Gordon D. Rubenfeld

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. Some recommendations were ungraded (UG). 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 hrs 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 hr of 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 hrs 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 (1C); 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, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (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 PaO2/FIO2 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 hrs) for patients with early ARDS and a Pao2/Fio2 < 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 hrs 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 hrs 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 to 10 mins (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.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROM EVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

Use of intensive care at the end of life in the United States: an epidemiologic study.

ObjectiveDespite concern over the appropriateness and quality of care provided in an intensive care unit (ICU) at the end of life, the number of Americans who receive ICU care at the end of life is unknown. We sought to describe the use of ICU care at the end of life in the United States using hospital discharge data from 1999 for six states and the National Death Index. DesignRetrospective analysis of administrative data to calculate age-specific rates of hospitalization with and without ICU use at the end of life, to generate national estimates of end-of-life hospital and ICU use, and to characterize age-specific case mix of ICU decedents. SettingAll nonfederal hospitals in the states of Florida, Massachusetts, New Jersey, New York, Virginia, and Washington. PatientsAll inpatients in nonfederal hospitals in the six states in 1999. InterventionNone. Measurements and Main ResultsWe found that there were 552,157 deaths in the six states in 1999, of which 38.3% occurred in hospital and 22.4% occurred after ICU admission. Using these data to project nationwide estimates, 540,000 people die after ICU admission each year. The age-specific rate of ICU use at the end of life was highest for infants (43%), ranged from 18% to 26% among older children and adults, and fell to 14% for those >85 yrs. Average length of stay and costs were 12.9 days and

Recommendations for end-of-life care in the intensive care unit: A consensus statement by the American College of Critical Care Medicine

24,541 for terminal ICU hospitalizations and 8.9 days and

Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries

8,548 for non-ICU terminal hospitalizations. ConclusionsOne in five Americans die using ICU services. The doubling of persons over the age of 65 yrs by 2030 will require a system-wide expansion in ICU care for dying patients unless the healthcare system pursues rationing, more effective advanced care planning, and augmented capacity to care for dying patients in other settings.

Critical care and the global burden of critical illness in adults

Background:These recommendations have been developed to improve the care of intensive care unit (ICU) patients during the dying process. The recommendations build on those published in 2003 and highlight recent developments in the field from a U.S. perspective. They do not use an evidence grading system because most of the recommendations are based on ethical and legal principles that are not derived from empirically based evidence. Principal Findings:Family-centered care, which emphasizes the importance of the social structure within which patients are embedded, has emerged as a comprehensive ideal for managing end-of-life care in the ICU. ICU clinicians should be competent in all aspects of this care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. Several key ethical concepts play a foundational role in guiding end-of-life care, including the distinctions between withholding and withdrawing treatments, between actions of killing and allowing to die, and between consequences that are intended vs. those that are merely foreseen (the doctrine of double effect). Improved communication with the family has been shown to improve patient care and family outcomes. Other knowledge unique to end-of-life care includes principles for notifying families of a patient’s death and compassionate approaches to discussing options for organ donation. End-of-life care continues even after the death of the patient, and ICUs should consider developing comprehensive bereavement programs to support both families and the needs of the clinical staff. Finally, a comprehensive agenda for improving end-of-life care in the ICU has been developed to guide research, quality improvement efforts, and educational curricula. Conclusions:End-of-life care is emerging as a comprehensive area of expertise in the ICU and demands the same high level of knowledge and competence as all other areas of ICU practice.

Family satisfaction with family conferences about end-of-life care in the intensive care unit: Increased proportion of family speech is associated with increased satisfaction

IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02010073.

Cytomegalovirus Reactivation in Critically-Ill Immunocompetent Patients

Summary Critical care has evolved from treatment of poliomyelitis victims with respiratory failure in an intensive care unit to treatment of severely ill patients irrespective of location or specific technology. Population-based studies in the developed world suggest that the burden of critical illness is higher than generally appreciated and will increase as the population ages. Critical care capacity has long been needed in the developing world, and efforts to improve the care of the critically ill in these settings are starting to occur. Expansion of critical care to handle the consequences of an ageing population, natural disasters, conflict, inadequate primary care, and higher-risk medical therapies will be challenged by high costs at a time of economic constraint. To meet this challenge, investigators in this discipline will need to measure the global burden of critical illness and available critical-care resources, and develop both preventive and therapeutic interventions that are generalisable across countries.

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Objective:Family members of critically ill patients report dissatisfaction with family-clinician communication about withdrawing life support, yet limited data exist to guide clinicians in this communication. The hypothesis of this analysis was that increased proportion of family speech during ICU family conferences would be associated with increased family satisfaction. Design:Cross-sectional study. Setting:We identified family conferences in intensive care units of four Seattle hospitals during which discussions about withdrawing life support were likely to occur. Participants:Participants were 214 family members from 51 different families. There were 36 different physicians leading the conferences, as some physicians led more than one conference. Interventions:Fifty-one conferences were audiotaped. Measurements:We measured the duration of time that families and clinicians spoke during the conference. All participants were given a survey assessing satisfaction with communication. Results:The mean conference time was 32.0 mins with an sd of 14.8 mins and a range from 7 to 74 mins. On average, family members spoke 29% and clinicians spoke 71% of the time. Increased proportion of family speech was significantly associated with increased family satisfaction with physician communication. Increased proportion of family speech was also associated with decreased family ratings of conflict with the physician. There was no association between the duration of the conference and family satisfaction. Conclusions:This study suggests that allowing family members more opportunity to speak during conferences may improve family satisfaction. Future studies should assess the effect of interventions to increase listening by critical care clinicians on the quality of communication and the family experience.

Withdrawing Life Support from Mechanically Ventilated Recipients of Bone Marrow Transplants: A Case for Evidence-Based Guidelines

CONTEXT Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined. OBJECTIVE To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons. DESIGN, SETTING, AND PARTICIPANTS We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models. MAIN OUTCOME MEASURES Association of CMV reactivation with prolonged hospital length of stay or death. RESULTS The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log(10) copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days. CONCLUSIONS These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.