Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce bile leakage after hepatic resection: the PREBOT-II trial.

INTRODUCTION: Bile leakage represents a major cause of morbidity following hepatic resection. Although most patients can be managed non-operatively, this complication requires diagnostics and therapeutic interventions. Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent bile leakage. The aim of the PREBOT-II trial is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent bile leakage following hepatic resection. METHODS AND ANALYSIS: The PREBOT-II trial is an investigator-initiated, exploratory, multicentre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups. 70 patients scheduled for hepatic resection will be randomised to either the intervention or the control group. Patients of the intervention group will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi 3-10 days before surgery, whereas in the control group only hepatic resection will be performed. The primary endpoint is the occurrence of a postoperative bile leakage within 30 days after hepatic resection according to the definition of the International Study Group of Liver Surgery. The secondary endpoints comprise further postoperative morbidity parameters such as severity of postoperative bile leakage, post-hepatectomy haemorrhage or liver failure, mortality and quality of life up to 3 months after hepatic resection. Safety and feasibility of the procedure will also be recorded. ETHICS, FUNDING AND DISSEMINATION: The PREBOT-II trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4044932) and the Ethics Committee of Heidelberg University (reference number AFmu-558/2021). This trial is supported by the German Federal Ministry of Education and Research. The results will be presented at national and international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00024061, EudraCT: 2020-006001-35.

Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce postoperative pancreatic fistula after distal pancreatectomy: the PREBOTPilot trial.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is still the most frequently occurring and clinically relevant complication after distal pancreatectomy (DP). Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent POPF. The aim of this project (PREBOTPilot) is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent clinically relevant POPF following DP. METHODS AND ANALYSIS: PREBOTPilot is an investigator-initiated, single-centre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups and an exploratory study design. 60 patients scheduled for DP will be randomised to intervention and control group. In the intervention group, patients will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi, whereas in the control group no preoperative endoscopy will be performed. The combined primary endpoint is the occurrence of clinically relevant POPF and/or death within 30 days after DP. The secondary endpoints comprise further postoperative outcome parameters and quality of life up to 3 months after DP as well as safety and feasibility of the procedure. Statistical analysis is based on the modified intention-to-treat population, excluding patients without status post DP. For safety analysis, rates of adverse events (AEs) and serious AEs will be calculated with 95% CIs for group comparisons. ETHICS, FUNDING AND DISSEMINATION: PREBOTPilot has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4043654) and the Ethics Committee of Heidelberg University (reference number AFmo-523/2019). This trial is supported by the German Federal Ministry of Education and Research (BMBF). The results of the trial will be presented at national and international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00020401.

Effect of Superficial Cervical Plexus Block on Baroreceptor Sensitivity in Patients Undergoing Carotid Endarterectomy.

OBJECTIVES: Regional anesthesia for patients undergoing carotid endarterectomy is associated with improved intraoperative hemodynamic stability compared with general anesthesia. The authors hypothesized that the reported advantages might be related to attenuated ipsilateral baroreflex control of blood pressure, caused by chemical denervation of the carotid bulb baroreceptor nerve fibers. DESIGN: A prospective cohort study. SETTING: Single-center university hospital. PARTICIPANTS: The study included 46 patients undergoing carotid endarterectomy using superficial cervical block. INTERVENTIONS: A noninvasive computational periprocedural measurement of baroreceptor sensitivity was performed in all patients. Two groups were formed, depending on the patients' subjective response to surgical stimulation regarding the necessity of additional intraoperative local anesthesia (LA) administration on the carotid bulb. Group A (block alone) included 23 patients who required no additional anesthesia, and group B (block + LA) consisted of 23 patients who required additional anesthesia. MEASUREMENTS AND MAIN RESULTS: Baroreceptor sensitivity showed no significant change after application of the block in both groups (group A: median [IQR], 5.19 [3.07-8.54] v 4.96 [3.1-9.07]; p = 0.20) (group B: median [IQR], 4.47 [3.36-8.09] v 4.53 [3.29-8.01]; p = 0.55). There was a significant decrease in baroreceptor sensitivity in group B after intraoperative LA administration (median [IQR], 4.53 [3.29-8.01] v 3.31 [2.26-7.31]; p = 0.04). CONCLUSIONS: Standard superficial cervical plexus block did not impair local baroreceptor function, and, therefore, it was not related to improved cerebral perfusion in awake patients undergoing carotid endarterectomy. However, direct infiltration of the carotid bulb was associated with the expected attenuation of baroreflex sensitivity.

Methylglyoxal as a new biomarker in patients with septic shock: an observational clinical study.

INTRODUCTION: The role of reactive carbonyl species, such as methylglyoxal (MG), has been overlooked within the context of the sepsis syndrome. The aims of this study were to assess the impact of MG formation in different inflammatory settings and to evaluate its use for early diagnosis as well as prognosis of the sepsis syndrome. METHODS: In total, 120 patients in three groups were enrolled in this observational clinical pilot study. The three groups included patients with septic shock (n = 60), postoperative controls (n = 30), and healthy volunteers (n = 30). Plasma samples from patients with septic shock were collected at sepsis onset and after 24 hours and 4, 7, 14, and 28 days. Plasma samples from postoperative controls were collected prior to surgery, immediately following the end of the surgical procedure as well as 24 hours later and from healthy volunteers once. Plasma levels of MG were determined by high-performance liquid chromatography. Additionally, plasma levels of procalcitonin, C-reactive protein, soluble CD14 subtype, and interleukin-6 were determined. RESULTS: Patients with septic shock showed significantly higher plasma levels of MG at all measured times, compared with postoperative controls. MG was found to identify patients with septic shock more effectively-area under the curve (AUC): 0.993-than procalcitonin (AUC: 0.844), C-reactive protein (AUC: 0.791), soluble CD14 subtype (AUC: 0.832), and interleukin-6 (AUC: 0.898) as assessed by receiver operating characteristic (ROC) analysis. Moreover, plasma levels of MG in non-survivors were significantly higher than in survivors (sepsis onset: *P = 0.018 for 90-day survival; **P = 0.008 for 28-day survival). Plasma levels of MG proved to be an early predictor for survival in patients with septic shock (sepsis onset: ROC-AUC 0.710 for 28-day survival; ROC-AUC 0.686 for 90-day survival). CONCLUSIONS: MG was identified as a marker for monitoring the onset, development, and remission of sepsis and was found to be more useful than routine diagnostic markers. Further studies are required to determine the extent of MG modification in sepsis and whether targeting this pathway could be therapeutically beneficial to the patient. TRIAL REGISTRATION: German Clinical Trials Register DRKS00000505. Registered 8 November 2010.

Comparative study of prescribing patterns of tigecycline for trial patients versus non-trial patients.

BACKGROUND: Comparing published trial patients and non-trial patients in clinical practice, clinicians often doubt whether critically ill patients are sufficiently represented in randomised clinical trials. PATIENTS AND METHODS: This study evaluated the extent of infection with multidrug-resistant (MDR) pathogens, anti-microbial combination therapy, off-label use and targeted-treatment in trial patients versus non-trial patients. RESULTS: Tigecycline therapy was prescribed for off-label use in more than half of the non-trial patients; 77% of trial patients received study medication as first-line therapy in contrast to 25% of non-trial patients (p<0.001). Tigecycline therapy was targeted for 27% of trial patients versus 73% of non-trial patients (p<0.001). Ninety-six percent of non-trial patients were treated for nosocomial infections compared to 23% of trial patients (p<0.001). In one out of 22 (4.5%) trial patients an ESKAPE pathogen was found, whereas rates of vancomycin- resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus and extended spectrum-ß lactamase- producing Enterobacteriaceae ranged between 13/165 (8%) and 23/165 (14%) for non-trial patients. CONCLUSION: Tigecycline was used for less critical populations in clinical trials than in clinical practice. Our findings confirm the particular need of potent substances such as tigecycline for critically ill patients.

Patients enrolled in randomised clinical trials are not representative of critically ill patients in clinical practice: observational study focus on tigecycline.

It is being increasingly recognised by clinicians and scientists that participants in randomised clinical trials (RCTs) of antibiotics of last resort do not represent the patients who will later be treated with these drugs. Data on this subject are limited and have not been investigated systematically. This observational study aimed to examine this hypothesis quantitatively, using the example of tigecycline. To evaluate the influence of recruitment, patients eligible for clinical trials were retrospectively compared with ineligible patients regarding baseline and clinical characteristics as well as outcome parameters, e.g. length of hospital stay, intensive care unit (ICU) stay, ventilation and mortality. The clinical characteristics of 187 patients illustrated differences in the nature and severity of disease, co-morbidities and outcome. Eligible and ineligible patients differed in a number of parameters, e.g. median APACHE II score (15.5 vs. 28.0), number of liver transplantations (5% vs. 18%; P=0.048), septic shock (21% vs. 49%; P=0.001), need for mechanical ventilation (30% vs. 79%; P<0.001), mean length of ICU stay (19.3 days vs. 40.7 days) and death (19% vs. 46%; P=0.001). Critically ill patients were under-represented in clinical trials. Moreover, only a minority of patients in clinical practice (13%) were potentially eligible for a pivotal RCT. The disparities likely result from strict exclusion criteria in RCTs and recruitment bias. These data emphasise the importance of including critically ill patients in RCTs of antibiotics against multiresistant bacteria in order to account for those who will later be treated.

Reactive metabolites and AGE-RAGE-mediated inflammation in patients following liver transplantation.

Recent investigations have indicated that reactive metabolites and AGE-RAGE-mediated inflammation might play an important role in the pathogenesis of ischemia-reperfusion injury in liver transplantation. In this observational clinical study, 150 patients were enrolled following liver transplantation from deceased donors. The occurrence of short-term complications within 10 days of transplantation was documented. Blood samples were collected prior to transplantation, immediately after transplantation, and at consecutive time points, for a total of seven days after transplantation. Plasma levels of methylglyoxal were determined using HPLC, whereas plasma levels of L-arginine, asymmetric dimethylarginine, advanced glycation endproducts-carboxylmethyllysine, soluble receptor for advanced glycation endproducts, and total antioxidant capacity were measured by ELISA. Patients following liver transplantation were shown to suffer from increased RAGE-associated inflammation with an AGE load mainly dependent upon reactive carbonyl species-derived AGEs. In contrast, carboxylmethyllysine-derived AGEs were of a minor importance. As assessed by the ratio of L-arginine/asymmetric dimethylarginine, the bioavailability of nitric oxide was shown to be reduced in hepatic IRI, especially in those patients suffering from perfusion disorders following liver transplantation. For the early identification of patients at high risk of perfusion disorders, the implementation of asymmetric dimethylarginine measurements in routine diagnostics following liver transplantation from deceased donors should be taken into consideration.

Pretransplant model for end stage liver disease score predicts posttransplant incidence of fungal infections after liver transplantation.

Liver transplant recipients are at a significant risk for invasive fungal infections (IFI). This retrospective study evaluated the impact of the pretransplant model for end stage liver disease (MELD) on the incidence of posttransplant IFI in a single centre. From 2004 to 2008, 385 liver transplantations were included, from which 210 transplantations were conducted allocated by Child Turcotte Pugh and 175 were allocated by MELD score. Both groups differed regarding the age of transplant recipients (50.1 ± 10.7 vs. 52.5 ± 9.9, P = 0.036), pretransplant MELD score (16.43 ± 8.33 vs. 18.29 ± 9.05), rate of re-transplantations, duration of surgery, demand in blood transfusions and rates of renal impairments. In the MELD era, higher incidences of IFI (pre-MELD 11.9%, MELD 24.0%, P < 0.05) and Candida infections (9% vs. 18.9%, P < 0.05) were observed. There was no difference in the incidence of probable or possible aspergillosis. Mortality, length of stay in intensive care or hospital, and duration of mechanical ventilation did not differ between the pre-MELD and MELD era. Regardless the date of transplantation, patients with fungi-positive samples showed higher mortality rates than patients without. MELD score was analysed as independent predictors for posttransplant IFI. Higher MELD scores predispose to a more problematic postoperative course and are associated with an increase in fungal infections.

Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): establishment of workflow and initial clinical data.

BACKGROUND: To report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center. MATERIALS AND METHODS: We treated 36 pediatric patients (aged 21 or younger) with particle therapy at HIT. Median age was 12 years (range 2-21 years), five patients (14%) were younger than 5 years of age. Indications included pilocytic astrocytoma, parameningeal and orbital rhabdomyosarcoma, skull base and cervical chordoma, osteosarcoma and adenoid-cystic carcinoma (ACC), as well as one patient with an angiofibroma of the nasopharynx. For the treatment of small children, an anesthesia unit at HIT was established in cooperation with the Department of Anesthesiology. RESULTS: Treatment concepts depended on tumor type, staging, age of the patient, as well as availability of specific study protocols. In all patients, particle radiotherapy was well tolerated and no interruptions due to toxicity had to be undertaken. During follow-up, only mild toxicites were observed. Only one patient died of tumor progression: Carbon ion radiotherapy was performed as an individual treatment approach in a child with a skull base recurrence of the previously irradiated rhabdomyosarcoma. Besides this patient, tumor recurrence was observed in two additional patients. CONCLUSION: Clinical protocols have been generated to evaluate the real potential of particle therapy, also with respect to carbon ions in distinct pediatric patient populations. The strong cooperation between the pediatric department and the department of radiation oncology enable an interdisciplinary treatment and stream-lined workflow and acceptance of the treatment for the patients and their parents.

Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury - a randomized interventional trial: the REnal Replacement Therapy Study in Intensive Care Unit PatiEnts.

INTRODUCTION: Acute kidney injury (AKI) is associated with a high mortality of up to 60%. The mode of renal replacement therapy (intermittent versus continuous) has no impact on patient survival. Sustained low efficiency dialysis using a single-pass batch dialysis system (SLED-BD) has recently been introduced for the treatment of dialysis-dependent AKI. To date, however, only limited evidence is available in the comparison of SLED-BD versus continuous veno-venous hemofiltration (CVVH) in intensive care unit (ICU) patients with AKI. METHODS: Prospective, randomized, interventional, clinical study at a surgical intensive care unit of a university hospital. Between 1 April 2006 and 31 January 2009, 232 AKI patients who underwent renal replacement therapy (RRT) were randomized in the study. Follow-up was assessed until 30 August 2009. Patients were either assigned to 12-h SLED-BD or to 24-h predilutional CVVH. Both therapies were performed at a blood flow of 100 to 120 ml/min. RESULTS: 115 patients were treated with SLED-BD (total number of treatments n = 817) and 117 patients with CVVH (total number of treatments n = 877).The primary outcome measure, 90-day mortality, was similar between groups (SLED: 49.6% vs. CVVH: 55.6%, P = 0.43). Hemodynamic stability did not differ between SLED-BD and CVVH, whereas patients in the SLED-BD group had significantly fewer days of mechanical ventilation (17.7 ± 19.4 vs. 20.9 ± 19.8, P = 0.047) and fewer days in the ICU (19.6 ± 20.1 vs. 23.7 ± 21.9, P = 0.04). Patients treated with SLED needed fewer blood transfusions (1,375 ± 2,573 ml vs. 1,976 ± 3,316 ml, P = 0.02) and had a substantial reduction in nursing time spent for renal replacement therapy (P < 0.001) resulting in lower costs. CONCLUSIONS: SLED-BD was associated with reduced nursing time and lower costs compared to CVVH at similar outcomes. In the light of limited health care resources, SLED-BD offers an attractive alternative for the treatment of AKI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00322530.

Pediatric patients with disabilities--assessment of satisfaction with anesthesia.

BACKGROUND: Opinions about satisfaction with care are rarely obtained from disabled children and their carers, and few studies of this type exist in the area of pediatric anesthesia. We specifically aimed to assess groups of children with disabilities and Down syndrome and aimed to identify factors influencing satisfaction in these groups. METHODS: We assessed two groups of children using the Paediatric Perianesthesia Questionnaire (PPQ). Families with Down syndrome children (Down syndrome group, DSG) were approached via a Down syndrome family support magazine, and families with disabled children were enrolled in hospitals. Two hundred and fifteen disabled children (125 from the journal, 90 from the hospitals) were compared to matching controls without disabilities. Controls were drawn randomly using computer-generated tables of random numbers using data from the PPQ validation, to match cases for confounding variables. RESULTS: Satisfaction was lower in both groups with disabilities (P < 0.05) (lowest in the DSG), fewer would choose the hospital or anesthetic department again. In both of the disabled groups, negative comments were related to the anesthetists' behavior during the consultation, the content of the consultation, and how anxiety was dealt with. Ninety five percent in the DSG reported that the anesthetist had not mentioned or enquired about atlantoaxial instability. Satisfaction was lower than the rest of the respective group if memories of the disclosure of the disabling condition were negative (P = 0.006) or if potential offensive terms had been used during the consultation (P < 0.001). CONCLUSIONS: This is the first study to assess families with disabled children for satisfaction with anesthesia. Our findings suggest that parents of children with disabilities are less satisfied with their anesthetic care than parents of children without disabilities. Potential bias comes from the self-selection of the DSG and the recall period in this group.

Cell death biomarkers as early predictors for hepatic dysfunction in patients after orthotopic liver transplantation.

BACKGROUND: Valid prognostic factors for early identification of a complicated course after orthotopic liver transplantation from deceased donors are rare. The aim of this study was to investigate the prognostic value of different cell death biomarkers and inflammatory markers in patients after orthotopic liver transplantation from deceased donors. METHODS: In total, 100 patients were evaluated for short-term complications within 10 days after orthotopic liver transplantation from deceased donors. Blood samples were collected before surgery, immediately after the end of the surgical procedure, and 1 day and 3, 5, and 7 days later. Plasma levels of total keratin 18, keratin 18 fragments, interleukin 6, tumor necrosis factor α, and soluble intercellular adhesion molecule 1 were measured. RESULTS: Total keratin 18 was demonstrated to be favorable in its prognostic value for early identification of a complicated course in comparison to routine markers of liver impairment (e.g., aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase). In contrast, inflammation markers (e.g., interleukin 6, tumor necrosis factor α and soluble intercellular adhesion molecule 1) were unsuitable for predicting early complications after liver transplantation from deceased donors. CONCLUSIONS: For early identification of patients at high risk for complications, the implementation of total keratin 18 measurements in routine diagnostics after orthotopic liver transplantation from deceased donors should be taken into consideration.

L-arginine and asymmetric dimethylarginine are early predictors for survival in septic patients with acute liver failure.

Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24 h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.

Right ventricular function during orthotopic liver transplantation: three-dimensional transesophageal echocardiography and thermodilution.

BACKGROUND: Right ventricular (RV) function is an important aspect of anesthesia management during orthotopic liver transplantation (OLT). Because of its geometrical complexity, assessment of RV dimensions with transesophageal echocardiography (TEE) is a difficult task. The aim of this prospective single-site study was to investigate the feasibility of intraoperative assessment of RV parameters based on reconstructive three-dimensional (3D) TEE and to compare the measurements to thermodilution-derived values acquired with a modified pulmonary artery catheter. MATERIAL/METHODS: Measurements were performed at four different time points during 30 OLT with 3D-TEE. At the same time comparative values of RV parameters were acquired with a fast-response thermistor pulmonary artery catheter. RESULTS: 3D reconstruction was feasible in all patients. RV dimensions measured with 3D-TEE averaged 119.4 ml (± 38.5 ml) for enddiastolic and 68.9 ml (± 27.7 ml) for endsystolic volumes. The RV ejection fraction was 42.2% (± 9.3%). The volumes obtained by thermodilution were 263.7 ml (± 64.5 ml) enddiastolic and 159.3 ml (± 47.5 ml) endsystolic, both significantly greater than by 3D-TEE, and the ejection fraction was found to be 39.5% (± 8.4%). No correlation was found between the volumes or the function determined by either method. CONCLUSIONS: Reconstructive 3D-TEE is a viable technique during OLT and leads to plausible RV parameters. However, no correlation was found with simultaneous measurements or parameters performed with thermodilution. However, based on our data cardiac output measurements by thermodilution appear reasonable. Due to both lack of agreement with 3D-TEE and extraordinary high RV volumes the question about the most valuable monitoring technique of RV dimensions and function during OLT can not finally be answered.

Left ventricular outflow tract: intraoperative measurement and changes caused by mitral valve surgery.

BACKGROUND: The impact of mitral valve surgery on left ventricular outflow tract (LVOT) dimensions is unclear. Real-time three-dimensional transesophageal echocardiography permits excellent visualization of the LVOT and might improve standard two-dimensional measurements. In this study, LVOT area and shape were assessed before and after mitral valve surgery. METHODS: Thirty-five patients undergoing mitral valve repair or replacement were retrospectively included in the study and compared with 15 patients undergoing coronary artery bypass grafting. LVOT area was measured by planimetry. Maximum possible methodologic errors by assuming a circular LVOT and an eccentricity index were calculated. LVOT diameter in a midesophageal long-axis view served to calculate the error for the circular LVOT determined in common intraoperative practice. RESULTS: Common intraoperative two-dimensional measurements underestimated actual LVOT area by 21%. Mitral valve surgery led to a significant reduction of LVOT area by 7%. Although LVOT height remained unchanged, width decreased from 2.72 to 2.53 cm (-7%), resulting in a more circular shape of the LVOT. This effect was more pronounced the smaller the size of the implanted annuloplasty ring or prosthesis. Coronary artery bypass grafting did not affect the LVOT. Left ventricular ejection fraction was significantly correlated with LVOT eccentricity. Impaired ventricular function and higher end-systolic volumes were associated with a rounder shape. CONCLUSIONS: The eccentric LVOT shape leads to a distinct underestimation of its area with two-dimensional measurements. LVOT eccentricity is less distinct in patients with low ejection fractions and higher end-systolic volumes. LVOT width is decreased through annuloplasty rings and prostheses, and the smaller the implanted device, the more profound the reduction.

Viral infections in septic shock (VISS-trial)-crosslinks between inflammation and immunosuppression.

BACKGROUND: Recent investigations provided evidence that herpes simplex virus (HSV-1) and cytomegalovirus (CMV) are reactivated in critically ill individuals. However, at this time, it remains unclear whether these viral infections are of real pathogenetic relevance or represent innocent bystanders. MATERIALS AND METHODS: In total, 60 patients with septic shock were enrolled. Blood samples and tracheal secretion were collected at the time of sepsis diagnosis (T0) as well as 7 d (T1), 14 d (T2), 21 d (T3), and 28 d (T4) later. The following virologic diagnostics were performed: (1) Viral load of herpes simplex virus type1 (HSV-1) and cytomegalovirus (CMV) in blood samples as well as tracheal secretion using polymerase chain reaction (PCR). (2) Detection of CMV-antigen (pp65) in blood samples using immunofluorescence microscopy. Furthermore plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were evaluated using ELISA-kits. RESULTS: Thirty-one patients (51.7%) were found to be positive for HSV-1, whereas in 16 patients (26.7%) CMV could be identified. Patients with a positive PCR for HSV-1 and/or CMV showed a significantly prolonged length of hospital stay and absolute time of respirator-dependant ventilation. Furthermore, survival curves of patients with a high HSV-1-load (>10E8) in tracheal secretion in comparison with those with a lower HSV-1-load (<10E8) revealed a significantly impaired survival. CONCLUSIONS: Viral superinfections with HSV-1 or CMV can frequently be observed in patients with septic shock, especially in those with increased disease severity and a prolonged need for respirator-dependant ventilation. In patients with a viral superinfection morbidity is increased, whereas differences in mortality seem to be dosage-dependant.

Experiences with a PDA-based documentation system in clinical research.

New clinical treatment concepts and the implementation of algorithms usually require extensive documentation for scientifical evaluation and quality assurance. A consequent electronic documentation approach potentially facilitates data integrity and availablity and decreases the amount of time spent with manual transfer from paper data into computer systems. The development and the components of the "Heidelberg PDA-based Clinical Documentation Suite" are described. This system allows electronic documentation and post-processing in a timely manner using an affordable standard Personal Digital Assistant (PDA). It features almost universal customizability to new documentation requirements and can be used with only minimal prior training. Initial experiences are reported and prospective improvement possibilities are discussed.

Surgical intensive care unit - essential for good outcome in major abdominal surgery?

PURPOSE: Surgical intensive care units (ICU) play a pivotal role in perioperative care of patients undergoing major abdominal surgery. Differences in quality of care provided by medical staff in ICUs may be linked to improved outcome. This review aims to elucidate the relationship between quality of care at various ICUs and patient outcome, with the ultimate aim of identifying key measures for achieving optimal outcome. METHODS: We reviewed the literature in PubMed to identify current ICU structural and process concepts and variations before evaluating their respective impact on quality of care and outcome in major abdominal surgery. RESULTS: ICU leadership, nurse and physician staffing, and provision of an intermediate care unit are important structural components that impact on patients' outcome. A "mixed ICU" model, with intensivists primarily caring for the patients in close cooperation with the primary physician, seems to be the most effective ICU model. Surgeons' involvement in intensive care is essential, and a close cooperation between surgeons and anesthesiologists is vital for good outcome. Current general process concepts include early mobilization, enteral feeding, and optimal perioperative fluid management. To decrease failure-to-rescue rates, procedure-specific intensive care processes are particularly focused on the early detection, assessment, and timely and consistent treatment of complications. CONCLUSIONS: Several structures and processes in the ICU have an impact on outcome in major abdominal surgery. ICU structures and care processes connected with optimal outcome could be transmitted to other centers to improve outcome, independent of procedure volume.

Infrahepatic inferior vena cava clamping for reduction of central venous pressure and blood loss during hepatic resection: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of infrahepatic inferior vena cava (IVC) clamping for reduction of central venous pressure (CVP) and blood loss during hepatic resection. BACKGROUND: Low CVP during parenchymal transection has been widely accepted to reduce intraoperative hemorrhage via the hepatic veins and is commonly achieved by anesthesiological interventions such as fluid restriction. We hypothesized that infrahepatic clamping of the IVC may lower the intraoperative blood loss more effectively and, moreover, prevent potential adverse effects of fluid restriction such as hemodynamic instability. METHODS: Patients scheduled for elective hepatic resection were enrolled and allocated randomly to CVP reduction by infrahepatic IVC clamping or anesthesiological interventions including primarily fluid restriction with additional use of diuretics, nitro compounds, and opioids (control group). The primary efficacy endpoint was total intraoperative blood loss. Analyses were done following intention-to-treat principles. The protocol was submitted to the clinicaltrials.gov registry (NCT00732979). RESULTS: From April 2007 to December 2009, a total of 152 patients were randomized and 128 were eligible for final analyses. Baseline data were similar between both study groups. Despite higher CVP values during resection (4.0 ± 3.2 vs. 2.6 ± 1.8 mm Hg; P = 0.003), infrahepatic IVC clamping significantly reduced total intraoperative blood loss [550 (350.0-1150) mL vs. 900 (500-1500) mL; P = 0.02] and blood loss during parenchymal transection [150 (85-500) mL vs. 400 (200-700) mL; P = 0.006] compared with the control group. Postoperative mortality [4 (6.1%) vs. 2 (3.2%); P = 0.42] and total morbidity rates [38 (58.5%) vs. 37 (58.7%); P = 0.97] were comparable between both study groups. Although intraoperative hemodynamic instability occurred less frequently in patients with infrahepatic IVC clamping [0 vs. 4 (6.3%); P = 0.04], the incidence of pulmonary embolism was increased in this study arm [4 (6.1%) vs. 0; P = 0.04]. CONCLUSIONS: Infrahepatic IVC clamping is associated with significantly less intraoperative blood loss and may reduce the incidence of intraoperative hemodynamic instability. The potential association with postoperative pulmonary embolism represents a significant concern.