Non-thyroidal Illness Syndrome (NTIS) is no independent predictor for mortality in ICU patients.

BACKGROUND: Low T3-(/T4-) syndrome, also known as non-thyroidal Illness Syndrome (NTIS) describes a decrease in free serum thyroid hormones without a concomitant increase in TSH, frequently observed in critically ill patients. However, whether NTIS is only a metabolic adaption to stress in critically ill or plays a crucial role as an independent risk factor for ICU mortality, remains unknown. Our study aimed to evaluate NTIS as an independent risk factor for increased ICU mortality. METHODS: All patients admitted to the interdisciplinary intensive care unit (ICU) at the University Hospital of Leipzig between 2008 and 2014 were retrospectively analyzed for thyroidal function. Baseline data, information on additional thyroid function tests, disease progression, hospital and ICU length of stay (LOS) and patient outcome were retrospectively analyzed from the hospitals digital information system. For statistical evaluation, univariate analysis, matched pairs analysis and multivariate logistic regression were conducted. RESULTS: One thousand, seven hundred ninety patients were enrolled in the study, of which 665 showed NTIS. Univariate analysis revealed a positive association of NTIS with ICU- and hospital-LOS, need for mechanical ventilation, incidence of sepsis, acute respiratory distress syndrome, acute liver failure and increased ICU mortality. Results of matched pair analysis confirmed these findings. In multivariate logistic regression, NTIS was associated with an increased ICU-LOS, increased duration of mechanical ventilation, acute kidney injury and liver failure, but showed no independent association with increased ICU-mortality. CONCLUSION: Duration of mechanical ventilation as well as incidence of acute kidney injury, sepsis and acute liver failure were detected as independent predictors of mortality in patients with NTIS. NTIS itself was no independent predictor of increased ICU-mortality.

In vitro validation and characterization of pulsed inhaled nitric oxide administration during early inspiration.

PURPOSE: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. METHODS: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5-40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. RESULTS: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. CONCLUSION: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes.

Extracorporeal Membrane Oxygenation Blood Flow and Blood Recirculation Compromise Thermodilution-Based Measurements of Cardiac Output.

The contribution of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) to systemic oxygen delivery is determined by the ratio of total extracorporeal blood flow () to cardiac output (). Thermodilution-based measurements of may be compromised by blood recirculating through the ECMO (recirculation fraction; Rf). We measured the effects of and Rf on classic thermodilution-based measurements of in six anesthetized pigs. An ultrasound flow probe measured total aortic blood flow () at the aortic root. Rf was quantified with the ultrasound dilution technique. was set to 0-125% of and was measured using a pulmonary artery catheter (PAC) in healthy and lung injured animals. PAC overestimated () at all settings compared to . The mean bias between both methods was 2.1 L/min in healthy animals and 2.7 L/min after lung injury. The difference between and increased with an of 75-125%/ compared to QEC <50%/. Overestimation of was highest when resulted in a high Rf. Thus, thermodilution-based measurements can overestimate cardiac output during VV ECMO. The degree of overestimation of depends on the EC/ ratio and the recirculation fraction.

Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung.

KEY POINTS: Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the mechanism of this action remains unknown. It has been postulated that carbonic anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO) from nitrite and that this formation is increased in the presence of acetazolamide. Acetazolamide reduces HPV in pigs without evidence of any NO generation, whereas nebulized sodium nitrite reduces HPV by NO formation; however; combined infusion of acetazolamide with sodium nitrite inhalation did not further increase exhaled NO concentration over inhaled nitrite alone in pigs exposed to alveolar hypoxia. We conclude that acetazolamide does not function as either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and probably other mammals, to explain its vasodilating actions in the pulmonary or systemic circulations. ABSTRACT: The carbonic anhydrase (CA) inhibitors acetazolamide and its structurally similar analogue methazolamide prevent or reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels, it has been reported that inhibition of CA leads to increased generation of nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the physiological relevance of augmented NO generation by CA from nitrite with acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo. We found that acetazolamide prevents HPV in anaesthetized pigs, as in other mammalian species. A single nebulization of sodium nitrite reduces HPV, but this action wanes in the succeeding 3 h of hypoxia as nitrite is metabolized and excreted. Pulmonary artery pressure reduction and NO formation as measured by exhaled gas concentration from inhaled sodium nitrite were not increased by acetazolamide during alveolar hypoxia. Thus, our data argue against a physiological role of carbonic anhydrase as a nitrous anhydrase or nitrite reductase as a mechanism for its inhibition of HPV in the lung and blood in vivo.

Prone positioning in the elderly extends perioperative process times: a retrospective analysis.

Objective: Cervical bone fractures describe a predominant trauma in the elderly. With demographic change, prone patient positions might create further stress on personnel resources. Therefore, the aim of this study was to conduct an age-related analysis of pre- and intraoperative process times in patients with cervical fractures. Methods: We reviewed all schedules with cervical spine surgery performed at a tertiary hospital. Two different operative patient positions were specified: prone and supine. We retrospectively analysed three study groups: comparison group (group 1: ≤59 years of age), old patients (group 2: 60-79 years), and very old patients (group 3: ≥80 years). We recorded date and kind of surgery, biometric data, and process times by screening recordings of internal software programs (COPRA® and SAP 710®). Group comparisons were conducted using the Kruskal-Wallis test with Dunn's post hoc test and Bonferroni correction, Pearson's chi-square test, and the Mann-Whitney U test, as required. Results: 330 patients (202 male; 128 female) were analysed. The number of patients in the resulting age-dependent groups 1-3 were n=102, n=123, and n=105, respectively. Patients of increasing age and in supine position showed a continuous increase in the time needed for anaesthesia induction (mean between 4 and 8 minutes (p<0.05). When compared to patients in supine position, this time further increased on average by 6 minutes (p<0.05) in old but prone patients. In old and very old patients, getting a patient into a prone position was associated with a time demand between 10 and 12 minutes (p<0.01), respectively. While time for surgery age-dependently decreased in patients that were supine positioned (p<0.001), surgery time was prolonged between 34 and 104 minutes (p<0.05) in patients that were prone. Conclusion: With prone position both anaesthesia-controlled and surgical-controlled times extended in patients of increasing age. With regard to demographic change, this aspect should be considered for future revenue calculations in flat-rate remuneration systems.

Central venous catheterization for acute trauma resuscitation: Tip position analysis using routine emergency computed tomography.

PURPOSE: Central venous catheter insertion for acute trauma resuscitation may be associated with mechanical complications, but studies on the exact central venous catheter tip positions are not available. The goal of the study was to analyze central venous catheter tip positions using routine emergency computed tomography. METHODS: Consecutive acute multiple trauma patients requiring large-bore thoracocervical central venous catheters in the resuscitation room of a university hospital were enrolled retrospectively from 2010 to 2015. Patients who received a routine emergency chest computed tomography were analyzed regarding central venous catheter tip position. The central venous catheter tip position was defined as correct if the catheter tip was placed less than 1 cm inside the right atrium relative to the cavoatrial junction, and the simultaneous angle of the central venous catheter tip compared with the lateral border of the superior vena cava was below 40°. RESULTS: During the 6-year study period, 97 patients were analyzed for the central venous catheter tip position in computed tomography. Malpositions were observed in 29 patients (29.9%). Patients with malpositioned central venous catheters presented with a higher rate of shock (systolic blood pressure <90 mmHg) at admission (58.6% vs 33.8%, p = 0.023) and a higher mean injury severity score (38.5 ± 15.7 vs 31.6 ± 11.8, p = 0.041) compared with patients with correctly positioned central venous catheter tips. Logistic regression revealed injury severity score as a significant predictor for central venous catheter malposition (odds ratio = 1.039, 95% confidence interval = 1.005-1.074, p = 0.024). CONCLUSION: Multiple trauma patients who underwent emergency central venous catheter placement by experienced anesthetists presented with considerable tip malposition in computed tomography, which was significantly associated with a higher injury severity.

Mechanical complications and outcomes following invasive emergency procedures in severely injured trauma patients.

This study aimes to determine the complication rates, possible risk factors and outcomes of emergency procedures performed during resuscitation of severely injured patients. The medical records of patients with an injury severity score (ISS) >15 admitted to the University Hospital Leipzig from 2010 to 2015 were reviewed. Within the first 24 hours of treatment, 526 patients had an overall mechanical complication rate of 26.2%. Multivariate analysis revealed out-of-hospital airway management (OR 3.140; 95% CI 1.963-5.023; p < 0.001) and ISS (per ISS point: OR 1.024; 95% CI 1.003-1.045; p = 0.027) as independent predictors of any mechanical complications. Airway management complications (13.2%) and central venous catheter complications (11.4%) were associated with ISS >32.5 (p < 0.001) and ISS >33.5 (p = 0.005), respectively. Chest tube complications (15.8%) were associated with out-of-hospital insertion (p = 0.002) and out-of-hospital tracheal intubation (p = 0.033). Arterial line complications (9.4%) were associated with admission serum lactate >4.95 mmol/L (p = 0.001) and base excess <-4.05 mmol/L (p = 0.008). In multivariate analysis, complications were associated with an increased length of stay in the intensive care unit (p = 0.019) but not with 24 hour mortality (p = 0.930). Increasing injury severity may contribute to higher complexity of the individual emergency treatment and is thus associated with higher mechanical complication rates providing potential for further harm.

The effects of hemoglobin glutamer-200 and iNO on pulmonary vascular tone and arterial oxygenation in an experimental acute respiratory distress syndrome.

INTRODUCTION: Hemoglobin-based oxygen carriers (HBOC) have been developed as an alternative to blood transfusions. Their nitric-oxide-scavenging properties HBOC also induce vasoconstriction. In acute lung injury, an excess of nitric oxide results in a general vasodilation, reducing oxygenation by impairing the hypoxic pulmonary vasoconstriction. Inhaled nitric oxide (iNO) is used to correct the ventilation perfusion mismatch. We hypothesized that the additional use of HBOC might increase this effect. In a rodent model of ARDS we evaluated the combined effect of HBOC and iNO on vascular tone and gas exchange. METHODS: ARDS was induced in anaesthetized Wistar rats by saline lavage and aggressive ventilation. Two groups received either hydroxyethylstarch 10% (HES; n = 10) or the HBOC hemoglobin glutamer-200 (HBOC-200; n = 10) via a central venous infusion. Additionally, both groups received iNO. Monitoring of the right ventricular pressure (RVP) and mean arterial pressure (MAP) was performed with microtip transducers. Arterial oxygenation was measured via arterial blood gas analyses. RESULTS: Application of HBOC-200 led to a significant increase of MAP and RVP when compared to baseline and to the HES group. This effect was reversed by iNO. The application of HBOC and iNO had no effect on the arterial oxygenation over time. No difference in arterial oxygenation was found between the groups. CONCLUSION: Application of HBOC led to an increase of systemic and pulmonary vascular resistance in this animal model of ARDS. The increase in RVP was reversed by iNO. Pulmonary vasoconstriction by hemoglobin glutamer-200 in combination with iNO did not improve arterial oxygenation in ARDS.

Pre-anesthetic assessment with three core questions for the detection of obstructive sleep apnea in childhood: An observational study.

BACKGROUND: Children with obstructive sleep apnea are at high risk for perioperative airway obstruction. Many "at risk" children may remain unrecognized. The aim of this study is to find a clinically practicable test to identify obstructive sleep apnea in childhood. METHODS: In this pilot study, we prospectively compared four parental questionnaires with the respective findings of subsequent sleep laboratory testing in children. Right before sleep laboratory testing, children's parents answered both the Pediatric Sleep Questionnaire, a subscale of the Sleep Related Breathing Disorder questionnaire (PSQ-SRBD-Subscale), and an eight-item questionnaire derived from it. Finally, we condensed the eight-item questionnaire to three core issues: Does your child regularly snore at night? Does your child demonstrate labored breathing during sleep? Does your child have breathing pauses during sleep? With it, two similar questionnaires were generated that differed in the formation of the resulting score. One questionnaire was built by a quotient comparable to the abovementioned questionnaires and a second as quick test that functioned as a simple sum score. Both sensitivity and specificity were determined by using a Receiver Operating Characteristic analysis. RESULTS: In total, 53 children were included in the study. Both the PSQ-SRBD-questionnaire and self-derived eight-item questionnaire failed to reach statistically significant results in detecting obstructive sleep apnea. The set of three core questions with a score built by a quotient was statistically significant and provided sensitivity and a moderate specificity of 0.944 and 0.543, respectively. This could be slightly optimized by creating a simple sum-score (specificity of 0.571). CONCLUSIONS: The use of three core-questions may facilitate the detection of pediatric obstructive sleep apnea within the scope of the anesthesia survey. While the study has some limitations, future studies with both unselective collectives and older children might prove this ultra-short questionnaire to be advantageous in detecting pediatric OSA in clinical practices. TRIAL REGISTRATION: German Clinical Trial Register ( DRKS00010408 , https://www.drks.de ); date of registration 26.07.2016.

Hydroxyethyl starch for volume expansion after subarachnoid haemorrhage and renal function: Results of a retrospective analysis.

BACKGROUND: Hydroxyethyl starch (HES) was part of "triple-H" therapy for prophylaxis and therapy of vasospasm in patients with subarachnoid haemorrhage (SAH). The European Medicines Agency restricted the use of HES in 2013 due to an increase of renal failure in critically ill patients receiving HES compared to crystalloid fluids. The occurrence of renal insufficiency in patients with SAH due to HES is still uncertain. The purpose of our study was to evaluate whether there was an association with renal impairment in patients receiving HES after subarachnoid haemorrhage. METHODS: Medical records of all non-traumatic SAH patients treated at the Departments of Anaesthesiology and Neurosurgery, University Hospital of Leipzig, Germany, between January 2009 and December 2014 were analysed. Patients received either HES 6% and/or 10% (HES group, n = 183) or exclusively crystalloids for fluid therapy (Crystalloid group, n = 93). Primary outcome was the incidence of acute kidney injury. RESULTS: The study groups had similar characteristics except for initial SAPS scores, incidence of vasospasm and ICU length of stay. Patients receiving HES fulfilled significantly more often SIRS (systemic inflammatory response syndrome) criteria. 24.6% (45/183) of the patients in the HES group had acute kidney injury (KDIGO 1-3) at any time during their ICU stay compared to 26.9% (25/93) in the crystalloid group (p = 0.679). Only few patients needed renal replacement therapy with no significant difference between groups (Crystalloid group: 4.3%; HES group: 2.2%; p = 0.322). The incidence of vasospasm was increased in the HES group when compared to the crystalloid group (33.9% vs. 17.2%; p = 0.004). CONCLUSION: In the presented series of patients with non-traumatic SAH we found no significant association between HES therapy and the incidence of acute kidney injury. Treatment without HES did not worsen patient outcome.

Laryngeal tube suction II or endotracheal intubation for laparoscopic radical prostatectomy in a head down position: A randomised controlled trial.

BACKGROUND: The laryngeal tube suction II (LTS II) is a supraglottic airway device (SAD) with a gastric drainage tube and enhanced seal properties as compared with other SADs. Therefore, its use has been proposed in situations with an elevated risk of aspiration. OBJECTIVES: To compare the safety and efficacy of airway management and controlled mechanical ventilation when using either an LTS II or an endotracheal tube for laparoscopic radical prostatectomy. DESIGN: Randomised, controlled, blinded and single-centre study. SETTING: Academic tertiary care centre in Leipzig from April 2014 to May 2015. PATIENTS: It was planned to include 100 patients but the study was stopped after 50 patients following an interim analysis. These 50 patients were randomised to either the LTS II group or the endotracheal tube group. All male patients aged more than 18 years for elective laparoscopic radical prostatectomy were eligible. Exclusion criteria included a BMI more than 30, American Society of Anesthesiologists class III or greater, a history of gastroesophageal reflux or other factors known to increase the risk of aspiration and a known difficult airway. INTERVENTIONS: All patients received general anaesthesia. Airway management was with either a LTS II or an endotracheal tube, according to the randomisation. MAIN OUTCOME MEASURES: The primary endpoint was successful insertion of the particular airway device during anaesthesia for laparoscopic radical prostatectomy. RESULTS: In 15 of the 28 patients randomised to LTS II, the device had to be removed and an endotracheal tube inserted, mainly because of an airway leak (n = 10) or swelling of the tongue (n = 3). Ventilation was successful in all patients (n = 22) randomised to endotracheal tube. Quality of ventilation was rated better in the endotracheal tube group. CONCLUSION: Our data suggest that LTS II should not be the preferred method of airway management in patients undergoing laparoscopic radical prostatectomy. TRIAL REGISTRATION: DRKS00008985 (German Clinical Trials Register).

Search for an animal model to investigate selective pulmonary vasodilation.

Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation. To do so, a haemodynamic stable pulmonary hypertension was initiated, with a 30 min duration deemed to be a sufficient time interval before and after a possible intervention. In anaesthetized and mechanically-ventilated Sprague-Dawley rats pulmonary hypertension was induced either by acute hypoxia due to reduction of the inspired oxygen fraction from 0.21 to 0.1 ( n = 6), a fixed infusion rate of the thromboxane analogue U46619 (240 ng/min; n = 6) or a monocrotaline injection (MCT; 60 mg/kg applied 23 days before the investigation; n = 7). The animals were instrumented to measure right ventricular and systemic arterial pressures. Acute hypoxia caused a short, and only transient, increase of pulmonary artery pressure as well as profound systemic hypotension which suggested haemodynamic instability. U46619 infusion induced variable changes in the pulmonary and systemic vascular tone without sufficient stabilization within 30 min. MCT provoked sustained pulmonary hypertension with normal systemic pressure values and inhalation of nitric oxide caused selective pulmonary vasodilation. In conclusion, out of the three examined rat animal models only MCT-induced pulmonary hypertension is a solid and reliable model for investigating selective pulmonary vasodilation.

Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS).

Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed.

Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study.

BACKGROUND: Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance. METHODS: Patients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH). RESULTS: Among 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1-1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates. CONCLUSIONS: Enterococci and Candida species play an important role in the microbial colonization of biliary stents. Therefore, empirical antimicrobial treatment of stent-associated cholangitis should be guided toward enterococci, Enterobacteriaceae, streptococci, anaerobes, and Candida. To determine causative pathogens, an accurate microbiological analysis of the extracted stent(s) may be helpful.

Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice.

BACKGROUND: Inhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it's biochemical mechanisms and effects on inflammatory reactions. METHODS: Mice (C57BL/6; n = 86) received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO2 = 0.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured. RESULTS: HPV was impaired after LPS-challenge (p < 0.01). CO exposure restored HPV-responsiveness if administered continuously for full 18 h, for the first 6 h and if given in the interval between the 3(rd) and 6(th) hour after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (p < 0.05). We found no effects on inflammatory plasma cytokines. CONCLUSION: Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

Restrictive transfusion practice during extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome.

Recommendations concerning the management of hemoglobin levels and hematocrit in patients on extracorporeal membrane oxygenation (ECMO) still advise maintenance of a normal hematocrit. In contrast, current transfusion guidelines for critically ill patients support restrictive transfusion practice. We report on a series of patients receiving venovenous ECMO (vvECMO) for acute respiratory distress syndrome (ARDS) treated according to the restrictive transfusion regimen recommended for critically ill patients. We retrospectively analyzed 18 patients receiving vvECMO due to severe ARDS. Hemoglobin concentrations were kept between 7 and 9 g/dL with a transfusion trigger at 7 g/dL or when physiological transfusion triggers were apparent. We assessed baseline data, hospital mortality, time on ECMO, hemoglobin levels, hematocrit, quantities of packed red blood cells received, and lactate concentrations and compared survivors and nonsurvivors. The overall mortality of all patients on vvECMO was 38.9%. Mean hemoglobin concentration over all patients and ECMO days was 8.30 ± 0.51 g/dL, and hematocrit was 0.25 ± 0.01, with no difference between survivors and nonsurvivors. Mean numbers of given PRBCs showed a trend towards higher quantities in the group of nonsurvivors, but the difference was not significant (1.97 ± 1.47 vs. 0.96 ± 0.76 units; P = 0.07). Mean lactate clearance from the first to the third day was 45.4 ± 28.3%, with no significant difference between survivors and nonsurvivors (P = 0.19). In our cohort of patients treated with ECMO due to severe ARDS, the application of a restrictive transfusion protocol did not result in an increased mortality. Safety and feasibility of the application of a restrictive transfusion protocol in patients on ECMO must further be evaluated in randomized controlled trials.

Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae after a large single-center outbreak in Germany.

BACKGROUND: The natural progress of intestinal colonization with Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae (KPC-2-KP) is almost unknown. METHODS: After a large, single-center outbreak of KPC-2-KP, we analyzed carrier prevalence through retrospective and prospective investigation of intestinal KPC-2-KP carriage 1 month, 3 months, 6 months, 1 year, and 2 years after acquisition, defined as the earliest date of KPC-2-KP detection. Rectal swabs or stool samples were collected at baseline and at each visit and submitted for both culture and KPC-specific polymerase chain reaction. Resolution of intestinal KPC-2-KP carriage was defined as a minimum of 3 consecutive negative polymerase chain reaction test results separated by at least 48 hours. RESULTS: In patients available for long-term evaluation 26 out of 84 patients (31%) tested negative for KPC-2-KP after 1 month, 14 out of 34 (41%) after 3 months, 17 out of 26 (65%) after 6 months, 14 out of 19 (74%) after 1 year, and 5 out of 6 (83%) after 2 years. Decolonization of KPC-2-KP was hampered in patients with prolonged or repeated hospitalization (P = .044-.140, depending on the time interval). Two patients retested positive for KPC-2-KP after they had previously shown 3 consecutive negative tests. The longest positive KPC-2-KP carrier status so far was observed after nearly 40 months (1,191 days). CONCLUSIONS: The majority of patients experienced spontaneous decolonization within 6 months after acquisition, mainly after discharge from the hospital. However, long-term carriage of >3 years is possible. Appropriate infection control measures must be taken when these patients are readmitted to health care facilities. A series of at least 4 consecutive negative rectal swabs or stool samples separated by sufficient time intervals appears necessary before the declaration of successful KPC-2-KP decolonization is made.

Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing Klebsiella pneumoniae: a single-centre experience.

After a single patient was transferred to Leipzig University Hospital from a hospital in Rhodes, Greece, the hospital experienced the largest outbreak due to a KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) strain thus far observed in Germany. Ninety patients hospitalised between July 2010 and October 2012 were affected. In an attempt to eliminate KPC-2-KP from their digestive tracts, 14 consecutive patients (16%) were treated with a short course (7 days) of selective digestive decontamination (SDD), employing colistin (1 million units q.i.d.) and gentamicin (80 mg q.i.d.) as oral solutions, and applying colistin/gentamicin gel (0.5 g) to the oral cavity. In a retrospective analysis, these 14 SDD patients were compared with the remaining 76 patients harbouring KPC-2-KP. KPC-2-KP carrier status was followed in all 14 SDD patients by submitting stool samples to KPC-specific PCR. The mean follow-up period was 48 days (range 12-103 days). Successful elimination of KPC-2-KP was defined as a minimum of three consecutive negative PCR test results separated by ≥48 h each. Decolonisation of KPC-2-KP was achieved in 6/14 patients (43%) after a mean of 21 days (range 12-40 days), but was also observed in 23/76 (30%) of the non-SDD controls (P = 0.102). SDD treatment resulted in the development of secondary resistance to colistin (19% increase in resistance rate) and gentamicin (45% increase) in post-treatment isolates. In the control group, no secondary resistance occurred. We conclude that the SDD protocol applied in this study was not sufficiently effective for decolonisation and was associated with resistance development.