Maximilian Ragaller

Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis: A Randomized Trial

CONTEXT Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial. OBJECTIVE To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. DESIGN, SETTING, AND PATIENTS A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. INTERVENTIONS Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. MAIN OUTCOME MEASURE Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. RESULTS Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43). CONCLUSION Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00534287.

Ventilation in chest trauma

Chest trauma is one important factor for total morbidity and mortality in traumatized emergency patients. The complexity of injury in trauma patients makes it challenging to provide an optimal oxygenation while protecting the lung from further ventilator-induced injury to it. On the other hand, lung trauma needs to be treated on an individual basis, depending on the magnitude, location and type of lung or chest injury. Several aspects of ventilatory management in emergency patients are summarized herein and may give the clinician an overview of the treatment possibilities for chest trauma victims.

Effects of posture on regional pulmonary blood flow in rats as measured by PET

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.

Pulmonary Blood Flow Increases in Damaged Regions Directly after Acid Aspiration in Rats

Background:After gastric aspiration events, patients are at risk of pulmonary dysfunction and the development of severe acute lung injury and acute respiratory distress syndrome, which may contribute to the development of an inflammatory reaction. The authors’ aim in the current study was to investigate the role of the spatial distribution of pulmonary blood flow in the pathogenesis of pulmonary dysfunction during the early stages after acid aspiration. Methods:The authors analyzed the pulmonary distribution of radiolabeled microspheres in normal (n = 6) and injured (n = 12) anesthetized rat lungs using positron emission tomography, computed tomography, and histological examination. Results:Injured regions demonstrate increased pulmonary blood flow in association with reduced arterial pressure and the deterioration of arterial oxygenation. After acid aspiration, computed tomography scans revealed that lung density had increased in the injured regions and that these regions colocalized with areas of increased blood flow. The acid was instilled into the middle and basal regions of the lungs. The blood flow was significantly increased to these regions compared with the blood flow to uninjured lungs in the control animals (middle region: 1.23 [1.1; 1.4] (median [25%; 75%]) vs. 1.04 [1.0; 1.1] and basal region: 1.25 [1.2; 1.3] vs. 1.02 [1.0; 1.05], respectively). The increase in blood flow did not seem to be due to vascular leakage into these injured areas. Conclusions:The data suggest that 10 min after acid aspiration, damaged areas are characterized by increased pulmonary blood flow. The results may impact further treatment strategies, such as drug targeting.

Late Life-Threatening Hemorrhage after Percutaneous Tracheostomy

Purpose. Formation of a tracheoinnominate artery fistula (TIF) and consecutive hemorrhage is a rare and life-threatening complication with high mortality. Warning symptoms can be absent. The current literature contains only few considerations for misleading signs, especially in cases where the contact between the tissue and the cannula is tight. Method and Results. We report two cases of life-threatening hemorrhages that appeared six days and two months after percutaneous dilatational tracheostomy (PDT) in two patients, respectively. In these cases, diagnosis of tracheoinnominate artery fistula (TIF) was difficult. Tracheal ring fracture after PDT and pressure ulceration caused by cannula were implicated in TIF formation. The cannula was overblocked to buy time before surgical closure. Both patients survived without any additional neurological deficiency. Conclusion. Massive hemorrhage in patients after tracheostomy is likely due to TIF. Ultrasound scanning before PDT and careful periodical followup of the trachea are required.

Practice of volume therapy in patients with severe sepsis: results from a nationwide sepsis prevalence study

Sir: The use of hydroxyethyl starch (HES) in patients with severe sepsis increased the incidence of acute renal failure (ARF) [1, 2] and at higher doses led to increased 90-day mortality [2]. Both the Schortgen and the VISEP studies [1, 2] were criticised for their design, which was felt to be in contrast to common clinical practice. We analysed data derived in 2003 from a point-prevalence survey of patients with severe sepsis from a nationwide representative sample of hospitals stratified by size. A total of 454 ICUs were visited by external trained intensivists [3]. Volume therapy was recorded in 415 patients with severe sepsis. Synthetic colloids were used in a third of patients (Table 1). Colloid or crystalloid use did not differ by hospital size, but synthetic colloids were used more frequently on operative ICUs. HES was the most frequently used colloid. It was given to 29.4% of all patients, and to 122 of 146 patients receiving synthetic colloids (83.6%). Eighty-six patients received HES 6% [median dose 500 ml/24 h, interquartile range (IQR) 500–1,000 ml/ 24 h] and 43 patients received HES 10% (median 500 ml/24 h, IQR 500– 1,000 ml/24 h). Fourteen patients had pre-existing chronic renal disease requiring dialysis, and six of these received HES. Data on acute renal failure were available in 397 of the residual 401 patients; 29.5% of patients with acute renal failure and 30.3% with renal replacement therapy received HES 6 or 10%. Patients receiving HES had a higher mean SOFA score than patients not receiving HES (9.89 ± 4.00 vs. 7.75 ± 4.12, p \ 0.0001). One hundred fifteen patients received HES between day 0 and day 63 after start of sepsis. These data were adjusted to account for the fact that a point-prevalence design overestimates the frequency of longstayers. Accordingly, 83.2% of patients (adjusted) received HES between days 0–4 and 16.8% of patients between days 5 and 63 after onset of sepsis. Our data show that it was common clinical practice to use HES frequently, for longer periods of time and irrespective of renal dysfunction, despite recommendations not to use it in patients with renal insufficiency. HES is eliminated from the serum not only through the kidneys, but also through lysosomal breakdown after tissue uptake and storage. In the presence of renal failure, it is known that HES uptake is increased. This may contribute to organ failure and long-term mortality [4]. A new metaanalysis that screened all randomised controlled studies using HES for acute volume therapy in critically ill patients from 1950 until December 2008 has confirmed an increased risk for renal replacement in all patients receiving HES versus non-HES fluids and a trend towards increased risk of death in association with HES in septic patients and in high-quality trials [5].