Effects of inverse ratio ventilation with PEEP on kidney function.

INTRODUCTION: Positive pressure ventilation influences hemodynamics and impairs renal function. The effects of inverse ratio ventilation (IRV) on hormonal response and renal function need to be investigated because this represents a highly invasive form of positive pressure ventilation. MATERIALS AND METHODS: Ten male patients were treated postoperatively for 60 min using five different ventilation modes. At the end of these periods, hemodynamics, urine production, fractional excretion of sodium (FESo), as well as the hormones, atrial natriuretic peptide (ANP), renin, angiotensin II, aldosterone, and antidiuretic hormone (ADH), were measured in plasma. RESULTS: Central venous pressure (CVP), ADH, and renin with a positive end-expiratory pressure (PEEP) of 15 cm H(2)O and an inspiration/expiration ratio (I:E) of 1:2 revealed significant increases from baseline, whereas CVP, renin, and FESo showed an increase with an PEEP of 15 cm H(2)O and an I:E ratio of 2:1. Urine production significantly decreased with an PEEP of 15 cm H(2)O and an I:E ratio of 2:1. CONCLUSIONS: IRV with PEEP induced clear effects on hemodynamics and hormonal responses (renin) as well as a decrease in urine production in patients with healthy renal and pulmonary systems after an operation. However, all parameters apart from FESo and renin remained within the normal range. Whether pathological values are also observed after longer periods of positive pressure ventilation shall be the subject of other studies.

Evaluation of sE-Selectin and sICAM-1 as parameters for renal function.

INTRODUCTION: In order to monitor acute renal failure, intensive care patients were examined, and routine as well as specialized parameters were compared. MATERIALS AND METHODS: Thirty-three patients at the Surgical Intensive Care Unit (ICU) were examined daily over the entire period for which they stayed in the ICU. The patients were retrospectively classified as being either with or without acute renal failure. Group 1 consisted of 22 patients who resided in the ICU for 11-15 (median 14) days without ARF. Group 2 consisted of 11 patients who developed an ARF during their stay of 13-18 (median 16) days in the ICU. In addition to the routine parameters of diuresis, serum creatinine/urea, and clearance of creatinine, specialized parameters for kidney function, including the excretion rates of alpha1-microglobulin, N-acetyl-beta-D-glucosaminidase, and total protein, were compared with the excretion rate of soluble ICAM-1 and sE-Selectin. RESULTS: Diuresis, serum creatinine, urea, and enzyme elimination were pathological among patients with ARF. Already on the day of admission, raised elimination rates of sICAM-1 were found in the urine of patients who had developed an ARF. While high values were still shown upon discharge, levels kept falling among patients without ARF. Clearly raised values were also shown for sE-Selectin compared to patients without ARF. CONCLUSIONS: sICAM-1 and sE-Selectin as supplementary parameters indicating renal function revealed early signs of kidney damage. These parameters may play a major role in the development of novel therapeutic approaches for ARF (antibodies against ICAM-1 or sE-Selectin).

[Dysregulation of homeostasis in severe sepsis: relevance and therapeutic options]. / Gestörte Homöostase in der Sepsis - Bedeutung und Therapie.

Severe sepsis and septic shock may have a lasting effect on all human endocrinologic, coagulatory and metabolic regulatory circuits with the consequence of severe dysregulation of homoeostasis. Adjunctive therapeutic options like intensive insulin therapy, low-dose hydrocortisone and modulation of coagulation by drotrecogin alfa (activated) are still controversial discussed, but should be used according to the national and international guidelines for a sophisticated treatment of septic heterostasis.

Quantitative determination of free intracellular alpha-keto acids in neutrophils.

For the first time, a procedure is described for the quantitative analysis of free alpha-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 alpha-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.

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.

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.

Renal effects of cardiopulmonary bypass in the elderly.

Cardiopulmonary bypass is widely believed to be injurious to renal function. The unknown consequences of renal dysfunction with modern techniques of bypass in the elderly caused us to examine creatinine clearance and the excretion of sensitive marker proteins in older adult patients undergoing CABG. Thirty male patients were divided into three groups: group I with an age up to 60 years, group II with an age between 61 and 70 years, inclusive and group III 71 years and over. Serum creatinine and urea, creatinine clearance, and alpha1-microglobulin (alpha1-MG), N-acetyl-beta-D-glucosaminidase (NAG), Tamm-Horsfall protein (TH) and immunoglobulin G (IgG) were all measured daily, pre- and postoperatively. Creatinine clearance remained lower in the older patients without significant differences. Raised excretion rates of alpha1-MG, and IgG were seen after CPB. The increase in alpha1-MG and NAG during the postoperative period revealed tubular damage in all elderly patients. Measurements of alpha1-MG, NAG and IgG represent useful supplements to standard clinical tests for recognizing early and differentiated changes in renal function.

Long-term monitoring of renal function in poly-traumatized intensive care patients.

INTRODUCTION: For the long-term monitoring of kidney function, polytraumatized patients were examined and routine as well as specialized parameters were compared. MATERIALS AND METHODS: 30 patients of the Surgical Intensive Care Unit (ICU) were examined daily over the entire period they stayed in the ICU. The patients were retrospectively classified as either survivors or deceased patients. Group 1 consisted of 20 patients who resided in the ICU for 11-15 (Median 14) days before they could be transferred to a normal hospital unit. Group 2 consisted of 10 patients who had passed away after 13-18 (Median 16) days in the ICU. In addition to the routine parameters diuresis, serum creatinine and serum urea, specialized parameters for kidney function including the excretion rates of alpha1-microglobulin (alpha1-MG), N-Acetyl-beta-D-glucosaminidase (NAG), angiotensinase A (ATA) and immunoglobulin G (IgG) were determined. RESULTS: Similar biometric data were shown by all patients at admission into the ICU, but differences did exist regarding the Revised Trauma Score, Injury Severity Score and the APACHE-II-Score. In the period between the 5th and 8th day of intensive treatment almost all patients showed pathological excretion rates of tubular and glomerular parameters whereby no increased frequency of unusual events could be determined at these time-points. CONCLUSION: During treatment in the ICU, all examined patients showed at times pathological excretion rates of specialized kidney function parameters. Such transient damage was only apparent in a few of the patients when the standard parameters serum creatinine and serum urea were employed. In 90% of the surviving patients the kidney parameters had normalized until the time they were transferred, indicating that such parameters reflected the general state of health of these patients.

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

PURPOSE: Significant 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). METHODS: Twenty-nine male heart transplant candidates because of dilated or ischemic cardiomyopathy with elevated PVR were included in the study. After assessing baseline hemodynamics, 50 micro g aerosolized IP were administered by inhalation. RESULTS: Inhalation of iloprost reduced PVR index (PVRI; 416 +/- 180 vs 349 +/- 173 dyn x sec(-1) x m(-2) x 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 x min(-1) x m(-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 IP. CONCLUSIONS: Inhaled 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.

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-1beta, 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 myocardial revascularization (MODS group), and 15 patients without organ dysfunctions (SIRS group). All cytokines (except IL-1beta) 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.

Effects of propofol and taurine on intracellular free amino acid profiles and immune function markers in neutrophils in vitro.

We have examined the effects of propofol, taurine, and the combination of propofol and taurine on amino acid profiles and the immune function markers superoxide anion (O2-), hydrogen peroxide (H2O2), and released myeloperoxidase (MPO) activity in neutrophils (PMN). Propofol led to significant changes in the dynamic PMN-free amino acid pool. Exogenous taurine significantly reduced PMN neutral amino acid and alpha-aminobutyrate (alpha-aba) as intracellular taurine increased. Incubation with propofol plus taurine resulted in lower intracellular taurine levels and elevated alpha-aba and neutral amino acid concentrations compared to propofol alone. Concerning PMN immune function markers, propofol significantly decreased O2- and H2O2 formation and released MPO. Taurine led to an increased release of MPO and concomitant significantly reduced O2- and H2O2 levels. When propofol and taurine were applied together they appeared to act additively with regard to superoxide and hydrogen peroxide formation. In the case of MPO, taurine neutralized propofol's effects, supporting the idea that MPO activity may be regulated by taurine. We believe therefore that taurine is important for strengthening PMN host defense capability, although the mechanisms are not yet clear. Moreover, taurine appears to act primarily by altering the PMN osmotic balance, while propofol seems to affect PMN amino acid metabolism and/or uptake and release.