The Dual Faces of Oestrogen: The Impact of Exogenous Oestrogen on the Physiological and Pathophysiological Functions of Tissues and Organs.

Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor ß (ESR2/Erß), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women's ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-ß belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis.

Potential drug-drug interactions analysis in Polish pediatric pneumonology units, including cystic fibrosis patients.

The lack of data on drug-drug interactions in pediatrics represents a relevant problem in making appropriate therapeutic decisions. Our study aimed to investigate the incidence and risk factors for potential drug-drug interactions (pDDIs) in pediatric pneumonology units, including cystic fibrosis patients. We performed a 6-month prospective observational study during which clinical pharmacists, using the Lexicomp Drug Interactions checker, screened medical records to identify pDDIs. Spearman's rank coefficient, logistic regression, and the Mann-Whitney U test were used to identify correlations, analyze risk factors for pDDIs, and compare cystic fibrosis patients with the rest, respectively. Recommendations were provided for the D and X pDDIs categories. Within the 218 patients, 428 pDDIs were identified, out of which 237 were classified as clinically significant. Almost 60% of patients were exposed to at least one relevant interaction. The number of pDDIs correlated with the number of; drugs (rs = 0.53, P <  .001), hospitalization length (rs = 0.20, P <  .01), and off-label medicines (rs = 0.25, P <  .001). According to the multivariate analysis, at least 6 administered medications (OR = 4.15; 95% CI = 2.21-7.78), 4 days of hospitalization (OR = 6.41; 95% CI = 2.29-17.97), and off-label therapy (OR = 3.37; 95% CI = 1.69-6.70) were the risk factor for pDDIs. Despite significant differences in the number of medications taken, comorbidities, and off-label drugs, cystic fibrosis patients were not more exposed to pDDI. Given the lack of data on pDDIs in the pediatric population, the need for close cooperation between clinicians and clinical pharmacists to improve the safety and efficacy of pharmacotherapy is highlighted.

Analgesic Efficacy of Oxycodone in Postoperative Dressings after Surgical Treatment of Burn Wounds: A Randomised Controlled Trial.

INTRODUCTION: This study aimed to assess the analgesic efficacy of oxycodone at doses of 10 mg and 20 mg in dressings after surgery of burn wounds. MATERIAL AND METHODS: Twenty adult patients who underwent surgical treatment of third-degree burn wounds under general anaesthesia were included. Burn wounds were treated with dressings, to which oxycodone was added at 20 mg in Group 1 and 10 mg in Group 2. After the surgery, plasma oxycodone and noroxycodone concentrations were assayed, and pain intensity was assessed with Numerical Rating Scale (NRS). RESULTS: In Group 1, no patient reported pain; in Group 2, four patients reported pain. The pain intensity, according to NRS, was 1-8. Plasma concentration of oxycodone in the blood serum was in the range of 1.24-3.15 ng/mL and 1.09-1.28 ng/mL in Group 1 and Group 2, respectively. Noroxycodone was not detected in the plasma. Adverse effects were not observed in any of the treated patients. CONCLUSIONS: Oxycodone in dressings provides patients with adequate and safe analgesia.

Population Pharmacokinetic-Pharmacodynamic Modeling and Probability of Target Attainment Analysis of Rocuronium and Sugammadex in Children Undergoing Surgery.

BACKGROUND AND OBJECTIVES: Probability of target attainment (PTA) curves are commonly used to support dose recommendations of antibiotics for different patient groups. In this study we propose PTA analysis to optimize sugammadex dosing in children. METHODS: This study involved data from an observational cohort study of 30 American Society of Anesthesiologists (ASA) Physical Status I and II children undergoing surgery requiring muscle relaxation. All patients received 0.6 mg/kg rocuronium, with sugammadex administered at the end of surgery in three different doses (0.5, 1.0, and 2.0 mg/kg) to reverse the neuromuscular blockade. RESULTS: The data were analyzed using a population Bayesian-based approach. The developed model was used to simulate pharmacokinetic-pharmacodynamic profiles for different patient groups and dosing regimens before the PTA analysis was performed to translate these simulations into a clinically useful measure. The target was defined as neuromuscular blockade reversal measured by Train-of-Four (TOF ratio > 90%) at 1.5, 3, and 5 min post sugammadex dose. The sugammadex doses leading to 90% PTA were determined for different patients' body weights, rocuronium doses, and time gaps between rocuronium and sugammadex administration assuming the model, priors, and gathered data. For comparison, PTA curves for a range of clinical scenarios are provided to illustrate the usefulness of PTA analysis in selecting the appropriate dose for a given patient. CONCLUSIONS: The proposed PTA analysis is useful to support the sugammadex dose selection in different clinical scenarios. TRIAL REGISTRATION: The study was registered by ClinicalTrials.gov under number NCT04851574 on 21 April 2021.

Analgesic Efficacy and Safety of Spinal Oxycodone in Total Hip Arthroplasty: A Preliminary Study.

AIM: The aim of this study was to assess the analgesic efficacy and safety of 1 mg and 0.5 mg oxycodone administration in a spinal block procedure for a total hip arthroplasty (THA). PATIENTS AND METHODS: Forty-two THA patients aged 59-81 with American Society Anesthesiology (ASA) II-III were included. All patients received anesthesia using spinal blockade, with bupivacaine 0.5% spinal heavy 2.5 ml, with 0.5 ml oxycodone hydrochloride 1.0 mg (group A; n = 28) or 0.5 mg (group B; n = 14). During surgery, each patient was sedated with 2-4 mg/kg/h intravenous propofol infusion. They received 100 mg intravenous ketoprofen at the end of the surgery at 8 pm and 8 am, with recommended doses every 12 h thereafter. Subcutaneous morphine 5 mg was used as a rescue analgesic, and the time to morphine use was recorded. After surgery, pain intensity (at the moment of patient report) was assessed using an 11-point numerical rating scale (NRS). The incidence of adverse effects was monitored. Blood samples were taken for assays of serum oxycodone, noroxycodone and bupivacaine levels. RESULTS: The time to rescue analgesia was 9.6 ± 5.6 h in group A and 7.3 ± 1.9 h in group B, and it did not differ between patient groups (P = 0.179). The mean NRS pain score was 4.5 in group A and 4.2 in group B. Three group A patients had detectable oxycodone levels: two < 7.1 ng/ml and in 1 spinal block induced anesthesia was unsuccessful and so he/she underwent general anesthesia (this patient was excluded from the analysis). Four group B patients had single values < 5 ng/ml. Noroxycodone levels were in all patients undetectable, and bupivacaine levels were 70-300 ng/ml. Regarding adverse effects, one patient had hypotension, one had bradycardia, and one had pruritus. CONCLUSION: Oxycodone in spinal block prolongs analgesia period, does not cause serious adverse effects and seems to be safe and effective opioid for patients undergoing THA.

The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery.

Cardiac output (CO) is expected to affect elimination and distribution of highly extracted and perfusion rate-limited drugs. This work was undertaken to quantify the effect of CO measured by the pulse pressure method on pharmacokinetics and pharmacodynamics of propofol and fentanyl administrated during total intravenous anesthesia (TIVA). The data were obtained from 22 ASA III patients undergoing abdominal aortic surgery. Propofol was administered via target-controlled infusion system (Diprifusor) and fentanyl was administered at a dose of 2-3 µg/kg each time analgesia appeared to be inadequate. Hemodynamic measurements as well as bispectral index were monitored and recorded throughout the surgery. Data analysis was performed by using a non-linear mixed-effect population modeling (NONMEM 7.4 software). Three compartment models that incorporated blood flows as parameters were used to describe propofol and fentanyl pharmacokinetics. The delay of the anesthetic effect, with respect to plasma concentrations, was described using a biophase (effect) compartment. The bispectral index was linked to the propofol and fentanyl effect site concentrations through a synergistic Emax model. An empirical linear model was used to describe CO changes observed during the surgery. Cardiac output was identified as an important predictor of propofol and fentanyl pharmacokinetics. Consequently, it affected the depth of anesthesia and the recovery time after propofol-fentanyl TIVA infusion cessation. The model predicted (not observed) CO values correlated best with measured responses. Patients' age was identified as a covariate affecting the rate of CO changes during the anesthesia leading to age-related difference in individual patient's responses to both drugs.

Rectal enema of bupivacaine in cancer patients with tenesmus pain - case series.

Introduction: Rectal tenesmus pain in cancer patients most frequently appears in patients with colon cancer, and as a consequence of radiotherapy of the hypogastrium region. Treatment with opioids and adjuvant analgesics is often ineffective. Patients and methods: Here, we report on two female patients diagnosed with colon and ovary cancer, respectively, who had very severe tenesmus pain (numerical rating scale 8-10) despite using high doses of opioids, including methadone with corticosteroids, anticonvulsants, antidepressants and ketamine. Results: In both patients, bupivacaine was administered via a rectal enema. In the first patient, bupivacaine was administered at a dose of 100 mg 0.1% (100 mL), and subsequently 100 mg 0.2% (50 mL), leading to effective analgesia for 8 and 12 hrs, respectively. In the second patient, 100 mg 0.1% (100 mL) was initially administered, followed by 100 mg 0.2% (50 mL), leading to effective analgesia for 12 and 17 hrs, respectively, with only dull abdominal pain reported that was relieved by 100 mg IV ketoprofen and complete disappearance of tenesmus pain. Rectal bupivacaine administration did not cause neurologic adverse effects, heart function disturbances or decreased blood pressure. A volume of 50 mL was enough to cover a painful area in the colon. Initial bupivacaine concentrations in the blood serum did not exceed 50 ng/mL and eventually dropped to 20 ng/mL and below. Conclusions: Administration of 100 mg bupivacaine as a rectal enema is safe and provides effective analgesia, and this procedure may be conducted in hospital departments and out-patient clinics. Furthermore, this procedure in the case of pain recurrence, can be repeated, and by providing effective pain relief often allows time for the patient to be transferred to a specialized pain center.

Pharmacokinetics of dexmedetomidine during analgosedation in ICU patients.

Dexmedetomidine (DEX) is a fairly new alfa2-agonist which has been increasingly used in recent years for analgosedation, mostly because it offers a unique ability of providing both moderate level of sedation and analgesia without respiratory depression. Despite of many papers published, there are still only a few concerning the PK of the drug given as long-term infusion in ICU patients. The aim of this work was to characterize the population pharmacokinetics of dexmedetomidine and to investigate the potential benefits of individualization of drug dosing based on patient characteristics in the heterogeneous group of medical and surgical patients staying in intensive care unit. This study was performed in the group of 17 males and 10 females patients with a median age of 59.5 years and median body weight of 75 kg. Blood samples for dexmedetomidine assay were collected from arterial catheter, during and after discontinuation of a standard infusion, that ranged from 24 to 102 h. The following covariates were examined to influence dexmedetomidine PK: age, sex, body weight, patients' health status described by Sequential Organ Failure Assessment Score (SOFA), inotropes usage, and infusion duration. The dexmedetomidine PK was best described by a two-compartment model. The typical values of PK parameters were estimated as 27 L for the volume of the central compartment, 87.6 L for the volume of the peripheral compartment, 38.5 L/h (9.2 mL/min/kg for a 70 kg patient) for systemic clearance and 46.4 L/h for the distribution clearance. Those values are consistent with literature findings. We were unable to show any significant relationship between collected covariates and dexmedetomidine PK. This study does not provide sufficient evidence to support the individualization of dexmedetomidine dosing based on age, sex, body weight, SOFA, and infusion duration.

Analgesic efficacy and safety of epidural oxycodone in patients undergoing total hip arthroplasty: a pilot study.

BACKGROUND AND OBJECTIVES: Oxycodone is poorly studied as an adjuvant to central blockades. The aim of this pilot study was to assess the efficacy and safety of oxycodone hydrochloride in epidural blockade among patients undergoing total hip arthroplasty (THA). PATIENTS AND METHODS: In 11 patients (American Society of Anesthesiologists physical status classification system II/III, age range: 59-82 years), THA was conducted with an epidural blockade using 15 mL 0.25% bupivacaine (37.5 mg) with 5 mg oxycodone hydrochloride and sedation with propofol infusion at a dose of 3-5 mg/kg/h. After the surgery, patients received ketoprofen at a dose of 100 mg twice daily. In the first 24 hours postoperative period, pain was assessed by numerical rating scale at rest and on movement; adverse effects (AEs) were recorded; and plasma concentrations of oxycodone, noroxycodone, and bupivacaine were measured. RESULTS: The administration of epidural oxycodone at a dose of 5 mg in patients undergoing THA provided analgesia for a mean time of 10.3±4.89 h. In one patient, mild pruritus was observed. Oxycodone did not evoke other AEs. Plasma concentrations of oxycodone while preserving analgesia were >2.9 ng/mL. Noroxycodone concentrations in plasma did not guarantee analgesic effect. CONCLUSION: The administration of epidural oxycodone at a dose of 5 mg prolongs the analgesia period to ~10 hours in patients after THA. Oxycodone may evoke pruritus. A 5 mg dose of oxycodone hydrochloride used in an epidural blockade seems to be a safe drug in patients after THA.

The pharmacokinetics of propofol in ICU patients undergoing long-term sedation.

The aim of this study was to characterize the pharmacokinetics (PK) of propofol in ICU patients undergoing long-term sedation and to assess the influence of routinely collected covariates on the PK parameters. Propofol concentration-time profiles were collected from 29 patients. Non-linear mixed-effects modelling in NONMEM 7.2 was used to analyse the observed data. The propofol pharmacokinetics was best described with a three-compartment disposition model. Non-parametric bootstrap and a visual predictive check were used to evaluate the adequacy of the developed model to describe the observations. The typical value of the propofol clearance (1.46 l/min) approximated the hepatic blood flow. The volume of distribution at steady state was high and was equal to 955.1 l, which is consistent with other studies involving propofol in ICU patients. There was no statistically significant covariate relationship between PK parameters and opioid type, SOFA score on the day of admission, APACHE II, predicted death rate, reason for ICU admission (sepsis, trauma or surgery), gender, body weight, age, infusion duration and C-reactive protein concentration. The population PK model was developed successfully to describe the time-course of propofol concentration in ICU patients undergoing prolonged sedation. Despite a very heterogeneous group of patients, consistent PK profiles were observed. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetics and pharmacodynamics of propofol and fentanyl in patients undergoing abdominal aortic surgery - a study of pharmacodynamic drug-drug interactions.

Propofol is routinely combined with opioid analgesics to ensure adequate anesthesia during surgery. The aim of the study was to assess the effect of fentanyl on the hypnotic effect of propofol and the possible clinical implications of this interaction. The pharmacokinetic/pharmacodynamic (PK/PD) data were obtained from 11 patients undergoing abdominal aortic surgery, classified as ASA III. Propofol was administered by a target-controlled infusion system. Fentanyl 2-3 µg/kg was given whenever insufficient analgesia occurred. The bispectral index (BIS) was used to monitor the depth of anesthesia. A population PK/PD analysis with a non-linear mixed-effect model (NONMEM 7.2 software) was conducted. Two-compartment models satisfactorily described the PK of propofol and fentanyl. The delay of the anesthetic effect in relation to PK was described by the effect compartment. The BIS was linked to propofol and fentanyl effect-site concentrations through an additive Emax model. Context-sensitive decrement times (CSDT) determined from the final model were used to assess the influence of fentanyl on the recovery after anesthesia. The population PK/PD model was successfully developed to describe simultaneously the time course and variability of propofol and fentanyl concentrations and BIS. Additive propofol-fentanyl interactions were observed and quantitated. The duration of the fentanyl infusion had minimal effect on CSDT when it was shorter than the duration of the propofol infusion. If the fentanyl infusion was longer than the propofol infusion, an almost two-fold increase in CSDT occurred. Additional doses of fentanyl administered after the cessation of the propofol infusion result in lower BIS values, and can prolong the time of recovery from anesthesia. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetics and pharmacodynamics of propofol in cancer patients undergoing major lung surgery.

Despite the growing number of cancer cases and cancer surgeries around the world, the pharmacokinetics (PK) and pharmacodynamics (PD) of anesthetics used in this population are poorly understood. Patients operated due to cancer are usually in severe state and often require chemotherapy. It might affect the PK/PD of drugs used in this population. Therefore, in this study we explored the PK/PD of propofol in cancer patients having a major lung surgery. 23 patients that underwent a propofol-fentanyl total intravenous anesthesia were included in the analysis. A large set of demographic, biochemical and hemodynamic parameters was collected for the purpose of covariate analysis. Nonlinear mixed effect modeling in NONMEM was used to analyze the collected data. A three-compartment model was sufficient to describe PK of propofol. The anesthetic effect (AAI index) was linked to the propofol effect site concentrations through a sigmoidal E max model. A slightly higher value of clearance, a lower value of distribution clearance, and a decreased volume of peripheral compartment were observed in our patients, as compared with the literature values reported for healthy volunteers by Schnider et al. and by Eleveld et al. Despite these differences, both models led to a clinically insignificant bias of -8 and -1 % in concentration predictions, as reflected by the median performance error. The C e50 and propofol biophase concentration at the time of postoperative orientation were low and equaled 1.40 and 1.13 mg/L. The population PK/PD model was proposed for cancer patients undergoing a major lung surgery. The large body of studied covariates did not affect PK/PD of propofol significantly. The modification of propofol dosage in the group of patients under study is not necessary when TCI-guided administration of propofol by means of the Schnider model is used.

Melatonin and clonidine premedication has similar impact on the pharmacokinetics and pharmacodynamics of propofol target controlled-infusions.

Recently oral melatonin has been proposed as an agent for premedication. In this study, we compared melatonin with clonidine, considering its anxiolytic properties as well as the influence of both agents on the pharmacokinetic, hypnotic, and hemodynamic effects of propofol during propofol-remifentanil total intravenous anesthesia (TIVA). The dataset under analysis included 32 patients scheduled for a functional endoscopic sinus surgery. The population pharmacokinetic modeling was done with NONMEM. The PK of propofol was described with a two-compartment disposition model, whereas the BIS and AAI were described with a sigmoidal Emax model linked with the propofol concentration via the biophase compartment. The anxiolytic effect was assessed by means of the visual analog scale for anxiety (VAS-A). The population PK/PD model was successfully developed to describe the data. No significant differences in the PK/PD of propofol were noted due to the premedication with clonidine and melatonin. Melatonin was less effective than clonidine in reducing patients' anxiety at the induction of anesthesia, whereas clonidine premedication was associated with greater decrease in heart rate and blood pressure. A decreased EC50 (2.47 vs. 3.17 mg/L) and increased slope (2.71 vs. 1.30) of the sigmoidal Emax relationship was observed for the AAI index, as compared with the BIS measurements.

Procedural sedation and analgesia in children undergoing digestive endoscopic procedures - paediatrician or anaesthesiologist?

Endoscopic procedures of the gastrointestinal tract were successfully introduced into paediatric practice in the 1970s. Recent expansive development has become useful for improvement of both diagnosis and treatment in many children with gastrointestinal diseases. Most of these procedures are performed under procedural sedation (PSA) knowing anatomical, physiological and psychological differences and requiring good experience from the paediatrician and anaesthesiologist. These principles help to provide the procedure safely and minimise adverse events, which are greater the smaller the child is. Procedural sedation and analgesia in healthy children can be performed by a paediatrician, but children with congenital defects and serious coexisting diseases (ASA ≥ III) and also during the usage of anaesthetics (e.g. propofol), should be managed by an anaesthesiologist.

Do we really know the pharmacodynamics of anaesthetics used in newborns, infants and children? A review of the experimental and clinical data on neurodegeneration.

The practices of anaesthesiology and intensive therapy are difficult to imagine without sedation or general anaesthesia, regardless of whether the patient is a newborn, baby, child or adult. The relevant concerns for children are distinct from those for adults, primarily due to the effects of anatomical, physiological and pharmacokinetic-pharmacodynamic (PK/PD) differences, which become increasingly important in the brains of children as they develop. The process of central nervous system maturation in humans lasts for years, but its greatest activity (myelination and synaptogenesis) occurs during the fetal period and the first two years of life. Many experimental studies have demonstrated that exposure to anaesthetic drugs during this period can induce neurodegenerative changes in the central nervous systems of animals. The extrapolation of these results directly to humans must be performed with great caution, but anaesthesiologists around the world must begin to debate the safety of general anaesthesia in humans. Prospective trials should continue being carried out, and anaesthesia and surgery, delayed if possible among the smallest patients. The simultaneous use of different anaesthetics with the same potential neurotoxicities should also be avoided, potentially in favour of regional anaesthesia techniques, in this group of patients.

Procedural sedation and analgesia for gastrointestinal endoscopy in infants and children: how, with what, and by whom?

Endoscopic procedures involving the gastrointestinal tract have been successfully developed in paediatric practice over the last two decades, improving both diagnosis and treatment in many children's gastrointestinal diseases. In this group of patients, experience and co-operation between paediatricians/endoscopists and paediatric anaesthesiologists should help to guarantee the quality and safety of a procedure and should additionally help to minimise the risk of adverse events which are greater the smaller the child is. This principle is more and more important especially since the announcement of the Helsinki Declaration on Patient Safety in Anaesthesiology in 2010, emphasising the role of anaesthesiology in promoting safe perioperative care. The Helsinki Declaration has been endorsed by all European anaesthesiology institutions as well as the World Health Organisation's 'Safe Surgery Saves Lives' initiative including the 'Surgical Safety Checklist'. Although most of these procedures could be performed by paediatricians under procedural sedation and analgesia, children with congenital defects and serious coexisting diseases (ASA ≥ III) as well as the usage of anaesthetics (e.g. propofol) must be managed by paediatric anaesthesiologists. We have reviewed the specific principles employed during qualification and performance of procedural sedation and analgesia for gastrointestinal endoscopy in paediatrics. We have also tried to answer the questions as to how, with what, and by whom, procedural sedation for gastrointestinal endoscopy in children should be performed.

Pharmacokinetics and pharmacodynamics of propofol in patients undergoing abdominal aortic surgery.

Available propofol pharmacokinetic protocols for target-controlled infusion (TCI) were obtained from healthy individuals. However, the disposition as well as the response to a given drug may be altered in clinical conditions. The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol during total intravenous anesthesia (propofol/fentanyl) monitored by bispectral index (BIS) in patients scheduled for abdominal aortic surgery. Population nonlinear mixed-effect modeling was done with Nonmem. Data were obtained from ten male patients. The TCI system (Diprifusor) was used to administer propofol. The BIS index served to monitor the depth of anesthesia. The propofol dosing was adjusted to keep BIS level between 40 and 60. A two-compartment model was used to describe propofol PK. The typical values of the central and peripheral volume of distribution, and the metabolic and inter-compartmental clearance were V(C) = 24.7 l, V(T) = 112 l, Cl = 2.64 l/min and Q = 0.989 l/min. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment with the rate constant for the distribution to the effector compartment equal to 0.240 min(-1). The BIS index was linked to the effect site concentrations through a sigmoidal E(max) model with EC(50) = 2.19 mg/l. The body weight, age, blood pressure and gender were not identified as statistically significant covariates for all PK/PD parameters. The population PK/PD model was successfully developed to describe the time course and variability of propofol concentration and BIS index in patients undergoing surgery.

Spectral frequency index monitoring during propofol-remifentanil and propofol-alfentanil total intravenous anaesthesia.

BACKGROUND: The aim of this study was to evaluate the usefulness of spectral frequency index (SFx) monitoring to assess the depth of anaesthesia during propofol-opioid total intravenous anaesthesia (TIVA). METHODS: Thirty-three patients scheduled for laparoscopic cholecystectomy under propofol TIVA were prospectively and randomly allocated to receive either remifentanil (bolus of 1.0 microg/kg, followed by continuous infusion from 0.25 to 0.05 microg/kg/min) [n = 18] or alfentanil (bolus of 10 microg/kg, followed by continuous infusion from 2.0 to 0.5 microg/kg/min) [n = 15]. EEG activity was monitored to achieve the desired depth of anaesthesia, and intravenous propofol was titrated to keep the SFx at 70-80%. The remifentanil and alfentanil groups were compared in relation to the plasma propofol concentration required for an adequate level of hypnosis during maintenance of anaesthesia, Pearson correlation coefficient for the relationship between the plasma propofol concentration and SFx values, recovery parameters, and recall of events during anaesthesia. RESULTS: The study groups were comparable with regard to demographic characteristics, type and duration of surgery, and time to resumption of spontaneous ventilation. No evidence of explicit recall was noted. The mean plasma propofol concentration required for an adequate level of hypnosis during maintenance of anaesthesia was significantly higher in the alfentanil group (3.20 microg/mL) compared with the remifentanil group (2.17 microg/L) [p < 0.05]. In both groups, the Pearson correlation coefficient test showed a linear correlation between SFx values and propofol concentration in the studied propofol concentration range. The mean time to orientation for name and place was significantly shorter (p < 0.05), the mean propofol concentration at orientation for name and place and at the resumption of spontaneous ventilation timepoints was significantly lower (both p < 0.01), and the mean SFx value at resumption of spontaneous ventilation timepoint was significantly higher (p < 0.01) in the remifentanil group. CONCLUSIONS: As SFx is linearly related to plasma propofol concentration, this index may be used to measure anaesthetic effect during propofol anaesthesia. The results of this clinical trial are consistent with a previous computer-simulated opioid-propofol model with regard to intraoperative and recovery variables, although the recovery occurred at different propofol concentration and SFx values.