J. Mühling

Alterations of acute phase reaction and cytokine production in patients following severe burn injury

To determine the acute immunologic reaction, mediated by cytokines, interleukines (ILs) and growth factors and the susceptibility to infections and sepsis after severe burn injury a prospective, single unit, longitudinal study of acute phase reactants and mediators who performed. After approval by the ethics committee of our hospital, we investigated the plasma concentrations of IL-2, -6, -8, -10, and -13, the soluble IL-2 receptor (sIL-2R), and the acute phase proteins procalcitonin (PCT) and C-reactive protein (CRP) at admission and every 3 days in 24 patients over a time course of 28 days after thermal injury and categorized by percent burn: < or =30% (group 1; n=12) and >30% (group 2; n=12). Shortly after burn injury we found higher concentrations of IL-2, -6, -10 and PCT in those patients >30% TBSA. During the study period, we found significant higher levels of acute phase proteins, IL-6 and -8 in patients >30% TBSA. The incidence of SIRS and MODS was three times increased in patients >30% TBSA. Our results show different patterns of cytokines and acute phase proteins in patients with different burned surface areas over a long time and continuous monitoring of a more distinct inflammatory response in these patients.

The systemic inflammatory response syndrome following cardiac surgery: different expression of proinflammatory cytokines and procalcitonin in patients with and without multiorgan dysfunctions

Cardiopulmonary bypass is associated with an injury that may cause pathophysiological changes in the form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated the inflammatory response of patients with multiple organ dysfunctions following open-heart surgery. Plasma levels of cytokines (IL-1β, IL-6, IL-8, IL-18) and procalcitonin (PCT) were measured on the first four postoperative days in 12 adult male patients with SIRS and two or more organ dysfunctions after myocar-dial revascularization (MODS group), and 15 patients without organ dysfunctions (SIRS group). All cytokines (except IL-1β) and PCT were significantly elevated in MODS patients, with peak values at the first two postoperative days. The results of our study show a different expression of members of the IL-1 family following extracorporeal circulation. For the first time, we can document that IL-18 is involved in the inflammatory response and the initiation of the MODS following cardiopulmonary bypass. In addition to APACHE-II score, PCT, IL-8, and IL-18 may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery. Furthermore, it must be noted that the duration of the surgical procedure is one of the most important factors for the initiation of the inflammatory response.

Hydroxyethyl starch (HES) does not directly affect renal function in patients with no prior renal impairment

STUDY OBJECTIVES To examine the effects of hydroxyethyl starch (HES) on renal function. DESIGN Randomized, controlled trial. SETTING Operating theatre of a university hospital. PATIENTS 60 ASA physical status I and II male patients undergoing middle ear surgery. INTERVENTIONS Patients received either lactated Ringers solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringers solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour. MEASUREMENTS Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously. MAIN RESULTS There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups. CONCLUSIONS Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation.

Hemodynamic effects of inhaled aerosolized iloprost and inhaled nitric oxide in heart transplant candidates with elevated pulmonary vascular resistance

OBJECTIVE An elevated pulmonary vascular resistance (PVR) is described as a predictor of postoperative right heart failure and increased mortality in patients undergoing orthotopic heart transplantation. The use of intravenous vasodilators is limited by their systemic effects. We evaluated the pulmonary and systemic hemodynamic effects of inhaled nitric oxide (NO) and inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated PVR. METHODS Fourteen male heart transplant candidates due to dilative or ischemic cardiomyopathia with elevated PVR (> or = 180 dyn s cm(-5)) were included in the study. Increasing concentrations of NO (5, 10 and 30 ppm) and 50 microg aerosolized IP were administered by inhalation. Hemodynamic measurements preceded and followed administration of each agent. RESULTS Inhalation of IP, 10, and 30 ppm NO reduced PVR and mean pulmonary artery pressure (MPAP), but did not affect blood pressure or systemic vascular resistance. Comparing the effectiveness of 10 ppm NO and IP, we found a significant higher reduction of MPAP in patients treated with IP. An increase of cardiac index and stroke index could only be shown with IP-inhalation. CONCLUSIONS Inhaled iloprost induces pulmonary vasodilation which is significantly greater than the effects of 10 and 30 ppm NO. The results of our study show, that inhaled iloprost induces a reliable hemodynamic response in the evaluation of heart transplant candidates. Further advantages of iloprost inhalation are the lack of adverse reactions and toxic side effects and an easier administration. Due to this facts we recommend iloprost as a routine screening drug for vascular reactivity in HTx-candidates. Based on our results it would be of great interest to investigate the role of iloprost in management of postoperative right heart insufficiency following cardiac transplantation.

Iloprost improves hemodynamics in patients with severe chronic cardiac failure and secondary pulmonary hypertension

PurposeSignificant pulmonary hypertension is a predictor of postoperative right heart insufficiency and increased mortality in patients undergoing orthotopic heart transplantation. Since the use of iv vasodilators is limited by their systemic effects, we evaluated the pulmonary and systemic hemodynamic effects of inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated pulmonary vascular resistance (PVR).MethodsTwenty-nine male heart transplant candidates because of dilated or ischemic cardiomyopathy with elevated PVR were included in the study. After assessing baseline hemodynamics, 50 μg aerosolized IP were administered by inhalation.ResultsInhalation of iloprost reduced PVR index (PVRI; 416 ± 180 vs 349 ± 173 dyn·sec−1·m−2·cm−5;P < 0.01) and mean pulmonary artery pressure (MPAP; 28.6 ± 9 vs 24.2 ± 9.1 mmHg;P < 0.01), but did not affect blood pressure or systemic vascular resistance. An additional improvement of ventricular performance with an increase of cardiac index (CI; 2.8 ± 0.7 vs 2.6 ± 0.7 L·min−1m−2;P < 0.05) and a decrease of pulmonary capillary wedge pressure (PCWP; 15.6 ± 6.8 vs 12.8 ± 7.1 mmHg;P < 0.01) was observed after inhalation of IPConclusionsInhaled aerosolized iloprost effectively reduces MPAP and is accompanied by an increase in CI and stroke index. Further advantages of iloprost inhalation are the lack of adverse reactions and ease of administration. Iloprost may be a useful drug to screen for vascular reactivity in cardiac transplantation patients.RésuméObjectifL’hypertension artérielle pulmonaire élevée est un prédicteur d’insuffisance postopératoire du cœur droit et elle accroît la mortalité des candidats à la transplantation cardiaque. L’usage des vasodilatateurs iv étant limité par leurs effets généraux, nous avons évalué les effets pulmonaires et généraux de l’iloprost (IP) en inhalation aérosol chez des candidats à la transplantation cardiaque présentant une résistance vasculaire pulmonaire élevée (RVP).MéthodeVingt-neuf hommes, candidats à une transplantation cardiaque à cause d’une cardiomyopathie dilatée ou ischémique et d’une RVP élevée, ont participé à l’étude. À la suite de l’évaluation hémodynamique de base, 50 μg d’IP en aérosol ont été administrés par inhalation.RésultatsL’inhalation d’iloprost a réduit l’index de RVP (IRVP; 416 ± 180 vs 349 ± 173 dyn·sec−1·m−2·cm−5; P < 0,01) et la pression artérielle pulmonaire moyenne (PAPM; 28,6 ± 9 vs 24,2 ± 9,1 mmHg; P < 0,01), mais n’a pas affecté la tension artérielle ou la résistance vasculaire générale. Une amélioration supplémentaire de la performance ventriculaire accompagnée d’une hausse de l’index cardiaque (IC; 2,8 ± 0,1 vs 2,6 ± 0,7 L·min−1·m−2; P < 0,05) ainsi qu’une baisse de la pression capillaire pulmonaire bloquée (PCPB; 15,6 ± 6,8 vs 12,8 ± 7,1 mmHg; P < 0,01) ont été observées après l’inhalation d’IPConclusionL’iloprost en aérosol administré par inhalation réduit efficacement la PAPM. Cet effet est accompagné d’une hausse de l’IC et de l’index systolique. Les autres avantages de l’inhalation d’iloprost sont l’absence de réactions indésirables et la facilité d’administration. L’iloprost pourrait servir au dépistage de la réactivité vasculaire chez les candidats à la transplantation cardiaque.

Quantitative determination of free intracellular amino acids in single human polymorphonuclear leucocytes. Recent developments in sample preparation and high-performance liquid chromatography

The described procedure allows quantitative, highly precise and reproducible analysis of free amino acid concentrations in single polymorphonuclear leucocytes (PMLs). This method is superior to previously described procedures with regard to sample size, PML separation, sample preparation and stability, as well as the chosen fluorescence high-performance liquid chromatography procedure, and can satisfy the high demands for ultra-sensitive and comprehensive amino acid analysis, especially for the continuous surveillance of severe diseases and organ dysfunction.

Quantitative determination of free intracellular α-keto acids in neutrophils

For the first time, a procedure is described for the quantitative analysis of free α-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular α-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.

Dysregulation of immune response following neurosurgical operations.

Background: Postoperative infections are common and potentially fatal complications in neurosurgical intensive care medicine. An impairment of immune function has been described after central nervous system surgery and in patients harboring malignant brain tumors. The aim of our study was to investigate whether differences in cell‐mediated immunity can be found in patients undergoing craniotomy for surgery of glioblastoma or clipping of an intracerebral aneurysm.

Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levels

Background: Cardiac surgery with an extracorporeal circulation cardiopulmonary bypass (CPB) is characterized by an oxidative stress response. Glutathione (GSH) belongs to the major antioxidative defense. In metabolic stress, glutamine (GLN) may be the rate‐limiting factor of GSH synthesis. Decreased GLN plasma levels were observed after various critical states. We evaluated, in patients undergoing open heart surgery with CPB, the effects of a peri‐operative GLN supplementation on GSH in whole blood and assessed their influence on the Sequential Organ Failure Assessment score and the intensive care unit length of stay.

Pharmacokinetics of Antibiotic Prophylaxis in Major Orthopedic Surgery and Blood-Saving Techniques

The pharmacokinetics of cefuroxime, cefotiam, cefamandole, and ampicillin/sulbactam were randomly measured in 40 patients undergoing major orthopedic surgery associated with high blood and volume turnover and intraoperative blood salvage. Serum and bone concentrations and the pharmacokinetics occurring in the context of these procedures were measured. No changes in elimination half-life relative to a normal population occurred with cefuroxime, cefotiam, and ampicillin. Serum and tissue concentrations were slightly lower with cefamandole and sulbactam, but reapplication of the initial dose was required with all antibiotics 4 hours after the first application.