Trends in the incidence and outcome of sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group-

Background Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated. Methods This was a retrospective cohort study. Adult patients, who had both presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic health record data from the Japanese nationwide medical claim database, which covered 71.5% of all acute care hospitals in 2017. Presumed serious infection was defined using blood culture test records and antibiotic administration. Acute organ dysfunction was defined using records of diagnosis according to the international statistical classification of diseases and related health problems, 10th revision, and records of organ support. The primary outcomes were the annual incidence of sepsis and death in sepsis per 1000 inpatients. The secondary outcomes were in-hospital mortality rate and length of hospital stay in patients with sepsis. Results The analyzed dataset included 50,490,128 adult inpatients admitted between 2010 and 2017. Of these, 2,043,073 (4.0%) patients had sepsis. During the 8-year period, the annual proportion of patients with sepsis across inpatients significantly increased (slope = + 0.30%/year, P < 0.0001), accounting for 4.9% of the total inpatients in 2017. The annual death rate of sepsis per 1000 inpatients significantly increased (slope = + 1.8/1000 inpatients year, P = 0.0001), accounting for 7.8 deaths per 1000 inpatients in 2017. The in-hospital mortality rate and median (interquartile range) length of hospital stay significantly decreased (P < 0.001) over the study period and were 18.3% and 27 (15–50) days in 2017, respectively. Conclusions The Japanese nationwide data indicate that the annual incidence of sepsis and death in inpatients with sepsis significantly increased; however, the annual mortality rates and length of hospital stay in patients with sepsis significantly decreased. The increasing incidence of sepsis and death in sepsis appear to be a significant and ongoing issue.

Orai1 Mediated Calcium Influx Improves Sepsis-induced T Lymphocyte Immunosuppression and Acute Organ Dysfunction

Sepsis-triggered immune paralysis, particularly CD4+ T-cell dysfunction, increases susceptibility to infections. Ca2+ signals arising from store-operated calcium entry (SOCE) in T lymphocytes are critical mediators to infection, inflammation, and autoimmunity. Orai1 is a major component of SOCE. The role of Orai1 and SOCE in sepsis-induced immunosuppression remain to be elucidated. In this study, we first identified the immunosuppression of splenic CD4+ T cells and CD4+CD25+Treg cell/T helper 17 (Th17) cell imbalance in septic mice. Following this, we found that Ca2+-calcineurin-calcineurin-nuclear factor of activated T cell (NFAT) signaling pathways as well as SOCE were inhibited in septic mice. Further, Upregulation of Orai1 not only can improve immune function of T cell in sepsis but also reduce the mortality and organ damage in septic mice. Lastly, Overexpression of Orai1 can partially recovery of SOCE in sepsis. These data suggest that Orai1 mediated calcium influx can improve sepsis-induced T lymphocyte immunosuppression and acute organ dysfunction.

Trends in the Incidence and Outcome of Sepsis Using Data from a Japanese Nationwide Medical Claims Database -the Japan Sepsis Alliance (JaSA) Study Group-

Background: Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated.Methods: This was a retrospective cohort study. Adult patients, who had both presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic health record data from the Japanese nationwide medical claim database, which covered 71.5% of all acute care hospitals in 2017. Presumed serious infection was defined using blood culture test records and antibiotic administration. Acute organ dysfunction was defined using records of diagnosis according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, and records of organ support. The primary outcome variables were the annual incidence of sepsis and death in sepsis per 1,000 inpatients. The secondary outcome variables were in-hospital mortality rate and length of hospital stay in patients with sepsis. Results: The analyzed dataset included 50,490,128 adult inpatients admitted between 2010 and 2017. Of these, 2,043,073 (4.0%) patients had sepsis. During the 8-year period, the annual proportion of patients with sepsis significantly increased (slope=+0.30%/year, P<0.0001), accounting for 4.9% of the total inpatients in 2017. The annual death rate of sepsis per 1,000 inpatients significantly increased (slope=+1.8/1,000 inpatients year, P=0.0001), accounting for 8.4 deaths per 1,000 inpatients in 2017. The in-hospital mortality rate and mean length of hospital stay significantly decreased (P<0.001) over the study period and were 18.3% and 41.9 days in 2017, respectively.Conclusions: The Japanese nationwide data indicate that the annual incidence of sepsis and death in inpatients with sepsis significantly increased; however, the annual mortality rates and length of hospital stay in patients with sepsis significantly decreased. The increasing incidence of sepsis and death in sepsis appear to be a significant and ongoing issue.

Frailty, Acute Organ Dysfunction, and Increased Disability After Hospitalization in Older Adults Who Survive Critical Illness: A Prospective Cohort Study

Purpose: We aimed to describe the association between prehospital frailty (PHF), acute organ dysfunction (AOD), and posthospital disability (PHD) outcome in older adults admitted to the intensive care unit (ICU). Methods: In a prospective observational cohort study, we assessed PHF using the Clinical Frailty Scale (CFS) and assessed the level of AOD using Sequential Organ Failure Assessment (SOFA) scores on ICU day 1. We assessed Activities of Daily Living disability levels through to 6 months after discharge and used generalized estimating equations (log link and negative binomial family) to determine the independent association of PHF and AOD with PHD. Results: Of the 302 patients enrolled, 221 (73.1%) survived the hospitalization. Prehospital frailty was associated with PHD (adjusted incident rate ratio [aIRR] 95% confidence interval [95% CI] per unit increase in CFS 1.38 [1.15-1.67], P = .001). Total day 1 SOFA score was weakly associated with PHD, (aIRR [95% CI] 1.05 [1.00-1.10], P = .037) while day 1 SOFA neurologic score was strongly associated with PHD (aIRR [95% CI] 1.42 [1.24-1.62] per unit increase in SOFA neurologic score, P < .001), and these effects were independent of PHF and other premorbid factors. Conclusions: Both PHF and early acute brain dysfunction are important factors associated with increasing PHD in older adults who survive critical illness.

Risk Factors for Maternal Readmission with Sepsis

Objective Our primary objective was to identify risk factors for maternal readmission with sepsis. Our secondary objectives were to (1) assess diagnoses and infecting organisms at readmission and (2) compare early (<6 weeks) and late (6 weeks to 9 months postpartum) maternal readmission with sepsis. Study Design We identified our cohort using linked hospital discharge data and birth certificates for California deliveries from 2008 to 2011. Consistent with the 2016 sepsis classification, we defined sepsis as septicemia plus acute organ dysfunction. We compared women with early or late readmission with sepsis to women without readmission with sepsis. Results Among 1,880,264 women, 494 (0.03%) were readmitted with sepsis, 61% after 6 weeks. Risk factors for readmission with sepsis included preterm birth, hemorrhage, obesity, government-provided insurance, and primary cesarean. For both early and late sepsis readmissions, the most common diagnoses were urinary tract infection and pyelonephritis, and the most frequently identified infecting organism was gram-negative bacteria. Women with early compared with late readmission with sepsis shared similar obstetric characteristics. Conclusion Maternal risk factors for both early and late readmission with sepsis included demographic characteristics, cesarean, hemorrhage, and preterm birth. Risks for sepsis after delivery persist beyond the traditional postpartum period of 6 weeks.

Levosimendan to prevent acute organ dysfunction in sepsis: the LeoPARDS RCT

BackgroundIn septic shock, cardiovascular resuscitation using catecholamine vasopressors and inotropes is standard therapy, but catecholamines have important side effects. Levosimendan (Simdax®; Orion Pharma, Newbury, UK) is a calcium-sensitising drug with inotropic and other properties that may have a role in sepsis.ObjectivesTo determine, in adult septic shock, whether or not levosimendan reduces the incidence and severity of acute organ dysfunction, the effect of levosimendan on individual organ function and the safety profile of levosimendan.DesignMulticentre, randomised, double-blind, parallel-group, placebo-controlled study.SettingUK intensive care units.ParticipantsAdult patients with sepsis and cardiovascular failure requiring vasopressors to maintain blood pressure despite adequate fluid resuscitation.InterventionLevosimendan, at a dosage of 0.05–0.2 µg/kg/minute, compared with placebo for 24 hours, in addition to standard care, within 24 hours of meeting inclusion criteria.Main outcome measureThe primary outcome was mean Sequential Organ Failure Assessment (SOFA) score on the intensive care unit after randomisation to a maximum of 28 days. Secondary outcomes were time to extubation, survival up to 6 months and serious adverse events.ResultsIn total, 2382 patients were screened at 34 centres, of whom 516 were randomised to treatment, 259 to levosimendan and 257 to placebo. Baseline characteristics were well balanced across treatment arms. There was no significant difference in mean ± standard deviation (SD) SOFA score between the levosimendan group (6.7, SD 4.0) and the placebo group (6.1, SD 3.9) [mean difference 0.61, 95% confidence interval (CI) –0.07 to 1.29]. The 28-day mortality rate was 34.5% and 30.9% in the levosimendan and placebo groups, respectively (absolute difference 3.6%, 95% CI –4.5% to 11.7%). Patients in the levosimendan group were less likely to be successfully extubated over 28 days than patients in the placebo group (hazard ratio 0.77, 95% CI 0.60 to 0.97). More patients in the levosimendan group had supraventricular tachyarrhythmias (3.1% vs. 0.4%; absolute difference 2.7%, 95% CI 0.1% to 5.3%), but there was no overall difference in serious adverse events.ConclusionsIn the population of septic shock patients randomised to treatment in this study, the addition of levosimendan to standard medical care did not reduce organ dysfunction or mortality. Levosimendan was associated with a reduced likelihood of successful extubation and an increased risk of supraventricular tachyarrhythmias.LimitationsThis was a trial of levosimendan added to standard care rather than a comparison against an alternative inotrope such as dobutamine. No echocardiographic analyses were performed to provide detailed information about changes in myocardial function; therefore, this trial cannot provide guidance as to which inotrope (if any) is best to use in the management of sepsis if a very low cardiac index is present.Future workLevosimendan could be compared against dobutamine and placebo in patients with a very low cardiac output in sepsis to test which, if any, inotrope should be used in this select group.Trial registrationCurrent Controlled Trials ISRCTN12776039.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. Study drugs were provided by Orion Pharma and additional research funds were provided by Tenax Therapeutics. The study was supported by the NIHR Biomedical Research Centre based at Imperial College, London, and the UK Intensive Care Foundation.

Hypertensive Emergencies (DRAFT)

Hypertensive emergencies may be encountered by rapid response teams (RRTs). Various forms of acute organ dysfunction separate hypertensive urgency from hypertensive emergency. These include acute heart failure, acute coronary syndrome, acute aortic dissection, ischemic stroke, hemorrhagic stroke, hypertensive encephalopathy, sympathetic crisis, postoperative hypertension, and hypertensive emergencies in pregnancy. RRTs must be able to rapidly assess the patient’s condition, initiate treatment, and triage the patient to the appropriate level of care. This chapter summarizes the initial evaluation and triage of the patient as well as the blood pressure reduction goals in the acute period for the various conditions associated with hypertensive emergencies, discussing suggested drugs with the dosages, and looking at common pitfalls.