Development and external validation of a dynamic risk score for early prediction of cardiogenic shock in cardiac intensive care units using machine learning.

BACKGROUND: Myocardial infarction and heart failure are major cardiovascular diseases that affect millions of people in the US with the morbidity and mortality being highest among patients who develop cardiogenic shock. Early recognition of cardiogenic shock allows prompt implementation of treatment measures. Our objective is to develop a new dynamic risk score, called CShock, to improve early detection of cardiogenic shock in cardiac intensive care unit (ICU). METHODS: We developed and externally validated a deep learning-based risk stratification tool, called CShock, for patients admitted into the cardiac ICU with acute decompensated heart failure and/or myocardial infarction to predict onset of cardiogenic shock. We prepared a cardiac ICU dataset using MIMIC-III database by annotating with physician adjudicated outcomes. This dataset that consisted of 1500 patients with 204 having cardiogenic/mixed shock was then used to train CShock. The features used to train the model for CShock included patient demographics, cardiac ICU admission diagnoses, routinely measured laboratory values and vital signs, and relevant features manually extracted from echocardiogram and left heart catheterization reports. We externally validated the risk model on the New York University (NYU) Langone Health cardiac ICU database that was also annotated with physician adjudicated outcomes. The external validation cohort consisted of 131 patients with 25 patients experiencing cardiogenic/mixed shock. RESULTS: CShock achieved an area under the receiver operator characteristic curve (AUROC) of 0.821 (95% CI 0.792-0.850). CShock was externally validated in the more contemporary NYU cohort and achieved an AUROC of 0.800 (95% CI 0.717-0.884), demonstrating its generalizability in other cardiac ICUs. Having an elevated heart rate is most predictive of cardiogenic shock development based on Shapley values. The other top ten predictors are having an admission diagnosis of myocardial infarction with ST-segment elevation, having an admission diagnosis of acute decompensated heart failure, Braden Scale, Glasgow Coma Scale, Blood urea nitrogen, Systolic blood pressure, Serum chloride, Serum sodium, and Arterial blood pH. CONCLUSIONS: The novel CShock score has the potential to provide automated detection and early warning for cardiogenic shock and improve the outcomes for the millions of patients who suffer from myocardial infarction and heart failure.

To cool or not to cool: Targeted temperature management to prevent ventricular tachycardia associated with Brugada syndrome.

Key Clinical Message: A robust inflammatory and febrile response from acute viral illness such as with SARS-CoV-2 in patients with Brugada syndrome may lead to triggering of ventricular arrhythmias. The use of targeted temperature management (TTM) using cooling devices may mitigate the febrile triggering of ventricular arrhythmias in patients with Brugada syndrome. Abstract: Brugada syndrome (BrS) is an autosomonal dominant genetic disorder, with a risk of ventricular tachycardia (VT). Triggers of VT in BrS include fevers. Here, we report a case of BrS secondary to SARSs-CoV-2 infection and the use of targeted temperature management (TTM) to decrease fever and prevent VT triggering.

Native mitral valve staphylococcus endocarditis with a very unusual complication: Ruptured posterior mitral valve leaflet aneurysm.

Infective endocarditis (IE) is a life-threatening disease associated with in-hospital mortality of nearly one in five cases. IE can destroy valvular tissue, which may rarely progress to aneurysm formation, most commonly at the anterior leaflet in instances of mitral valve involvement. We present a remarkable case of a patient with IE and a rare complication of a ruptured aneurysm of the posterior leaflet of the mitral valve. Two- and Three-dimensional transesophageal echocardiography, intra-operative videography, and histopathologic analysis revealed disruption at this unusual location-at the junction of the P2 and P3 scallops, surrounded by an annular abscess.

Characteristics and outcomes of surgically ineligible patients with multivessel disease treated with percutaneous coronary intervention.

OBJECTIVES: In this study we evaluated the clinical characteristics and outcomes of surgically ineligible patients with coronary artery disease (CAD) who underwent multivessel percutaneous coronary intervention (PCI). BACKGROUND: Patients with multivessel CAD who are surgically ineligible and undergo PCI are not well represented in large trials. METHODS: Out of 1,061 consecutive patients who underwent a non-emergent PCI for unprotected left main or multivessel CAD at the University of Virginia Medical Center, 137 patients were determined to be surgically ineligible for coronary artery bypass graft (CABG) surgery by a heart team. The clinical characteristics and reasons for surgical ineligibility were collected. The coronary angiograms were reviewed and the SYNTAX score calculated. The Society of Thoracic Surgeons (STS) score was calculated. Outcomes were determined at 30 days and 1-year. RESULTS: The mean age of the cohort was 71 and 59% were women. Hypertension, hyperlipidemia, tobacco abuse, and diabetes were common comorbidities. The average SYNTAX score was 22. The most commonly cited reasons for surgical ineligibility were advanced age, frailty, severe lung disease, ejection fraction ≤ 30% and STS score ≥ 8%. Outcomes at 30 days were excellent and better than those predicted by STS for surgery. Frailty and STS score predicted one-year outcomes. CONCLUSIONS: Patients undergoing PCI for multivessel disease who are surgically ineligible have multiple risk factors and comorbidities. Frailty, lung disease, poor left ventricular function, and high STS score represent common reasons for surgical ineligibility. Frailty and the STS score better predict one-year outcomes after PCI compared to the SYNTAX score.

A National Survey: Current Clinical Practice in Pediatric Anesthesia for Congenital Heart Surgery.

BACKGROUND: Providing anesthesia for pediatric patients undergoing congenital cardiac surgery is complex and requires profound knowledge and clinical experience. Prospective studies on best anesthetic management are missing, partially due to different standards. The aim of the present study was to survey the current standard practice in anesthetic management in pediatric cardiac surgical centers in Germany. METHODS: All 78 cardiac surgical centers in Germany were reviewed for a congenital cardiac surgery program. Centers with an active program for congenital cardiac surgery were interviewed to participate in the present online questionnaire to assess their current anesthetic practice. RESULTS: Twenty-seven German centers running an active program for congenital heart surgery were identified, covering more than 3,000 pediatric cardiac surgeries annually. Of these centers, 96.3% (26/27) participated in our survey. Standard induction agents were etomidate in 26.9% (7/26), propofol in 19.2% (5/26), a combination of benzodiazepines and ketamine in 19.2% (5/26), and barbiturates in 11.5% (3/26). General anesthesia was preferentially maintained using volatile agents, 61.5% (16/26), with sevoflurane being the most common volatile agent within this group, 81.2% (13/16). Intraoperative first-choice/first-line inotropic drug was epinephrine, 53.8% (14/26), followed by milrinone, 23.1% (6/26), and dobutamine 15.4% (4/26). Fast-track programs performing on-table extubation depending on the type of surgical procedure were established at 61.5% (16/26) of the centers. CONCLUSION: This study highlights the diversity of clinical standards in pediatric cardiac anesthesia for congenital cardiac surgery in Germany.

The Impact of Basal Septal Hypertrophy on Outcomes after Transcatheter Aortic Valve Replacement.

BACKGROUND: The role of basal septal hypertrophy (BSH) on preprocedural transthoracic echocardiography in transcatheter aortic valve replacement (TAVR) is unknown. METHODS: Medical charts and preprocedural transthoracic echocardiograms of 378 patients who underwent TAVR were examined. The association between BSH and the primary composite outcome of valve pop-out, recapture, embolization, aborted procedure, conversion to open procedure, new conduction disturbance, or need for permanent pacemaker ≤30 days after TAVR was evaluated. Patients with preexisting pacemakers were excluded. Sensitivity analyses were performed varying the definition of BSH. RESULTS: Of 296 TAVR patients (78.3%) with interpretable images, 55 (18.6%) had BSH at a median of 40 days (interquartile range, 19-62 days) before TAVR. Age and sex were similar among those with and without BSH. BSH patients received postdilation more frequently (BSH+ vs BSH-: 41.8% vs 29.9%, P = .04). A total of 50 individuals (16.9%) received pacemakers within 30 days, and 128 (43.2%) developed conduction disturbances (with left bundle branch block most common), without differences between groups. BSH was unrelated to the primary outcome on multivariate analysis (adjusted odds ratio BSH+ vs BSH-, 0.94; 95% CI, 0.42-2.11; P = .88). CONCLUSIONS: In this convenience sample of TAVR recipients at a large academic medical center, patients with BSH were more likely to receive postdilation. BSH was not associated with procedural or conduction outcomes after TAVR in patients without preexisting pacemakers.

Model-Based Quantification of Left Ventricular Diastolic Function in Critically Ill Patients with Atrial Fibrillation from Routine Data: A Feasibility Study.

INTRODUCTION: Left ventricular diastolic dysfunction (LVDD) and atrial fibrillation (AF) are connected by pathophysiology and prevalence. LVDD remains underdiagnosed in critically ill patients despite potentially significant therapeutic implications since direct measurement cannot be performed in routine care at the bedside, and echocardiographic assessment of LVDD in AF is impaired. We propose a novel approach that allows us to infer the diastolic stiffness, ß, a key quantitative parameter of diastolic function, from standard monitoring data by solving the nonlinear, ill-posed inverse problem of parameter estimation for a previously described mechanistic, physiological model of diastolic filling. The beat-to-beat variability in AF offers an advantageous setting for this. METHODS: By employing a global optimization algorithm, ß is inferred from a simple six parameter and an expanded seven parameter model of left ventricular filling. Optimization of all parameters was limited to the interval ]0, 400[ and initialized randomly on large intervals encompassing the support of the likelihood function. Routine ECG and arterial pressure recordings of 17 AF and 3 sinus rhythm (SR) patients from the PhysioNet MGH/MF Database were used as inputs. RESULTS: Estimation was successful in 15 of 17 AF patients, while in the 3 SR patients, no reliable estimation was possible. For both models, the inferred ß (0.065 ± 0.044 ml-1 vs. 0.038 ± 0.033 ml-1 (p=0.02) simple vs. expanded) was compatible with the previously described (patho) physiological range. Aortic compliance, α, inferred from the expanded model (1.46 ± 1.50 ml/mmHg) also compared well with literature values. CONCLUSION: The proposed approach successfully inferred ß within the physiological range. This is the first report of an approach quantifying LVDF from routine monitoring data in critically ill AF patients. Provided future successful external validation, this approach may offer a tool for minimally invasive online monitoring of this crucial parameter.

Ultrasound anatomy of the transversus abdominis plane region in pregnant women before and after cesarean delivery.

BACKGROUND: After cesarean delivery, analgesia is often incomplete and a multimodal approach to analgesia is necessary. Transverse abdominal plane (TAP) block has been advocated in this setting, yet no systematic description of the ultrasound anatomy in pregnant women exists in the literature. Therefore, we aimed to describe the sonographical features of relevant structures in pregnant women before and after elective cesarean. METHODS: Sixty women at, or close to term scheduled for elective cesarean delivery underwent a standardized ultrasound examination before and after delivery. We assessed the visibility of the muscular layers and measured the distance from the skin to the layers of the abdominal wall muscles in the region for TAP block before and after cesarean section on both side. RESULTS: The three muscular layers of the lateral abdominal wall (external oblique, internal oblique and transversus abdominis muscle) were visible in all examinations. Before cesarean section the median TAP distance was shorter: 2.9 cm (interquartile range 2.6-3.6) compared to 3.9 cm (3.1-4.5) after cesarean section (left side, p < 0.001). The external and internal oblique muscles were located closer to the skin surface before cesarean section. An increased body mass is associated with increased the TAP distance before and after birth (p < 0.001). CONCLUSION: Relevant anatomical landmarks for a TAP block are sonographically well visible after cesarean delivery. Postoperatively, depth of the TAP as compared to before birth is increased significantly. Scanning the abdominal wall before CD will underestimate the target depth of the TAP after delivery. The obstetric anesthetist needs to be aware of these changes when planning a TAP block in the context of cesarean delivery.

Introducing Hyperthermic Intraperitoneal Chemotherapy into Gynecological Oncology Practice - Feasibility and Safety Considerations: Single-Center Experience.

BACKGROUND: Within the surgical oncology community interest is increasingly focusing on combining surgical cytoreduction and regional chemotherapeutic drug delivery to manage solid abdominal tumors. In particular, the role of hyperthermic intraperitoneal chemotherapy (HIPEC) is evolving for treating epithelial ovarian carcinomas (EOCs), as EOCs remain confined to the peritoneal cavity for most of their natural history. Currently there is no evidence from prospective trials to confirm an overall survival benefit associated with HIPEC. In addition, there are no generally accepted regimens, which results in heterogeneous clinical procedures. METHODS: We have initiated a HIPEC program at our institution and completed a phase I study of HIPEC with cisplatin in patients with platinum-sensitive recurrent EOC. The data have been published and prove the feasibility of this approach. In the process of introducing HIPEC, several safety measures had to be taken into consideration. RESULTS: We present the implications and requirements of introducing HIPEC in clinical practice and discuss our proposed procedure referring to the recent literature. CONCLUSION: HIPEC is feasible and can be performed safely in daily gynecological oncology routine provided that certain considerations and precautions are taken into account during its introduction to guarantee a proper and safe operating sequence.

Impact of Extended Primary Surgery on Suboptimally Operable Patients With Advanced Ovarian Cancer.

OBJECTIVES: Extensive surgical efforts to achieve an optimal debulking (no residual tumor) in primary surgery of ovarian cancer are today's criterion standard in gyneco-oncologic surgery. However, it is controversial whether extensive surgery, including resections of metastases in the upper abdomen and bowel resections, is justifiable in patients with not completely operable lesions. METHODS: All patients who had undergone surgery for ovarian cancer in the years 2002 to 2013 at our institution were viewed (n = 472). We retrospectively identified 278 operations for primary ovarian cancer. Ninety-six (35%) of the 278 patients showed postoperative tumor residuals and were included in this study. RESULTS: Fifty-five (57%) of 96 patients underwent bowel resection, showing significantly higher complication rates (64% vs 39% minor complications, P = 0.017; 31% vs 9.8% severe complications, P = 0.013) compared with patients without bowel resections as well as no improvement in progression-free or overall survival (median overall survival, 19.5 vs 32.9; P = 0.382). Multiple anastomoses (≥2) were associated with higher rates for anastomotic leakage (16.7% vs 2.6%, P = 0.02) and a higher mortality (16.7% vs 0%, P = 0.04) compared with patients with only 1 anastomosis. Extensive surgery of the upper abdomen was not associated with a significant increase in complication rates. CONCLUSIONS: Because of the increased morbidity of bowel resections without any evidence for improvement of survival, we suggest to restrain from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumor bulk.

Conception, Pregnancy, and Lactation Despite Chronic Intestinal Failure Requiring Home Parenteral Nutrition.

BACKGROUND: Short-term parenteral nutrition is commonly accepted to be safe in pregnancy, but knowledge about the management of pregnancy during long-term home parenteral nutrition (HPN) is sparse. METHODS AND RESULTS: A systematic literature review revealed that the published experience is limited to 15 pregnancies with parenteral nutrition from preconception to delivery and beyond. Maternal morbidity was surprisingly low, and fetal outcome was good; however, micronutrient deficiencies may have contributed to fetal anomalies. Herein, we additionally report the case of a 26-year-old Caucasian woman with long-term HPN dependence secondary to short bowel syndrome caused by recurrent thromboembolic mesenteric infarctions who delivered a healthy fetus at 37 weeks of gestation. Individual macronutrient support and adequate micronutrient supplementation ensured normal maternal weight gain and fetal development. Based on the individual maternal risk of recurrent thrombosis, anticoagulant treatment was carefully titrated throughout pregnancy. Furthermore, loss of abdominal domain with a rigid maternal abdominal wall secondary to short bowel syndrome and multiple laparotomies resulted in food intolerance during the third trimester. Still, with multidisciplinary efforts, both mother and the breast-fed infant were in good health at 12 months after delivery. CONCLUSIONS: Taking the reported literature into consideration, we conclude that under the premise of optimal medical care, the risk:benefit ratio for pregnancy of HPN-dependent women seems to be justifiable. To minimize the risks, we recommend preconception counseling and early referral to a tertiary center offering both a high-risk pregnancy unit and a nutrition service. In particular, maternal micronutrient levels should be monitored.

HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.

This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.

Total or subtotal colectomy in patients undergoing surgery for primary or recurrent epithelial ovarian cancer.

BACKGROUND: There is controversy as to whether performing a total or subtotal colectomy is justified in patients with advanced ovarian cancer, given its potential for morbidity and a negative effect on long-term quality of life. The aim of this study was to assess the perioperative complications, mortality and outcomes of patients who underwent total or subtotal colectomy as part of the surgical procedure for primary or recurrent epithelial ovarian cancer. PATIENTS AND METHODS: All patients who had undergone surgery including a total or subtotal colectomy for advanced or recurrent ovarian cancer between 2005 and 2013 at our institution were retrospectively identified. RESULTS: In this time period, 339 patients underwent surgery for epithelial ovarian cancer, which in 11 (3%) patients included a total or subtotal colectomy. Severe grade 3-4 postoperative complications occurred in 3 (27%) patients, and 1 (9%) patient died within 60 days of surgery. CONCLUSION: A total or subtotal colectomy is associated with increased but acceptable morbidity in selected patients undergoing primary cytoreductive surgery. However, in the recurrent/palliative setting, total or subtotal colectomy should be avoided as the prognosis is poor and the morbidity outweighs the clinical benefit.

Clinical validation of a new thermodilution system for the assessment of cardiac output and volumetric parameters.

INTRODUCTION: Transpulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040) METHODS: Seventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO2™ device (Pulsion Medical Systems SE). RESULTS: For CO, GEDV, and EVLW, the systems showed a high correlation (r(2) = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView™ algorithm compared to the PiCCO™ algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049). CONCLUSIONS: For CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm. TRIAL REGISTRATION: clinicaltrials.gov NCT01405040.

Peristaltic pneumatic compression of the legs reduces fluid demand and improves hemodynamic stability during surgery: a randomized, prospective study.

BACKGROUND: Perioperative fluid restriction might be beneficial in specific clinical settings. In this prospective, randomized and blinded study, we assessed whether peristaltic pneumatic compression of the legs can support restrictive fluid management strategies by reducing intraoperative fluid demand and improving hemodynamic stability. METHODS: Seventy patients scheduled for minor surgery were randomly assigned to receive either intraoperative peristaltic pneumatic compression or placebo compression. Both groups received fluid therapy according to a goal-directed protocol with a crystalloid base rate of 2 ml · kg⁻¹ · h⁻¹ and bolus infusions of 250 ml crystalloids triggered by hypotension, tachycardia, or high Pleth Variability Index. RESULTS: Patients treated with peristaltic pneumatic compression received less intravenous fluid: median (interquartile range) 286 (499) versus 921 (900) ml (P < 0.001), resulting in a median difference of 693 ml (95% CI, 495-922 ml) and a median difference of 8.4 ml/kg (95% CI, 5.3-11.5 ml; P < 0.001). After the anesthesia induction phase, median overall infusion rates were 12.2 (14.1) ml · kg⁻¹ · h⁻¹ in the control group and 1.9 (0.4) ml · kg⁻¹ · h⁻¹ in the pneumatic peristaltic compression group (P < 0.001). Among patients treated with pneumatic peristaltic compression, the median cumulative time of hypotension was shorter (0 [12.5] vs. 22.6 [22.8] min; P = 0.002), fewer hypotensive events were recorded (39 vs. 137; P = 0.001), and median lowest individual systolic pressure was higher (92 [8] vs. 85 [16] mmHg; P = 0.002). CONCLUSIONS: This study demonstrates that peristaltic pneumatic compression of the legs significantly improves hemodynamic stability and reduces fluid demand during minor surgery.

Display of information in the operating room.

PURPOSE OF REVIEW: The ongoing development of new sensors and parameters for intraoperative monitoring has outpaced the development of display design, leading to a gap between the load of information and the quality of its delivery. This is not a circumstantial problem, as a large portion of critical incidents is attributable to inadequate situation awareness and the failure to recognize readily monitored data. This review also addresses improvements of current threshold alarms. RECENT FINDINGS: Research has focused on advanced integrated displays, drawing on the findings of human factor science and on the exploitation of alternative sensory pathways. Integrated displays, as well as auditory, vibrotactile and head-mounted displays have been shown to promote situation awareness and reduce cognitive workload. Intelligent alarm design can successfully reduce the number of false alarms. SUMMARY: Improvement of the display of information in the operating room is warranted, and recent developments are promising. However, their introduction into mass market is not yet on the horizon, although the shortcomings of the traditional single-sensor-single-indicator principle are known for a long time. If manufacturers are reluctant to implement new techniques into their devices, they should at least facilitate access to monitoring raw data in order to allow independent development of displays.

The performance of a target-controlled infusion of propofol in combination with remifentanil: a clinical investigation with two propofol formulations.

Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery lasting longer than 1 h received a combined TCI of propofol (Marsh parameter set; propofol randomly either dissolved with long- or middle-/long-chain triglycerides) and remifentanil. Arterial propofol plasma concentrations and hemodynamic and derived electroencephalogram variables were determined at various stages before, during, and after surgery. Measured propofol plasma concentrations exceeded the predicted values by 59%, and 48% when recalculated with the Schnider parameter set. Pharmacokinetic population analysis showed a small central volume of distribution (3.55 L) and reduced clearance (1.31 L/min) for propofol. ASA status and sex were the only variables that had a significant influence on propofol pharmacokinetics. In a second step, a new pharmacokinetic variable set for propofol was determined in the first 27 patients. Post hoc performance analysis of the remaining 27 patients showed improved accuracy using the new variable set. Our results show that when remifentanil and propofol are combined, the Marsh and Schnider parameter sets systematically underestimate propofol plasma concentrations. Presented, in part, at the Annual Meeting of the European Society of Anesthesiologists, Amsterdam, The Netherlands, June 1, 1999, and the Annual Meeting of the American Society of Anesthesiologists, Dallas, Texas, October 12, 1999.