Pharmacodynamic response modelling of arterial blood pressure in adult volunteers during propofol anaesthesia

International audienceBackground: Concentration effect relationships are commonly described with a direct response model as for example the sigmoid Emax model with one effect compartment as site of action. In this study we investigated whether models with more than one effect site, or indirect response, or counter-regulatory response models may be more appropriate for modelling the propofol effect on arterial blood pressure.Methods: Nine young healthy volunteers received propofol as target controlled infusion with predefined increasing and decreasing plasma target concentrations. Propofol concentrations were determined from arterial blood samples. Arterial blood pressure was measured invasively at radial artery site. Pharmacokinetic/-pharmacodynamic modelling was performed by population analysis with MONOLIX, testing different direct, indirect and counter-regulatory response models.Results: Propofol plasma concentrations were well described by a three-compartment model. The propofol effect on arterial blood pressure was best described by a direct sigmoid Emax model with two effect site compartments.Conclusions: Two effect sites were needed to describe the propofol effect on arterial blood pressure. This may reflect different pathways of arterial blood pressure response to propofol

Procalcitonin - Influence of Temperature, Storage, Anticoagulation and Arterial or Venous Asservation of Blood Samples on Procalcitonin Concentrations

Peer Reviewe

Does introduction of a Patient Data Management System (PDMS) improve the financial situation of an intensive care unit?

Background Patient Data Management Systems (PDMS) support clinical documentation at the bedside and have demonstrated effects on completeness of patient charting and the time spent on documentation. These systems are costly and raise the question if such a major investment pays off. We tried to answer the following questions: How do costs and revenues of an intensive care unit develop before and after introduction of a PDMS? Can higher revenues be obtained with improved PDMS documentation? Can we present cost savings attributable to the PDMS? Methods Retrospective analysis of cost and reimbursement data of a 25 bed Intensive Care Unit at a German University Hospital, three years before (2004–2006) and three years after (2007–2009) PDMS implementation. Results Costs and revenues increased continuously over the years. The profit of the investigated ICU was fluctuating over the years and seemingly depending on other factors as well. We found a small increase in profit in the year after the introduction of the PDMS, but not in the following years. Profit per case peaked at 1039 € in 2007, but dropped subsequently to 639 € per case. We found no clear evidence for cost savings after the PDMS introduction. Our cautious calculation did not consider additional labour costs for IT staff needed for system maintenance. Conclusions The introduction of a PDMS has probably minimal or no effect on reimbursement. In our case the observed increase in profit was too small to amortize the total investment for PDMS implementation. This may add some counterweight to the literature, where expectations for tools such as the PDMS can be quite unreasonable

Post-resuscitation haemodynamics in a novel acute myocardial infarction cardiac arrest model in the pig

Background and objectives Although a considerable amount of promising experimental research has been performed on cardiopulmonary resuscitation, clinical data indicate an ongoing limited outcome in human beings. One reason for this discrepancy could be that experimental studies use healthy animals whereas most human beings undergoing cardiopulmonary resuscitation suffer from acute or chronic myocardial dysfunction. To overcome this problem, we sought to develop a new model of myocardial infarction, that is easy to perform in all kind of laboratories and compromises on the myocardial function significantly. Methods Following approval by the local authorities, 14 domestic pigs were instrumented for measurement of arterial, central venous, left atrial and left ventricular pressures. Myocardial infarction was induced in eight pigs by clipping the circumflex artery close to its origin from the left coronary artery (infarction group; n = 8). Six animals (no infarction group, n = 6) served as no-infarct controls. Following a 4-min period of cardiac arrest, internal cardiac massage was performed in these two groups, and haemodynamics were recorded during the first 30 min of reperfusion. Results All animals were resuscitated successfully. Compared to the no-infarction group, the infarction group showed significantly decreased myocardial contractility, coronary perfusion pressure and cardiac index (30 min after restoration of spontaneous circulation: infarction group: 57 ± 7 and 89 ± 19 mL min−1 kg−1 in the no-infarction group; mean ± SD; P < 0.05) during reperfusion. Two animals from the infarction group (25%), but none of the animals in the no-infarction group, died during the reperfusion period. Conclusion These data demonstrate that clipping of the circumflex artery leads to a reduced myocardial performance after successful resuscitation, whereas the rate of restoration of spontaneous circulation is not reduced. Therefore, this set-up provides a reproducible model for future studies of post-resuscitation haemodynamics and treatment

Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors

Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain