Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

[Hemodynamic effects of cafedrine/theodrenaline on anesthesia-induced hypotension]. / Hämodynamisches Wirkungsspektrum von Cafedrin/Theodrenalin bei Anästhesie-assoziierter Hypotension.

BACKGROUND: There is insufficient knowledge about the hemodynamic effects of cafedrine/theodrenaline (caf/theo), a commercially available drug combination, to treat hypotension. METHODS: This prospective observational study investigated the hemodynamic effects of caf/theo on anesthesia-induced hypotension in 20 patients scheduled for elective major abdominal surgery. After induction of total intravenous anesthesia (TIVA) with propofol and remifentanil, a decrease in mean arterial blood pressure (MAP) below 60 mm Hg (n = 12) was treated with 60 mg/3 mg caf/theo. The systemic vascular resistance index (SVRI), cardiac index (CI), global end-diastolic index (GEDI), maximum pressure increase in the aorta (dPmx) and global ejection fraction (GEF) were assessed by transpulmonary thermodilution (PiCCO2-Monitor). RESULTS: The MAP increased by approximately 60% 10 min after administration of caf/theo. The increase in MAP was a result of the simultaneous effects on various cardiovascular determinants. An increase in peripheral resistance (SVRI +42%) and CI (+17%) could be determined. Data further indicated that the increase in CI was a consequence of an increase in both dPmx (+31%) and GEDI (+9%) but the GEF remained constant. CONCLUSION: In anesthesia-induced hypotension caf/theo effectively increased the mean arterial blood pressure by combined effects on preload, contractility, and afterload without altering cardiovascular efficiency.

[Piritramide : A critical review]. / Piritramid : Eine kritische Übersicht.

BACKGROUND: In many European countries and particularly in Germany, piritramide is the first choice opioid analgesic for the management of postoperative and posttraumatic pain. OBJECTIVE: The aim of this study was to review the pharmacological properties of piritramide and to evaluate whether these result in any clinical advantages with respect to effectiveness, safety and side effect profile compared to other strong opioids. MATERIAL AND METHODS: A systematic literature search was conducted in PubMed and Google Scholar and 27 articles published between 1961 and 2015 were retrieved and included in this review. RESULTS: Piritramide is a strong opioid that can only be administered parenterally. After intravenous injection it is effective after 17 min with pain relief lasting for up to 6 h. It is metabolized in the liver to inactive compounds, which is advantageous compared to morphine where active metabolites can accumulate in patients with renal failure. Piritramide is highly lipophilic resulting in a long context-sensitive half-life, making it unsuitable for continuous infusions. Studies further suggest that the side effect profile of piritramide is comparable to morphine. CONCLUSION: So far there is little evidence to support the widespread use of piritramide as first-line opioid analgesic for postoperative pain management in Germany. Especially lacking are in-depth studies about its mechanisms of action, receptor pharmacology, dose-response relationships and clinical dosing regimens. It is therefore questionable why piritramide is given priority.

[Cardiac preload and central venous pressure]. / Kardiale Vorlast und zentraler Venendruck.

The force of cardiac contraction is strongly influenced by myocardial fibre length at the beginning of systole. Because the length of cardiac sarcomers and muscle fibres primarily depends on the end-diastolic ventricular volume, filling pressures a priori can only act as indirect parameters of cardiac preload. Central venous pressure (CVP) gives information on right ventricular end-diastolic pressure, which parallels changes in left ventricular end-diastolic pressure as long as ventricular function is not impaired. Since the pressure-volume relationship of cardiac ventricles is not linear and shows great variability, filling of the ventricles cannot be directly derived from end-diastolic pressure. Further limitations of CVP as a surrogate variable of preload are caused by the influence of intrathoracic and intra-abdominal pressures. A valid parameter of preload should describe the relationship between preload and stroke volume as given by the Frank-Starling law. Furthermore, estimates of cardiac preload should enable prediction of fluid responsiveness. Many studies have demonstrated that under clinical conditions CVP cannot meet these demands and thus does not appear to be a useful predictor of cardiac preload. Variables which more directly represent end-diastolic ventricular volume (e.g. intrathoracic blood volume or end-diastolic ventricular area) offer a higher validity as estimates of cardiac preload. Furthermore, dynamic parameters of ventricular preload, such as pulse pressure variation or stroke volume variation, seem to be more predictive of volume responsiveness in ventilated patients than CVP. These limitations, however, do not impair the importance of CVP as the downstream pressure of the systemic venous system.

Intra- and extravascular volume status in patients undergoing mitral valve replacement: crystalloid vs. colloid priming of cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Cardiopulmonary bypass is associated with changes of intra- and extravascular volume status often resulting in cardiopulmonary dysfunction. The purpose of this prospective double-blind study was to evaluate the influence of different priming solutions of the extracorporeal circuit on intra- and extravascular volume status and haemodynamics in patients undergoing elective mitral valve replacement. METHODS: Twenty-two patients with mitral valve insufficiency were randomly allocated into two equal groups. In Group 1 cardiopulmonary bypass was primed with a nearly isooncotic solution consisting of 4% albumin. The second group received a pure crystalloid priming solution. The thermo-dye indicator dilution technique was used for the assessment of cardiac output, central and pulmonary blood volume, right ventricular end-diastolic volume and total blood volume. RESULTS: Patients in the crystalloid group showed increased intraoperative fluid requirements. Significantly more fluid was accumulated in the extravascular space whereas total blood volume was decreased after surgery. Stroke volume index (SVI) was significantly decreased in the immediate postoperative period when compared to baseline. As indicated by the increase in extravascular fluid content after surgery, both colloid and crystalloid priming volumes were transferred to the extravascular space. CONCLUSION: The use of colloid priming solutions in patients with mitral valve insufficiency leads to less fluid requirements and significantly reduced fluid shift in the interstitium. However, these changes are not associated with changes in haemodynamic parameters or short term outcome.

Instantaneous diastolic pressure-flow relationship in arterial coronary bypass grafts.

OBJECTIVE: The objective of this study was to describe the diastolic pressure-flow relationship and to assess critical occlusion pressure in arterial coronary bypass grafts in human beings. METHODS AND RESULTS: Fifteen patients were studied following elective surgical coronary artery bypass grafting. Flow in the left internal mammary artery bypass to the left anterior descending artery was measured and simultaneously, aortic pressure, coronary sinus pressure and left ventricular end-diastolic pressure were recorded. The zero-flow pressure intercept as a measure of critical occlusion pressure was extrapolated from the linear regression analysis of the instantaneous diastolic pressure-flow relationship. Mean diastolic flow was 46 +/- 17 mL min(-1), mean diastolic aortic pressure was 60.5 +/- 10.0 mmHg. Diastolic blood flow was linearly related to the respective aortic pressure in all patients (R-values 0.7-0.99). The regression lines had a mean slope of 2.1 +/- 1.2 mL min(-1) mmHg(-1). Mean critical occlusion pressure was 32.3 +/- 9.9 mmHg and exceeded mean coronary sinus pressure and mean left ventricular end-diastolic pressure by factors of 3.1 and 2.6, respectively. CONCLUSIONS: Our data demonstrate the presence of a vascular waterfall phenomenon in the coronary circulation after internal mammary artery bypass grafting. Critical occlusion pressure in arterial grafts considerably exceeds coronary sinus pressure as well as left ventricular end-diastolic pressure and should thus be used as the effective downstream pressure when calculating coronary perfusion pressure. Our data further suggest that the slope of diastolic pressure-flow relationships provides a more rational approach to assess regional coronary vascular resistance than conventional calculations of coronary vascular resistance.

Cerebral inflammatory response during and after cardiac surgery.

BACKGROUND AND OBJECTIVE: Neurological dysfunction is a common problem after cardiac surgery with cardiopulmonary bypass (CPB). Cerebral ischaemia associated with the use of CPB may result in a release of neuronal-ischaemic markers and a subsequent cerebral inflammatory response which may additionally release inflammatory cytokines. In order to locate the origin and to quantify the release of neuronal-ischaemic markers and cytokines we investigated arterial-cerebral venous concentration gradients during and after CPB in a clinical setting. METHODS: In twenty-five patients scheduled for coronary artery bypass grafting surgery we measured the plasma concentration of neuron-specific enolase, S-100beta protein as well as interleukins (IL) IL-6, IL-8 and IL-10 from arterial and cerebral venous blood samples prior to surgery (baseline), during hypothermic CPB at 32 degrees C, after termination of bypass, as well as 2, 4 and 6 h after admission to the intensive care unit. RESULTS: Arterial-cerebral venous concentration gradients of neuron-specific enolase, S-100beta, IL-6, IL-8 and IL-10 were neither detectable during nor after CPB. Compared to the baseline period, S-100beta and neuron-specific enolase significantly increased during hypothermic CPB. After termination of CPB, neuronal-ischaemic markers as well as cytokines were increased and remained elevated during the investigated time course without reaching baseline values. CONCLUSIONS: Although we found an overall increase in plasma concentrations of neuronal-ischaemic markers, IL-6, IL-8 and IL-10 during and after CPB, arterial-cerebral venous gradients were not detectable for any of these parameters. Our results suggest that the increase of investigated parameters associated with the use of CPB are not primarily caused by a cerebral inflammatory response but rather reflect a release from other sources in the systemic circulation.

Influence of intra-aortic balloon pumping on cerebral blood flow pattern in patients after cardiac surgery.

BACKGROUND AND OBJECTIVE: The effects of intra-aortic balloon pumping (IABP) on cerebral perfusion are still a matter of debate. End-diastolic reversal of blood flow in cerebral arteries has been observed in a small number of patients. We prospectively investigated the incidence and the amount of transient cerebral artery blood flow reversal during balloon pumping in patients recovering from cardiac surgery. METHODS: In 23 patients receiving IABP support, blood flow velocities in the right middle cerebral artery were assessed by transcranial Doppler-sonography. Additionally, systemic haemodynamics were monitored. In each patient, measurements were performed at three different pump settings: without support, assist ratio 1 : 1 and assist ratio 1 : 2. RESULTS: In 8 of 23 patients, balloon pumping caused a transient diastolic reversal of blood flow in the middle cerebral artery during balloon deflation. Antegrade mean flow velocity in the middle cerebral artery significantly increased from 57 +/- 27 to 61 +/- 26 (assist ratio 1 : 1) and 61 +/- 29 cm s(-1) (assist ratio 1 : 2) (P < 0.05). Taking transient blood flow reversal into account, net mean flow velocity did not increase with balloon pump support. Systemic haemodynamic parameters remained unchanged. CONCLUSION: Left ventricular support with IABP significantly changed flow patterns in basal cerebral arteries of our patients. In 35% of patients, support resulted in a transient reversal of intracranial blood flow which counterbalanced a slight increase in mean antegrade flow.

Extrapolation to zero-flow pressure in cerebral arteries to estimate intracranial pressure.

BACKGROUND: Cerebral perfusion pressure (CPP) is commonly calculated from the difference between arterial blood pressure (AP) and intracranial pressure (ICP). ICP can be considered the effective downstream pressure of the cerebral circulation. Consequently, cerebral circulatory arrest would occur when AP equals ICP. Estimation of AP for zero-flow pressure (ZFP) may thus allow estimation of ICP. We estimated ZFP from cerebral pressure-flow velocity relationships so that ICP could be measured by transcranial Doppler sonography. METHODS: We studied 20 mechanically ventilated patients with severe head injury, in whom ICP was monitored by epidural pressure transducers. AP was measured with a radial artery cannula. Blood flow velocity in the middle cerebral artery (V(MCA)) ipsilateral to the site of ICP measurement was measured with a 2 MHz transcranial Doppler probe. All data were recorded by a microcomputer from analogue-digital converters. ZFP was extrapolated by regression analysis of AP-V(MCA) plots and compared with simultaneous measurements of ICP. RESULTS: ZFP estimated from AP-V(MCA) plots was linearly related to ICP over a wide range of values (r=0.93). There was no systematic difference between ZFP and ICP. Limit of agreement (2 SD) was 15.2 mm Hg. Short-term variations in ICP were closely followed by changes in ZFP. CONCLUSION: Extrapolation of cerebral ZFP from instantaneous AP-V(MCA) relationships enables detection of severely elevated ICP and may be a useful and less invasive method for CPP monitoring than other methods.

[A comparison of the Proseal laryngeal mask to the standard laryngeal mask on anesthesized, non-relaxed patients]. / Ein Vergleich der Larynxmaske (LMA) vom Typ Proseal gegen die Standard-LMA bei anästhesierten, nicht relaxierten Patienten. Ergebnisse einer deutschen Multizenterstudie.

It was our goal to compare the Proseal-laryngeal mask airway (PLMA) with the classical laryngeal mask airway (LMA) in a german multicenter trial. Handling of the instruments and application criteria were to be tested. 7 anaesthesia departments were able to take part in this study. 280 patients could be investigated after approval of the ethics committee of the medical faculty of the university of Goettingen. 145 patients received the PLMA and 135 the LMA. The surgical interventions were small to moderate procedures with a duration of at least 20 minutes in the sections general surgery, trauma/orthopedic surgery, urology, vascular surgery, gynecology, ENT-surgery and ophthalmology. There was equivalence of the two instruments PLMA and LMA concerning duration and ease of insertion, endoscopic position check, observations on emergence, potential for injury and some postoperative complaints. This equivalence could be confirmed statistically. Laryngospasm was observed in three, Bronchospasm in two patients with the PLMA, in no one with the LMA. In one case of laryngospasm and another of bronchospasm a mechanism of supraglottic laryngeal stenosis has been involved which may occur in rare instances with the PLMA. This mechanism is due to the double cuff of the PLMA with the instruments proximity to the laryngeal inlet. The seal pressure in both groups differs significantly (p = 0.001). The mean value for the seal pressure was 29,3 +/- 0,21 mbar for the PLMA and 20,9 +/- 0,21 mbar for the LMA. In the PLMA the gastric tube could be positioned with the first attempt in 118 patients, with the second attempt in 17 cases. In 10 patients the gastric tube could not be placed. Contrary to the LMA the tip of the PLMA cuff may be bent in some cases with loss of airway safety and positioning of the gastric tube. The symptoms sore throat and painful swallowing on the first postoperative day were more frequent with LMA application. These differences could be confirmed statistically (sore throat p = 0.01, painful swallowing p = 0.04). They may be explained by the more rigid LMA compared to the PLMA and by the fact that the LMA in this study was older than the PLMA, loosing plasticizer. The drainage tube within the PLMA offers safety from aspiration in patients with no primary aspiration risk, additional reassurance for a correct position and a better stability of the airway. Our data may support a wider indication range for the PLMA compared with the LMA. The PLMA may be applied in laparoscopies and lower abdominal surgical interventions. Careful clinical observation will show, if the minimal invasiveness of the PLMA offers an advantage for these patients. The PLMA should not be applied in patients with increased aspiration risk.

Reliability of cerebral blood flow measurements by transcerebral double-indicator dilution technique.

BACKGROUND AND OBJECTIVE: The recently developed transcerebral double-indicator dilution technique has proven to be a feasible monitoring alternative to measure global cerebral blood flow at the bedside. However, the short-term repeatability of transcerebral double-indicator dilution measurements has not yet been investigated. The present study was designed to investigate the accuracy in terms of reliability for repeated transcerebral double-indicator dilution measurements to assess global cerebral blood flow during a definite carbon dioxide challenge in a clinical trial. METHODS: The investigation was performed in 10 patients scheduled for elective coronary artery bypass grafting. After induction of anaesthesia, repeated cerebral blood flow measurements using transcerebral double-indicator dilution were performed during target normocapnia, hypocapnia and hypercapnia. For transcerebral double-indicator dilution measurements, a bolus injection of ice-cold indocyanine green was administered into a central vein. The resulting thermal dye dilution curves were recorded simultaneously in the aorta and the jugular bulb using combined fibreoptic thermistor catheters. Cerebral blood flow was calculated from the mean transit times of the indicators through the brain. Additionally, transcranial Doppler sonography was simultaneously performed to measure transient changes in the cerebral blood flow velocity. RESULTS: Transcerebral double-indicator dilution measurements revealed a reasonable coefficient of repeatability with 9.1, 9.7 and 20.2 mL min-1 100 g-1 during normo-, hypo- and hypercapnic conditions, respectively. However, a total of 20% of the administered measurements had to be rejected for methodological reasons. CONCLUSIONS: Repeated measurements with the transcerebral double-indicator dilution method show a reasonable repeatability. With consideration to the limitations of the transcerebral double-indicator dilution technique, this new method proves to be a reliable monitoring tool to measure global cerebral blood flow at the bedside.

Assessment of cardiac preload by indicator dilution and transoesophageal echocardiography.

BACKGROUND AND OBJECTIVE: Assessment of cardiac preload is of major importance in the management of critically ill patients. Echocardiographic determined left ventricular end-diastolic area and indicator dilution derived intrathoracic blood volume are used as surrogates for cardiac preload. However, no controlled comparison studies on the relationship between induced changes in end-diastolic area and intrathoracic blood volume and concomitant changes in stroke volume index are available. METHODS: The effects of a change in body position on these variables were investigated in 10 anaesthetized patients. RESULTS: Intrathoracic blood volume and end-diastolic area decreased by 18 +/- 11% and 27 +/- 13% respectively. Stroke volume index concomitantly decreased by 19 +/- 11%. Correlation analysis revealed a close relation between stroke volume index and intrathoracic blood volume (r=0.75) and end-diastolic area (r=0.76). CONCLUSIONS: Within the observed range of data, intrathoracic blood volume and end-diastolic area are equivalent indices of cardiac preload.

Changes in cardiac output and intrathoracic blood volume: a mathematical coupling of data?

BACKGROUND: Measurements of intrathoracic blood volume (ITBV) provide volumetric information about cardiac preload and are used to investigate the cause of alterations in cardiac output (CO). On the other hand, CO is required to calculate ITBV. Thus, concerns have been raised with respect to a mathematical coupling of data. The aim of this prospective, clinical study was to investigate whether a variation in CO induced by high-dose beta-blockade influences thermodilution measurements of ITBV in the absence of changes in intravascular volume in patients undergoing minimally invasive coronary artery bypass grafting. METHODS: Sixteen patients undergoing elective minimally invasive direct coronay artery bypass (MIDCAB) surgery were studied. Transpulmonary thermodilution measurements of ITBV and CO were simultaneously performed before bypass grafting, during beta-blockade induced by high-dose esmolol and at the end of surgery. RESULTS: During esmolol administration, CO significantly decreased by 33%, whereas ITBV remained unchanged compared to control values (876+/-46 ml m-2 during control versus 860+/-61 ml m-2 during esmolol administration). After the end of esmolol administration, CO significantly increased by 79%. Again, ITBV remained virtually unchanged (860+/-61 ml m-2 during esmolol administration versus 911+/-38 ml m-2 after esmolol administration). CONCLUSIONS: The results of the present study demonstrate that substantial alterations in CO as a consequence of high-dose esmolol infusion are not associated with changes in ITBV. Because haemodynamic changes were induced by factors other than variation of preload, these findings suggest that changes in cardiac output do not influence thermodilution measurements of ITBV in this setting.

Doppler-sonographic evidence of cerebral microembolism originating from a biventricular assist device.

The use of extracorporeal assist devices in heart failure is associated with the risk of thromboembolic complications [1]. Prove of thromboembolic material in the ventricles and tubes of the assist devices is difficult, and the clinical relevance of thrombotic material in the tubes is not clear. Here, we report on a patient with severe heart failure caused by endstage dilated cardiomyopathy who was bridged to transplantation using a biventricular assist device (BVAD). Five weeks after implantation, transcranial Doppler sonography (TCD) revealed high intensity transient signals (HITS) in basal cerebral arteries, suggesting continued cerebral microembolism. Apart from a correlation of these Doppler sonographic findings with neurological symptoms, macroscopic evidence of fibrin thrombi in the artificial ventricle, and post mortem confirmation of cerebral infarction could be proved.

Cerebrovascular tone rather than intracranial pressure determines the effective downstream pressure of the cerebral circulation in the absence of intracranial hypertension.

Cerebral perfusion pressure is commonly calculated from the difference between mean arterial pressure and intracranial pressure because intracranial pressure is known to represent the effective downstream pressure of the cerebral circulation. Studies of other organs, however, have shown that effective downstream pressure is determined by a critical closing pressure located at the arteriolar level. This study was designed to investigate the effects of PCO2-induced variations in cerebrovascular tone on the effective downstream pressure of the cerebral circulation. Sixteen patients recovering from head injury were studied. Intracranial pressure was assessed by epidural pressure transducers. Blood flow velocity in the middle cerebral artery was monitored by transcranial Doppler sonography. Effective downstream pressure was derived from the zero flow pressure as extrapolated by regression analysis of instantaneous arterial pressure/middle cerebral artery flow velocity relationships. PaCO2 was varied between 30 and 47 mm Hg in randomized sequence. Intracranial pressure decreased from 18.5+/-5.2 mm Hg during hypercapnia to 9.9+/-3.1 mm Hg during hypocapnia. In contrast, effective downstream pressure increased from 13.7+/-9.6 mm Hg to 23.4+/-8.6 mm Hg and exceeded intracranial pressure at hypocapnic PaCO2 levels. Our results demonstrate that, in the absence of intracranial hypertension, intracranial pressure does not necessarily represent the effective downstream pressure of the cerebral circulation. Instead, the tone of cerebral resistance vessels seems to determine effective downstream pressure. This suggests a modified model of the cerebral circulation based on the existence of two Starling resistors in a series connection.

Myocardial consequences of remifentanil in patients with coronary artery disease.

Remifentanil may be an alternative to conventional opioids for minimally invasive direct coronary artery bypass surgery because of its extremely short duration of action. The aim of this study was to investigate the effects of remifentanil on myocardial blood flow, metabolism and systemic haemodynamic variables in patients with coronary artery disease. After approval by the local ethics committee, 12 male patients were investigated before elective coronary artery bypass grafting. Systemic haemodynamic variables, myocardial blood flow and metabolism were measured when patients were awake and when they were anaesthetized with high-dose remifentanil (2.0 micrograms kg-1 min-1), or with remifentanil 0.5 microgram kg-1 min-1 combined with propofol (target-controlled infusion aiming at a plasma concentration of 2.0 micrograms ml-1). Myocardial blood flow was measured using a modified Kety-Schmidt technique. High-dose remifentanil anaesthesia significantly reduced cardiac index (CI) (-25%) as a consequence of a decrease in stroke volume index (SVI) (-14%) and heart rate (-13%). Mean arterial pressure (MAP) was 30% lower than that in the awake patient. Myocardial blood flow and myocardial oxygen uptake (MVO2) decreased by 30% and 42%, respectively. In contrast to high-dose remifentanil anaesthesia, systemic vascular resistance index (-14%) during remifentanil/propofol anaesthesia was significantly lower than that in the awake patient. Other haemodynamic variables, and myocardial blood flow and MVO2, did not significantly differ from the high-dose remifentanil period. In conclusion, high-dose remifentanil reduces SVI, heart rate, MAP, myocardial blood flow and MVO2 and its effects do not differ from those of remifentanil/propofol anaesthesia.