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Background: Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI., Methods: This is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury., Results: A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (interquartile range (IQR)) 0.37 (0.21-0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2-13) mmol/l) and multi-organ failure. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2-13) mmol/l vs. 24 h: 4.4 (2.5-9.1) mmol/l, p < 0.001) with 22 patients (52.4%) reaching a lactate reduction > 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (hazard ratio 0.409; 95% CI, 0.14-0.631, p = 0.005)., Conclusions: A reduction of lactate concentrations was observed following implementation of intra-arterial therapy, and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration Retrospectively registered on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1 ., (© 2022. The Author(s).)

Background: Owing to the emerging problem of MDR bacteria, interest in 'old' antibiotics such as colistin has re-emerged. However, research on the dosing of colistin in patients undergoing renal replacement therapy (RRT), such as prolonged intermittent renal replacement therapy (PIRRT), is scarce., Objectives: The aim of this study was to evaluate single- and multiple-dose pharmacokinetics of colistin and its prodrug colistin methanesulfonate in ICU patients with acute kidney injury (AKI) undergoing PIRRT., Methods: We performed a prospective clinical pharmacokinetic single- and multiple-dose study. Eight ICU patients with AKI undergoing treatment with PIRRT and receiving intravenous colistin were studied on day 1 and days 5-9 of treatment, depending on the timing of dialysis. Six million IU (MIU) of colistin methanesulfonate was administered 8 h prior to the PIRRT session followed by 3 MIU every 8 h. The study was registered under clinicaltrails.gov (NCT02556190)., Results: PIRRT removed a considerable amount of colistin and colistin methanesulfonate with a median dialyser plasma CL of 70.1 mL/min (IQR 36.6-96.2) for colistin and 69.3 mL/min (IQR 56.3-318.7) for colistin methanesulfonate. The median amount of colistin in the total collected dialysate was 154 mg (IQR 105-175), corresponding to about 50% of the daily dose. Median colistin peak concentrations accumulated from 5.79 mg/L (IQR 4.14-8.79) on day 1 to 9.49 mg/L (IQR 8.39-10.41) on days 5-9. Cmax was significantly and inversely correlated with body weight., Conclusions: PIRRT eliminates about half of the daily administered colistin dose. Even a 6 MIU loading dose of colistin methanesulfonate may not ensure immediate sufficient colistin plasma levels in all critically ill patients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient.

Background: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy., Methods: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression., Results: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result., Conclusions: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC., Clinical Trials Registration: NCT01122368., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Although central nervous system complications (CNSCs) are common after orthotopic liver transplantation (OLT), standardized prospective studies are still lacking. This prospective study was aimed at determining the incidence of CNSCs, describing their clinical presentations, and establishing predicting factors. One hundred thirty-six adult patients who underwent OLT at Hannover Medical School between December 2008 and June 2011 were included. Weekly examinations were performed by a neurologist during the hospital stay after OLT. Patient data, donor data, and operative and postoperative variables were collected. Patients with cerebral dysfunction after OLT underwent a diagnostic work-up, which included brain imaging and, if necessary, cerebrospinal fluid analysis. Patients with central nervous system (CNS) symptoms but negative imaging and cerebrospinal fluid results and patients with pontine myelinolysis or posterior reversible encephalopathy syndrome were placed in a metabolic-toxic CNSC group, and patients with strokes, intracranial hemorrhaging, or CNS infections were placed in a nonmetabolic CNSC group. Multiple regression analysis was used to identify independent risk factors for the development of metabolic-toxic CNSCs. After excluding two patients that died after OLT without regaining consciousness, forty-four (32.8%) patients developed CNSCs: 37 of these patients (27.6%) had metabolic-toxic CNSCs, and 7 (5.2%) had nonmetabolic CNSCs. Acute-on-chronic liver failure, the number of subsequent surgeries, and primary sclerosing cholangitis were identified as independent predictors for the development of metabolic-toxic CNSCs. Metabolic-toxic CNSCs were associated with prolonged hospital stays, and nonmetabolic CNSCs were associated with higher mortality. In conclusion, CNSCs are common and relevant complications after OLT. Patients after OLT, especially with risk factors, should undergo a regular standardized neurological examination that would allow early detection of these complications., (© 2014 American Association for the Study of Liver Diseases.)

Introduction: Recent experimental data suggest that continuous external negative-pressure ventilation (CENPV) results in better oxygenation and less lung injury than continuous positive-pressure ventilation (CPPV). The effects of CENPV on patients with acute respiratory distress syndrome (ARDS) remain unknown., Methods: We compared 2 h CENPV in a tankrespirator ("iron lung") with 2 h CPPV. The six intubated patients developed ARDS after pulmonary thrombectomy (n = 1), aspiration (n = 3), sepsis (n = 1) or both (n = 1). We used a tidal volume of 6 ml/kg predicted body weight and matched lung volumes at end expiration. Haemodynamics were assessed using the pulse contour cardiac output (PiCCO) system, and pressure measurements were referenced to atmospheric pressure., Results: CENPV resulted in better oxygenation compared to CPPV (median ratio of arterial oxygen pressure to fraction of inspired oxygen of 345 mmHg (minimum-maximum 183 to 438 mmHg) vs 256 mmHg (minimum-maximum 123 to 419 mmHg) (P < 0.05). Tank pressures were -32.5 cmH2O (minimum-maximum -30 to -43) at end inspiration and -15 cmH2O (minimum-maximum -15 to -19 cmH2O) at end expiration. NO Inspiratory transpulmonary pressures decreased (P = 0.04) and airway pressures were considerably lower at inspiration (-1.5 cmH2O (minimum-maximum -3 to 0 cmH2O) vs 34.5 cmH2O (minimum-maximum 30 to 47 cmH2O), P = 0.03) and expiration (4.5 cmH2O (minimum-maximum 2 to 5) vs 16 cmH2O (minimum-maximum 16 to 23), P =0.03). During CENPV, intraabdominal pressures decreased from 20.5 mmHg (12 to 30 mmHg) to 1 mmHg (minimum-maximum -7 to 5 mmHg) (P = 0.03). Arterial pressures decreased by approximately 10 mmHg and central venous pressures by 18 mmHg. Intrathoracic blood volume indices and cardiac indices increased at the initiation of CENPV by 15% and 20% (P < 0.05), respectively. Heart rate and extravascular lung water indices remained unchanged., Conclusions: CENPV with a tank respirator improved gas exchange in patients with ARDS at lower transpulmonary, airway and intraabdominal pressures and, at least initially improving haemodynamics. Our observations encourage the consideration of further studies on the physiological effects and the clinical effectiveness of CENPV in patients with ARDS.

Background and Objectives: The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2) of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method., Design, Setting, Participants, & Measurements: Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients., Results: The mean dialyzer clearance for ampicillin/sulbactam was 80.1 ± 7.7/83.3 ± 12.1 ml/min. The t(1/2) of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8 ± 0.8 hours and 3.5 ± 1.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam., Conclusions: Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing.

Background: Daptomycin is a new intravenous cyclic lipopeptide antibiotic, licensed for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms including both susceptible and resistant strains of Staphylococcus aureus and for the treatment of various infections due to susceptible organisms, including serious and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis with associated bacteremia. Currently, no dosing recommendations exist for this drug for patients with acute kidney injury (AKI) undergoing renal replacement therapy. The aim of this study was to evaluate pharmacokinetics of daptomycin in critically ill patients with AKI undergoing extended dialysis (ED), a frequently used mean of renal replacement therapies in intensive care units (ICUs) around the world. Patients and methods. A prospective, single-dose pharmacokinetic study was performed in the medical and surgical ICUs of a tertiary care center. The aim was to investigate critically ill patients with anuric AKI being treated with ED and receiving daptomycin (n = 10). Daptomycin (6 mg/kg) was administered 8 h before ED was started., Results: Key pharmacokinetic parameters like half-life in critically ill patients treated with ED were comparable to healthy controls. The dialyser clearance for daptomycin was 63 +/- 9 ml/min. Based on the amount of the drug recovered from the collected spent dialysate, the mean fraction of the drug removed by one dialysis treatment was 23.3%., Conclusion: Our data suggest that patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; ED time, 480 min) and employing current dosing regimen, 6 mg/kg daptomycin every 48 h, run the risk of becoming significantly under dosed if one adheres to a twice daily dosing schedule that is recommended for patients on maintenance haemodialysis. Our data suggest that a daily dose of 6 mg/kg daptomycin is necessary in this special patient population to avoid under dosing, which may have detrimental effects in critically ill patients suffering from life-threatening infections.

Objective: The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay., Design: Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy., Methods: Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave., Results and Conclusions: Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patient's quality of life by the complete avoidance of hypothyroidism.

Today transplantation of different vital organs is an often and successfully applied clinical method. After organ transplantation the degree of recovery mainly depends on graft function. Besides social, work and school reintegration as well as the development of independence and self-responsibility are decisive for a general recovery. Therefore a rehabilitation should be planned in the scope of the medical care after transplantation. For this reason the rehabilitation center for children and juvenile was founded in Stronach, Austria in 1992. Since then until March 1995 136 kidney- and 54 liver transplanted patients have been treated. There is a significant increase of hemoglobine in all cases and a significant decrease of creatinine as a parameter of graft function in kidney-transplanted patients. By spiroergometric testing the heartrate at the aerobic-anaerobic threshold can be easily estimated in children and juvenile and in consideration of these results the physical endurance can be distinctively increased by an individual training program.

A rare case of Cruveilhier-Baumgarten syndrome with exceptional deep subcutaneous portosystemic collaterals is reported. Undetected these anastomoses represent potentially dangerous sites for hemorrhage complications. Ultrasound in combination with color-coded duplex sonography is a reliable technique in identifying portosystemic anastomoses as well as in providing valuable information about the etiology of portal hypertension.

A plastic lung working on the same principles as an iron lung has been developed at the Medical School in Hannover. Functional and practical tests were performed in a representative group of patients. Respirators support following the principles of an iron lung may be provided as a supplement or an alternative to existing artificial respirator therapy. The modern artificial respirators are superior to the plastic lung, which however, has advantages for particular indications: Respiratory therapy performed in a plastic lung is well tolerated by the patients. It requires specific skills which can easily be learned by the medical staff. Routine use certainly cannot be instituted before further technical improvement has been achieved; in particular the noise level should be reduced. The plastic lung is suitable for short-term ventilation (2-10 h); in view of the restricted nursing procedures possible, prolonged artificial respiration cannot be recommended. In conclusion, immediate postoperative ventilation is the area of application for the plastic lung. Several advantages are known: the endotracheal tube can be removed, there is no indication for sedative drugs, cardiac function and organ blood flow are positively influenced, mucolysis and lung expansion are adequate. A patient whose spontaneous respiratory activity is borderline benefits from short-term therapy, which can be repeated as necessary. Protracted artificial ventilation can be avoided. The gradual process of weaning from the ventilator following prolonged artificial respiration is facilitated by the use of a plastic lung. Plastic lung therapy is superior to other common methods of treating persistent atelectasis, because its mucolytic effects lead to expansion of the atelectatic lobe or segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Historically, there are three phases of development: initially, prophylactic operations in transplant candidates were performed frequently, particularly to minimize complications of infection and stress ulceration. As a consequence of advanced experience and reduced immuno-suppression, the need for those operations declined. Today, by extending transplant indications to elderly patients and to more complicated situations, prophylactic surgery-particularly for concomitant cardiovascular disease-plays an increasing role. Indications for prophylactic surgery are also provided in endocrinal, oncologic and immunologic conditions.

Postoperative artificial ventilation by using an endotracheal tube may cause a pulmonary infection. A possibly necessary permanent sedation and relaxation may result in an additional danger for the patient. The principle of the "iron lung" represents an alternative to endotracheal artificial respiration, which applies especially to endangered patients who are under postoperative artificial respiration. After an abdominal operation five patients have been extubated and artificially respirated by using the "iron lung" principle while not being able to breath by themselves. The degree of the sedation was monitored both intraoperatively and postoperatively using an automatic EEG classification. The performance spectrum of the respiratory curve enabled very early detection of the onset of spontaneous respiration.

Intravenous fluid replacement via a peripheral catheter harbours several risks. The study presented emphasizes that about 50% of the patients show complications during the first days after positioning of an intravenous line. Women patients have been affected more often than male patients. Small catheters positioned in a major vessel away from a joint in the forearm, yield the best results. Peripheral lines should be removed within 8 to 12 hours after surgical procedures, when early symptoms are observed. Complications can be avoided by following these recommendations.

In order to prevent symptoms of drug withdrawal during pregnancy, we treated a woman with clonidine, an alpha-2 adrenergic agonist with central and peripheral actions. We saw a good response of the withdrawal symptoms without any period of severe hypotension or bradycardia. Two healthy babies were subsequently delivered by cesarean section.

Total atelectasis of the left lung occurred in a 61-year-old woman after several weeks ventilator-assisted breathing following an operation for ileus, when the tracheal cannula was removed. It was quickly replaced and artificial ventilation resumed. But despite daily bronchoscopic suction for three weeks the patient's state failed to improve (vital capacity 39%, arterial pO2 47 mm Hg, pCO2 37 mm Hg). Mechanical ventilation with an "iron lung" was therefore instituted over a six month period, at first for two hours daily (as an in-patient) and then weekly (as out-patient). During this time her condition and general state clearly improved. On re-hospitalization to remove the tracheal cannula her vital capacity was 75%, pO2 78 mm Hg and pCO2 38 mm Hg.