Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: 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 wasdeveloped 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 subgroupsand among the entire committee served as an integral part of the development. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.(AU)

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

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 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. Methods: 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. Results: 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 7­9 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<150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >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 5­10 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). Conclusions: 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.

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Osteoprogenitor cells of mature human skeletal muscle tissue: an in vitro study.

The presence of osteogenic progenitors in human skeletal muscle is suggested by the formation of ectopic bone in clinical and experimental conditions, but their direct identification has not yet been demonstrated. The aims of this study were to identify osteogenic progenitor cells in human skeletal muscle tissue and to expand and characterize them in culture. Specimens of gracilis and semitendinosus muscle were obtained from young adults and digested to separate the connective tissue and satellite cell fractions. The cells were cultured and characterized morphologically and immunohistochemically using antibodies known to be reactive with primitive osteoprogenitor cells, pericytes, intermediate filaments, and endothelial cells. Alkaline phosphatase activity and osteocalcin gene expression were also determined. In the early stages of culture, the connective tissue cells obtained were highly positive for primitive osteoprogenitor cell and for pericyte markers. Alkaline phosphatase activity was detectable at early stages of culture and rose as a function of time, whereas primitive osteoprogenitor cell markers declined and osteocalcin mRNA expression became detectable by reverse transcriptase-polymerase chain reaction (RT-PCR). It is shown that human skeletal muscle connective tissue contains osteogenic progenitor cells. Their identification as pericytes, perivascular cells with established osteogenic potential, suggests a cellular link between angiogenesis and bone formation in muscle tissue. These cells are easily cultured and expanded in vitro by standard techniques, providing an alternative source of osteogenic progenitor cells for possible cell-based therapeutic use in certain conditions.

Infected aortic pseudoaneurysm following laparoscopic cholecystectomy.

A 38-year-old hemodialysis-dependent diabetic female patient underwent a laparoscopic cholecystectomy for symptomatic cholelithiasis. Postoperatively, she developed chronic back pain. Eight months following laparoscopic cholecystectomy, she developed fevers and recurrent bacteremia with methicillin-resistant Staphylococcus aureus, despite removal of all indwelling intravenous dialysis access. An abdominal CT scan demonstrated a 7-cm pseudoaneurysm extending from the right anterolateral lower abdominal aorta. Following resection of her infected aneurysm and extraanatomic bypass, she cleared her bacteremia and recovered. This first report of an aortic pseudoaneurysm following laparoscopic cholecystectomy is presented in the context of other vascular complications reported following the same procedure.

Evaluating our end-of-life practice.

Ferrand et al's recent study of withholding and withdrawing life support in intensive care units in France reminds us that reporting end-of-life practices is an important step towards enhancing end-of-life care. The study highlights differences between the paternalistic approach to decision making in Europe, and the patient autonomy model in the USA. However, the reasons intensivists report for withholding or withdrawing life support are similar in both cultures. Intensivists in France make decisions despite a lack of formal guidelines in their country. This study should serve as a stimulus for educating the public and motivating more groups to monitor their end-of-life practices.

End-of-life care in the intensive care unit: can we do better?

Everywhere we turn these days, it seems that we are confronted with a new study that reports the dissatisfaction expressed by families with the quality of care received by their loved ones who have died while in the intensive care unit. It is difficult for caregivers to accept this information, which is now commonly reported both in published studies and in the lay press. As clinicians, most of us believe that we truly care about our patients and are trying, as best we can, to act in their best interest. No caregiver wants to hear that he or she does not do a good job when caring for dying patients and their families. It is ironic that clinicians recognize and accept the need for continuing education. Yet many clinicians resent the suggestion that the skills required for end-of-life care might be viewed in the same manner, as a lifelong learning process. It is unusual for physicians to identify end-of-life-care as an area of competency that can be improved or updated. Perhaps this is why end-of-life-care has been so difficult to teach to clinicians in training. Although many medical schools offer courses on the ethics of death and dying, formal training in end-of-life care skills is not routinely given in most postgraduate training programs. Learning these skills is a matter of on-the-job training for most caregivers. Not only have we been unable to measure any beneficial impact from education initiatives for end-of-life care, we have yet to identify clear indicators for end-of-life care. For caregivers, enhancing end-of-life skills may be a matter of improved listening skills, attention to the proper environment for end-of-life discussions, and a willingness to facilitate end-of-life decision-making. Encouraging caregivers to view end-of-life skills as a lifelong educational process, identifying core competencies in end-of-life care, and training clinicians in these skills are the challenges for the future. The quality of care our patients receive at the end of life will depend on our ability to answer these difficult questions.

Prediction of post-extubation work of breathing.

OBJECTIVE: To evaluate which mode of preextubation ventilatory support most closely approximates the work of breathing performed by spontaneously breathing patients after extubation. DESIGN: Prospective observational design. SETTING: Medical, surgical, and coronary intensive care units in a university hospital. PATIENTS: A total of 22 intubated subjects were recruited when weaned and ready for extubation. INTERVENTIONS: Subjects were ventilated with continuous positive airway pressure at 5 cm H2O, spontaneous ventilation through an endotracheal tube (T piece), and pressure support ventilation at 5 cm H2O in randomized order for 15 mins each. At the end of each interval, we measured pulmonary mechanics including work of breathing reported as work per liter of ventilation, respiratory rate, tidal volume, negative change in esophageal pressure, pressure time product, and the airway occlusion pressure 100 msec after the onset of inspiratory flow, by using a microprocessor-based monitor. Subsequently, subjects were extubated, and measurements of pulmonary mechanics were repeated 15 and 60 mins after extubation. MEASUREMENTS AND MAIN RESULTS: There were no statistical differences between work per liter of ventilation measured during continuous positive airway pressure, T piece, or pressure support ventilation (1.17+/-0.67 joule/L, 1.11+/-0.57 joule/L, and 0.97+/-0.57 joule/L, respectively). However, work per liter of ventilation during all three preextubation modes was significantly lower than work measured 15 and 60 mins after extubation (p < .05). Tidal volume during pressure support ventilation and continuous positive airway pressure (0.46+/-0.11 L and 0.44+/-0.11 L, respectively) were significantly greater than tidal volume during both T-piece breathing and spontaneous breathing 15 mins after extubation (p < .05). Negative change in esophageal pressure, the airway occlusion pressure 100 msec after the onset of inspiratory flow, and pressure time product were significantly higher after extubation than during any of the three preextubation modes (p < .05). CONCLUSIONS: Work per liter of ventilation, negative change in esophageal pressure, the airway occlusion pressure 100 msec after the onset of inspiratory flow, and pressure time product all significantly increase postextubation. Tidal volume during continuous positive airway pressure or pressure support ventilation overestimates postextubation tidal volume.

Endovascular surgery based solely on noninvasive preprocedural imaging.

PURPOSE: Conventional pre-endovascular procedural evaluation uses both noninvasive testing and diagnostic arteriography. Diagnostic and therapeutic procedures often must be performed separately because of concerns about excessive contrast administration or inappropriate location of vascular access for the interventional procedure. We wanted to determine if patients could successfully undergo endovascular procedures based on noninvasive modalities alone. METHODS: One hundred nineteen consecutive patients requiring intervention for lower-extremity ischemia were evaluated by means of physical examinations and segmental pressure measurements. Patients then underwent magnetic resonance angiography (MRA) to image native vessels or duplex scanning for failing bypass grafts. Suitable patients underwent endovascular procedures with "road map" arteriography, which was compared with preoperative duplex scanning or MRA findings. Costs of the conventional and noninvasive approaches were compared, on the basis of estimated hospital cost schedule. RESULTS: Sixty consecutive endovascular procedures were performed in 56 patients (105 lesions angioplastied), either alone (30, 50%) or in combination (30, 50%) with another vascular reconstruction. Completely noninvasive evaluation was accomplished in 43 procedures (72%), either by means of duplex scanning (11, 18%) or MRA (32, 53%). Conventional arteriography (CA) was required in 2 patients (3%) because of MRA contraindications and in 1 patient because of complex previous arterial reconstruction. Fourteen patients had earlier CAs. The findings of the noninvasive modalities were confirmed in every case by means of intraoperative arteriography, and no additional lesions were revealed (no false positive or negative studies). After endovascular interventions, the mean patient ankle-brachial index (ABI) improved from 0.64 +/- 0.03 to 0.81 +/- 0.03 (P <.001) and the mean limb-status category improved from 3.4 +/- 0.2 to 0.8 +/- 0.2 (P <.001). There were 4 initial technical failures (7%), 1 morbidity (1%), and no mortalities. The noninvasive approach was less costly than if preprocedural diagnostic CA had been used, allowing $551 saved for each duplex scanning case and $235 saved for each MRA case. If the cost of a short-stay unit after a diagnostic arteriogram was included, the savings were greater: $695 saved for each duplex scanning case and $379 saved for each MRA case. CONCLUSION: Endovascular procedures can be performed based on preprocedural noninvasive modalities alone. For patients requiring endovascular procedures, knowledge of the arterial anatomy before obtaining arterial access avoids the need for additional punctures or sessions (eg, antegrade puncture for femoral angioplasty after retrograde puncture for the diagnostic arteriogram). This approach is less costly than performing preprocedural diagnostic arteriography and avoids the hazards of arterial puncture and nephrotoxic contrast agents.

Extracranial repair of pediatric traumatic cerebrospinal fluid rhinorrhea.

OBJECTIVE: To examine the methods of extracranial repair of traumatic defects in the cribriform plate and ethmoid roof resulting in persistent cerebrospinal fluid (CSF) rhinorrhea in pediatric patients. DESIGN: Retrospective case series. SETTING: A single-institution, tertiary care, pediatric hospital. PATIENTS: Four children, ranging in age from 3 1/2 to 9 years, who sustained fractures in the cribriform plate or ethmoid roof. INTERVENTION: Transnasal endoscopic repair in 4 patients, with 2 patients also undergoing external ethmoidectomy because of the large bony defect and the need for further exposure for repair. MAIN OUTCOME MEASURES: Time free from CSF leaks or recurrence, meningitis, and other postoperative complications. RESULTS: All patients except 1 have been free of recurrent CSF leaks, meningitis, and other postoperative complications. The 3 patients who solely underwent the extracranial approach did not experience the complications of the traditional intracranial approach. CONCLUSIONS: In a select group of pediatric patients, the extracranial approach for the repair of CSF leaks is appropriate. Successful use of an extracranial approach in 3 of 4 patients supports this method.

Evidence-based medicine. A tool for enhancing critical care practice.

Evidence-based medicine (EBM) involves caring for patients by explicitly integrating clinical research evidence with pathophysiologic reasoning, caregiver experience, and patient preferences. EBM is a style of practice and teaching which may also help plan future research. This article discusses the application of EBM to critical care.

An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary resuscitation.

The use of bicarbonate is rooted in three decades of clinical experience and observational studies. For many years, bicarbonate passed the tried and true test for clinical therapies; however, administration of sodium bicarbonate during cardiac arrest and hypoxic acidosis has become increasingly controversial. The controversy provides an excellent opportunity to evaluate the impact an evidence-based approach might have on a common clinical practice. Is bicarbonate efficacious in the treatment of the severe acidosis that accompanies cardiac arrest during cardiopulmonary resuscitation (CPR)? Are the deleterious effects of bicarbonate clinically relevant? What is the evidence upon which a rational decision may be based? This review evaluates and ranks the evidence supporting the use of sodium bicarbonate in the therapy of acidosis associated with cardiac arrest during CPR.

How to use a review article: prophylactic endoscopic sclerotherapy for esophageal varices. Evidence Based Critical Care Medicine Group.

OBJECTIVE: To assess the validity of a meta-analysis about sclerotherapy for the primary prevention of bleeding from esophageal varices, to interpret the results, and discuss whether they apply in practice. DATA SOURCES: Critical appraisal techniques for systematic reviews. DATA EXTRACTION: Systematic reviews are distinct from narrative reviews in that they answer specific clinical questions, and have explicit and reproducible methods for searching, selecting, and appraising the primary studies, to create the most valid synthesis of the evidence. DATA SYNTHESIS: Meta-analyses are systematic reviews containing a critical appraisal and statistical summary of individual study results and their confidence limits, whereas qualitative systematic reviews provide a narrative executive summary of study results. CONCLUSIONS: High-quality systematic reviews are being used increasingly to guide practice, strengthening the link between research results and improved health outcomes. Understanding their strengths and limitations helps us to use them appropriately in practice.

How to use practice guidelines in the intensive care unit: Diagnosis and management of unstable angina.

OBJECTIVE: Practice guidelines are often based on expert opinion, and are sometimes based on research evidence, but are usually a mix of both. The goal of this article is to aid in the evaluation of the validity of practice guidelines. DATA SYNTHESIS: The Agency for Health Care Policy and Research Practice Guideline on Management of Unstable Angina and other relevant primary and synthetic research. METHODS: Critical appraisal of guidelines requires understanding how guideline developers identified, appraised, and summarized the evidence, and how they chose the values reflected in their recommendations. To determine whether guidelines are applicable in our practice, we look for clear and concise recommendations about specific populations, describing common options linked to clinically important outcomes. Guidelines must be considered in light of local skills, culture, and resources, and need to be individualized to different patients and settings. CONCLUSIONS: As better evidence and new clinical insights emerge, guidelines require updating. The ultimate value of a guideline is determined by evaluating its effect on process of care, resource utilization, and most importantly, patient outcomes.

Pulmonary capillary pressure and tissue perfusion: clinical implications during resuscitation from shock.

During shock resuscitation, a combination of fluids, vasopressors, vasodilators, and inotropes is administered in order to achieve a cardiac output or overall oxygen delivery as per guidelines of individual clinicians. The measurement of ventricular end-diastolic pressure allows a clinician to describe a therapeutic goal of optimum cardiac output response to changes in end-diastolic pressure. This concept has formed the backbone of resuscitative strategies in many forms of shock. Ventricular end-diastolic pressure is indirectly measured as the pulmonary artery occlusion pressure (PAOP) in critically ill patients with the use of a pulmonary artery catheter. Cytokines and other mediators may injure the pulmonary capillary endothelium which will affect the rate of leakage in the pulmonary capillaries. This may have important clinical implications in the therapy of shock in inflammatory states such as sepsis and the adult respiratory distress syndrome. Therefore, the true edema-forming pressure within the pulmonary bed is of considerable importance to the intensivist at the bedside. True pulmonary capillary pressure represents the midpoint of the capillary bed and is the hydrostatic pressure which directly drives the rate of pulmonary interstitial edema formation. During shock resuscitation in disorders in which vascular integrity may be impaired, the ability to measure pulmonary capillary pressure would be of great clinical benefit. It is impossible to directly measure pulmonary capillary hydrostatic pressure in the intact lung and, therefore, only indirect measurements are clinically possible. Numerous studies have demonstrated the lack of consistent relationship between the pulmonary capillary pressure, PAOP, pulmonary artery diastolic pressure, and the severity of acute lung injury. The assumption that PAOP, and thus left atrial pressure, is a good indirect measurement of pulmonary filtration pressure within the capillary bed is erroneous, in particular in the presence of increased resistance within the pulmonary venous bed between the capillaries and the left atrium, as may exist in disorders in which there is cytokine production. It is now clear that a significant gradient between pulmonary capillary pressure and PAOP may be present in inflammatory disorders which are not present in noninflammatory states, and that pulmonary capillary pressure may be measured at the bedside of critically ill patients. Bedside measurement of pulmonary capillary pressure may allow for added precision in our therapeutic goals in resuscitation from inflammatory shock. If further studies confirm the reliability and reproducibility of bedside measurement, pulmonary capillary pressure may become an invaluable part of the hemodynamic profile in the critically ill patient in shock.

Pulmonary capillary pressure. Clinical implications.

Pulmonary capillary pressure (Pcap) is the true edema-forming pressure within the pulmonary vascular bed. Pulmonary artery occlusion pressure has long been used to approximate Pcap. These two pressures may not always be well correlated, which has significant implications for fluid resuscitation and the evolution of pulmonary edema. This article reviews the technique for bedside measurement of Pcap.