Alexander Krannich

Agreement Between 24-Hour Salt Ingestion and Sodium Excretion in a Controlled Environment

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects’ daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials.

Salt-responsive gut commensal modulates TH17 axis and disease

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH17) cells, which can also contribute to hypertension. Induction of TH17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased TH17 cells and increased blood pressure. Our results connect high salt intake to the gut–immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.

Regional cerebral oxygen saturation after cardiac arrest in 60 patients—A prospective outcome study

INTRODUCTION Non-invasive near-infrared spectroscopy (NIRS) offers the possibility to determine regional cerebral oxygen saturation (rSO2) in patients with cardiac arrest. Limited data from recent studies indicate a potential for early prediction of neurological outcome. METHODS Sixty cardiac arrest patients were prospectively enrolled, 22 in-hospital cardiac arrest (IHCA) and 38 out-of-hospital cardiac arrest (OHCA) patients respectively. NIRS of frontal brain was started after return of spontaneous circulation (ROSC) during admission to ICU and was continued until normothermia. Outcome was determined at ICU discharge by the Pittsburgh Cerebral Performance Category (CPC) and 6 months after cardiac arrest. RESULTS A good outcome (CPC 1-2) was achieved in 23 (38%) patients, while 37 (62%) had a poor outcome (CPC 3-5). Patients with good outcome had significantly higher rSO2 levels (CPC 1-2: rSO2 68%; CPC 3-5: rSO2 58%; p<0.01). For good and poor outcome median rSO2 within the first 24h period was 66% and 59% respectively and for the following 16h period 68% and 59% (p<0.01). Outcome prediction by area of rSO2 below a critical threshold of rsO2=50% within the first 40h yielded 70% specificity and 86% sensitivity for poor outcome. CONCLUSION On average, rSO2 within the first 40h after ROSC is significantly lower in patients with poor outcome, but rSO2 ranges largely overlap between outcome groups. Our data indicate limited potential for prediction of poor outcome by frontal brain rSO2 measurements.

Therapeutic temperature management after cardiac arrest and the risk of bleeding: Systematic review and meta-analysis

AIM Prognosis after cardiac arrest in the era of modern critical care is still poor with a high mortality of approximately 90%. Around 30% of the survivors have neurological impairments. Targeted temperature management (TTM) is the only treatment option which can improve mortality and neurological outcome. It is so far unclear if bleeding complications occur more often in patients undergoing TTM treatment. METHODS We conducted a systematic literature research in September 2013 including three major databases i.e. MEDLINE, EMBASE and CENTRAL. All studies were rated in respect to the ILCOR Guidelines and concerning their level of evidence and quality. We then performed a meta-analysis on bleeding disposition under TTM. RESULTS We initially found 941 studies out of which 34 matched our requirements and were thus included in our overview. Five studies including 599 patients were summarized in a meta-analysis concerning bleeding complications of all severities. There was a trend toward higher bleeding in patients treated with TTM (RR: 1.30, 95% CI: 0.97-1.74) which did not reach significance (p=0.085). Seven studies with an overall 599 patients were included in our meta-analysis on bleeding requiring transfusion. There was no significant difference in the incidence of severe bleeding with a risk ratio of 0.97 (95% CI: 0.61-1.56, p=0.909). CONCLUSIONS The data included in our meta-analysis indicate that, concerning the risk of bleeding, TTM is a safe method for patients after cardiac arrest. We did not observe a significantly higher risk for bleeding in patients undergoing TTM.

Early deep sedation is associated with decreased in-hospital and two-year follow-up survival.

IntroductionThere is increasing evidence that deep sedation is detrimental to critically ill patients. The aim of this study was to examine effects of deep sedation during the early period after ICU admission on short- and long-term survival.MethodsIn this observational, matched-pair analysis, patients receiving mechanical ventilation that were admitted to ICUs of a tertiary university hospital in six consecutive years were grouped as either lightly or deeply sedated within the first 48 hours after ICU admission. The Richmond Agitation-Sedation Score (RASS) was used to assess sedation depth (light sedation: −2 to 0; deep: −3 or below). Multivariate Cox regression was conducted to investigate the impact of early deep sedation within the first 48 hours of admission on in-hospital and two-year follow-up survival.ResultsIn total, 1,884 patients met inclusion criteria out of which 27.2% (n = 513) were deeply sedated. Deeply sedated patients had longer ventilation times, increased length of stay and higher rates of mortality. Early deep sedation was associated with a hazard ratio of 1.661 (95% CI: 1.074 to 2.567; P = 0.022) for in-hospital survival and 1.866 (95% CI: 1.351 to 2.576; P <0.001) for two-year follow-up survival.ConclusionsEarly deep sedation during the first 48 hours of intensive care treatment was associated with decreased in-hospital and two-year follow-up survival. Since early deep sedation is a modifiable risk factor, this data shows an urgent need for prospective clinical trials focusing on light sedation in the early phase of ICU treatment.

Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis - A Pilot Study

Preclinical studies show that blocking Interleukin–1 (IL–1) retards the progression of Amyotrophic Lateral Sclerosis (ALS). We assessed the safety of Anakinra (ANA), an IL–1 receptor antagonist, in ALS patients. In a single arm pilot study we treated 17 ALS patients with ANA (100 mg) daily for one year. We selected patients with dominant or exclusive lower motor neuron degeneration (LMND) presentation, as peripheral nerves may be more accessible to the drug. Our primary endpoint was safety and tolerability. Secondary endpoints included measuring disease progression with the revised ALS functional rating scale (ALSFRSr). We also quantified serum inflammatory markers. For comparison, we generated a historical cohort of 47 patients that fit the criteria for enrolment, disease characteristics and rate of progression of the study group. Only mild adverse events occurred in ALS patients treated with ANA. Notably, we observed lower levels of cytokines and the inflammatory marker fibrinogen during the first 24 weeks of treatment. Despite of this, we could not detect a significant reduction in disease progression during the same period in patients treated with ANA compared to controls as measured by the ALSFRSr. In the second part of the treatment period we observed an increase in serum inflammatory markers. Sixteen out of the 17 patients (94%) developed antibodies against ANA. This study showed that blocking IL–1 is safe in patients with ALS. Further trials should test whether targeting IL–1 more efficiently can help treating this devastating disease. Trial Registration ClinicalTrials.gov NCT01277315

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.

Association of Comorbidities With Postoperative In-hospital Mortality: A Retrospective Cohort Study

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Observational clinical study on the effects of different dosing regimens on vancomycin target levels in critically ill patients: Continuous versus intermittent application

Different dosing regimens for vancomycin are in clinical use: intermittent infusion and continuous administration. The intention of using these different dosing regimens is to reduce toxicity, to achieve target levels faster and to avoid treatment failure. The aim of this phase IV study was to compare safety and effectiveness in both administration regimens. The study was conducted in 2010 and 2011 in three postoperative intensive care units (ICUs) in a tertiary care university hospital in Berlin, Germany. Adult patients with vancomycin therapy and therapeutic drug monitoring were included. Out of 675 patients screened, 125 received vancomycin therapy, 39% with intermittent and 61% with continuous administration. Patients with continuous administration achieved target serum levels significantly earlier (median day 3 versus 4, p=0.022) and showed fewer sub-therapeutic serum levels (41% versus 11%, p<0.001). ICU mortality rate, duration of ICU stay and duration of ventilation did not differ between groups. Acute renal failure during the ICU stay occurred in 35% of patients with intermittent infusion versus 26% of patients with continuous application (p=0.324). In conclusion, continuous administration of vancomycin allowed more rapid achievement of targeted drug levels with fewer sub-therapeutic vancomycin levels observed. This might indicate that patients with more severe infections or higher variability in renal function could benefit from this form of administration.

A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries—The SPAME trial results

INTRODUCTION International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. METHODS This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. RESULTS The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34°C for 24h, and 33% had changed the target temperature to 36°C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p<0.01), as well as the use of a computer feedback device (p=0.03) for TTM. CONCLUSION This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.