[Severe Candida sepsis in a 28-year-old female patient with initial diagnosis of diabetes mellitus and marked hyperosmolar coma]. / Fulminante Candida-Sepsis bei einer 28-jährigen Patientin mit Erstdiagnose eines Diabetes mellitus und ausgeprägtem hyperosmolarem Koma.

We report on a 28-year-old female patient who had no history of diseases and who was brought to our intensive care unit in a comatose state by the ambulance service. The clinical picture corresponded to sepsis with a massively increased blood sugar concentration (> 2000 mg/dl) as well as a pronounced skin mycosis in the groin region of the very obese patient (body mass index [BMI]: 33.7 kg/m2) in the physical examination. The treatment of sepsis was initially supplemented by a calculated antifungal treatment. The blood culture diagnosis confirmed the presence of Candida albicans and Candida glabrata. Despite adequate anti-infective treatment, the patient developed a septic shock in the further course, so that the additional escalation of treatment was initiated by renal replacement therapy on the second day and venovenous extracorporeal membrane oxygenation because of an ARDS. Despite all of these measures and maximum intensive care treatment, the patient developed a progressive multiple organ failure. When the pupils became rigid to light, a cerebral computed tomography was carried out. This showed evidence of a severe cerebral edema without signs of cerebral bleeding. Multiple examinations of somatosensory evoked potentials and electroencephalograms showed signs of irreversible brain damage. In view of this poor prognosis the therapeutic measures were limited. The patient died on day 24 after admission to the intensive care unit. The case study shows that antifungal treatment should definitely be considered in the context of sepsis treatment if there is a clinically justified suspicion.The role of the severely altered metabolic situation with massive hyperglycemia and ketoacidosis cannot be finally assessed.

Systemic acidemia impairs cardiac function in critically Ill patients.

BACKGROUND: Acidemia, is associated with reduced cardiac function in animals, but no studies showing an effect of acidemia on cardiac function in humans are reported. In the present study, we examined the effect of acidemia on cardiac function assessed with transpulmonary thermodilution technique with integrated pulse contour analysis (Pulse Contour Cardiac Output, PiCCO™) in a large cohort of critically ill patients. METHODS: This was a prospective multicenter observational cross-sectional study of 297 patients from 6 intensive care units in London, England selected from all patients admitted consecutively between May 2018 and March 2019. Measurements of lowest plasma pH and concurrent assessment of cardiac function were obtained. FINDINGS: There was a significant difference between two pH categories (pH ≤ 7.28 vs. pH > 7.28) for the following variables of cardiac function: SVI (difference in means 32.7; 95% CI: 21 to 45 mL/m2; p < 0.001); GEF (18; 95% CI: 11 to 26%; p < 0.001), dPmax (-331; 95% CI: -510 to -153 mmHg/s; p = 0.001), CFI (0.7; 95% CI: 0.2 to 1.3 1/min; p = 0.01) and CPI (0.09; 95% CI: 0.03 to 0.15 W/m2; p < 0.001). However, there was no significant difference in CI (0.13; 95% CI: -0.20 to 0.47 L/min/m2; p = 0.12) between the pH categories. Also, a significant relationship was found between the quantitative pH and the following variables: SVI (132; 95% CI: 77 to 188 mL/m2; p < 0.001), GEF (74.7; 95% CI: 37.1 to 112.4%; p < 0.001), dPmax (-1587; 95% CI: -2361 to -815 mmHg/s; p < 0.001), CFI (3.5; 95% CI: 0.9 to 6.1 /min; p = 0.009), CPI (0.62; 95% CI: 0.36 to 0.88 W/m2; p < 0.001) and CI (regression coefficient 1.96; 95% CI:0.45 to 3.47 L/min/m2; p = 0.01). INTERPRETATION: Acidemia is associated with impaired cardiac function in seriously ill patients hospitalized in the intensive care unit supporting the potential value of early diagnosis and improvement of arterial pH in these patients. FUNDING: The study was partially supported by unrestricted funds from the UCLA School of Medicine.

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.

Reduction of nosocomial bloodstream infections and nosocomial vancomycin-resistant Enterococcus faecium on an intensive care unit after introduction of antiseptic octenidine-based bathing.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) is emerging in German intensive care units (ICUs). On a 32-bed surgical ICU at a university hospital, increasing numbers of nosocomial cases occurred despite enforcement of hand hygiene and environmental disinfection. AIM: To introduce universal octenidine-based bathing in order to reduce the burden of VRE. METHODS: Between January 2012 and March 2014, patients were screened for VRE on admission and twice weekly. Active surveillance was undertaken for VRE infections and colonizations, and for bloodstream infections (BSI) with any pathogen. Intervention in this before-after study comprised of standardized octenidine-based bathing. Distinct subgroups of VRE colonizations or infections were defined and used for statistical analysis of frequency, prevalence and incidence density. FINDINGS: In the pre-intervention period (January 2012 to April 2013), the admission prevalence of VRE was 4/100 patients and the mean incidence density of nosocomial cases was 7.55/1000 patient-days (PD). Pulsed-field gel electrophoresis analysis revealed prevalence of three vanA and two vanB clusters. In the post-intervention period (August 2013 to March 2014), the admission prevalence of VRE was 2.41/100 patients and the mean incidence density of nosocomial cases was 2.61/1000 PD [P = 0.001 (pre- vs post-intervention)]. Thirteen nosocomial VRE infections were identified in the pre-intervention period, compared with one nosocomial VRE infection in the post-intervention period. Incidence densities of BSI pre- and post-intervention were 2.98 and 2.06/1000 PD (P = 0.15), respectively. CONCLUSION: The epidemiology of emerging VRE appeared as a complex mix of admitted cases and transmissions in small clusters, challenging infection control measures. The implementation of universal octenidine-based bathing combined with a standardized washing regime led to a significant reduction in nosocomial VRE.

Comparison of PulsioFlex® uncalibrated pulse contour method and a modified Fick principle with transpulmonary thermodilution measurements in critically ill patients.

Monitoring of cardiac index (CI) by uncalibrated pulse contour (PC) methods has been shown to be inaccurate in critically ill patients. We tested accuracy and trending of a new pulse contour method and a modified Fick method using central venous oxygen saturation. We studied 21 critically ill and mechanically ventilated patients (age 20-86 years) monitored by PC (PulsioFlex®) and transpulmonary thermodilution (TPTD, PiCCO2®) as reference. At baseline, reference and PC-derived CI (CIPC) were recorded and CI obtained by Fick's method (FM, CIFICK). After four hours, measurements were performed analogously for trending analysis. CI are given in l/min/m2 as mean±standard deviation. At baseline CITPTD was 3.7±0.7, CIPC 3.8±0.7 and CIFICK 5.2±1.8. After 4 hours, CITPTD was 3.5±0.6, CIPC 3.8±1.2 and CIFICK 4.8±1.7. Mean bias for PC at baseline was -0.1 (limits of agreement [LOA] -1.4 to 1.2) and -0.4 (LOA -2.6 to 1.9) after four hours. Percentage errors (PE) were 34% and 60% respectively. FM revealed a bias of -1.5 (LOA -4.8 to 1.8, PE 74%) at baseline and -1.5 (LOA -4.5 to 1.4, PE 68%) at four hours. With an exclusion window of 10% of mean cardiac index, trending analysis by polar plots showed an angular bias of 5° (radial LOA±57°) for PC and 16° (radial LOA±51°) for FM. Although PC values at baseline were marginally acceptable, both methods fail to yield clinically acceptable absolute values. Likewise, trending ability is not adequate for both methods to be used in critically ill patients.

A prospective multicenter evaluation of direct molecular detection of blood stream infection from a clinical perspective.

BACKGROUND: Rapid diagnosis and appropriate antimicrobial therapy are of major importance to decrease morbidity and mortality in patients with blood stream infections (BSI). Blood culture, the current gold standard for detecting bacteria in blood, requires at least 24-48 hours and has limited sensitivity if obtained during antibiotic treatment of the patient. The aim of this prospective multicenter study was to clinically evaluate the application of a commercial universal 16S/18S rDNA PCR, SepsiTest™ (PCR-ST), directly on whole blood. METHODS: In total 236 samples from 166 patients with suspected sepsis were included in the study. PCR-ST results were compared to blood culture, the current gold standard for detecting BSI. Because blood cultures can give false-negative results, we performed an additional analysis to interpret the likelihood of bloodstream infection by using an evaluation based on clinical diagnosis, other diagnostic tests and laboratory parameters. RESULTS: Clinical interpretation of results defined the detected organism to be contaminants in 22 of 43 positive blood cultures (51.2 %) and 21 of 47 positive PCR-ST results (44.7 %). Excluding these contaminants resulted in an overall sensitivity and specificity of the PCR-ST of 66.7 and 94.4 % respectively. Of the 36 clinically relevant samples, 11 BSI were detected with both techniques, 15 BSI were detected with PCR-ST only and 10 with blood culture only. Therefore, in this study, SepsiTest™ detected an additional 71 % BSI compared to blood culture alone. CONCLUSIONS: More clinically relevant BSI were diagnosed by molecular detection, which might influence patient treatment. An improved SepsiTest™ assay suited for routine use can have additional value to blood culture in diagnosing bacteremia in septic patients.

Evaluation of a transcutaneous method to assess canine liver function by indocyanine green plasma disappearance rate in healthy adult Beagle dogs.

A non-invasive, transcutaneous method using near infrared spectroscopy to assess indocyanine green plasma disappearance rate (ICG-PDR) in healthy dogs subjected to different conditions was evaluated in eight healthy purpose-bred Beagles under isoflurane-anaesthesia (Trial 1) and when they had initially recovered from anaesthesia (Trial 2). Plasma ICG concentrations (0, 5, 10, 15, 30 min after rapid ICG injection (0.5 mg/kg) into a peripheral vein were determined by high-performance liquid chromatography in parallel with transcutaneous measurements. ICG clearance (mL/min/kg) and retention rate after 15 min (R15, %) were calculated from plasma concentrations to be 3.09 ± 0.83 (mean ± SD) and 30.6 ± 8.3 in anaesthetised dogs and 3.63 ± 0.88 and 28.1 ± 7.3 in recovering dogs, respectively. ICG-PDR (%/min) and R15 (%) obtained using the transcutaneous method were 7.11 ± 3.18 and 34.6 ± 12.4 (Trial 1) and 7.79 ± 3.33 and 32.3 ± 9.2 (Trial 2). The coefficients of determination (r(2)) for ICG clearance and ICG-PDR were 0.14 (Trial 1) and 0.81 (Trial 2) and 0.47 (Trial 1) and 0.29 (Trial 2) for R15, respectively. The mean bias (lower, upper limit of agreement) for R15 were 5.6 (-12.3, 23.5) (Trial 1) and 3.9 (-12.4, 20.1) (Trial 2). The results suggest good agreement between the two methods in dogs recovering from isoflurane-anaesthesia and the transcutaneous method might be useful in real-time assessment of liver function in conscious dogs.

[Neuroleptic malignant syndrome : Rare cause of fever of unknown origin]. / Malignes neuroleptisches Syndrom : Seltene Ursache für Fieber unklarer Genese.

Neuroleptic malignant syndrome (NMS) is a possible cause of fever of unknown origin (FUO) and is a potentially fatal adverse effect of various drugs, especially of neuroleptics. First generation antipsychotics, such as received by the patient described in this article, are more likely to cause NMS than second generation antipsychotics. The key symptoms are the development of severe muscle rigidity and elevated temperature associated with the use of neuroleptic medication. Malignant catatonia (MC) is an important differential diagnosis of NMS. While neuroleptics can trigger NMS and must be immediately discontinued if NMS occurs, neuroleptic therapy represents the first line treatment for MC. This article describes the case of a patient with schizoaffective disorder where initially the diagnosis of NMS was not clear. Eventually, fever and a markedly elevated serum creatine kinase (CK) led to the correct diagnosis and the appropriate therapy with dantrolene, bromocriptine and amantadine. Furthermore, a thorough review of the currently available literature on NMS is provided.

[Bilateral carotid artery dissection in a kite surfer by strangulation with the kite lines]. / Bilaterale Karotisdissektion eines Kitesurfers durch Strangulation mit Kiteleinen.

While a kite surfer was preparing the kite it was caught by a gust of wind, which blew it 10 m into the air and the cords became entangled around the neck of the kite surfer causing strangulation. After admittance to hospital, the diagnostics revealed multiple injuries including a bilateral dissection of the internal carotid arteries, cerebral edema and multiple fractures. As kitesurfing is gaining popularity severe injuries are becoming more frequent. Safety precautions, such as preparing the kite with two persons, wearing safety equipment and using bars with a safety leash can prevent severe injuries.

Usefulness of broad-range PCR plus sequencing for the diagnosis of bacteremia due to a lung abscess.

The early detection and treatment of sepsis in patients is essential for a positive outcome. Microbiological analysis of blood cultures, as the gold standard for diagnosis, is rather slow. However, more rapid methods like PCR have become available recently and are being evaluated clinically. We present data from the monitoring of a patient with sepsis who was on anti-infective treatment. The patient was positive for Streptococcus pneumoniae by broad-range PCR and sequence analysis in a blood sample and resected lung tissue specimen, the latter embedded in paraffin, while blood culture diagnostics remained negative.

Pre-procedure ultrasound increases the success and safety of central venous catheterization†.

BACKGROUND: Real-time ultrasound (US) in central venous catheterization is superior to pre-procedure US. However, moving real-time US into routine practice is impeded by its perceived expense and difficulty. Currently, pre-procedure US and landmark (LM) methods are most widely used. We investigated these techniques in internal jugular vein (IJV) catheterization in respect of operator experience, complications, and risk factors. METHODS: In an observational non-randomized study, we investigated 606 of ∼1300 procedures, that is, 200 patients were treated under pre-procedure US and 406 under LM [pathfinder (PF) n=202, direct cannulation (DC) n=204]. We recorded first needle pass success rate, success rate after the third attempt, and the cannulation time. Procedures were performed by inexperienced (<100) or experienced (>100 catheterizations) operators. RESULTS: Pre-procedure US was associated with more successful attempts and shorter cannulation times. Under pre-procedure US, 88% of first attempts were successful and 100% of third attempts. The median (range) cannulation time was 39 (10-330) s. Under PF, only 56% of first, and 87% of third, attempts were successful with a median (range) cannulation time of 100 (25-3600) s. Under DC, 61% of first and 89% of third attempts were successful; the median (range) cannulation time was 70 (10-3600) s. Remarkably, inexperienced operators using pre-procedure US (n=38) were significantly faster than experienced operators using PF or DC (n=343) (cannulation time: median 60 s, range 12-330, for inexperienced; 60 s, range 10-3600, for experienced). First puncture success rates were higher (pre-procedure US, inexperienced 84%, PF or DC, experienced 57%). CONCLUSIONS: Pre-procedure US for IJV catheterization is safe, quick, and superior to LM.

[Penetrating neck injury of a blacksmith by splitter projectile]. / Penetrierende Halsverletzung durch ein Splitterprojektil bei Schmiedearbeiten.

Laryngeal injuries are rare but potentially life-threatening injuries. Due to the topography of the neck, accompanying injuries of the greater blood vessels, cervical nerves, thoracic organs and spinal cord are common. Therefore in initial diagnostics, these must be excluded from injuries which determine the prognosis. A patient presented with ventral perforation of the larynx, initial dyspnea, hematemesis and left-sided emphysema of the neck. Cause of the findings, we treated the patient non-operatively in interdisciplinary consensus.

Non-invasive continuous arterial pressure monitoring with Nexfin does not sufficiently replace invasive measurements in critically ill patients.

BACKGROUND: In this study, we tested the reliability of a non-invasive finger-cuff-based continuous arterial blood pressure monitoring device (Nexfin, BMEYE, Amsterdam, NL) in critically ill surgical patients. METHODS: Invasive intra-arterial and non-invasive arterial pressure measurements from 25 patients during a 4-h period were compared at five time points. Correlation and linear regression analysis were used and mean bias, precision [sd of bias] and limits of agreement (LOA) [bias (2.0 sd)] were calculated using the Bland-Altman method. RESULTS: Eight data pairs were excluded because of error message from the non-invasive technique, and thus a total of 117 data pairs were analysed. Overall, correlation between mean arterial pressure (MAP) was r(2)=0.50. Bias, precision, and LOA between invasive and non-invasive MAP were 6 (12) and -18 to +30 mm Hg. In patients requiring norepinephrine (83 data pairs), correlation was r(2)=0.28 and bias, precision, and LOA were 6 (13) and -20 to +32 mm Hg, whereas in patients not receiving norepinephrine (34 data pairs) r(2) was 0.80 and mean bias, precision, and LOA were 6 (11) and -16 to +28 mm Hg. In patients with peripheral oedema (49 data pairs), r(2) was 0.40 and mean bias, precision and LOA were 7 (15) and -23 to +37 mm Hg. In patients without oedema (64 data pairs), r(2) was 0.66 and mean bias, precision, and LOA were 5 (9) and -13 to +23 mm Hg. CONCLUSIONS: Non-invasive blood pressure monitoring with Nexfin does not seem to be sufficiently accurate to replace intra-arterial invasive blood pressure measurements in critically ill patients.

Severe sepsis caused by a linezolid-resistant Enterococcus faecium in a 10-year-old girl after multiple trauma.

While infections caused by Enterococcus faecium resistant to vancomycin (VRE) are increasing, linezolid-resistant strains are still rare. We present the case of a 10-year-old girl with severe sepsis caused by a linezolid-resistant E. faecium (Van-B VRE) after multiple trauma and right-sided hemipelvectomy. The off-label use of a targeted antimicrobial therapy with daptomycin (350 mg/day; approximately 8 mg/kg) for 17 days resulted in rapid normalization of infection parameters and improved clinical status. No side effects were observed and the patient was successfully discharged from the intensive care unit.

Extravascular lung water in ARDS patients.

Acute respiratory distress syndrome (ARDS) is a common entity in critical care medicine and associated with many diagnoses, including trauma and sepsis, which may lead to multiple organ failure and death. Pathophysiologically, increased capillary permeability is the hallmark of ARDS which is characterized by damage of the capillary endothelium and alveolar epithelium in association with impaired fluid removal from the alveolar space and the accumulation of protein-rich fluid inside the alveoli. The clinical management of patients with ARDS is even more difficult, because in the presence of capillary leakage in the lungs, adequate intravascular volume and cardiac preload are required to maintain organ perfusion. The amount of pulmonary edema fluid is, however, difficult to determine at the bedside. Pulmonary edema can be detected on physical examination and may be confirmed by chest radiography. However, it has been shown to be difficult to quantify the extent of pulmonary edema based on chest radiography or other non-invasive measures. The transpulmonary thermo-dye dilution technique has been introduced as an instrument to quantify the fluid in the pulmonary capillary bed, i.e., extravascular lung water (EVLW). This technique has shown to be potentially valuable in the management of critically ill patients and has been further developed to be clinically available nowadays as single transpulmonary thermodilution. The following review deals with the measurement of EVLW and its place in the management of critically ill patients with ARDS.

Influence of prone positioning on the measurement of transpulmonary thermodilution-derived variables in critically ill patients.

BACKGROUND: Patients with respiratory failure undergoing prone positioning (PP) are often monitored by the transpulmonary thermodilution (TPTD) technique. However, it remains unclear whether the measurement of TPTD-derived variables is influenced by PP. We investigated the effects of 135° PP on the accuracy of TPTD-derived variables and their changes over an 8-10 h period of time. METHODS: We studied 16 mechanically ventilated patients who underwent PP for acute respiratory distress syndrome or acute lung injury and received hemodynamic monitoring by the TPTD technique. Measurements of extravascular lung water index (EVLWI), global end-diastolic volume index (GEDVI), ejection fraction corrected GEDVI (cGEDVI), pulmonary vascular permeability index (PVPI) and hemodynamic variables were obtained 10 min before and after positioning and repositioning. One-way analysis of variance and Friedman's test with Student-Newman-Keuls method for all pairwise multiple comparisons were used for statistical analysis. RESULTS: EVLWI increased after proning (12.7 ± 4.7 vs. 14.8 ± 7.8 ml/kg) and remained elevated until end of prone positioning (15.1 ± 7.2 vs. 12.8 ± 4.9 ml/kg) with P < 0.05 for difference between respective time points. After proning, GEDVI remained unchanged (571 ± 153 vs. 593 ± 152 ml/m²). At the end of prone positioning GEDVI was 610 ± 55 ml/m² and decreased after returning to supine to 553 ± 14 ml/m². Proning increased cGEDVI from 525 ± 136 to 570 ± 11 ml/m² and repositioning decreased cGEDVI from 558 ± 116 to 496 ± 121 ml/m². No significant changes in PVPI were observed during the study period. CONCLUSIONS: EVLWI and GEDVI measurements are possibly influenced by prone positioning. In spite of statistical significance, the differences in EVLWI and GEDVI are low and presumably of no clinical relevance.