Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Can regional anaesthesia for lymph-node dissection improve the prognosis in malignant melanoma?

BACKGROUND: Optimized anaesthetic management might improve the outcome after cancer surgery. A retrospective analysis was performed to assess the association between spinal anaesthesia (SpA) or general anaesthesia (GA) and survival in patients undergoing surgery for malignant melanoma (MM). METHODS: Records for 275 patients who required SpA or GA for inguinal lymph-node dissection after primary MM in the lower extremity between 1998 and 2005 were reviewed. The follow-up ended in 2009. Survival was calculated as days from surgery to the date of death or last patient contact. The primary endpoint was mortality during a 10 yr observation period. RESULTS: Of 273 patients included, 52 received SpA and 221 GA, either as balanced anaesthesia (sevoflurane/sufentanil, n=118) or as total i.v. anaesthesia (propofol/remifentanil, n=103). The mean follow-up period was 52.2 (sd 35.69) months after operation. Significant effects on cumulative survival were observed for gender, ASA status, tumour size, and type of surgery (P=0.000). After matched-pairs adjustment, no differences in these variables were found between patients with SpA and GA. A trend towards a better cumulative survival rate for patients with SpA was demonstrated [mean survival (months), SpA: 95.9, 95% confidence interval (CI), 81.2-110.5; GA: 70.4, 95% CI, 53.6-87.1; P=0.087]. Further analysis comparing SpA with the subgroup of balanced volatile GA confirmed this trend [mean survival (months), SpA: 95.9, 95% CI, 81.2-110.5; volatile balanced anaesthesia: 68.5, 95% CI, 49.6-87.5, P=0.081]. CONCLUSIONS: These data suggest an association between anaesthetic technique and cancer outcome in MM patients after lymph-node dissection. Prospective controlled trials on this topic are warranted.

The effect of rosiglitazone on asymmetric dimethylarginine (ADMA) in critically ill patients.

Asymmetric dimethylarginine (ADMA) plays a crucial role in the arginine-nitric oxide pathway. Critically ill patients have elevated levels of ADMA which proved to be a strong and independent risk factor for ICU mortality. The aim of this study was to investigate the effect of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone on ADMA plasma levels in critically ill patients. In a randomized controlled pilot study, ADMA, arginine and symmetric dimethylarginine (SDMA) were measured in 21 critically ill patients on the intensive care unit (ICU). Twelve patients received 4mg rosiglitazone once a day for a maximum of 6 weeks or until discharge or death. Nine patients served as control patients. In addition, total sequential organ failure assessment (SOFA score), kidney function and liver function were determined. Compared to the ADMA levels of healthy individuals as specified in earlier studies, ADMA plasma levels of critically ill patients were significantly higher (0.42+/-0.06 versus 0.73+/-0.2micromol/L, respectively; p<0.001). Both ADMA (B=3.5; 95% CI: 0.5-6.5; p=0.023) and SDMA (B=1.7; 95% CI: 0.7-2.7; p=0.001) were independently related to SOFA scores. Overall, rosiglitazone treatment had no effect on ADMA levels, which only significantly differed between the rosiglitazone and control groups at day 7 (p=0.028). The SOFA score in the rosiglitazone group was lower compared to the control group but the difference was only statistically significant at day 10 (p=0.01). In conclusion, in critically ill patients plasma ADMA levels were elevated and associated with the extent of multiple organ failure, but no significant ADMA-lowering effect of the PPAR-gamma agonist rosiglitazone was observed.

[Sepsis-associated Guillain-Barré syndrome]. / Das Sepsis-assoziierte Guillain-Barré-Syndrom.

This article reports on the case of a multiple trauma patient, who was admitted to the intensive care unit with haemorrhagic shock and severe hypoxaemia. Following posttraumatic septic shock the patient developed quadriplegia 3 weeks after admittance. After having excluded any traumatic and cerebral origins, an analysis of the cerebrospinal fluid was performed and revealed a"dissociation albuminocytologique". This finding in association with limb quadriplegia led to the diagnosis of Guillain-Barré syndrome. Therapy with high-dose i.v. immunoglobulins led to a complete recovery.

Changing from a specialized surgical observation unit to an interdisciplinary surgical intensive care unit can reduce costs and increase the quality of treatment.

BACKGROUND AND OBJECTIVES: In Germany there is considerable variability in the organizational forms of intensive-care medicine. We present economical data that arose during the reorganization of an intensive care unit with the implementation of the continuous presence of a trained intensivist. The unit was changed from an intensive-observational unit managed by four surgical departments without continuous presence of a trained intensivist to an interdisciplinary surgical intensive care unit managed by the Department of Anaesthesia in co-operation with the surgical departments with the continuous presence of trained intensivists. METHODS: Measurement of costs for personnel, medical equipment and external services, revenues, length of hospital stay and complications of cardiac surgical patients. RESULTS: Per year costs for personnel increased by approximately euro240,000, while expenses for medical equipment were reduced by euro245,000. In all, 466 hospital days were saved by the reduction in the length of hospital stay, providing capacity for 22 additional cardiac surgical cases. In addition, the presence of trained intensivists made it possible to provide care for more severely ill patients, which gained approximately 100 additional case-mix points and increased the hospital's revenues by more than euro300,000. Emergency readmission to the intensive care unit was reduced by 17%. The number of patients requiring renal replacement therapy and those developing non-occlusive mesenteric ischaemia was substantially reduced. CONCLUSION: In addition to the medical advantages, staffing the intensive care unit with trained intensivists 24 h a day was of appreciable economical benefit.

Anesthetic management in pediatric patients with epidermolysis bullosa: a single center experience.

BACKGROUND: Anesthesia in children with dystrophic epidermolysis bullosa (EB) presents a significant challenge as many children have a difficult airway and are at risk for additional blistering. In this retrospective study we compared deep sedation/ analgesia and general anesthesia for safety and efficiency. Procedure, type of anesthesia, airway management, complications, time for induction and awakening, length of stay in recovery room, length of procedure were noted and compared, qualitatively and with statistic tests as appropriate. METHODS: Fourteen children underwent 148 procedures: 79 under general anesthesia, 67 under sedation. RESULTS: Several complications - including intubation difficulties and the need for change of airway management - were observed in the general anesthesia group, none in the sedated group. Induction time was 36 min vs. 17 min (P<0.001), mean time to recovery 23 min vs. 6 min (P<0.001). Surgical duration did not differ between groups. CONCLUSIONS: In children with dystrophic EB deep sedation/ analgesia can be safely performed and is less time consuming than traditional management.

Non-return valves do not prevent backflow and bacterial contamination of intravenous infusions.

Non-return valves (NRVs) are designed to avoid backflow of infusion fluid against the designated direction of flow (DDF) when more than one infusion is delivered via one venous access. We tested in vitro whether NRVs reliably prevent flow against the DDF at clinically relevant low flow rates. Since catheter-related infections caused by the infusion of contaminated fluids represent a relevant problem in patient care, we tested whether NRVs preclude bacterial contamination of infusions proximal to the NRVs and thus might play a role in preventing healthcare-associated infections. Additionally, the incidence of bacterial contamination of drips and infusion fluids in our intensive care unit (ICU) was quantified. In vitro, a low flow against the DDF of ten examples each of five different NRV models was applied and the integrity for fluid and transmigration of three different indicator micro-organisms was tested. Second, we investigated whether contamination of intravenous infusion tubing collected from patients treated on our ICU occurred. Largely independent from the model, 40% of the tested NRVs were not leak-tight for fluids when a pressure against the DDF was built up slowly. In 30%, bacteria migrated against the DDF and were detected proximal to the valve. In 6.7% of the tubing samples collected from ICU patients we detected bacterial contamination. In conclusion, contamination of drips is a relevant problem on ICU. NRVs neither reliably prevent backflow of fluids nor serve as micro-organism filters. Therefore they cannot be recommended as a way of reducing healthcare-associated infections.

Ultrasound-guided axillary plexus block in a child with dystrophic epidermolysis bullosa.

We report the use of ultrasound-guided axillary brachial plexus block in a child with dystrophic epidermolysis bullosa needing surgical treatment of the right hand. The regional anaesthesia was used in association with sedation/ anaesthesia. This technique is suitable for these difficult patients because it can minimise the risk of new bullae formation due to palpation of landmarks or unintentional intra- or subcutaneous injections. Initial anaesthesia/sedation was provided with sevoflurane until intravenous access was obtained, following which intravenous propofol infusion with ketamine boluses without any invasive airway management was continued for performance of the block and the procedure. This management plan provided good surgical conditions, early postoperative analgesia, minimised stress for the patient and avoided the need to manipulate the airway with instruments and the associated risk of mucosal bullae. The classification and breadth of clinical manifestation of epidermolysis bullosa is complex and briefly summarised. The anaesthetist should clarify the details of a particular patient's form of epidermolysis bullosa, especially in terms of mucosal involvement, as this may greatly influence planning for a procedure.

[Glycemic control in sepsis and septic shock: friend or foe?]. / Blutzuckerkontrolle bei Patienten mit Sepsis und septischem Schock: Freund oder Feind?

INTRODUCTION: Intensive care patients commonly suffer from hyperglycemia. Evidence is growing that strictly maintaining normoglycemia by intensive insulin therapy (IIT) ameliorates outcome in these patients. Whether or not this also holds true for patients with sepsis and septic shock is the issue of this post-hoc analysis of the database (2,748 patients) of 2 recent prospective clinical trials. MATERIAL AND METHODS: A total of 950 patients suffering from sepsis were identified and of these 462 fulfilled the diagnostic criteria of septic shock upon admission to the intensive care unit (ICU). Patients were treated by either IIT [mean glycemia 5.88 mmol/l (106 mg/dl)] or conventional glucose management [mean glycemia 8.44 mmol/l (152 mg/dl)]. RESULTS: Under IIT the mortality of patients treated for more than 3 days in the ICU was lowered by 7.6% (p=0.03) in septic patients and by 8.7% (p=0.08) in septic shock patients. Polyneuropathy occurred less frequently under IIT compared to conventional glucose management (sepsis -9.8%, septic shock -14%; p<0.001). The incidence of acute renal failure was not affected by either treatment regimen (sepsis -3.3%, septic shock -3.1%; p<0.25). Intensive insulin therapy was associated with an increased risk of hypoglycemia (sepsis +16.7%, septic shock +18.8; p<0.0001) which did not, however, directly affect morbidity nor mortality. CONCLUSIONS: These data suggest that IIT improves outcome of patients with sepsis or septic shock. Hypoglycemia is a frequent complication, but its clinical relevance remains to be defined.

Levosimendan: a promising treatment for myocardial stunning?

We report a case of a 55-year-old male undergoing major orofacial cancer surgery. A stent to the left anterior descending artery had been implanted for ischaemic heart disease 3 years previously. Twenty-four hours after uneventful anaesthesia and surgery, the patient developed myocardial infarction and cardiogenic shock. Immediate percutaneous transluminal coronary angioplasty, intra aortic balloon counterpulsation, and catecholamine therapy failed to stabilise haemodynamics. In light of successful reperfusion therapy and an only moderate elevation of troponin I, myocardial stunning rather than myonecrosis was considered to be the major contributor to life-threatening left ventricular failure. Therefore, the calcium-sensitising drug levosimendan, which exerts positive inotropic activity without increasing myocardial oxygen demand, was administered as a rescue medication. Within 24 h, levosimendan resulted in decreased filling pressures, reduced left ventricular end-diastolic volume, and augmented systemic pressures. Seven days following surgery, the patient was discharged from the intensive care unit in good clinical condition.

[Functional rasterstereographic images. A new method for biomechanical analysis of skeletal geometry]. / Rasterstereographische Funktionsaufnahmen. Eine neue Methode zur biomechanischen Analyse der Skelettgeometrie.

Video rasterstereography has been developed for optical back shape measurement and for biomechanical analysis of spinal and pelvic geometry. Analysis of one single measurement permits 3-dimensional reconstruction of the back surface and calculation of shape parameters including pelvis tilt and torsion. In addition, estimates of the lateral deviation of the spinal midline and of vertebral rotation are provided. Its extended analytic potential makes rasterstereography a very appropriate tool for functional examinations. The term "functional examinations" refers in this context to biomechanical analysis of functional movements of the spine and pelvis caused by quasi-continuous changes of posture, if these can be observed as changes in back shape. Two examples are given to illustrate the aim and performance of functional examinations. Shoe elevation is used to correct leg-length discrepancy and is therefore prescribed for prevention and correction of scoliosis produced by pelvic obliquity. In a previous study it was shown that simulating leg-length discrepancy by raising a foot causes the pelvis to perform a torsional movement about the transverse axis. In effect, this movement reduces to some extent the effect of shoe elevation; thus a larger elevation might give better results. 42 scoliotic patients underwent functional examination. Leg-length discrepancies were simulated in 7 steps, and the resulting back shape was analysed by rasterstereography. The measurements were corrected for pelvic torsion. This method provided satisfactory correspondence with radiographically recorded leg-length discrepancies, i.e. 0.7 mm +/- 11.2 mm. One specific advantage of this procedure is that it covers aspects relating to spinal lateral deviation and vertebral rotation. It is concluded, however, that the 7 measurements used are hardly sufficient for this application and that better results are therefore to be expected from extended series. Kyphosis and lordosis clearly depend on posture. This is confirmed in a functional examination where these angles are measured under voluntary changes of posture. In forward bending, the trunk straightens and kyphosis and lordosis angles decrease. The reverse case applies to backward bending. If this effect is taken into quantitative consideration, an improved accuracy of measurements is obtained by reference to a standardised, mathematically defined posture. The resulting rms-error of kyphosis/lordosis measurement is then reduced from 3.10 degrees/2.95 degrees to 1.65 degrees/1.40 degrees. These figures open up new applications in the follow-up of kyphotic and lordotic deformities.