Faculty Bibliography

OBJECTIVE:A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN/METHODS:Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING/METHODS:Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS/METHODS:A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS/RESULTS:A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS:A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.

OBJECTIVE:A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN/METHODS:Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING/METHODS:Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS/METHODS:A panel of multinational, multiprofessional, and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS/RESULTS:A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds) were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS:A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 µg per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.

OBJECTIVES/OBJECTIVE:The practice of limiting life-sustaining therapy (LST) at end-of-life is widespread globally. The goal of this study was to evaluate whether patient's age influences end-of-life limitations overall and of various LST in ICUs worldwide. DESIGN/METHODS:Multinational, multicenter, prospective observational study. SETTING/METHODS:One hundred ninety-nine ICUs in 36 countries worldwide. PATIENTS/METHODS:Consecutive adult patients admitted to ICUs who died and/or had LST limitations (withholding, withdrawing, or active shortening of the dying process) were included during a 6-month period between September 2015 and September 2016. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Patients were grouped: younger than 65 years, 65-79 years old, and 80 years old or older. A total of 12,200 patients were included. In multivariate logistic regression analysis, odds ratio (OR) for any LST limitation in the 80 years old or older group was higher than in younger than the 65 years old group (OR 1.47 [95% CI, 1.22-1.76], p < 0.001). When stratified by region, this association was significant in Central and Southern Europe (OR 1.56 [95% CI, 1.11-2.20], p = 0.037 and OR 2.23 [95% CI, 1.58-3.17], p < 0.001, respectively), but not in the other regions. The proportion of withholding therapy of each LST was highest in the group of individuals 80 years or older, whereas the proportion of withdrawing therapy was highest in the group younger than 65 years. The 80-year-old or older group also had a shorter time from ICU admission to first limitation. The predominant reason for any LST limitation in all age groups was unresponsiveness to maximal therapy, followed by neurologic and chronic diseases. Patient age was rarely the primary reason for limitations for all groups. CONCLUSIONS:End-of-life limitations were higher in patients 80 years or older compared to those 65 years old or younger, with regional variations. The main reasons for limitations were comparable across age groups, with age not being the primary reason.

Cardiovascular collapse and arrest in the periprocedural setting and intensive care unit differ from arrests in other contexts (such as out-of-hospital or hospital ward) because clinicians almost always witness the event, and the most likely precipitating cause may be known. In comparison to other settings, the response can be timelier and more focused on treating the underlying cause(s). Since many patients deteriorate over minutes to hours, clinicians can evaluate the patient expeditiously, generate a diagnosis, and initiate appropriate treatment more rapidly than in other arrest circumstances. This iteration of Perioperative Resuscitation and Life Support (PeRLS) employs Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology to review the most recent evidence on preventing and managing cardiac arrest during the perioperative period. Furthermore, many of the recommendations and algorithms may also be applicable to areas outside the operating room, such as the intensive care unit and emergency room.

Clinical decision-making often simplifies continuous risk data into discrete levels using round-number thresholds. These simplifications can distort risk assessments. To systematically uncover these distortions, we develop an interpretable machine learning model that identifies anomalies caused by threshold-based practices. Through simulations, real-world data, and longitudinal studies, we demonstrate how round-number thresholds can lead to discontinuities and counter-causal paradoxes in mortality risk. Despite advances in medicine, these anomalies persist, underscoring the need for dynamic and nuanced risk assessment methods in healthcare. Our findings suggest continuous reassessment of clinical protocols, especially in critical settings like intensive care, to improve patient outcomes by aligning thresholds with the continuous nature of risk.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol use disorder. Although benzodiazepines are the mainstay of treatment, some patients may be resistant to them, requiring rapidly escalating doses. Phenobarbital has emerged as an effective adjunct therapy in severe alcohol withdrawal, but studies have yielded inconsistent results and carry safety risks. The purpose of our study was to examine the effectiveness and the potential harm of phenobarbital in AWS. METHODS:In this multi-center, retrospective cohort study, patients who were admitted for AWS and received phenobarbital with benzodiazepine were compared to patients who received benzodiazepine monotherapy. The primary outcome was time to AWS resolution. Other secondary and safety outcomes included length of stay (LOS), rate of mechanical ventilation, and incidence of aspiration pneumonia. RESULTS:The phenobarbital group received significantly higher doses of benzodiazepines compared to the benzodiazepine monotherapy group (660 mg vs 340 mg, p < 0.0001). After adjustment, the use of phenobarbital was associated with significantly reduced time to AWS resolution (141.65 h vs 165.72 h, p < 0.0001). However, the use of phenobarbital was associated with the likelihood of mechanical ventilation (19.42 %vs. 0.96 %, p < 0.0001), aspiration pneumonia (22.33 % vs 5.77 %, p = 0.0006), and increased hospital LOS (8 days vs. 6 days, p = 0.0197). In the combination group, earlier phenobarbital initiation (within 24 h) was associated with significantly lower cumulative benzodiazepine dose (530 mg vs 887.50 mg, p = 0.002) and hospital LOS (6 days vs 10 days, p = 0.0017). CONCLUSION AND RELEVANCE/CONCLUSIONS:In our study, patients who received phenobarbital in combination with benzodiazepines had a quicker resolution of AWS but also had a higher incidence of mechanical ventilation, prolonged hospital LOS, and an increased risk of aspiration pneumonia. For patients at high risk of severe alcohol withdrawal, earlier initiation of phenobarbital appeared to yield the most optimal benefit.

With the growth of the older adult population, the number of older adults waitlisted for and undergoing kidney and liver transplantation has increased. Transplantation is an important and definitive treatment for this population. We present a contemporary review of the unique preoperative, intraoperative, and postoperative issues that patients older than 65 y face when they undergo kidney or liver transplantation. We focus on geriatric syndromes that are common in older patients listed for kidney or liver transplantation including frailty, sarcopenia, and cognitive dysfunction; discuss important considerations for older transplant recipients, which may impact preoperative risk stratification; and describe unique challenges in intraoperative and postoperative management for older patients. Intraoperative challenges in the older adult include using evidence-based best anesthetic practices, maintaining adequate perfusion pressure, and using minimally invasive surgical techniques. Postoperative concerns include controlling acute postoperative pain; preventing cardiovascular complications and delirium; optimizing immunosuppression; preventing perioperative kidney injury; and avoiding nephrotoxicity and rehabilitation. Future studies are needed throughout the perioperative period to identify interventions that will improve patients' preoperative physiologic status, prevent postoperative medical complications, and improve medical and patient-centered outcomes in this vulnerable patient population.