Tilman von Spiegel

Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function.

BackgroundMechanical ventilation with high tidal volumes (VT) in contrast to mechanical ventilation with low VT has been shown to increase plasma levels of proinflammatory and antiinflammatory mediators in patients with acute lung injury. The authors hypothesized that, in patients without previous lung injury, a conventional potentially injurious ventilatory strategy with high VT and zero end-expiratory pressure (ZEEP) will not cause a cytokine release into systemic circulation. MethodsA total of 39 patients with American Society of Anesthesiologists physical status I–II and without signs of systemic infection scheduled for elective surgery with general anesthesia were randomized to receive mechanical ventilation with either (1) VT = 15 ml/kg ideal body weight on ZEEP, (2) VT = 6 ml/kg ideal body weight on ZEEP, or (3) VT = 6 ml/kg ideal body weight on positive end-expiratory pressure of 10 cm H2O. Plasma levels of proinflammatory and antiinflammatory mediators tumor necrosis factor, interleukin (IL)-6, IL-10, and IL-1 receptor antagonist were determined before and 1 h after the initiation of mechanical ventilation. ResultsPlasma levels of all cytokines remained low in all settings. IL-6, tumor necrosis factor, and IL-1 receptor antagonist did not change significantly after 1 h of mechanical ventilation. IL-10 was below the detection limit (10 pg/ml) in 35 of 39 patients. There were no differences between groups. ConclusionsInitiation of mechanical ventilation for 1 h in patients without previous lung injury caused no consistent changes in plasma levels of studied mediators. Mechanical ventilation with high VT on ZEEP did not result in higher cytokine levels compared with lung-protective ventilatory strategies. Previous lunge damage seems to be mandatory to cause an increase in plasma cytokines after 1 h of high VT mechanical ventilation.

Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial.

IntroductionThe development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients.MethodsAll patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to <1 ng/ml or the PCT value was >1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days.ResultsA total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome.ConclusionsMonitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine.AnnotationResults were previously published in German in Anaesthesist 2008; 57: 571–577 (PMID: 18463831).Trial registrationISRCTN10288268

The effects of prone positioning on intraabdominal pressure and cardiovascular and renal function in patients with acute lung injury.

To detect any harmful effects of prone positioning on intraabdominal pressure (IAP) and cardiovascular and renal function, we studied 16 mechanically ventilated patients with acute lung injury randomly in prone and supine positions, without minimizing the restriction of the abdomen. Effective renal blood flow index and glomerular filtration rate index were determined by the paraaminohippurate and inulin clearance techniques. Prone positioning resulted in an increase in IAP from 12 ± 4 to 14 ± 5 mm Hg (P < 0.05), Pao2/fraction of inspired oxygen from 220 ± 91 to 267 ± 82 mm Hg (P < 0.05), cardiac index from 4.1 ± 1.1 to 4.4 ± 0.7 L/min (P < 0.05), mean arterial pressure from 77 ± 10 to 82 ± 11 mm Hg (P < 0.01), and oxygen delivery index from 600 ± 156 to 648 ± 95 mL · min−1 · m−2 (P < 0.05). Renal fraction of cardiac output decreased from 19.1% ± 12.5% to 15.5% ± 8.8% (P < 0.05), and renal vascular resistance index increased from 11762 ± 6554 dynes · s · cm−5 · m2 to 15078 ± 10594 dynes · s · cm−5 · m2 (P < 0.05), whereas effective renal blood flow index, glomerular filtration rate index, filtration fraction, urine volume, fractional sodium excretion, and osmolar and free water clearances remained constant during prone positioning. Prone positioning, when used in patients with acute lung injury, although it is associated with a small increase in IAP, contributes to improved arterial oxygenation and systemic blood flow without affecting renal perfusion and function. Apparently, special support to allow free chest and abdominal movement seems unnecessary when mechanically ventilated, hemodynamically stable patients without abdominal hypertension are proned to improve gas exchange.

The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone.

ObjectiveTo investigate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe sepsis by stimulating with corticotropin-releasing hormone (CRH). DesignProspective observational study in consecutive intensive care unit patients with severe sepsis. SettingSurgical intensive care unit and outpatient department of endocrinology in a university hospital. PatientsThe study included 20 patients with the diagnosis of severe sepsis; six critically ill, nonseptic patients after major surgery; ten patients with primary adrenal insufficiency; ten patients with anterior pituitary insufficiency; and ten individuals without clinical signs of HPA axis disturbance. InterventionsCRH tests were performed with an intravenous bolus injection of 100 &mgr;g of human CRH. Measurements and Main Results We studied the functional integrity of the HPA axis in patients with severe sepsis by performing the CRH test. In addition, during the period of severe sepsis, we repeatedly measured basal plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased significantly in nonsurvivors with severe sepsis (288.8 ± 29.1 [sem] nmol/L) compared with survivors (468.1± 18.6 nmol/L;p < .01). By calculating the ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe sepsis (0.02 ± 0.008) and survivors (0.01 ± 0.002) were significantly lower compared with the index of patients with primary adrenal insufficiency (6.8 ± 1.0;p < .001). In contrast, in nonsurvivors with severe sepsis, the plasma cortisol response to CRH stimulation was impaired compared with survivors: The mean basal cortisol concentration within the CRH test was 269.4 ± 39.8 nmol/L in nonsurvivors compared with 470.8 ± 48.4 nmol/L in survivors and increased to a peak value of 421.6 ± 72.6 nmol/L in nonsurvivors and 680.7 ± 43.8 nmol/L in survivors (p < .02). However, the change in plasma cortisol, expressed as mean ± sem and calculated by subtracting the basal cortisol from the peak cortisol after CRH stimulation, was not significantly different in survivors with severe sepsis (243.5 ± 36.1, range 111.0–524.0 nmol/L, n = 15) compared with nonsurvivors (161.0 ± 38.9, range 42.0–245.0 nmol/L, n = 5;p > .05). ConclusionsWe found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.

Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass.

Background Cardiac surgery with cardiopulmonary bypass is often associated with postoperative hemodynamic instability. In this regard beneficial effects of corticosteroids are known. The purpose of this study was to investigate whether these effects are due mainly to a modification of the intravascular and extravascular volume status or whether a more direct improvement of cardiovascular performance by corticosteroids is the underlying mechanism. Methods Twenty patients undergoing elective coronary bypass grafting were included in this randomized double-blind study. Patients of the treatment group received 1 mg/kg−1 dexamethasone after induction of anesthesia. In addition to the use of standard monitors and detailed fluid balance assessments, the transpulmonary double-indicator technique was used to measure extravascular lung water, total blood volume, and intrathoracic blood volume. Measurements were done after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery. Results After cardiopulmonary bypass, no relevant increase in extravascular lung water was observed, despite highly positive fluid balances in all patients. A significantly smaller increase in extravascular fluid content was observed in the dexamethasone group. Total blood volume and intrathoracic blood volume did not differ in the two groups. Patients pretreated with dexamethasone had a decreased requirement for vasoactive substances and, in contrast with the control group, no increase in pulmonary artery pressure. Conclusions Extravascular fluid but not extravascular lung water is increased in patients after surgery with cardiopulmonary bypass. Pretreatment of adult patients with 1 mg/kg−1 dexamethasone before coronary bypass grafting decreases extravascular fluid gain and seems to improve postoperative cardiovascular performance. This effect is not caused by a better intravascular volume status.

Bedside Assessment of Cerebral Blood Flow by Double-indicator Dilution Technique

Background Currently, quantitative measurement of global cerebral blood flow (CBF) at bedside is not widely performed. The aim of the present study was to evaluate a newly developed method for bedside measurement of CBF based on thermodilution in a clinical setting. Methods The investigation was performed in 14 anesthetized patients before coronary bypass surgery. CBF was altered by hypocapnia, normocapnia, and hypercapnia. CBF was measured simultaneously by the Kety-Schmidt inert-gas technique with argon and a newly developed transcerebral double-indicator dilution technique (TCID). For TCID, bolus injections of ice-cold indocyanine green were performed via a central venous line, and the resulting thermo-dye dilution curves were recorded simultaneously in the aorta and the jugular bulb using combined fiberoptic thermistor catheters. CBF was calculated from the mean transit times of the indicators through the brain. Results Both methods of measurement of CBF indicate a decrease during hypocapnia and an increase during hypercapnia, whereas cerebral metabolic rate remained unchanged. Bias between CBFTCID and CBFargon was −7.1 ± 2.2 (SEM) ml · min−1 · 100 g−1; precision (± 2 · SD of differences) between methods was 26.6 ml · min−1 · 100 g−1. Conclusions In the clinical setting, TCID was feasible and less time-consuming than alternative methods. The authors conclude that TCID is an alternative method to measure global CBF at bedside and offers a new opportunity to monitor cerebral perfusion of patients.

Cardiorespiratory Effects of Automatic Tube Compensation during Airway Pressure Release Ventilation in Patients with Acute Lung Injury

Background Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury. Methods Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Trans-diaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs. Results Automatic tube compensation during APRV increased airway pressure amplitude from 7.7 ± 1.9 to 11.3 ± 3.1 cm H2O (mean ± SD;P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45 ± 27 to 27 ± 15 cm H2O · s−1 · min−1 (P < 0.05), whereas tracheal pressure am-plitude remained essentially unchanged (10.3 ± 3.5 vs. 10.1 ± 3.5 cm H2O). Minute ventilation increased from 10.4 ± 1.6 to 11.4 ± 1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52 ± 9 to 47 ± 6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806 ± 991 to 3,009 ± 994 ml (P < 0.05). Analysis of tracheal pressure–time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator. Conclusion In the studied patients with acute lung injury, automatic tube compensation markedly unloaded the inspiratory muscles and increased alveolar ventilation without compromis-ing cardiorespiratory function and end-expiratory lung volume.

Transpulmonale Indikatorverfahren in der Intensivmedizin

ZusammenfassungDie mittels transpulmonaler Indikatortech- nik gewonnenen Meßwerte erlauben im Gegensatz zum PAK nicht die Berechnung des pulmonalen Gefäßwiderstands und des globalen Sauerstoffverbrauchs, die Messung des pulmonalarteriellen Drucks ist nicht möglich. Vorteile: Die transpulmonalen Indikatorverfahren ergeben jedoch gerade für kritisch kranke Intensivpatienten wertvolle Informationen. Die Thermodilutionsmessung des HZV ist transpulmonal weniger invasiv als die pulmonalarteriell unter Verwendung eines PAK registrierte. Auch können HZV-Messungen bei Kleinkindern (bis hinab zu einem Körpergewicht von etwa 3 kg) vorgenommen werden, für die bisher kein ausreichend zuverlässiges Verfahren zur Verfügung stand. Die bei bekanntem HZV zu berechnenden hämodynamischen Parameter Gefäßwiderstand, Schlagvolumen und globales Sauerstoffangebot sind Voraussetzung für eine rationale Therapie mit positiv inotropen und/oder vasoaktiven Substanzen. Eine individuell angepaßte, optimierte Volumentherapie wird bei den typischen Problempatienten der heutigen Intensivtherapie verstärkt gefordert. Dies gilt gleichermaßen für Patienten mit einer primären kardialen Problematik wie für Patienten mit einer schweren systemischen Entzündungsreaktion (SIRS) oder einem akuten Lungenversagen (ARDS). Die bisher vielfach vorgenommene indirekte Einschätzung der kardialen Füllung durch Messung des ZVD bzw. PCWP zeigt insbesondere bei der Erfassung längerfristiger Veränderungen erhebliche – methodisch und physiologisch zu begründende – Fehlermöglichkeiten. Das ebenfalls durch transpulmonale Thermodilution, genauer aber durch arterielle Farbstoffverdünnungskurven abzuschätzende ITBV ist ein besserer Parameter der kardialen Füllung. Insbesondere unter gleichzeitiger Beachtung des EVLW läßt sich die Volumengabe kritisch monitoren. Der häufig erforderliche Kompromiß zwischen einer ausreichenden regionalen Organperfusion und der Vermeidung eines pulmonalen und intestinalen Ödems ist fundierter möglich als mit bisher zur Verfügung stehenden diagnostischen Verfahren. Die zusätzlich aus der Farbstoffverdünnungskurve zu ermittelnde ICG-Clearance kann als Leberfunktionsparameter hilfreich sein. Ausblick: Entscheidend für die Beurteilung der Wertigkeit auch der transpulmonalen Indikatorverfahren wird es sein, inwieweit es gelingt, in prospektiven, größeren Studien letztlich einen Effekt auf die Inzidenz von Organversagen und Überlebensrate zu zeigen.AbstractThe management of critically ill patients often requires an advanced hemodynamic monitoring. Beside pulmonary artery catheter (PAC) and transesophageal echocardiography (TEE) the transpulmonary indicator dilution technique (TPID) with arterial registra-tion of the indicator dilution curves is a possi-ble approach to get additional hemodynamic information. Being less invasive, measurements of cardiac output by trans-pulmonary thermodilution are as reliable as the thermodilution using a PAC.Transpulmonary thermodilution can be used even in small children. In addition, intrathoracic blood volume (ITBV) and extravascular lung water (EVLW) can be estimated. ITBV seems to be a better surrogate of cardiac filling than central venous pressure and pulmonary capillary wedge pressure. EVLW can be of special value in the fluid-management of patients with systemic inflammatory response syndrom or acute respiratory failure. By using the dye indocyanine green (ICG) as a second indicator TPID can be performed as transpulmonary double indicator dilution technique. The resulting thermodilution and dye curves are measured with a combined fiberoptic-thermistor catheter. This allows the more accurate measurement of ITBV and EVLW and in addition the assessment of total circulating blood volume and ICG-clearance. ICG-clearance serves clinically as a rapidly reacting indirect measure of liver function. As with the other methods of advanced hemodynamic monitoring the data available at present do not show a positive effect on the incidence of organ failure and mortality by monitoring critically ill patients with TPID. Before applying an advanced hemodynamic monitoring it should be asked critically which parameter is needed for the therapy-management of the individual patient. Based on this a differenciated monitoring decision has to be made.

STUDIES ON LOW PROTEIN C-EXPRESSION IN SEVERE SEPSIS: 527

OBJECTIVES Low concentration of protein C in severe sepsis may be associated with increased morbidity and mortality. The present study was designed to clarify to what extent there are differences in the time course of plasma concentrations of protein C in patients with systemic inflammatory response syndrome or patients with severe sepsis. In addition, the cause of decreased expression of protein C in severe sepsis was examined. METHODS 32 patients with severe sepsis and 10 patients with systemic inflammatory response syndrome admitted to a surgical intensive care unit were enrolled in the study. While the patients stayed in the intensive care unit protein C plasma concentrations and the clotting factors thrombin-antithrombin-complex and factor VII were determined twice weekly. RESULTS Comparing patients with severe sepsis and systemic inflammatory response syndrome there was no significant difference concerning plasma levels of protein C, thrombin-antithrombin-complex and factor VII. In contrast, surviving patients with severe sepsis exhibited significant higher protein C levels compared to non-survivors. In addition, significant lower plasma levels of thrombin-antithrombin-complex were determined in survivors compared to non-survivors. However, factor VII displayed no significant group difference. CONCLUSIONS Surviving patients with severe sepsis exhibited higher plasma concentrations of protein C than patients who died during severe sepsis. The lower plasma concentrations of protein C in non-survivors may be caused by an increased turnover of protein C served as endogenous anticoagulant in sepsis associated activation of coagulation.