To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with 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 these critically ill patients with high mortality
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.
Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients.The Acute Kidney Injury–Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge.A total of 1032 ICU patients out of 1802 [57.3 %; 95 % confidence interval (CI) 55.0–59.6] had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables; odds ratio of stage 1 = 1.679 (95 % CI 0.890–3.169; p = 0.109), stage 2 = 2.945 (95 % CI 1.382–6.276; p = 0.005), and stage 3 = 6.884 (95 % CI 3.876–12.228; p < 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m2 in 47.7 % (95 % CI 43.6–51.7) versus 14.8 % (95 % CI 11.9–18.2) in those without AKI, p < 0.001.This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions.
Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock.The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575–590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? Four types of statements were used: definition, recommendation, best practice and statement of fact.Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring.This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock.
The purpose of this study is to provide evidence-based and expert consensus recommendations for lung ultrasound with focus on emergency and critical care settings.A multidisciplinary panel of 28 experts from eight countries was involved. Literature was reviewed from January 1966 to June 2011. Consensus members searched multiple databases including Pubmed, Medline, OVID, Embase, and others. The process used to develop these evidence-based recommendations involved two phases: determining the level of quality of evidence and developing the recommendation. The quality of evidence is assessed by the grading of recommendation, assessment, development, and evaluation (GRADE) method. However, the GRADE system does not enforce a specific method on how the panel should reach decisions during the consensus process. Our methodology committee decided to utilize the RAND appropriateness method for panel judgment and decisions/consensus.Seventy-three proposed statements were examined and discussed in three conferences held in Bologna, Pisa, and Rome. Each conference included two rounds of face-to-face modified Delphi technique. Anonymous panel voting followed each round. The panel did not reach an agreement and therefore did not adopt any recommendations for six statements. Weak/conditional recommendations were made for 2 statements, and strong recommendations were made for the remaining 65 statements. The statements were then recategorized and grouped to their current format. Internal and external peer-review processes took place before submission of the recommendations. Updates will occur at least every 4 years or whenever significant major changes in evidence appear.This document reflects the overall results of the first consensus conference on “point-of-care” lung ultrasound. Statements were discussed and elaborated by experts who published the vast majority of papers on clinical use of lung ultrasound in the last 20 years. Recommendations were produced to guide implementation, development, and standardization of lung ultrasound in all relevant settings.
To update the World Society of the Abdominal Compartment Syndrome (WSACS) consensus definitions and management statements relating to intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS).We conducted systematic or structured reviews to identify relevant studies relating to IAH or ACS. Updated consensus definitions and management statements were then derived using a modified Delphi method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, respectively. Quality of evidence was graded from high (A) to very low (D) and management statements from strong RECOMMENDATIONS (desirable effects clearly outweigh potential undesirable ones) to weaker SUGGESTIONS (potential risks and benefits of the intervention are less clear).In addition to reviewing the consensus definitions proposed in 2006, the WSACS defined the open abdomen, lateralization of the abdominal musculature, polycompartment syndrome, and abdominal compliance, and proposed an open abdomen classification system. RECOMMENDATIONS included intra-abdominal pressure (IAP) measurement, avoidance of sustained IAH, protocolized IAP monitoring and management, decompressive laparotomy for overt ACS, and negative pressure wound therapy and efforts to achieve same-hospital-stay fascial closure among patients with an open abdomen. SUGGESTIONS included use of medical therapies and percutaneous catheter drainage for treatment of IAH/ACS, considering the association between body position and IAP, attempts to avoid a positive fluid balance after initial patient resuscitation, use of enhanced ratios of plasma to red blood cells and prophylactic open abdominal strategies, and avoidance of routine early biologic mesh use among patients with open abdominal wounds. NO RECOMMENDATIONS were possible regarding monitoring of abdominal perfusion pressure or the use of diuretics, renal replacement therapies, albumin, or acute component-parts separation.Although IAH and ACS are common and frequently associated with poor outcomes, the overall quality of evidence available to guide development of RECOMMENDATIONS was generally low. Appropriately designed intervention trials are urgently needed for patients with IAH and ACS.
Our objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition.The European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2 days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision.The Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1 week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO2/FiO2 thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy.This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice.
Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500–1000). The median time was 24 min (40–60 min), and the median rate of FC was 1000 [500–1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57–61 %). In 43 % (CI 41–45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34–37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20–24 %). No safety variable for the FC was used in 72 % (CI 70–74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account.
To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock.Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay.From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 % [495/2134] versus control: 22.4 % [582/2601]; pooled OR 1.01 [95 % CI 0.88–1.16], P = 0.9, with heterogeneity [I 2 = 57 %; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95 % CI 0.86–1.15), P = 0.93] with no heterogeneity (I 2 = 0.0 %; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95 % CI 1.10–1.41]; P < 0.001) and ICU admission [OR 2.19 (95 % CI 1.82–2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I 2 = 71 %; P < 0.001) but did not change overall results [pooled OR 0.94 (95 % CI 0.82 to 1.07); P = 0.33].EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.
Care bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.In this single-center trial, we examined the effect of a “KDIGO bundle” consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] > 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.AKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5–27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p < 0.05), less hyperglycemia (p < 0.001) and use of ACEi/ARBs (p < 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.An implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.
Acute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (V T) strategy (V T ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS.Seventy-nine patients were enrolled after a ‘stabilization period’ (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low V T ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality.Ventilation with very low V T’s was easy to implement with extracorporeal CO2-removal. VFD’s within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5 %) and did not differ between groups.The use of very low V T combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a ‘normal’ lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).
Acute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (V (T)) strategy (V (T) a parts per thousand 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS. Seventy-nine patients were enrolled after a 'stabilization period' (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low V (T) ventilation (a parts per thousand 3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (a parts per thousand 6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality. Ventilation with very low V (T)'s was easy to implement with extracorporeal CO2-removal. VFD's within 60 days were not different between the study group (33.2 +/- A 20) and the control group (29.2 +/- A 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 a parts per thousand currency sign150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 +/- A 12.8) compared to control (28.2 +/- A 16.4, p = 0.033). The mortality rate was low (16.5 %) and did not differ between groups. The use of very low V (T) combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a 'normal' lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).
The evolution of the epidemiology and mortality of extracorporeal membrane oxygenation (ECMO) remains unclear. The present study investigates the evolving epidemiology and mortality of various ECMO techniques in Germany over time, used for both severe respiratory and cardiac failure. Data on all patients receiving venovenous (vv-ECMO) and venoarterial (va-ECMO) ECMO as well as pumpless extracorporeal lung assist/interventional lung assist (PECLA/ILA) outside the operating room in Germany from 1 January 2007 through 31 December 2014 were obtained from the Federal Statistical Office of Germany and analyzed. The incidence of vv-ECMO and va-ECMO in the population increased threefold from 1.0:100,000 inhabitants/year in 2007 to a maximum of 3.0:100,000 in 2012, and from 0.1:100,000 in 2007 to 0.7:100,000 in 2012 and to a maximum of 3.5:100,000 in 2014, respectively. The incidence of arteriovenous PECLA/ILA also increased from 0.4:100,000 to a maximum of 0.6:100,000 in 2011, but decreased thereafter to 0.3:100,000 in 2014. The relative proportion of older patients receiving ECMO is steadily increasing. In-hospital mortality decreased over time and reached 58 and 66 % for vv-ECMO and va-ECMO in 2014, respectively. In addition, mortality steadily increased with age and was especially high in the first 48 h of ECMO use. In a high-income country like Germany, the use of ECMO has been rapidly increasing since 2007 for both respiratory and cardiac support, with a recent plateau in vv-ECMO use. In-hospital mortality decreased with increasing ECMO utilization, but remains high, especially in older patients and in the first 48 h of use.
Despite evidence demonstrating the value of performance initiatives, marked differences remain between hospitals in the delivery of care for patients with sepsis. The aims of this study were to improve our understanding of how compliance with the 3-h and 6-h Surviving Sepsis Campaign (SSC) bundles are used in different geographic areas, and how this relates to outcome.This was a global, prospective, observational, quality improvement study of compliance with the SSC bundles in patients with either severe sepsis or septic shock.A total of 1794 patients from 62 countries were enrolled in the study with either severe sepsis or septic shock. Overall compliance with all the 3-h bundle metrics was 19 %. This was associated with lower hospital mortality than non-compliance (20 vs. 31 %, p < 0.001). Overall compliance with all the 6-h bundle metrics was 36 %. This was associated with lower hospital mortality than non-compliance (22 vs. 32 %, p < 0.001). After adjusting the crude mortality differences for ICU admission, sepsis status (severe sepsis or septic shock), location of diagnosis, APACHE II score and country, compliance remained independently associated with improvements in hospital mortality for both the 3-h bundle (OR = 0.64 (95 % CI 0.47−0.87), p = 0.004)) and 6-h bundle (OR = 0.71 (95 % CI 0.56−0.90), p = 0.005)).Compliance with all of the evidence-based bundle metrics was not high. Patients whose care included compliance with all of these metrics had a 40 % reduction in the odds of dying in hospital with the 3-h bundle and 36 % for the 6-h bundle.
This study was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)-treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors’ health-related quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies.Data from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008–2012) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status.Main ARDS etiologies were bacterial (45 %), influenza A[H1N1] (26 %) and post-operative (17 %) pneumonias. Six months post-ICU discharge, 84 (60 %) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre-ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16 % for PRESERVE classes 0–2, 3–4, 5–6 and ≥7 (p < 0.001), respectively. HRQL evaluation in 80 % of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16 %, respectively.The PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population.
To provide clinicians with an evidence-based overview of all topics related to ultrasound vascular access.An international evidence-based consensus provided definitions and recommendations. Medical literature on ultrasound vascular access was reviewed from January 1985 to October 2010. The GRADE and the GRADE-RAND methods were utilised to develop recommendations.The recommendations following the conference suggest the advantage of 2D vascular screening prior to cannulation and that real-time ultrasound needle guidance with an in-plane/long-axis technique optimises the probability of needle placement. Ultrasound guidance can be used not only for central venous cannulation but also in peripheral and arterial cannulation. Ultrasound can be used in order to check for immediate and life-threatening complications as well as the catheter’s tip position. Educational courses and training are required to achieve competence and minimal skills when cannulation is performed with ultrasound guidance. A recommendation to create an ultrasound curriculum on vascular access is proposed. This technique allows the reduction of infectious and mechanical complications.These definitions and recommendations based on a critical evidence review and expert consensus are proposed to assist clinicians in ultrasound-guided vascular access and as a reference for future clinical research.
The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes.A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008.Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P < 0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (P = 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5–8.4%).The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.
An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control. Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8-10.0 mmol/L) or to group 2 (target BG 4.4-6.1 mmol/L). While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1-9.0) (median of all values) and 7.7 mmol/L (IQR 6.7-8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0-7.2) and 6.1 mmol/L (IQR 5.5-6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5-50.0) and 39.3 (26.2-53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%). In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4-6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8-10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440).
To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004.Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding.We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation  indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations  indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations.Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D).Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B).There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
To compare the effects of two arginine vasopressin (AVP) dose regimens on the hemodynamic response, catecholamine requirements, AVP plasma concentrations, organ function and adverse events in advanced vasodilatory shock.In this prospective, controlled, open-label trial, patients with vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery requiring norepinephrine >0.6 μg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033 IU/min (n = 25) or 0.067 IU/min (n = 25). The hemodynamic response, catecholamine doses, laboratory and organ function variables as well as adverse events (decrease in cardiac index or platelet count, increase in liver enzymes or bilirubin) were recorded before, 1, 12, 24 and 48 h after randomization. A linear mixed effects model was used for statistical analysis in order to account for drop-outs during the observation period.Heart rate and norepinephrine requirements decreased while MAP increased in both groups. Patients receiving AVP at 0.067 IU/min required less norepinephrine (P = 0.006) than those infused with AVP at 0.033 IU/min. Arterial lactate and base deficit decreased while arterial pH increased in both groups. During the observation period, AVP plasma levels increased in both groups (both P < 0.001), but were higher in the 0.067 IU/min group (P < 0.001) and in patients on concomitant hydrocortisone. The rate of adverse events and intensive care unit mortality was comparable between groups (0.033 IU/min, 52%; 0.067 IU/min, 52%; P = 1).A supplementary AVP infusion of 0.067 IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033 IU/min.