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.

[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.

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.

Induction of interleukin-6 in murine bone marrow-derived macrophages stimulated by the Mycoplasma arthritidis mitogen MAS.

Cell-free supernatant of cultures from Mycoplasma arthritidis (MAS) functions as an extremely potent T-cell mitogen for human and murine lymphocytes. The T-cell response is dependent on the presence of accessory cells, presenting the intact E2 molecule on the cell surface. Until now, pure MAS protein has not been available. We developed a new multi-step method for MAS purification. The main steps in this protocol are ammonium sulfate precipitation, anion exchange and hydroxyapatite chromatography followed by gel filtration. With this efficient protocol we obtained fractions of extremely potent mitogenic properties, the purification rate was about 5 x 10(5). Although this protease-sensitive mitogenic activity was highly enriched, we failed to detect the protein by sensitive staining methods of SDS-PAGE. In previous studies, we showed that MAS induces the synthesis of interferon gamma in human and murine lymphocyte cultures. Here we demonstrate that MAS induces interleukin-6 (IL-6) in murine bone-marrow derived macrophage cultures. Since IL-6 is also induced by endotoxin, we used C3H/HeJ mice, which are known to be LPS-nonresponders, in all our studies.

Heart transplantation after successful donor postpartum pulmonary embolectomy.

A fulminant pulmonary embolism can be treated surgically if thrombolytic therapy is contraindicated. A 31-year-old woman developed a fulminant pulmonary embolism after right-sided deep venous thrombosis 1 day after undergoing a cesarean section. A pulmonary embolectomy with cardiopulmonary bypass was performed, but the patient was brain-dead. After 2 days of echocardiographic observation, her heart was explanted for a 61-year-old man with ischemic cardiomyopathy. His right heart data were unremarkable, and he remains well 16 months after transplantation. Despite the sudden strain on the right ventricle that occurs with a pulmonary embolism, such a heart may be transplanted successfully after a pulmonary embolectomy.

A new paediatric metabolic monitor.

OBJECTIVE: A paediatric option for the measurement of VO2 and VCO2 (20 to 150 ml/min) has recently been introduced for the adult Deltatrac metabolic monitor (Datex Instrumentarium, Finland) to use in ventilated and spontaneously breathing children. This paper describes a laboratory validation of the paediatric option for ventilated children with regard to the influence of respiratory variables. DESIGN: Respiratory variables were varied within the following ranges: FIO2 0.21-0.8, FIO2-FEO2 (DFO2) 0.01-0.05, FECO2 0.01-0.05, VE 300-6000 ml/min, VT 8-300 ml, RR 10-50/min, P(aw) 10-60 mbar, relative humidity 10% and 60%, and resulted in 107 test situations. SETTING: Gas exchange was simulated by injection of nitrogen and CO2 at a RQ close to 1. PATIENTS OR PARTICIPANTS: Different situations of paediatric patients ventilated in controlled mode were simulated on a gas injection model. INTERVENTIONS: Respiratory and metabolic variables were varied independently to result in a range of 8 to 210 ml/min of VO2 and VCO2. MEASUREMENTS AND RESULTS: Reference measurements were carried out by mass spectrometry and wet gas spirometry. The mean VCO2 difference for all tests ranging from 20 ml/min to 210 ml/min was -2.4% (2SD = +/- 12%). The respective VO2 difference was -3.2% (2SD = +/- 23%). Measurement agreement for VO2 in neonatal respirator treatment (20-50 ml/min) compared to older children (50-210 ml/min) showed a mean difference of -3.9% (2SD = +/- 26%) versus -2.8% (2SD = +/- 20%). The respective differences for VCO2 were -7.1% (2SD = +/- 7%) versus +0.4% (2SD = +/- 10%). The mean difference for VO2 as well as VCO2 indicated a high systematic agreement of both methods. The variability (+/- 2SD) in VCO2 measurement is acceptable for all applications. The overall variability in VO2 measurement (2SD = +/- 23%) can be reduced by exclusion of all tests with a FECO2 and DFO2 below 0.03. This results in a mean difference of -3.2% (2SD = +/- 13.7%). CONCLUSION: Within this limitation the paediatric measurement option seems to introduce a valuable method for clinical application in paediatric intensive care medicine.

Oxygen cost of breathing for assisted spontaneous breathing modes: investigation into three states of pulmonary function.

OBJECTIVE: We investigated the effects of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) on the oxygen cost of breathing (VO2resp) for different states of pulmonary function. Additionally VO2resp was measured during spontaneous breathing. DESIGN: This was done in a controlled and prospective study. Ventilatory modes were applied randomly. SETTING: Measurements were performed in a quiet room on volunteers (VOL) and inpatients treated for chronic obstructive pulmonary disease (COPD). Post-operative patients after aortocoronary bypass surgery (ACB) were studied on the cardio-thoracic intensive care unit just before and after extubation. PATIENTS: Healthy volunteers (n = 14), postoperative patients after aorto-coronary bypass surgery (n = 15) and patients with COPD (n = 9, xFEV1 47.7%) were the objects of study. INTERVENTIONS: Demand flow CPAP (5 mbar) and PSV (7 mbar, PEEP 5 mbar), using the Hamilton Veolar ventilator, were investigated in comparison to spontaneous breathing. MEASUREMENTS AND RESULTS: VO2 was measured by a Datex Deltatrac metabolic monitor. VO2resp was calculated by subtraction of total oxygen uptake (VO2tot) in controlled mode ventilation (CMV) from that in the respective spontaneous breathing mode. For VOL and COPD patients who were not intubated, a CPAP facemask connected to a short 7.5 mm tube was used as connection to the ventilator. Breathing spontaneously under a canopy system VOL showed a VO2resp of 4.5 +/- 4.0% compared to 9.2 +/- 3.5% for ACB and 15.4 +/- 7.7% for COPD. CPAP changed the VO2resp to 7.8 +/- 3.9%, 12.0 +/- 4.0% and 9.1 +/- 3.6% respectively. PSV reduced the VO2resp to 7.9 +/- 3.8% in ACB and 7.7 +/- 5.5% in COPD. CONCLUSIONS: This investigation confirms findings that postoperative patients have a mild increase in VO2resp. COPD exhibit the highest increase in VO2resp. Tracheal tubes, masks and CPAP on a demand flow apparatus increases VO2resp in volunteers and postoperative patients after cardiac surgery. The same amount of CPAP in contrary reduces VO2resp in patients with COPD. Pressure support ventilation can offset the additional VO2resp induced by CPAP but at the same level does not further reduce VO2resp in COPD patients.

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.

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.

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.

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.

[Percutaneous lumbar facet denervation. Indications and significance in chronic backache]. / Die perkutane lumbale Facettdenervation. Indikation und Bedeutung bei chronischen Rückenschmerzen.

The lumber facet joints have been established as a source of low back pain which may radiate to the leg. Because there are no reliable clinical signs which confirm the diagnosis injections of an anaesthetic agent into the joints are necessary. Therapeutically a percutaneous radiofrequency destruction of the medial branches of lumbar dorsal rami may relieve such pain. Success rate, however, is depending on a careful selection of patients.

[Intraoperative acute aortic obstructive embolism]. / Intraoperativer Nachweis eines akuten embolischen Aortenverschlusses.

UNLABELLED: We report a case of acute embolic obstruction of the aorta in a 36-year-old patient undergoing coronary artery bypass surgery. After declamping of the aorta at the end of extracorporeal circulation, blood pressure measured in the femoral artery dropped to 10-20 mmHg. Neither clinical signs of arterial hypotension nor a dysfunction of the arterial line could be observed. Cannulation of the left radial artery revealed a normal systemic blood pressure. After the end of surgery, pale and pulseless lower extremities were observed, suggesting arterial obstruction. A 6 X 3 cm embolus occluding the aortic bifurcation could be extracted with a Fogarty catheter; its origin was presumably an aneurysmatic area of the left ventricle. Surgical manipulation had mobilised the mural thrombus, which caused Leriche's syndrome after aortic declamping and defibrillation of the heart. CONCLUSION: In case of sudden alterations of lower extremity perfusion, anaesthetists and surgeons should consider the rare complication of acute embolic obstruction of the aorta originating from intracardiac thrombotic material. Routine monitoring with transoesophageal echocardiography should thus be considered in patients at risk for intracardiac thrombus formation.