A sirs-based automated alarm system for the diagnosis of sepsis after burn injury.

The present study examined the effectiveness of an automated systemic inflammatory response syndrome (SIRS)-based alarm system for the early detection of sepsis in adult burn patients. In addition, the relevance of the sepsis criteria from the American Burn Association (ABA) and the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) for this patient group was determined. In this prospective observational study, we included 41 consecutive patients who were admitted to our burn ICU within a one-year period. SIRS alarms were calculated for these patients according to predefined criteria using the PREDEC ALARM automated alarm system and alarms generated according to ABA criteria and daily Sequential Organ Failure Assessment (SOFA) results. The alarms were not visible to the treating doctors and nurses. The alarms identified were related to episodes of sepsis with positive blood cultures. Twenty-one sepsis events were recorded in 41 patients. The receiver operating characteristic (ROC) curve revealed an area under the curve (AUC) of 0.72 for alarms using 2 SIRS criteria, 0.77 for 3 SIRS criteria, and 0.61 for 4 SIRS criteria. AUC values of 0.53 and 0.59 were calculated for the ABA criteria and Sepsis-3 definition, respectively. An alarm system using 3 SIRS criteria proved to be suitable for the early detection of sepsis in burn patients. The frequent number of false alarms requires further refinement of the alarm system. Based on the results of our study, the ABA criteria and the Sepsis-3 definition provide no advantages over the SIRS criteria in the early diagnosis of sepsis after burn injury.

Cette étude évalue l'efficacité d'un système automatique fondé sur les paramètres de SIRS pour la détection précoce du sepsis chez des adultes brûlés. En outre, il étudie la pertinence des critères d'infection de l'ABA et des critères de sepsis selon la conférence Sepsis- 3 chez ces patients. Nous avons inclus 41 patients consécutifs, admis dans notre USI pour brûlés, dans cette étude observationnelle rospective. Les alarmes du système automatique PREDEC ALARM ont été calibrées selon les critères de l'ABA et le score SOFA et comparés aux 21 épisodes septiques à hémocultures positives. Elles étaient cachées aux médecins et infirmières. Les aires sous courbes ROC étaient de 0,72 pour les alarmes basées sur 2 critères de SIRS ; 0,77 pour 3 critères et 0,61 pour 4 critères. Elles étaient de 0,53 pour les critères ABA et 0,59 pour les critères Sepsis-3. Une alarme basée sur 3 critères de SIRS semble donc être utilisable pour détecter précocement un sepsis chez les brûlés, mais le nombre élevé de faux positif nécessite un affinement du système. Les critères ABA et Sepsis-3 ne semblent pas plus efficaces dans ce but.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

[Decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension]. / Dekompensierte Rechtsherzinsuffizienz, Intensiv- und Perioperativ-Management bei Patienten mit pulmonaler Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.

[Management and Outcome of Surgery in Patients with Severe Pulmonary Hypertension--A Single-Center Experience]. / Management und postoperatives Überleben bei chirurgischen Eingriffen an Patienten mit schwerer pulmonaler Hypertonie--etrospektive Analyse eines Zentrums.

BACKGROUND: Patients with pulmonary hypertension (PH) are at high risk when undergoing surgery. Up to one-third of patients suffer complications; recent studies report a mortality rate of 1 to 7%. Frequent events are deterioration of right heart function and infectious or bleeding complications. METHODS: Data of patients (age ≥ 18) with precapillary PH who need to undergo elective surgery between January 2006 and March 2015 were included in this retrospective analysis. All patients who were planned for surgery underwent the same procedure. First, patients were evaluated in the PH center. Thereafter, PH-relevant data were discussed with the surgeon/anesthesiologist team for risk-adapted planning of anesthesia and intervention. The present analysis comprises patient characteristics and information about surgery and post-interventional course. RESULTS: This study analyzes 31 surgical procedures carried out in PH patients (male: n = 8; PH-group I: n = 23, group III: n = 3, group IV: n = 5, mean age: 59.5 ± 15.3 years). Patients were characterized by compromised hemodynamics and exercise capacity: pulmonary vascular resistance: 805.4 ± 328.5 dyn*s*cm(-5), mean pulmonary arterial pressure: 46.3 ± 9.3 mmHg, 6-minute walking distance: 350.3 ± 123.3 m.The majority of interventions were performed under general anesthesia (n = 24). In 25 cases, the intraoperative monitoring was complemented with right heart catheterization.Eight interventions were associated with complications, three of which were serious. One patient died postoperatively owing to sepsis and right heart failure. CONCLUSION: A careful and structured planning of surgical interventions in patients with PH and the choice of surgical procedure and anesthesia adapted to the conditions of PH might help avoid complications. Further multicentric studies are needed.

Multimodal evoked potential monitoring in asleep patients versus neurological evaluation in awake patients during carotid endarterectomy: a single-centre retrospective trial of 651 patients.

BACKGROUND: A controversy exists regarding which monitoring technique is superior in cases in which general anesthesia (GA) is necessary for carotid endarterectomy (CEA). Multimodal evoked potential (mEP) monitoring was investigated under GA during CEA and compared with a historical control group undergoing neurological evaluations awake under loco-regional anesthesia (LA). METHODS: We retrospectively studied 651 patients undergoing elective CEA. In groupHISTORY (N.=349; 1997-1999) LA was provided using superficial or deep/superficial cervical plexus blocks. In groupmEP, (N.=302; 2009-2013) GA was performed by administering remifentanil/propofol infusion. The multimodal EPs included the median-nerve-somatosensory and motor evoked potentials. The primary outcome was the rate of technical failure. The arterio-arterial shunt rate and immediate postoperative motor outcomes were also compared. RESULTS: GroupmEP showed a significantly lower rate of technical failure (OR 0.17; CI 0.03-0.6; P=0.002). Because the groups differed systematically, logistic regression analysis was used to compare shunt rates and motor outcomes. Since shunt rates were 8.3% (groupmEP) versus 8.2% (groupHISTORY), but logistic regression model showed significant differences (OR 3.77; CI 1.67-8.95; P=0.001) correct comparison was impossible. Immediate postoperative deficits were 4.3% (groupmEP) and 4.9% (groupHISTORY); logistic regression analysis: transient OR 0.77, CI 0.28 to 0.22, P=0.61 and permanent OR 0.37, CI 0.02-7.74, P=0.49. CONCLUSION: Monitoring mEPs was associated with less technical failure than awake evaluation and showed similar motor outcomes. Because the groups differed systematically, the interpretation of shunt rates was impossible. Monitoring mEP should be considered to detect intraoperative ischemia in cases in which patients undergo CEA under GA.

Transcranial motor evoked potentials during anesthesia with desflurane versus propofol--A prospective randomized trial.

OBJECTIVE: This study aimed to evaluate differences in transcranial electrical motor evoked potential (tcMEP) amplitudes between desflurane/remifentanil and propofol/remifentanil anesthesia treatment plans in patients without preexisting motor deficits (PMDs) undergoing carotid endarterectomy (CEA). METHODS: This prospective trial included 21 patients who were randomly assigned to an effect group (Group(DESFLURANE); n=14) or a control group (Group(STANDARD-PROPOFOL); n=7). tcMEP amplitudes were measured 35 min post-induction (T1) either with desflurane or propofol. Treatment was then changed to propofol in Group(DESFLURANE). After an additional 35 min, the tcMEP amplitudes were reevaluated (T2). Differences in amplitudes (DW) between T1 and T2 were calculated for each patient, and the means of these differences were compared between groups. RESULTS: tcMEPs were recorded in all 21 patients. At T1, the mean amplitude was 840.1 (SD 50.3) µV and 358.9 (SD 74) µV for Group(STANDARD-PROPOFOL) and Group(DESFLURANE), respectively. The absolute mean difference (T1-T2) between groups was -496.75 µV (p=0.0006). CONCLUSION: Desflurane reduces the tcMEP amplitude significantly more than propofol in patients without PMDs undergoing CEA. SIGNIFICANCE: TcMEPs were recorded in all patients regardless of the anesthesia regimen. In patients with initially small amplitudes, desflurane may limit tcMEP recording because it produces a remarkable amplitude reduction, even in patients without PMDs.

Intraoperative sRAGE kinetics. A new age-related outcome predictor of cardiac surgery.

BACKGROUND: Glycated proteins (advanced glycation endproducts, AGE) in tissue are associated with degenerative diseases. This study evaluated the role of sRAGE (soluble receptor for advanced glycation endproducts), a decoy receptor of AGEs in blood, for the outcome of patients after coronary artery bypass grafting (CABG). METHODS: A total of 90 patients undergoing CABG were analysed in two centres. Perioperative blood samples were collected before surgery up to 1 week postoperatively. sRAGE was measured by ELISA. Patients were subdivided regarding age (< 64 versus > 70 years, 14 % versus 35 % female), euroSCORE (< 3 versus > 4, 14 % versus 29 % female) and sRAGE changes between sternotomy and end of the operation (< 30 % versus > 45 %, 33 % versus 33 % female) and subsequently analysed with respect of postoperative outcome parameters. RESULTS: Preoperative sRAGE values did not correlate with the outcome of the patients. sRAGE levels increase within 10 min from 1,539 ± 96 to 5,311 ± 187 pg/ml after sternotomy, then returning to baseline levels within 2 days after surgery. Comparing the analysed possible risk factors age, euroSCORE and sRAGE changes, no difference was observed regarding 30-day mortality. Age and the euroSCORE are superior with respect of tachyarrythmia, whereas sRAGE kinetics seems to be superior with respect of prolonged postoperative respiration time/stay in the intensive care unit or catecholamine support. CONCLUSION: A prolonged, increased intraoperative sRAGE level is a new outcome predictor for patients undergoing CABG surgery, mutually complementary to the euroSCORE.

Glutamine and alanine-induced differential expression of intracellular IL-6, IL-8, and TNF-α in LPS-stimulated monocytes in human whole-blood.

To investigate the effects of the commonly-used immunomodulators l-glutamine, l-alanine, and the combination of both l-alanyl-l-glutamine (Dipeptamin(®)) on intracellular expression of IL-6, IL-8, and TNF-α during endotoxemia, lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system were investigated by flow cytometry. Whole blood of twenty-seven healthy volunteers was stimulated with LPS and incubated with three different amino acid solutions (1. l-glutamine, 2. l-alanine, 3. l-alanyl-l-glutamine, each concentration 2 mM, 5 mM, incubation time 3 h). CD14(+) monocytes were phenotyped in whole-blood and intracellular expression of cytokines was assessed by flow cytometry. Our investigations showed for the first time in whole blood probes, imitating best physiologically present cellular interactions, that l-glutamine caused a dose-independent inhibitory effect on IL-6 and TNF-α production in human monocytes stimulated with LPS. However, l-alanine had contrary effects on IL-6 expression, significantly upregulating expression of IL-6 in LPS-treated monocytes. The impact of l-alanine on the expression of TNF-α was comparable with glutamine. Neither amino acid was able to affect IL-8 production in LPS-stimulated monocytes. The combination of both did not influence significantly IL-6 and IL-8 expression in monocytes during endotoxemia, however strongly reduced TNF-α production. For the regulation of TNF-α, l-glutamine, l-alanine and the combination of both show a congruent and exponentiated downregulating effect during endotoxemia, for the modulation of IL-6, l-glutamine and l-alanine featured opposite regulation leading to a canceling impact of each other when recombining both amino acids.

[Enrolment of intensive care patients in clinical studies. Ethical, legal and organizational problems from an interdisciplinary point of view]. / Der Einschluss von Intensivpatienten in klinische Studien. Ethische, rechtliche und organisatorische Probleme aus interdisziplinärer Sicht.

Nowadays, most patients in hospital die in the intensive care unit from sepsis and multiple organ failure. Clinical research in this critically ill and vulnerable patient population bears a lot of ethical and legal problems; however, it remains a must in order to develop evidence-based diagnostic and therapeutic strategies for life-threatening diseases with special respect to limited health care resources. With regard to the Declaration of Helsinki, good clinical practice guidelines (GCP) from the European Medicines Agency (EMA) and the German medical drug law (AMG) this article discusses ethical and legal aspects of patient inclusion for clinical trials as well as incentives for appropriate patient recruitment from an interdisciplinary point of view.

Intraoperative monitoring of carotid endarterectomy by transcranial motor evoked potential: a multicenter study of 600 patients.

OBJECTIVE: This study was to investigate the utility of motor evoked potential monitoring elicited by transcranial electrical stimulation (tcMEP) during CEA in addition to the established median nerve somatosensory evoked potentials (mSSEPs). METHODS: We retrospectively reviewed data from 600 patients undergoing CEA under general anesthesia with monitoring of mSSEPs and tcMEPs in a multicenter study. MSSEP and tcMEP parameters were recorded during internal carotid artery (ICA) cross clamping and compared with the postoperative motor outcome, demographic and patient history data. RESULTS: The intraoperative monitoring of tcMEPs was successful in 594 of the patients (99%) and selective shunt was performed in 29 of them (4.83%). Nine of the patients showed a transient contralateral loss of tcMEPs, without changes in mSSEPs and required intervention (1.5% "false-negative"). Three of them showed postoperative motor deficits. The time period from tcMEP loss to intervention was significantly longer (p = 0.01) in this group compared to the patients without postoperative motor deficit. CONCLUSION: TcMEPs during CEA may be an adjunct to mSSEP monitoring to avoid "false-negative" mSSEP results, as mSSEPs seem to lack specificity for detecting isolated ischemia of corticospinal pathway. SIGNIFICANCE: TcMEPs seem to improve postoperative outcome, especially in case of a timely correction of cerebral ischemia.

[Nutrition in the critically ill]. / Ernährung bei Intensivpatienten.

The prognostic impact of inadequate energy and protein supply in malnourished intensive care patients has been recently reemphasized. Consent exists about the beneficial effects of early enteral nutrition in the critically ill. However, gastrointestinal intolerance of the critically ill may be a major problem for the feasibility of enteral nutrition bearing additional risks. In case adequate enteral nutrition cannot be realized, there is controversy about the appropriate time to start total parenteral or combined enteral / parenteral nutrition. Due to potential adverse effects immune-enhancing substrates have to be cautiously administered. For standardization implementation of a guideline based nutritional protocol is recommended. The review refers to the recent guidelines of the European Society for Clinical Nutrition and Metabolism (2009), the American Society for Parenteral and Enteral Nutrition (ASPEN) (2009) and the German Sepsis Society (DSG) (2010).

[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen. Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

[Perioperative infusion therapy in children].

A volume replacement therapy compensates a reduced intravascular volume to stabilize and maintain hemodynamics and vital signs. For this therapy, a physiologically-based solution comprising both, osmotic and colloid osmotic components, should be administered. The basic requirement for a sufficient fluid replacement and volume resuscitation therapy in children are the profound and special knowledge of the physiological and pathophysiological interactions in water balance and electrolyte metabolism in childhood, the pharmacology of the applied solutions and the adequate monitoring of this fluid and volume replacement therapy. Wrong dosages and side effects are reasons for a negative postoperative outcome in children.

[Training of anesthesiologists in Germany].

A structured and well-organized postgraduate professional education in medical doctors is an important and necessary component in health care these days. It is the foundation for a high quality and safety of physicians' daily work. The article describes the anesthesiological educational program, which is required to finish anesthesia residency in Germany successfully.

[Postoperative therapy for pain in children].

Treatment of acute pain is one of the most important tasks of perioperative pediatric anesthesia. Pain-relieving drugs are usually administered on the basis of the concept of balanced analgesia, which involves a combination of analgesics with either synergic or additive effects. The concept of balanced analgesia is successful under many circumstances, but continuous efforts are needed to improve management in dificult cases. The key problem is to decide if a child has pain. Establishing a high standard at an institution requires a regular evaluation and documentation of pain scores. Non-opioid analgesics are frequently administered just in the induction of anesthesia due to their long-term effects, and then combined with opioids or regional anesthetic techniques. The present review focuses on non-opioid analgesics that can be intravenously injected for the perioperative treatment of acute pain.

[Sepsis and multiple organ dysfunctions--pathophysiology and the topical concepts of treatment].

Severe sepsis with multiple organ dysfunctions is still the leading cause of death in non-cardiac intensive care units (ICU). The incidence is expected to rise in the future due to the growing number of older and immunocompromized patients, the use of invasive procedures, and an increase in the percentage of aggressive or resistant microorganisms. Despite the enormous investment in critical care resources, severe sepsis mortality remains to be high and ranges from 28 to 50%. Based on the disappointing experiences with anti-inflammatory strategies, the authors now realize that sepsis is more than just an inflammation. By taking into account pathophysiological changes, the new therapeutic concepts combine successful modulation with an improvement of the ICU management of multiple organ dysfunctions. This review discusses the actual sepsis intensive care concepts that may be useful in reducing unacceptable high mortality rates in patients with severe sepsis.

E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes.

OBJECTIVE AND DESIGN: In this ex vivo laboratory study, we investigated the effects of E5564 (eritoran), a toll-like receptor 4-directed endotoxin antagonist, on intracellular expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated human monocytes assessed by flow cytometry. MATERIAL AND METHOD: Whole blood samples from 10 healthy volunteers (average age: 32 +/- 2 years) were pre-incubated with 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1 and 10 ng/ml E5564 for 45 min and after this stimulated with LPS (0.2 ng/ml), a dose we found to be the most effective for stimulation. Samples were incubated for 3 h at 37 degrees C and 5% CO(2). Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry. RESULTS: Our investigation showed that E5564 (0.03 ng/ml up to 10 ng/ml) caused a dose-dependent inhibitory effect on IL-6 and TNF-alpha production in LPS-stimulated human monocytes. CONCLUSIONS: The results of this investigation led us to conclude that E5564 has a remarkable LPS inhibitory activity manifested via down-regulation of the intracellular generation of pro-inflammatory cytokines IL-6 and TNF-alpha in human monocytes.