnea with desaturation (peripheral oxygen saturation < 90%; 0 vs 9, P = .002) and less remifentanil consumption (94.9 ± 25.5 μg vs 106.2 ± 21.2 μg, P = .034) compared to Group 2. In transrectal ultrasound-guided prostate biopsy, target-controlled infusion with remifentanil Minto model target 2.0 ng/mL with 3 to 4 mg midazolam use provided sufficient analgesia and sedation, and appropriate hemodynamic and respiratory conditions.

Influence of body fatness on propofol requirements for loss of consciousness in target-controlled infusion: A STROBE-compliant study.

This prospective observational study evaluated the effects of body fat on the pharmacologic effect of propofol. Hundred patients aged 18 to 75 years who were scheduled to undergo orthopedic surgery under regional block were enrolled. All participants underwent bioelectrical impedance analysis and were allocated into 2 groups: the high and normal adiposity group, according to percent body fat. Following successful regional block, propofol was incrementally infused until loss of consciousness (LOC) with a target-controlled infusion pump. The effect-site concentration of propofol at LOC and the total infused dose of propofol per total body weight until LOC were recorded. At the end of the surgery, the infusion of propofol was stopped. The elapsed time to recovery of consciousness (ROC) and the effect-site concentration at ROC were recorded. These pharmacologic data were compared between 2 groups. The effect-site concentration of propofol at LOC (µg/mL) was significantly lower in the high adiposity group than in the normal group in both sexes (3.5 ± 0.4 vs 3.9 ± 0.6; P = .020 in males, and 3.4 [interquartile range: 2.9–3.5] vs 3.8 [interquartile range: 3.3–3.9]; P = .006 in females). Total dose per total body weight until LOC (mg/kg) were also significantly lower in the high adiposity group than in the normal group. There was no significant difference in the data related to ROC. The pharmacologic effects of propofol may be affected by the composition of body components. The concentration of propofol using a target-controlled infusion system may be diminished in patients with a high proportion of body fat.

The requirement of propofol for induction of anesthesia in patients with traumatic brain injury determined using bilateral bispectral index and target controlled infusion - An observational cohort study.

Patients with traumatic brain injury (TBI) frequently require emergency surgery. There is a paucity of literature with regard to anesthetic requirements in these patients. The aim of the study was to compare the dose of propofol required for induction of anesthesia in patients with different grades of TBI. This prospective, observational study included patients with mild, moderate, and severe grades of TBI undergoing emergency surgery within 48 h of injury. Bispectral Index (BIS) values were recorded using a bilateral BIS sensor. Anesthesia was induced with a target controlled infusion (TCI) pump. Once BIS reached 40, plasma (Cp) and effect-site (Ce) concentration and total dose of propofol required were noted from the TCI pump. Of the 96 patients recruited, 27, 36, and 33 patients belonged to mild, moderate, and severe TBI (sTBI) groups, respectively. The Ce of propofol in mild, moderate, and sTBI groups was 6 ± 0.9, 5.82 ± 0.98, and 4.48 ± 1.5 μg/mL (P < 0.001), and the dose of propofol required was 1.9 ± 0.2, 1.8 ± 0.4, 1.41 ± 0.5 mg/kg, respectively (P < 0.001). Baseline BIS on the injured side was 80 ± 7.8, 71 ± 9.4, 55 ± 11.6, and on the uninjured side was 89 ± 5.5, 81 ± 8.4, and 65 ± 12 in mild, moderate, and sTBI groups, respectively. The requirement of propofol was reduced in patients with sTBI. The dose of propofol required for induction of anesthesia as determined using Ce was significantly lower only between sTBI and mild TBI and not between patients with sTBI and moderate TBI or between mild and moderate head injury. BIS values were significantly different between the groups (highest in mild TBI and lowest in sTBI) and between normal and injured sides within each group.

Non-intubated general anesthesia in prone position for advanced biliopancreatic therapeutic endoscopy: A single tertiary referral center experience.

Background and Study Aim:Advance biliopancreatic endoscopies are nowadays performed in non-operating room anesthesia (NORA) under general anesthesia (GA). We evaluate the outcomes of non-intubated patients in prone position who received GA for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in a tertiary referral center for digestive endoscopy.Patients and Methods:Anesthesiological records, anamnestic, and intraoperative data of patients who underwent advanced therapeutic biliopancreatic endoscopies at our tertiary referral center from January 2019 until January 2020 were collected in the present observational study.Results:One hundred fifty-three patients (93 M; median age: 68-year-old; mean ASA status: 2) were considered eligible for a procedure in the prone position with GA in spontaneous breathing. Prone position was always the initial setting. Propofol administration through a target-controlled infusion (TCI) pump was the choice to achieve GA. In our experience, desaturation appears to be the most frequent adverse event, accounting for 35% of cases (55/153). Treatment foresaw additional oxygen through a nasopharyngeal catheter, which proved to be a sufficient measure in almost all patients (52/55). Other adverse events (i.e., inadequate sedative plan, pain, and bradycardia) accounted for 2.6% of cases (4/153).Conclusions:Non-intubated GA in the prone position may be regarded as a safe procedure, as long as the anesthesiological criteria of exclusion are respected and the anesthesiological team has become acquainted with the peculiar NORA setting and familiar with the management of possible adverse events.

Estimation of median effective effect-site concentration (EC50) during target-controlled infusion of propofol for dilatation and curettage - A prospective observational study.

Background and Aims:Propofol is the drug of choice for sedation in daycare procedures due to its pharmacokinetic properties. Propofol delivery using target-controlled infusion (TCI) pump reduces adverse effects like hypotension and apnoea. In this study, we estimated the median effective effect-site concentration of propofol in patients undergoing dilatation and curettage.Methods:Patients of the American Society of Anesthesiologists physical status class I–III, aged 40–70 years, undergoing elective dilatation and curettage were recruited for the study. All patients received 1 μg/kg fentanyl and 20 mg lignocaine. The first patient received an effect-site concentration of propofol at 4 μg/mL with TCI Schneider pharmacokinetic model. Failure was defined as patient movement at any time during the procedure. According to the ‘BiasedCoin Design’ up-and-down sequential method, the response of the previous patient determined the effect-site concentration of propofol of the next patient. The study was terminated once forty patients completed the procedures successfully. Probit analysis was used to determine EC50.Results:Fifty-three patients were recruited for the study. The various effect-site concentrations of propofol EC50, EC90, and EC95 in providing sedation for dilatation and curettage were 3.38 μg/mL, 4.29 μg/mL, and 4.60 μg/mL, respectively. The incidence of hypotension and apnoea were comparable among the various concentrations of propofol. The mean duration of the propofol infusion was 20 ± 2.86 min. The time to recovery from propofol sedation was 6.97 ± 1.76 min.Conclusion:A median effective effect-site concentration of 3.38 μg/mL of propofol is required to prevent patient movement during uterine dilatation and curettage.

Different behaviour of target-controlled infusion pumps despite apparently using the same Schnider pharmacokinetic model

BACKGROUND Target-controlled infusion (TCI) pumps deliver an initial bolus of drug to achieve a preset drug target concentration quickly. OBJECTIVE We investigated whether differences exist in the initial bolus dose between different TCI pumps despite apparently using the same pharmacokinetic (PK) model. DESIGN Observational study. SETTING Laboratory data from a German University Hospital. Experiments were performed between February 2019 and September 2020. PARTICIPANTS Four TCI pumps set to the Schnider model in effect-site mode with a target propofol concentration of 3.5 μg ml−1 were studied. The algorithms of two pumps employed a fixed equilibration rate constant (k e0) of 0.456 min−1 (Perfusor® Space® and Injectomat TIVA Agilia®), while the other two used a fixed time to peak concentration (t peak) of 1.6 min (Alaris® PK and Syramed® μSP6000). Pump performance was assessed on 13 virtual patients with different combinations of age, sex, height and weight: the initial propofol dose injected was measured on a high precision scale. MAIN OUTCOME MEASURES Propofol bolus dose, as if delivered for anaesthesia induction. RESULTS A small difference in propofol bolus doses was observed for some simulations: for example, 56.4 ± 1.2 and 59.7 ± 0.2 mg with a Syramed μSP6000 and an Alaris pharmacokinetic pump, respectively, in a virtual 54-year old man with a height of 170 cm and a weight of 74 kg. In contrast, significant differences were found in other simulated patients: for example, 72.0 ± 1.0 and 111.9 ± 1.2 mg (P &lt; 0.001) using a Perfusor Space and an Alaris TCI pump in a virtual 60-year-old, obese man with a height of 182 cm and a weight of 139 kg. CONCLUSIONS Discrepancies in the initial bolus dose can be explained by differences in k e0. Anaesthetists should be aware that differences exist in the implementation of the Schnider model between manufacturers, which could lead to disparities in the initial propofol bolus in some patients.

Comparison of the effects of target-controlled infusion-remifentanil/midazolam and manual fentanyl/midazolam administration on patient parameters in dental procedures.

BackgroundModerate sedation is an integral part of dental care delivery. Target-controlled infusion (TCI) has the potential to improve patient safety and outcome. We compared the effects of using TCI to administer remifentanil/manual bolus midazolam with manual bolus fentanyl/midazolam administration on patient safety parameters, drug administration times, and patient recovery times.MethodsIn this retrospective chart review, records of patients who underwent moderate intravenous sedation over 12 months in a private dental clinic were assessed. Patient indicators (pre-, intra-, and post-procedure noninvasive systolic and diastolic blood pressure, respiration, and heart rate) were compared using independent t-test analysis. Patient recovery time, procedure length, and midazolam dosage required were also compared between the two groups.ResultsEighty-five patient charts were included in the final analysis: 47 received TCI-remifentanil/midazolam sedation, and 38 received manual fentanyl/midazolam sedation. Among the physiological parameters, diastolic blood pressure showed slightly higher changes in the fentanyl group (P = 0.049), respiratory rate changes showed higher changes in the fentanyl group (P = 0.032), and the average EtCO2 was slightly higher in the remifentanil group (P = 0.041). There was no significant difference in the minimum SpO2 levels and average procedure length between the fentanyl and remifentanil TCI pump groups (P > 0.05). However, a significant difference was observed in the time required for discharge from the chair (P = 0.048), indicating that patients who received remifentanil required less time for discharge from the chair than those who received fentanyl. The dosage of midazolam used in the fentanyl group was 0.487 mg more than that in the remifentanil group; however, the difference was not significant (P > 0.05).ConclusionThe combination of TCI administered remifentanil combined with manual administered midazolam has the potential to shorten the recovery time and reduce respiration rate changes when compared to manual administration of fentanyl/midazolam. This is possibly due to either the lower midazolam dosage required with TCI remifentanil administration or achieving a stable, steady-state low dose remifentanil concentration for the duration of the procedure.

Pharmacokinetic concepts for dexmedetomidine target-controlled infusion pumps in children.

Pharmacokinetic parameter estimates are used in mathematical equations (pharmacokinetic models) to describe concentration changes with time in a population and are specific to that population. Simulation using these models and their parameter estimates can enrich understanding of drug behavior and serve as a basis for study design. Pharmacokinetic concepts are presented pertaining to future designs of dexmedetomidine target-controlled infusion pumps in children. This manuscript provides the pediatric anesthesiologist with an understanding of the nuances that should be considered when using target-controlled infusion pumps; how the central volume may differ between populations, how clearance changes with age, and the impact of adverse effects on dose. In addition, the ideal loading dose and rate of delivery to achieve target concentration without adverse cardiovascular effects are reviewed, and finally, dose considerations for obese children, based on contact-sensitive half-time, are introduced. An understanding of context-sensitive half-time changes with age enables anesthetic practitioners to better estimate duration of effect after cessation of dexmedetomidine infusion. Use of these known pharmacokinetic parameters and covariate information for the pediatric patient could readily be incorporated into commercial target-controlled infusion pumps to allow effective and safe open-loop administration of dexmedetomidine in children.

Assessment of the clinical validity of an adjusted Marsh pharmacokinetic model using an effect-site rate constant (ke0) of 1.21 min-1

Introduction: The first commercially available target-controlled infusion pump, the “Diprifusor”, employed a “Marsh” pharmacokinetic-pharmacodynamic parameter set, and this model (the Diprifusor-Marsh model) is also available in several of today’s pumps. However, it is unsuited for effect-site, target-controlled infusions (Ce TCI) because it assumes slow transfer between blood and the effect-site (ke0 = 0.26 min-1). We hypothesised that a faster ke0 of 1.21 min-1 (Adjusted-Marsh model) for Ce-TCI would result in hypnotic effects equivalent to that of the Schnider parameter set (Schnider model). Methods: We replicated a previously published study that demonstrated the Diprifusor-Marsh model’s unsuitability for Ce-TCI. We randomised 40 unpremedicated young adults into two groups to receive Ce-TCI, employing either the Schnider model or the Adjusted-Marsh model. We infused propofol at 3 000 mg.hour-1, while running a pharmacokinetic simulation and recording the electroencephalographic bispectral index (BIS) electronically. At loss of consciousness (LOC), indicated by a syringe-drop, we converted the infusion to Ce-TCI, targeting the effect-site concentration (Ce) observed at LOC, for 20 minutes. We regarded a difference of 10 BIS-units as clinically important. Results: There were no statistically significant differences between the group medians regarding time-to-LOC, induction-dose, BIS at LOC and Ce-target. BIS decreased monotonically in both groups from a median of 78.5 at LOC to a steady-state median (25–27) at 15 minutes. The BIS of the Adjusted-Marsh model group closely followed the BIS of the Schnider model group. At steady state, the median BIS difference (95% CI) was -0.3 (-5.7 to 5.3), which was within the predefined interval for declaring equivalence. The Schnider model group’s mean BIS at steady state did not differ from that of the previous study’s Schnider model group. Conclusion: Reasons for the progressive BIS decrease to lower than expected values include delayed response-times by the BIS monitor, Ce overshoot explained by front-end kinetics, neural inertia and the choice of surrogate LOC indicator. We conclude that Ce-TCI using the Adjusted-Marsh parameter set results in equivalent hypnotic effects to those of the Schnider model, with the proviso that this may apply only to young adults of normal body habitus.

Correlation between the transverse dimension of the maxilla, upper airway obstructive site, and OSA severity.

Acquiring a better comprehension of obstructive sleep apnea physiopathology can contribute to improving patient selection for surgical treatments. We hypothesize that maxillary transverse deficiency restricts the space available for the tongue, leading to upper airway obstruction during sleep. Our primary hypothesis was that maxillary transverse deficiency increases the prevalence of tongue collapse during drug-induced sleep endoscopy (DISE). The secondary hypothesis was that maxillary transverse deficiency will also increase the prevalence of circumferential collapse at the velopharynx. The exploratory hypothesis was that maxillary transverse deficiency is associated with increased obstructive sleep apnea severity. The objectives of this study were to correlate maxillary morphometric measurements with (1) the anatomic level of obstruction during DISE and (2) the apnea-hypopnea index on polysomnography. We made a cross-sectional analysis of patients with obstructive sleep apnea undergoing DISE in search of positive airway pressure alternative treatment. Maxillary measurements were collected from a computed tomography scan (interpremolar distance, intermolar distance [IMD] and sella-nasion A point angle), findings from DISE, and sleep study variables from polysomnography. Correlation between computed tomography, DISE, and polysomnography data was assessed using Pearson's correlation, and receiver operating characteristic curves were determined for each facial measurement. Sixty-nine patients were included in the study. The group with velopharyngeal circumferential collapse had mean IMD = 26.30 mm (25.5-31.45), and the group with anteroposterior collapse had mean IMD = 29.20 mm (26.8-33.10; P = .040). The group with complete tongue-base obstruction had mean interpremolar distance = 26.40 mm (25.1-28) and IMD = 26.30 mm (25.6-28.4), and the group without obstruction had mean interpremolar distance = 28.7 mm (27.2-30; P = .003) and IMD = 34.06 mm (32.1-37; P < .001). The receiver operating characteristic curve determined an IMD cutoff of 29.8 mm for predicting tongue-base obstruction. The maxillary transverse deficiency, identified by reduction in interpremolar distance and IMD, predicted the occurrence of complete tongue-base obstruction, complete concentric collapse at the velopharynx, and multilevel obstruction during DISE. We did not find an association between the maxillary measurements and obstructive sleep apnea severity. These associations hold some promise in ultimately supplanting insights previously available only through DISE.