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Background: Clinical studies such as VISEP-study, which show a negative outcome after the administration of hydroxyethyl starch (HES), are often criticized for an "incorrect" use of HES. It is argued that HES used in these studies differed from usual practice and that recommendations for maximal dosage, duration, and creatinine values were ignored, not enough "free water" was provided and more modern HES solutions should have been used. These comments imply that renal adverse events in clinical studies are the consequence of an inappropriate use of HES. We therefore searched for evidence whether these suggested measures are beneficial., Methods: Narrative review; post hoc statistical analysis of epidemiologic data from a representative nationwide survey., Results: It is evident from published clinical studies that the renal risk of HES increases with cumulative dose and rising serum creatinine values, but no safe upper dose limit or creatinine threshold is known. Suggested safety measures were not able to prevent HES-induced renal failure in clinical studies. Published clinical trials with modern HES solutions are not suited to prove its assumed increased safety because of small sample sizes, low cumulative doses, short observation periods, and inadequate control fluids. Use of HES in a clinical study with negative outcomes conformed to clinical practice, indicating the generalizability of study results., Conclusion: There is no evidence for the assumption that HES-associated renal impairment may be avoided by accompanying measures. Because HES use does not improve clinical outcome, the question arises whether it should be used at all in patients at risk.

Inhalation of perfluorohexane vapor (PFH) and high-frequency oscillatory ventilation (HFOV) both have been shown to improve lung function in acute lung injury (ALI). Their combination implies synergistic action. The authors investigated technical aspects of PFH vaporization during HFOV and effects on gas exchange in a pilot study of experimental ALI. Eighteen anesthetized sheep were randomly assigned to HFOV or HFOV with PFH inhalation after oleic acid-induced ALI. HFOV was set to a continuous distending pressure of 25 cm H₂O, and an oscillation of 80 to 100 cm H₂O at a frequency of 5 Hz. PFH vapor was delivered by means of bypassed high-flow oxygen through a thin endotracheal tube. PFH concentration was measured by infrared absorption. Blood gases and hemodynamic data were taken. PaO₂ significantly increased from 9.1 ± 0.9 to 32.7 ± 9.5 kPa (mean ± SEM) in the HFOV group and from 12.5 ± 1.1 to 27.0 ± 6.8 kPa in the HFOV PFH group. PaCO₂ significantly decreased from 6.3 ± 0.3 to 5.5 ± 0.5 kPa in the HFOV group and from 5.7 ± 0.4 to 4.9 ± 0.5 kPa in the HFOV PFH group. Changes in gas exchange were not different between groups. These results show that the inhalation of PFH during HFOV is technically feasible, but did not enhance gas exchange in a 210-minute observation period of experimental ALI.

Background: Structures in intensive care medicine comprise human as well as material resources, organization, and management and may be related to processes thereby affecting patients' outcomes. Utilizing a unique data base we evaluated structures of German intensive care units (ICUs)., Methods: The study was carried out by the German Competence Network Sepsis (SepNet). Data were prospectively collected on a cross-sectional basis in a representative random sample of German hospitals utilizing a questionnaire. Structures were related to ICU outcome of patients with severe sepsis or septic shock. The sample was subdivided in 5 strata according to hospital size., Results: A total of 454 ICUs cared for 3877 patients including 415 patients (11%) with severe sepsis or septic shock. The mean number of beds per ICU was 10.4, the ratio of ICU to hospital beds 1:27, both with significant differences depending on hospital size. 81% of the ICUs provided around the clock physician presence (range: 66-98% across hospital strata, p < 0.001). Shift-wise, one nurse was responsible for a mean number of 2.7 patients (morning 1:2.3, afternoon 1:2.6, night 1:3.3 patients) with significant variation according to hospital size (smaller hospitals 1:2.9, university hospitals 1:2.1, p < 0.001). More than half of all German ICUs are lead by anesthesiologists. Neither physician nor nurse staffing was associated with mortality in the subset of patients with sepsis., Conclusions: In a representative, nationwide sample of German ICUs key elements of structures varied considerably with respect to hospital size. This has to be considered when proposing standards, reimbursement strategies, or quality assessment.

Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1(st) revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the "German Instrument for Methodological Guideline Appraisal" of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Using small animal PET with (68)Ga-radiolabeled human albumin microspheres (Ga-68-microspheres), we investigated the effect of posture on regional pulmonary blood flow (PBF) in normal rats. This in vivo method is noninvasive and quantitative, and it allows for repeated longitudinal measurements. The purpose of the experiment was to quantify spatial differences in PBF in small animals in different postures. Two studies were performed in anesthetized, spontaneously breathing Wistar rats. Study 1 was designed to determine PBF in the prone and supine positions. Ga-68-microspheres were given to five prone and eight supine animals. We found that PBF increased in dorsal regions of supine animals (0.75) more than in prone animals (0.70; P = 0.037), according to a steeper vertical gradient of flow in supine than in prone animals. No differences in spatial heterogeneity were detected. Study 2 was designed to determine the effects of tissue distribution on PBF measurements. Because microspheres remained fixed in the lung, PET was performed on animals in the position in which they received Ga-68-microsphere injections and thereafter in the opposite posture. The distribution of PBF showed a preference for dorsal regions in both positions, but the distribution was dependent on the position during administration of the microspheres. We conclude that PET using Ga-68-microspheres can detect and quantify regional PBF in animals as small as the rat. PBF distributions differed between the prone and supine postures and were influenced by the distribution of lung tissue within the thorax.

In 2003 an anonymous reporting system for critical incidents was implemented in the Department of Anaesthesiology and Intensive Care Medicine of the University Hospital Dresden. This reporting system was modified to an intranet-based version and extended to the intensive care unit (ICU). During the first 18 months 70 anonymous reports originating from the ICU were registered. The most common errors involved fluid management, followed by errors in airway management, cardio-vascular management, neurological problems and errors in drug administration. The main causes were lack of attention, missing check of measures, work load of nurses, experience and communication deficits. The article discusses the incidence of errors in the ICU setting and their potential effects.

Background: The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids., Methods: In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points., Results: The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate., Conclusions: The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.), (2008 Massachusetts Medical Society)

In severe sepsis and septic shock the severe impairment of the microcirculation is one of the main reasons for tissue hypoxia, multiple organ failure and death. Fast resuscitation of the microvascular blood flow to improve the reduced functional capillary density is necessary. Based scientific evidence, an early haemodynamic stabilisation directed by predefined haemodynamic and metabolic goals and the application of activated protein C (rhAPC) according to the guidelines could be recommended. The specific effects of dobutamine and rhAPC on the microcirculation as well as the effects selective inhibitors of iNOS or vasodilators may be therapeutic options in the future.

In critically ill patients fever is associated with an increased morbidity and mortality rate. However, it remains unclear whether fever is an associated symptom of the underlying severe disease or a stimulator of specific pathophysiological cascades considered responsible for a deleterious outcome. Hyperthermia per se induces systemic changes like increased energy and oxygen demands, tachycardia, or fluid loss which might be harmful especially in septic patients due to congestion of the cardiovascular system. In this constellation a reduction of fever by antipyretic strategies might be indicated to decrease oxygen and energy demands. On the other hand the increasing body temperature obviously plays an important role in the inflammatory hemostasis during infections. Fever optimises humoral and cellular responses to infection and has some direct effects on bacteria and other microorganisms. Therefore, in severe sepsis or septic shock, fever reduction might impair the immune competency of the patients. According to the currently available evidence a body temperature higher than 40 degrees C is definitely harmful and should be treated in any case. A temperature range between 36 degrees C and 39 degrees C should be achieved for patients with severe sepsis and septic shock. At present there are no data showing the superiority of any of the different antipyrectic strategies in septic patients. Hence, external cooling with cold blankets or other devices may induce shivering of the muscles with a substantial increase of oxygen demand and is hardly tolerated in conscious patients. However, antipyretic therapy in patients with severe sepsis or septic shock should be indicated while considering the individual pathophysiology of every patient.

Objective: To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size., Design: Prospective, observational, cross-sectional 1-day point-prevalence study., Setting: 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003)., Patients: Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay., Measurements and Results: Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9-13.8%) for sepsis and 11.0% (95% CI, 9.7-12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (

Osmotherapy, i.e. the intravenous administration of hyperosmolar solutions, is one of the mainstays of therapy for reduction of a pathologically increased intracranial pressure, in addition to analgosedation and raising the upper body of the patient. The administration of mannitol as a osmotherapeutic agent is, however, marred by considerable side-effects. A possible alternative is the use of hypertonic saline solution (NaCl). The advantages and disadvantages of this option are considered as well as points still in question.

The severe impairment of the microcirculation plays a substantial role in the pathogenesis of severe sepsis and septic shock, and leads to multiple organ failure and death. Therapeutic strategies to resuscitate the microcirculatory blood flow and to improve the functional capillar density are therefore essential to surmount the microcirculatory pathology and to avoid tissue hypoxia. Based on reasonable scientific evidence, early fluid resuscitation directed by defined haemodynamic and metabolic goals (EGDT) as well as the application of activated protein C (rhAPC) according to the guidelines could be recommended. Dobutamine is the first choice to improve cardiac output and to overcome myocardial depression in septic shock whereas phosphodiesterase-III-inhibitors and levosimendane are still experimental options. Furthermore selective inhibitors of iNOS, nitroglycerol, as well as vasopressin have to be investigated relating to their specific effects on the microcirculation and their influence on survival in seevere sepsis and septic shock.

Objectives: To improve the cross-correlation method for noninvasive, continuous monitoring of cerebral autoregulation, to evaluate this method in humans with intact and impaired autoregulatory capacity, and to compare it to the cuff deflation test., Design and Setting: Prospective study in the intensive care unit of a university hospital., Patients and Participants: Fourteen patients with severe head injury, six patients with subarachnoid hemorrhage, and nine healthy volunteers., Interventions and Measurements: Middle cerebral artery flow velocities and arterial blood pressure were monitored continuously. Aaslid's thigh cuff tests were performed and results were scored using Tiecks' model for autoregulation index. Data were then collected without any patient manipulation. The mean time delay between slow spontaneous oscillations of blood pressure and middle cerebral artery flow velocity was calculated by cross-correlation analysis. Data are expressed as median (lower/upper quartile)., Results: Healthy subjects had a higher autoregulation index than patients, 5.0 (5.0/5.5) vs. 3.3 (2.0/4.5). Slow oscillations of blood pressure and middle cerebral artery flow velocity showed a time delay of -2.0 s (-2.7/-1.7) in healthy subjects but were almost synchronal in patients, -0.07 s (-0.5/0.45). Inter-method agreement in diagnosing an intact or impaired cerebral autoregulation was obtained in 108 of 147 examinations of autoregulation (73.5%) and was considered moderate., Conclusions: Cross-correlation analysis may serve as a simple, noninvasive, and continuous measure of cerebral autoregulation. The time delay of -2.0[Symbol: see text]s in healthy subjects is in good agreement with other studies. Short-term autoregulation tests and monitoring techniques based on slow spontaneous oscillations should not be used interchangeably.

A recent survey conducted by the publicly funded Competence Network Sepsis (Sep- Net) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approx. 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approx. 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organisation of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to according to the requirements of the Working Group of Scientific Medical Societies (AWMF).

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approximately 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approximately 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organization of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to the requirements of the Working Group of Scientific Medical Societies (AWMF).

Toxic epidermal necrolysis (TEN) is the maximal variant of severe bullous drug reactions with a high mortality rate of 30-40%. Treatment should be interdisciplinary and is best provided in an intensive care setting. Since no specific therapy has been established, supportive intensive care and topical treatment are of crucial importance. Between 1995 and 2005, nine patients with TEN were treated in the anesthesiology intensive care unit in cooperation with dermatology in the University Hospital of Dresden. All patients initially received corticosteroids and five patients were additionally treated with intravenous immunoglobulins (IVIG). The overall mortality of 33% was underestimated by the SAPS II-Score, whereas it was overestimated by the TEN-specific SCORTEN. In more severely affected patients, other scoring systems in addition to SCORTEN should be used for prediction of prognosis and evaluation of therapy. The mortality rate of our IVIG treated patients was 20% vs. 50% compared to the non-IVIG-group. However, due to the small number of patients and contradictory results in the literature, IVIG cannot be generally recommended for the treatment of TEN, but should be considered in early stages of the disease.

Background: As of October 1, 2003, a new government-initiated legislative basis for undergraduate medical education was initiated in Germany which resulted in substantial changes to the structure of the medical curriculum and in a heightened teaching load., Methods: The Medical Faculty of the University of Dresden established an interdisciplinary reform curriculum in 1998. Since then a hybrid model of traditional lectures, seminars, practical and problem-based learning courses has been implemented for all courses in undergraduate medical training (Dresdener Integrated Problem-based Learning: DIPOL)., Results: Examplarly for all other DIPOL courses, the 2003 evaluation results of the "Emergency medicine-Injuries-Intensive care medicine" are presented and show that the course was very well received by students and tutors, and that 95% of the students passed the exams., Conclusions: The DIPOL anesthesiology course conforms with the new German federal law. A continuous further evaluation is an essential part of quality control and is necessary for the further development of a new curriculum.

Introduction: The application of perfluorohexane (PFH) vapor led to an improvement of oxygenation and mechanical lung function in a model of oleic acid-induced ARDS in sheep. The aim of this study was to investigate the effects of PFH on gas exchange over an extended time period and to reduce the invasiveness of ventilation., Method: ARDS was induced in sheep ( n=12) by injecting 0.1 ml/kg body weight oleic acid intravenously. Six sheep were treated for 30 min with 18 vol.% PFH (PFH-Tx) and followed up over a time period of 240 min while untreated sheep ( n=6) served as controls. Subsequently the F(I)O(2) was reduced to generate a p(a)O(2) between 100-140 mmHg. Gas exchange, respiratory and hemodynamic data were collected at regular intervals. Data were analysed using covariance analysis., Results: PFH treatment led to an improvement in oxygenation ( p<0.01) and in mechanical lung function ( p<0.01). Furthermore, mean pulmonary artery pressure ( p<0.01) and shunt ( p<0.01) were lower in PFH-Tx. F(I)O(2) could be reduced in all PFH-treated animals ( p<0.01)., Conclusion: Treatment of oleic acid-induced lung injury with PFH vapor improved oxygenation and mechanical lung function over a extended time period allowing a reduction in the invasiveness of ventilation.

Unlabelled: Hypertriglyceridemia is a possible unwanted effect during long-term propofol sedation while using a formulation containing long-chain triglycerides (LCT) from soybean oil. The use of propofol formulated in a solvent consisting of medium-chain triglycerides (MCT) and LCT might reduce the risk. Because a new solvent may affect the pharmacological profile of propofol, in this prospective, randomized, controlled, and double-blinded study we compared the pharmacodynamic and kinetic characteristics of propofol diluted in MCT/LCT fat solution with those of propofol formulated in LCT fat emulsion. In addition, serum triglyceride levels were measured during and after the administration of both drugs. Thirty patients likely to require mechanical ventilation over at least 48 h were randomized to receive either propofol 2% MCT/LCT (Group 1) or propofol 2% LCT (Group 2). Infusion rates of propofol (2.34 +/- 0.83 mg. kg(-1). h(-1) in Group 1 versus 2.31 +/- 0.6 mg. kg(-1). h(-1) in Group 2), the plasma propofol concentrations during infusion (0.95 +/- 0.53 versus 0.98 +/- 0.32 micro g/mL), and the concentrations and arousal behavior after discontinuation of the drug did not show significant differences. Plasma triglyceride concentrations during sedation did not differ between the groups, whereas there was a tendency toward a more rapid triglyceride elimination in Group 1 after termination of the propofol administration., Implications: Propofol diluted in an emulsion of medium- and long chain-triglycerides shows equivalent pharmacological properties during long-term sedation compared with its hitherto well known formulation containing long-chain triglycerides only. In addition, potential favorable effects on the plasma triglyceride profile could be found.

Objective: To investigate a possible time-dependent effect of propofol sedation on electroencephalographic activity, we analyzed the electroencephalogram frequency behavior while keeping patients at a constant level of sedation., Design: Prospective, controlled trial., Setting: Intensive care unit of a university hospital., Patients: Twenty patients without neurologic or metabolic disorders., Measurements and Main Results: During sedation with propofol (1-4 mg x kg(-1) x hr(-1)), a bifrontally recorded processed electroencephalogram was obtained. For 48 hrs, sedation was kept constant at a level according to Ramsay Scale 3 while we adjusted the dosage of propofol given per hour. At hours 6, 18, 30, and 42, blood samples were taken to assess the plasma concentration of propofol. The electroencephalogram values of 60 mins obtained during 1 hr before blood sampling were taken for further calculation. From the data, relative band power of the beta-, alpha-, theta, and delta-bands, spectral median frequency, and spectral edge frequency 90 and 95 were computed. For statistical analysis, a polynomial three-factorial repeated-measures analysis of variance with covariates was performed. Relative power of beta- and alpha-wavebands showed a constant and significant decrease over time (beta, 15.5%, 10.3%, 10.3%, 7.6%; alpha, 14.8%, 13.4%, 10.0%, 8.3%), whereas relative delta power increased (delta, 56.4%, 63.4%, 70.7%, 72.3%). The theta-waveband remained unchanged. Accordingly, spectral edge frequency 90 and 95 and spectral median frequency decreased significantly. From hours 6 to 18, a significant increase of the plasma propofol concentration was found. Subsequently, the level remained constant., Conclusion: Despite constant sedation, a longer period of propofol application induces a time-dependent electroencephalogram frequency deceleration. The use of electroencephalogram derivatives to monitor depth of sedation in the intensive care unit thus should be regarded cautiously.

Objectives: To investigate the changes in pulmonary function and gas exchange during application of 18% perfluorohexane vapor in healthy and in oleic acid-injured animals and compare it with an injured control group., Design: Prospective randomized controlled study., Setting: Experimental research laboratory at a university medical center., Subjects: Nineteen sheep weighing 31.4 +/- 4.1 kg., Interventions: Lung injury was induced in 14 sheep by the intravenous injection of 0.1 mL/kg oleic acid. After establishment of lung injury (PaO(2)/F(IO(2)) ratio, <200; pulmonary artery occlusion pressure, <19 torr), seven animals were treated with 18% perfluorohexane vapor for 30 mins whereas seven animals served as controls. After the start of perfluorohexane treatment, blood gases and respiratory and hemodynamic data were collected in 10-min intervals throughout the study period of 1 hr. In addition, five healthy animals received perfluorohexane vapor for 30 mins and were followed up for 2 hrs to exclude delayed negative effects., Measurements and Main Results: Treatment of healthy animals with 18% perfluorohexane vapor was not accompanied by any significant adverse effects. It was associated with a significant decrease of alveolar-arterial oxygen difference during perfluorohexane application (p <.05). In injured animals, 18% perfluorohexane led to a sustained improvement of peak inspiratory pressures within 10 mins of treatment (p <.001). The concomitant increase in compliance was equally significant (p <.001). Significant improvements in PaO(2) occurred despite a decrease in F(IO(2)) to 0.81 at the end of vaporization., Conclusion: Healthy animals tolerated perfluorohexane vapor well without significant changes in oxygenation and mechanical lung function for 2 hrs. In injured animals, application of perfluorohexane vapor primarily improved peak inspiratory pressure and compliance. The increase of oxygenation therefore could be secondary to an improvement in compliance.

Intracerebral hemorrhage in leptospirosis is a rare event. We report on a fatal case of intracerebral hemorrhage complicating leptospirosis in a 47-year-old sewage drain worker. Since substantial thrombocytopenia was observed during the course of the disease, postmortem autopsy was performed to further elucidate the genesis of platelet destruction. Due to immunohistological findings, immunologically mediated thrombolysis was considered responsible for thrombocytopenia, whereas no signs of disseminated intravasal coagulopathy or deranged platelet production in the bone marrow were detected.

Objectives: To evaluate the performance of a new device for noninvasive measurement of nonshunted pulmonary capillary blood flow (PCBF) by partial CO2 rebreathing., Design and Setting: Prospective clinical trial in an intensive care unit of a university hospital., Patients and Participants: Twenty mechanically ventilated patients with acute lung injury., Interventions: Variations in PEEP of +/-3 cmH2O., Measurements and Results: Initially PCBF was measured invasively as cardiac output minus venous admixture (Q(VA)/Q(t)) flow, and by partial CO2 rebreathing at baseline PEEP (PEEP(b)). The PEEP was then reduced by 3 cmH2O (to PEEP(b-3)) and measurements were repeated after 30 min. PEEP was then increased by 6 cmH2O (to PEEP(b+3)), and measurements were repeated after 10, 20, and 30 min. The overall correlation coefficient between noninvasive and invasive PCBF measurements at PEEP(b) was high ( r=0.97), with close agreement between methods being observed (0.1+/-0.6 l/min, bias and precision, respectively). Accordingly, both the correlation coefficient and agreement between methods for changes in PCBF from PEEP(b-3) to PEEP(b+3) levels were satisfactory ( r=0.71; 0.2+/-0.5 l/min, bias and precision). The new device was able to detect the correct PCBF trend in 17 of 20 patients investigated and in all patients who showed invasive PCBF changes equal to or greater than 0.3 l/min ( n=12). Noninvasive PCBF changes were stable as early as 10 min after variation in PEEP, as compared to 30 min values., Conclusions: The new device appears to be clinically useful for the monitoring of PCBF in patients suffering from acute lung injury. Our results suggest that titration of PEEP aimed at improving PCBF can be performed with the new device.

Objective: To evaluate the effects of PFC aerosol compared to PGI2 aerosol and NaCl aerosol on gas exchange and lung mechanics in oleic acid-induced acute lung injury., Design: A prospective, controlled, randomised, in vivo animal laboratory study., Setting: Research laboratory at an university hospital., Subjects: Twenty one (n = 21) adult sheep of either gender weighing 26.8+/-6.4 kg., Interventions: The animals were randomised to three groups: PFC aerosol (perfluorooctane), PFC group; prostacyclin aerosol (Flolan), PGI2 group; and NaCl aerosol (0.9% sodium chloride solution), control group. After induction of anaesthesia and placement of vascular catheters, lung injury was induced with 0.12 ml x kg(-1) oleic acid. Aerosols were continuously administered for 2 h using a jet nebuliser. Gas exchange, pulmonary mechanic, and haemodynamic parameters were obtained at regular intervals., Measurements and Main Results: PFC aerosol increased oxygenation (PaO2) 15 min after the initiation of treatment up to 120 min (P < 0.05). Transpulmonary shunt improved in the PFC group (P < 0.05) while it did not change in the two other groups. PFC aerosol reduced maximum airway pressure (Pmax) (median) significantly from (median) 38 mbar to 32 mbar (P < 0.05). Static compliance improved significantly in the PFC group (P < 0.05)., Conclusion: The inhalation of a PFC aerosol led to a significant improvement in pulmonary mechanics and gas exchange, which was not observed in the other two groups. These data suggest that a small dose of perfluorocarbon will have beneficial effects on gas exchange and respiratory mechanics. Therefore, the non-invasive aerosol application technique seems to be a reasonable alternative to administer perfluorocarbons in severe lung injury.

Sepsis and systemic inflammatory response syndrome-induced severe disruption of microcirculation and consecutive tissue hypoxia is considered a key factor in the development of organ dysfunction and multiple organ failure. The conventionally measured global variables such as lactate or macrohemodynamic parameters using a pulmonary artery catheter do not adequately mirror microcirculatory disturbances. Evaluation of the severity of microcirculatory distress and the effectiveness of resuscitation strategies requires new clinical technologies aimed at the microcirculation. It is anticipated that novel techniques such as optical spectroscopy and intelligent biosensors will play a major role in the development of new monitoring systems. In general, the current monitoring of organ dysfunction is characterized by a trend from invasive to noninvasive and "safe" techniques, which provide bedside or even on-line monitoring and allow a more precise and earlier detection of organ dysfunction. Techniques for the assessment of regional perfusion and microcirculatory bioenergetics to direct therapeutic procedures are expected to refine and optimize clinical treatment of critically ill patients in the future. This article addresses the question of which variables should be monitored, what is feasible, and what is valid for therapeutic consequences. Recent developments in monitoring of macro- and microcirculation and organ-specific dysfunction, e.g., lung, kidney, are described with respect to their advantages and limitations, and future directions are outlined.

Maintenance and restoration of intravascular volume are essential tasks of critical care management to achieve sufficient organ function and to avoid multiple organ failure in critically ill patients. Inadequate intravascular volume followed by impaired renal perfusion is the predominate cause of acute renal failure. Crystalloid solutions are the first choice to correct fluid and electrolyte deficits in these patients. However, in case of major hypovolemia, particularly in situations of increased capillary permeability, colloid solutions are indicated to achieve sufficient tissue perfusion. Whereas albumin should be avoided for correction of intravascular hypovolemia, synthetic colloids can restore intravascular volume and stabilize hemodynamic conditions. In addition to a faster, more effective and prolonged restoration of intravascular volume, colloid solutions are able to improve microcirculation. Of the synthetic colloids, hydroxyethyl starch (HES) solutions with a low in vivo molecular weight, such as HES 200/0.5, offer the best risk/benefit ratio. These solutions are safe with respect to effects on coagulation, platelets, reticuloendothelial system, and renal function, if used below their upper dosage limits. For patients with acute renal dysfunction, daily monitoring of renal function is necessary if colloids are required to stabilize hemodynamic conditions. In these patients, measurement of the colloidal osmotic pressure and adequate amounts of crystalloid solutions will reduce the risk of hyperoncotic renal failure. Of all colloids, gelatin and HES solutions with low in vivo molecular weight are preferred in these cases. In the very specific situation of kidney transplantation, colloid solutions should be administered in a restricted manner to organ donors and kidney recipients.

Background: Despite knowledge about compromised host defence in the course of diabetes mellitus and pancreatitis, epidural analgesia (EA) is recommended for pain management during pancreatitis., Case Report: We present the case of a diabetic patient with pancreatitis who developed an epidural abscess after 3 days with an epidural catheter. Natural killer and T-helper cell counts were distinctively reduced in the absence of HIV serology. Furthermore, a synthesis failure of the liver was observed and evidenced by low cholinesterase, low whole protein fraction and low antithrombin III in the peripheral blood., Conclusion: We suggest that the combination of pancreatitis, diabetes and compromised immunity might be a contraindication to epidural analgesia.

Fluid resuscitation with hypertonic hydroxyethyl starch solutions (HES) is effective in haemorrhagic shock due to the rapid mobilisation of fluids into the intravascular compartment. Declamping of the abdominal aorta with acute redistribution of blood into the vessels of the lower body half causes declamping-induced hypotension. Usually large amount of fluids or vasopressors are necessary to restore hemodynamic stability. Therefore, infusion of a hypertonic colloid solution may be an attractive option to achieve hemodynamic stability. This study was conducted to determine the amount of fluid of either hypertonic HES (HES 6%;7.2% NaCl) or isotonic HES (HES 6%;0.9% NaCl) needed to attain best wedge pressure (PCWP) cardiac index (CI) relation after declamping. Thirty-two high-risk patients undergoing elective abdominal aneurysm resection were enrolled in a prospective, randomised, double blinded study. The individual optimised PCWP/CI relation was determined after induction of anaesthesia. After declamping, both solutions were titrated in small boluses of 100 mL until the previously determined best wedge was reached. The amount of fluid after declamping was significantly reduced in the hypertonic HES- group 162 mL vs. 265 mL in the control group (P < 0.05). Resuscitation time was shortened, and cardiac index was slightly higher in the treatment group. The use of hypertonic HES-solution after aortic declamping led to a significant reduction of fluids necessary to attain optimised PCWP/CI relation. In this clinical trial with moderate blood loss in high-risk patients, hypertonic HES applied in a titrated fashion restored hemodynamic stability faster and without volume overload.

The introduction of Perfluorochemicals into medicine and especially into the treatment of severe lung injury is a fascinating scientific task. Many recall the famous experiments from Clark et al. in 1966 when he demonstrated "liquidventilation with perfluorocarbons" in the mammal species for the first time. After this hallmark, perfluorocarbons were subsequently introduced in research of acute lung injury by the techniques of Total- and Partial-Liquid-Ventilation (TLV; PLV). Perfluorocarbons (saturated organofluorids) have unique chemical and physical properties which made them attractive substances for intraalveolar application. The strong C-F bindings in the perfluorocarbon molecules are responsible for their chemical stability, biochemical inertness, high capacity to dissolve respiratory gases, low surface tension and high vapor pressures. Furthermore, the high density of the PFC lead to radio-opacity and their distribution to dependent lung areas. The efficacy of PFC liquid, applied by TLV/PLV has been demonstrated in numerous animal studies using different models of acute lung injury. Currently, several mechanisms of action of perfluorocarbon fluids in acute lung injury are discussed: recruitment of atelectatic alveoli, prevention of endexpiratory collapse of alveoli ("liquid PEEP"), redistribution of perfusion, oxygen transport, surfactant like effects and decrease of inflammation. Since total liquid ventilation has been used only in experimental models of lung injury, partial liquid ventilation has been introduced successfully into clinical trials (phase I-II). However, the results of the first randomised, controlled study of PLV in 90 adult patients suffering from severe respiratory failure (ALI/ARDS) showed no differences between PLV and conventional treatment. Furthermore, the instillation of relatively large amounts of liquid into the lungs poses several technical challenges and may be associated with complications such as liquithoraces, pneumothoraces and hypoxia. Since mammal lungs are evolutionary specialised to gas exchange using atmospheric oxygen, the application of liquids, even if they transport respiratory gases very well is not physiologic. To overcome these unwanted side effects, we developed a technique of perfluorocarbon vaporisation in analogy to the application of inhalation anaesthetic agents. After resolving some technical issues, this application technique was used successfully in an animal model of acute lung injury. Vaporisation of perfluorohexane in a concentration of 18 Vol.% of inspired gas improved significantly oxygenation and lung compliance. Though these results are promising, mechanisms of action, dose-efficacy relation, surfactant-perfluorocarbon interaction or anti-inflammatory effects of vaporised perfluorohexane are still unclear. These questions need to be clarified before this technique can be applied clinically. However, the inhalation of vapor, a technique already familiar to anaesthesiologists should avoid risks of large amounts of fluids in the bronchoalveolar space. Furthermore, this technique can be administered by established anaesthetic equipment with the advantage of exact dosing, continuous monitoring, and demand application in a way near to clinical routine.

Background: Perfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid-induced lung injury., Methods: Two vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals., Results: Vaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376+/-182 mmHg (mean +/- SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward., Conclusion: Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury.

Unlabelled: The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured., Results: In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP., Conclusion: The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.

The use of artificial organs in cases of acute renal failure, acute respiratory distress syndrome (ARDS) and multiorgan dysfunction syndrome (MODS) has lead to a significant reduction of mortality. However, the interaction between body and biomaterials results in the activation of the coagulation system and in the induction of systemic inflammatory response syndrome. The necessary anticoagulation may be contraindicated and may even further increase the risk for the patient. This article evaluates the currently applied polymeric materials used in intensive care units (ICU) and gives a possible outlook into future developments. It is emphasized that systematic interdisciplinary research of physicians and biomaterial scientists is essential for the successful development of new polymers with improved biocompatibility. For this purpose a brief overview of analytical techniques for surface characterization is given, and future developments to a fully biocompatible polymer are described.

Objective: To determine the validity and clinical utility of the partial CO2 rebreathing technique for measurement of nonshunted pulmonary capillary blood flow and cardiac output., Design: Prospective, controlled animal laboratory investigation and clinical trial., Settings: Animal research facility and intensive care unit of a university hospital., Subjects: Fifteen adult sheep, weighting 58 to 78 kg., Patients: Mechanically ventilated patients with different underlying diseases (n = 12) and with adult respiratory distress syndrome (ARDS) (n = 8)., Interventions: CO2 elimination rate (VCO2) was measured breath-by-breath with a system developed for the study and also by gas collection (validation procedure in patients with different underlying diseases). Partial CO2 rebreathing maneuvers, cardiac output by thermodilution, and blood gas analysis were performed in sheep with lung atelectasis and in patients with ARDS., Measurements and Main Results: The degree of correlation between VCO2 measured with the system developed and gas collection was very good (r2 = .95, p < .0001), and bias and precision calculations (1 +/- 9 mL/min) showed close agreement between methods. The overall degree of correlation between partial CO2 rebreathing measurements and cardiac output was moderate (r2 = .54, p < .0001), the noninvasive method tending to underestimate cardiac output, as shown by bias and precision calculations (-1.69 +/- 1.90 L/min). In contrast, the overall degree of correlation between partial CO2 rebreathing measurements and nonshunted pulmonary capillary blood flow was good (r2 = .73, p < .0001). Bias and precision calculations (0.25 +/- 0.83 L/min) showed a tendency for the partial CO2 rebreathing technique to slightly overestimate pulmonary capillary blood flow. Variance differences between partial CO2 rebreathing measurements and cardiac output could be mostly explained by intrapulmonary right-to-left shunt fraction (r2 = .51, p < .0001)., Conclusions: Our results support the use of the system developed for breath-by-breath VCO2 measurements. The lack of agreement between partial CO2 rebreathing measurements and cardiac output was mostly explained by intrapulmonary right-to-left shunt, suggesting that this technique may not be appropriate for monitoring cardiac output in patients with increased venous admixture. In contrast, our results demonstrate that the partial CO2 rebreathing technique is reliable for measurement of the effective nonshunted pulmonary capillary blood flow. This technique may prove useful to guide ventilatory therapy adjustments in an attempt to optimize nonshunted pulmonary capillary blood flow.

Myxedema coma is characterized by severe lack of thyroid hormones, unconsciousness and serious restriction of vital functions. The mortality rate still ranges between 50 and 80%. In patients with inapparent hypothyroidism myxedema coma occasionally follows surgery, anesthesia or severe infection. A case of myxedema coma following surgery is reported. CASE REPORT. A 46-year-old woman was anesthesized for hip replacement. The intraoperative cardiovascular situation was characterized by hypotension and tachycardia. On the first postoperative day, unexpectedly a cardiac arrest occurred. Resuscitation with high doses of epinephrine was successful. There was no evidence of myocardial infarction, hypoxia and pulmonary embolism as causative factors for cardiac arrest. A pulmonary artery catheter was inserted and showed low cardiac output. Catecholamines and intravascular fluids were administered without hemodynamic improvement. In the next 5 days pneumonia was followed by ARDS and acute renal failure. After successful treatment of these complications the patient remained in deep coma. An intracerebral disease could be excluded by computerized tomography. Evaluation showed low thyroid hormones (T3; T4) and elevated TSH. The diagnosis of a myxedema coma was assumed. After failure of oral therapy with L-thyroxine (0.025-0.05 mg/day) for 10 days, intravenous therapy with 0.5 mg L-thyroxine was performed. Thirty-six hours later the patient regained consciousness, without cardiac complications. The patient progressed uneventfully under oral therapy with 0.1 mg L-thyroxine and was discharged from the hospital 6 weeks later. DISCUSSION. Pathophysiology and symptomatology of a case of postoperative myxedema coma are described (Tables 1-4). In this patient, the following symptoms occurred: low thyroid hormones (T3; T4), elevated TSH, deep coma, decreased ventilatory response to CO2, diminished myocardial contractility under catecholamine stimulation, impaired renal water excretion. After failure of oral substitution of L-thyroxine, intravenous therapy had to be performed in spite of the high risk of further cardiac complications in this patient. This led to complete recovery with normal neuropsychological and cardiopulmonary parameters. CONCLUSION. Myxedema coma is a rare complication in postoperative care, but in cases of inexplicable unconsciousness thyroid failure should be excluded. If myxedema coma is evident, intravenous therapy with L-thyroxine should be performed under the conditions of extended monitoring.