Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao
 2/Fio
 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao
 2/Fi
 o
 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

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Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

Prospective Cohort Study

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Die COVID-19-Pandemie hat das deutsche Gesundheitssystem vor enorme Herausforderungen gestellt und den Bedarf an Strategien zu Rekrutierung, Schulung und Einsatzplanung von medizinischem Personal verdeutlicht. Bislang existierte kein ganzheitliches Konzept, welches Medizinstudierende als Unterstutzung der Fachkrafte auf Intensivstationen (ICU) einsetzt, um Personalengpasse in der medizinischen Versorgung zu vermeiden. In einem gros angelegten Pilotprojekt wurden 265 Medizinstudierende fur den Einsatz auf ICU trainiert. Begleitet wurde das innovative Schulungsmodul mit einem Pra-post-Fragebogen zur Selbsteinschatzung uber die erlernten Fertigkeiten. 22 Wochen nach dem Schulungsmodul und noch wahrend des Pandemieeinsatzes wurden mit einem weiteren Fragebogen Erfahrungen im Einsatz und Effizienz des Trainingsmoduls in Bezug auf die Vorbereitung fur den ICU-Einsatz evaluiert. Die Analyse ergab signifikante Mittelwertdifferenzen fur alle COVID-19-spezifischen Variablen (Sicherheitsdimension) zugunsten des Schulungsmoduls (n = 168). Die Einsatzevaluation zeigte fur n = 69 von insgesamt 89 eingesetzten Studierenden eine uneinheitliche Bewertung des Schulungskonzeptes als Vorbereitung auf den Arbeitseinsatz (53 % Zustimmung/47 % Ablehnung). Die Ergebnisse zeigen eine gute Realisierbarkeit des innovativen Trainingskonzeptes fur Medizinstudierende in Bezug auf einen Pandemieeinsatz als Helfende auf Intensivstationen. Das Konzept ist geeignet, um zusatzliche Hilfskrafte wahrend einer Pandemie auf den Intensivstationen zur Verfugung zu stellen. Die uneinheitliche Bewertung deutet jedoch auf Anpassungsbedarf des Konzeptes hin.

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Medizinstudierende als Helfende in der Pandemie

Enkephalins are opioid peptides and enkephalin and its precursor pro-enkephalin (pro-ENK) are found to be widely distributed in organ tissues including the kidney [1]. Pro-ENK is a predictor for acute kidney injury (AKI) in patients after cardiac surgery and can detect severity of AKI in patients admitted to the emergency department with sepsis [2, 3]. In surgical ICU-patients with sepsis, information on the suitability of pro-ENK to determine kidney function is lacking.

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Pro-enkephalin in plasma of surgical icu-patients with sepsis - a pilot study

Synthesis and liberation of adrenomedullin (ADM) are found in different tissues and endothelial cells and ADM is induced by hypoxia, oxidative stress, and pro-inflammatory cytokines [1]. The prognostic value of ADM is described in general patient populations, in medical patients and in particular recently in patients with suspected sepsis in the emergency department [2, 3]. In surgical patients, the obstacle is to differentiate between postoperative inflammation and sepsis and to assess the patients' prognosis.

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Adrenomedullin in plasma of surgical ICU-patients with sepsis - a pilot study

There is legitimate interest in the effects of recombinant human activated protein C (rhAPC) on various organs and individual patients, but the specific effects on organ tissues during early sepsis...

https://journals.sagepub.com/doi/pdf/10.1177/1721727X17721088

Organ-specific effects on inflammation and apoptosis of recombinant human activated protein C in a murine model of sepsis:

Sir, We read with interest the comment of P.G. Berthelsen. Our experimental model is well established (1–3). To compare measures such as cardiac output (CO) between individuals, the correct method of presentation is as an index related to the body surface area (BSA) in humans. The underlying reason is that the cardiac index (CI) provides a more individual-specific measure of cardiac performance. Therefore, we disagree completely with Dr Berthelsen’s comment that we have chosen an ‘odd’ way of presenting our results. We divided CO by the weight of the animal to yield the CI in order to eliminate weight-related differences. This is the scientifically correct and generally accepted way of presenting CO data in the chosen experimental design (1, 4, 5). Furthermore, Dr Berthelsen’s extrapolation of animal data to an average human man is inappropriate and incorrect. We have already established that arterial transpulmonary thermodilution (ATD) is a reliable technique for the measurement of CO. Previously, our group compared ATD and pulmonary artery thermodilution (PATD) with the physiological standard, indirect calorimetry, using our model (6). The correlation between the indirect calorimetry-derived CO estimation and transpulmonary CO was high (r 1⁄4 0.91, r 1⁄4 0.83, P < 0.001). The bias was 0.75 ml/min/kg (95% CI, –3.8 to 5.3 ml/min/kg) with limits of agreement of –39.7 to 41.2 ml/min/kg. The data analysis in the present study was performed in accordance with Altman and Bland. Furthermore, pulse-contour-derived CO has been demonstrated to be reliable in comparison with pulmonary arteryderived CO (7) and in hemodynamically unstable cardiac surgery patients (8). In conclusion, even during hemodynamic instability in septic shock, the correlation of ATDand PATD-derived CO with indirect calorimetry is good. In the present study, we demonstrated that pulse-contour-derived CO is a reliable way of measuring CO continuously up to 5 h. As CO obtained by arterial thermodilution is less invasive than that obtained by PATD, it may offer practical advantages.

Gernot Marx

Papers

Medizinstudierende als Helfende in der Pandemie

Pro-enkephalin in plasma of surgical icu-patients with sepsis - a pilot study

Adrenomedullin in plasma of surgical ICU-patients with sepsis - a pilot study

Organ-specific effects on inflammation and apoptosis of recombinant human activated protein C in a murine model of sepsis:

Pulse-contour-derived cardiac output is unreliable in septic shock. Authors' reply