Randomized controlled study to evaluate the safety and clinical impact of percutaneous auricular vagus nerve stimulation in patients with severe COVID-19.

Introduction: A severe course of COVID-19 is characterized by a hyperinflammatory state resulting in acute respiratory distress syndrome or even multi-organ failure along a derailed sympatho-vagal balance. Methods: In this prospective, randomized study, we evaluate the hypothesis that percutaneous minimally invasive auricular vagus nerve stimulation (aVNS) is a safe procedure and might reduce the rate of clinical complications in patients with severe course of COVID-19. In our study, patients with SARS-CoV-2 infection admitted to the intensive care unit with moderate-to-severe acute respiratory distress syndrome, however without invasive ventilation yet, were included and following randomization assigned to a group receiving aVNS four times per 24 h for 3 h and a group receiving standard of care (SOC). Results: A total of 12 patients were included (six in the aVNS and six in the SOC group). No side effects in aVNS were reported, especially no significant pain at device placement or during stimulation at the stimulation site or significant headache or bleeding after or during device placement or lasting skin irritation. There was no significant difference in the aVNS and SOC groups between the length of stay in the intensive care unit and at the hospital, bradycardia, delirium, or 90-day mortality. In the SOC group, five of six patients required invasive mechanical ventilation during their stay at hospital and 60% of them venovenous extracorporeal membrane oxygenation, compared to three of six patients and 0% in the aVNS group (p = 0.545 and p = 0.061). Discussion: Vagus nerve stimulation in patients with severe COVID-19 is a safe and feasible method. Our data showed a trend to a reduction of progression to the need of invasive ventilation and venovenous extracorporeal membrane oxygenation which encourages further research with larger patient samples.

Elevation of neutrophil-derived factors in patients after multiple trauma.

Trauma represents one of the leading causes of death worldwide. Traumatic injuries elicit a dynamic inflammatory response with systemic release of inflammatory cytokines. Disbalance of this response can lead to systemic inflammatory response syndrome or compensatory anti-inflammatory response syndrome. As neutrophils play a major role in innate immune defence and are crucial in the injury-induced immunological response, we aimed to investigate systemic neutrophil-derived immunomodulators in trauma patients. Therefore, serum levels of neutrophil elastase (NE), myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) were quantified in patients with injury severity scores above 15. Additionally, leukocyte, platelet, fibrinogen and CRP levels were assessed. Lastly, we analysed the association of neutrophil-derived factors with clinical severity scoring systems. Although the release of MPO, NE and CitH3 was not predictive of mortality, we found a remarkable increase in MPO and NE in trauma patients as compared with healthy controls. We also found significantly increased levels of MPO and NE on Days 1 and 5 after initial trauma in critically injured patients. Taken together, our data suggest a role for neutrophil activation in trauma. Targeting exacerbated neutrophil activation might represent a new therapeutic option for critically injured patients.

Elevated EMMPRIN Serum Levels Indicate Plaque Vulnerability in Patients With Asymptomatic High Grade Carotid Stenosis.

OBJECTIVE: Carotid atherosclerosis is an important cause of cerebral ischaemic stroke. Sonographic plaque characteristics are inappropriate for exact prediction of possible future ischaemic events. Additional markers are needed to predict the clinical outcome in high grade carotid stenosis. This study aimed to test extracellular matrix metalloproteinase inducer (EMMPRIN), due to its involvement in plaque formation and destabilisation, as a potential marker of high risk vulnerable plaques. METHODS: EMMPRIN was analysed in pre-operative serum samples from patients with symptomatic and asymptomatic carotid artery stenosis by a specific ELISA. Pre-operative duplex sonography classified the atherosclerotic plaque due to echogenicity. Histopathological analysis of vulnerable and non-vulnerable plaques was based on the American Heart Association (AHA) classification. RESULTS: The study included 265 patients undergoing carotid endarterectomy: 90 (m:f, 69:21) patients with symptomatic and 175 (m:f, 118:57) with asymptomatic disease. Analysis of circulating EMMPRIN revealed significantly higher levels in patients with echolucent plaques (4 480; IQR 3 745, 6 144 pg/mL) compared with echogenic plaques (4 159; IQR 3 418, 5 402 pg/mL; p = .025). Asymptomatic patients with vulnerable plaques had significantly higher levels of EMMPRIN (4 875; IQR 3 850, 7 016 pg/mL) compared with non-vulnerable plaques (4 109; IQR 3 433, 5 402 pg/mL; p < .001). In logistic regression analysis, duplex sonography combined with age, gender, and clinical risk factors predicted vulnerable plaques in asymptomatic patients with an AUC of 0.71 (95% CI 0.61 - 0.80). EMMPRIN significantly improved the AUC in asymptomatic patients (AUC 0.79; 95% CI 0.71 - 0.87; p = .014). CONCLUSION: Patients with high risk plaques according to ultrasound and histopathological characteristics demonstrated increased serum EMMPRIN levels. EMMPRIN on top of clinical risk factors, including age, gender, and duplex sonography may be used for pre-operative risk stratification in asymptomatic patients.

What is the optimal anesthetic monitoring regarding immediate and short-term outcomes after liver transplantation?-A systematic review of the literature and expert panel recommendations.

BACKGROUND: Liver transplant centers vary in approach to intraoperative vascular accesses, monitoring of cardiac function and temperature management. Evidence is limited regarding impact of selected modalities on postoperative outcomes. OBJECTIVES: To review the literature and provide expert panel recommendations on optimal intraoperative arterial blood pressure (BP), central venous pressure (CVP), and vascular accesses, monitoring of cardiac function and intraoperative temperature management regarding immediate and short-term outcomes after orthotopic liver transplant (OLT). METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Recommendations made for: (1) Vascular accesses, arterial BP and CVP monitoring, (2) cardiac function monitoring, and (3) Intraoperative temperature management (CRD42021239908). RESULTS: Of 2619 articles screened 16 were included. Studies were small, retrospective, and observational. Vascular access studies demonstrated low rates of insertion complications. TEE studies demonstrated low rates of esophageal hemorrhage. One study found lower hospital-LOS and 30-day mortality in patients monitored with both PAC and TEE. Other monitoring studies were heterogenous in design and outcomes. Temperature studies showed increased blood transfusion and ventilation times in hypothermic groups. CONCLUSIONS: Recommendations were made for; routine arterial and CVP monitoring as a minimum standard of practice, consideration of discrepancy between peripheral and central arterial BP in patients with hemodynamic instability and high vasopressor requirements, and routine use of high flow cannulae while monitoring for extravasation and hematoma formation. Availability and expertise in PAC and/or TEE monitoring is strongly recommended particularly in hemodynamic instability, portopulmonary HT and/or cardiac dysfunction. TEE use is recommended as an acceptable risk in patients with treated esophageal varices and is an effective diagnostic tool for emergency cardiovascular collapse. Maintenance of intraoperative normothermia is strongly recommended.

Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study.

BACKGROUND: Although the number of lung transplantations (LTx) performed worldwide for COVID-19 induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of most severly ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx to the pandemic are unknown. METHODS: A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-Cov-2) infection admitted between January 1, 2020 and May 30, 2021 in Austria. Patients referred to one of the two Austrian LTx centers were analyzed and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared to patients who underwent LTx for other indications. RESULTS: Between January 1, 2020 and May 30, 2021, 39.485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation, 183 received extra-corporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. With a median follow-up of 134 (47-450) days, 14/19 patients are alive. CONCLUSIONS: Early referral of ECMO patients to a LTx center is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.

Suitable CO2 Solubility Models for Determination of the CO2 Removal Performance of Oxygenators.

CO2 removal via membrane oxygenators during lung protective ventilation has become a reliable clinical technique. For further optimization of oxygenators, accurate prediction of the CO2 removal rate is necessary. It can either be determined by measuring the CO2 content in the exhaust gas of the oxygenator (sweep flow-based) or using blood gas analyzer data and a CO2 solubility model (blood-based). In this study, we determined the CO2 removal rate of a prototype oxygenator utilizing both methods in in vitro trials with bovine and in vivo trials with porcine blood. While the sweep flow-based method is reliably accurate, the blood-based method depends on the accuracy of the solubility model. In this work, we quantified performances of four different solubility models by calculating the deviation of the CO2 removal rates determined by both methods. Obtained data suggest that the simplest model (Loeppky) performs better than the more complex ones (May, Siggaard-Anderson, and Zierenberg). The models of May, Siggaard-Anderson, and Zierenberg show a significantly better performance for in vitro bovine blood data than for in vivo porcine blood data. Furthermore, the suitability of the Loeppky model parameters for bovine blood (in vitro) and porcine blood (in vivo) is evaluated.

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial.

The use of colloids may impair hemostatic capacity. However, it remains unclear whether this also holds true when colloids are administered in a goal-directed manner. The aim of the present study was to assess the effect of goal-directed fluid management with 6% hydroxyethyl starch 130/0.4 on hemostasis compared to lactated Ringer's solution in patients undergoing partial hepatectomy. We included 50 patients in this prospective, randomized, controlled trial. According to randomization, patients received boluses of either hydroxyethyl starch or lactated Ringer's solution within the scope of goal-directed fluid management. Minimum perioperative FIBTEM maximum clot firmness (MCF) served as the primary outcome parameter. Secondary outcome parameters included fibrinogen levels and estimated blood loss. In the hydroxyethyl starch (HES) group the minimum FIBTEM MCF value was significantly lower (effect size -6 mm, 95% CI -10 to -3, p < 0.001) in comparison to the lactated Ringer's solution (RL) group. These results returned to normal within 24 h. We observed no difference in plasma fibrinogen levels (RL 3.08 ± 0.37 g L-1 vs HES 2.65 ± 0.64 g L-1, p = 0.18) or the amount of blood loss between the two groups (RL 470 ± 299 mL vs HES 604 ± 351 mL, p = 0.18). We showed that goal-directed use of HES impairs fibrin polymerization in a dose-dependent manner when compared with RL. Results returned to normal on the first postoperative day without administration of procoagulant drugs and no differences in blood loss were observed.

Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation.

BACKGROUND: Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT). METHODS: Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival. RESULTS: Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374-5133] vs 3838 [3202-4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival. CONCLUSIONS: Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.

Urinary [TIMP-2] × [IGFBP-7] for predicting acute kidney injury in patients undergoing orthotopic liver transplantation.

BACKGROUND: The product of the concentrations of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (urinary [TIMP-2] × [IGFBP-7]) has been suggested as biomarker for early detection of acute kidney injury (AKI) in various clinical settings. However, the performance of urinary [TIMP-2] × [IGFBP-7] to predict AKI has never been assessed in patients undergoing orthotopic liver transplantation (OLT). Thus, the aim of this study was to assess the early predictive value of urinary [TIMP-2] × [IGFBP-7] for the development of AKI after OLT. METHODS: In this observational study, urinary [TIMP-2] × [IGFBP-7] was measured in samples from adult OLT patients. AKI was diagnosed and classified according to KDIGO criteria. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of urinary [TIMP-2] × [IGFBP-7] for the development of AKI. RESULTS: Forty patients (mean age 55 ± 8 years) were included. Twenty-eight patients (70%) developed AKI stage 1, 2, or 3 within 48 h after OLT. Urinary [TIMP-2] × [IGFBP-7] was not predictive for AKI at the end of OLT (AUC: 0.54, CI [0.32-0.75], P = 0.72), at day 1 (AUC: 0.60, CI [0.41-0.79], P = 0.31), or day 2 after OLT (AUC: 0.63, CI [0.46-0.8], P = 0.18). CONCLUSION: Based on our results, routine clinical use of urinary [TIMP-2] × [IGFBP-7] cannot be recommended for risk assessment of AKI in patients undergoing OLT.

Basic Performance Tests of the MILL Intravascular CO2 Removal Catheter.

Currently available treatment methods for acute lung failure show high rates of complications. There is an urgent need for alternative treatment methods. A catheter device which can be minimal invasively inserted into the vena cava for intracorporeal gas exchange was developed. Main components of the device are a drive unit and a membrane module. In this study, the flow behavior in a vena cava model with inserted catheter prototype was investigated in experiments and basic computational fluid dynamic (CFD) simulations. Main findings are that the miniature blood pump has suitable characteristics and generates sufficient power to overcome the pressure drop induced in the membrane module, and that the design of the membrane outlet might be critical to avoid additional pressure losses. Parts manufactured with a high resolution 3D printer have proven to be suitable for the prototyping process.

Impact of a remifentanil supply shortage on mechanical ventilation in a tertiary care hospital: a retrospective comparison.

BACKGROUND: The continuous administration of opioids in critical care patients is a common therapy for the tolerance of mechanical ventilation. Opioid choice has a crucial impact on the length of mechanical ventilation. Owing to its very short context-sensitive half-life, remifentanil widens the available options for sedoanalgetic strategies. Supply disruption of such established intensive care medication has been reported to worsen clinical outcomes. METHODS: This retrospective study investigated the influence of a nationwide supply shortage of remifentanil on mechanical ventilation and ventilation-associated outcomes at three perioperative intensive care units (ICUs) in a tertiary care hospital in Vienna. Two groups were followed: patients admitted to the ICU during the remifentanil shortage (July 1, 2016 to September 30, 2016) and a control group one year after the remifentanil shortage (July 1, 2017 to September 30, 2017). Included patients were adults, received mechanical ventilation for at least 6 h, were admitted less than 90 days in the respective ICU, and survived their admission. RESULTS: For comparison, Poisson count regression models and logistic regression models were computed. To compensate for multiple testing, the significance level was split (0.02 for the primary and 0.006 for secondary outcome parameters). Patients in the remifentanil shortage group received significantly longer mechanical ventilation (risk ratio 2.19, 95% confidence interval 2.14-2.24, P <0.001) with significantly prolonged ICU stay (P <0.001), days with non-invasive ventilation (P <0.001), and length of hospital stay (P <0.001). No significant difference was found in the occurrence of pneumonia (P = 0.040) and sepsis (P = 0.061). A greater proportion of patients in the shortage group underwent secondary tracheostomy (P <0.001). CONCLUSIONS: The remifentanil shortage caused a significant impairment of essential outcome parameters in the ICU.

Increased serum concentrations of soluble ST2 predict mortality after burn injury.

BACKGROUND: Large burn injuries induce a systemic response in affected patients. Soluble ST2 (sST2) acts as a decoy receptor for interleukin-33 (IL-33) and has immunosuppressive effects. sST2 has been described previously as a prognostic serum marker. Our aim was to evaluate serum concentrations of sST2 and IL-33 after thermal injury and elucidate whether sST2 is associated with mortality in these patients. METHODS: We included 32 burn patients (total body surface area [TBSA] >10%) admitted to our burn intensive care unit and compared them to eight healthy probands. Serum concentrations of sST2 and IL-33 were measured serially using an enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: The mean TBSA was 32.5%±19.6%. Six patients (18.8%) died during the hospital stay. Serum analyses showed significantly increased concentrations of sST2 and reduced concentrations of IL-33 in burn patients compared to healthy controls. In our study cohort, higher serum concentrations of sST2 were a strong independent predictor of mortality. CONCLUSIONS: Burn injuries cause an increment of sST2 serum concentrations with a concomitant reduction of IL-33. Higher concentrations of sST2 are associated with increased in-hospital mortality in burn patients.

Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

OBJECTIVES: Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept. METHODS: All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed. RESULTS: Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population. CONCLUSIONS: Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides stable postoperative conditions and seems to further improve the results.

Graft-derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation.

Experimental studies suggest that macrophage migration inhibitory factor (MIF) mediates ischemia/reperfusion injury during liver transplantation. This study assessed whether human liver grafts release MIF during preservation, and whether the release of MIF is proportional to the extent of hepatocellular injury. Additionally, the association between MIF and early allograft dysfunction (EAD) after liver transplantation was evaluated. Concentrations of MIF, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured in effluents of 38 liver grafts, and in serum of recipients. Concentrations of MIF in the effluent were greater than those in the recipients' serum before and after reperfusion (58 [interquartile range, IQR:23-79] µg/mL vs 0.06 [IQR:0.03-0.07] µg/mL and 1.3 [IQR:0.7-1.8] µg/mL, respectively; both P<.001). Effluent MIF concentrations correlated with effluent concentrations of the cell injury markers ALT (R=.51, P<.01), AST (R=.51, P<.01), CK (R=.45, P=.01), and LDH (R=.56, P<.01). Patients who developed EAD had greater MIF concentrations in effluent and serum 10 minutes after reperfusion than patients without EAD (Effluent: 80 [IQR:63-118] µg/mL vs 36 [IQR:20-70] µg/mL, P=.02; Serum: 1.7 [IQR:1.2-2.5] µg/mL vs 1.1 [IQR:0.6-1.7] µg/mL, P<.001). CONCLUSION: Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.

Increased trefoil factor 2 levels in patients with chronic kidney disease.

In chronically damaged tissue, trefoil factor family (TFF) peptides ensure epithelial protection and restitution. In chronic kidney disease (CKD), TFF1 and TFF2 are reported to be upregulated. Especially in the early phase, CKD is associated with silently ongoing renal damage and inflammation. Moreover, many patients are diagnosed late during disease progression. We therefore sought to investigate the potential of TFF2 as biomarker for CKD. We followed 118 patients suffering from predialysis CKD and 23 healthy volunteers. TFF2 concentrations were measured using ELISA. Our results showed, that median TFF2 serum levels were significantly higher in patients with later CKD stages as compared to healthy controls (p < 0.001) or early stages (p < 0.001). In patients with mid CKD stages TFF2 serum levels were significantly higher than in healthy controls (p = 0.002). Patients with early or mid CKD stages had significantly higher TFF2 urine concentrations than later CKD stages (p < 0.001 and p = 0.009, respectively). Fractional TFF2 excretion differed significantly between early CKD stages and healthy controls (p = 0.01). ROC curve showed that TFF2 levels can predict different CKD stages (AUC > 0.75). In conclusion, urine and serum TFF2 levels of CKD patients show a different profile dependent on CKD stages. Whereas TFF2 urine levels continuously decreased with disease progression, TFF2 serum concentrations progressively increased from the early to later CKD stages, indicating changes in renal function and offering the potential to examine the course of CKD.

A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients.

BACKGROUND: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. METHODS: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 µg or 200 µg IC43 with adjuvant, or 100 µg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. RESULTS: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 µg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups. CONCLUSION: This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 µg IC43 without adjuvant compared with 200 µg IC43 with adjuvant, the 100 µg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.

Practice of hemodynamic monitoring and management in German, Austrian, and Swiss intensive care units: the multicenter cross-sectional ICU-CardioMan Study.

BACKGROUND: Hemodynamic instability is frequent and outcome-relevant in critical illness. The understanding of complex hemodynamic disturbances and their monitoring and management plays an important role in treatment of intensive care patients. An increasing number of treatment recommendations and guidelines in intensive care medicine emphasize hemodynamic goals, which go beyond the measurement of blood pressures. Yet, it is not known to which extent the infrastructural prerequisites for extended hemodynamic monitoring are given in intensive care units (ICUs) and how hemodynamic management is performed in clinical practice. Further, it is still unclear which factors trigger the use of extended hemodynamic monitoring. METHODS: In this multicenter, 1-day (November 7, 2013, and the preceding 24 h) cross-sectional study, we retrieved data on patient monitoring from ICUs in Germany, Austria, and Switzerland by means of a web-based case report form. One hundred and sixty-one intensive care units contributed detailed information on availability of hemodynamic monitoring. In addition, detailed information on hemodynamic monitoring of 1789 patients that were treated on due date was collected, and independent factors triggering the use of extended hemodynamic monitoring were identified by multivariate analysis. RESULTS: Besides basic monitoring with electrocardiography (ECG), pulse oximetry, and blood pressure monitoring, the majority of patients received invasive arterial (77.9 %) and central venous catheterization (55.2 %). All over, additional extended hemodynamic monitoring for assessment of cardiac output was only performed in 12.3 % of patients, while echocardiographic examination was used in only 1.9 %. The strongest independent predictors for the use of extended hemodynamic monitoring of any kind were mechanical ventilation, the need for catecholamine therapy, and treatment backed by protocols. In 71.6 % of patients in whom extended hemodynamic monitoring was added during the study period, this extension led to changes in treatment. CONCLUSIONS: Extended hemodynamic monitoring, which goes beyond the measurement of blood pressures, to date plays a minor role in the surveillance of critically ill patients in German, Austrian, and Swiss ICUs. This includes also consensus-based recommended diagnostic and monitoring applications, such as echocardiography and cardiac output monitoring. Mechanical ventilation, the use of catecholamines, and treatment backed by protocol could be identified as factors independently associated with higher use of extended hemodynamic monitoring.

Impact of different sedation protocols and perioperative procedures on patients admitted to the intensive care unit after maxillofacial tumor surgery of the lower jaw: A retrospective study.

Maxillofacial tumor surgery often necessitates prolonged invasive ventilation to prevent blockage of the respiratory tract. To tolerate ventilation, continuously administered sedatives are recommended. Half-time of sedative or analgesic medication is an important characteristic by which narcotic drugs are chosen, due to the fact that weaning period increases with half-time. The aim of our study was to investigate whether a change in sedation regimen would affect the length of invasive ventilation or intensive care unit stay and medical costs. Additionally, the impact of various surgical procedures was analyzed. Data of 157 patients after mandibular surgery were retrospectively analyzed over 5 years in count regression models. Of those patients, 84 received a sedation regimen with sufentanil and midazolam and 73 with remifentanil and propofol. The impact of the surgical procedures (tracheostomy, tumor resection, neck dissection and length of operation) and the patient age and sex were analyzed with respect to length of ventilation and ICU days. Cost savings were calculated. Our data show that patients receiving remifentanil/propofol had fewer ventilation days (2.5 ± 2.5 versus 6.1 ± 4.6 days, P < 0.001) and were discharged earlier from the intensive care unit than patients receiving sufentanil/midazolam (5.1 ± 3.8 versus 9.2 ± 6.2 days, P < 0.001), leading to calculated cost savings of about 8000 Euro per patient. Length of operation negatively influenced length of ICU stay (P < 0.001). In conclusion, short-acting drugs such as remifentanil/propofol, as well as tracheostoma and shortened surgery duration may reduce the postoperative need for invasive ventilation and length of intensive care unit stay.