Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

/pdf/surviving-sepsis-campaign-international-guidelines-for-1trp1tl9am.pdf

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.

https://www.kidney-international.org/article/S0085-2538(19)30601-5/pdf

Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

/pdf/covid-19-associated-acute-kidney-injury-consensus-report-of-2bwe86imwi.pdf

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

Sepsis is defined as organ dysfunction resulting from the host's deleterious response to infection. One of the most common organs affected is the kidneys, resulting in sepsis associated acute kidney injury (SA-AKI) that contributes to the morbidity and mortality of sepsis. A growing body of knowledge has illuminated the clinical risk factors, pathobiology, response to treatment, and elements of renal recovery that have advanced our ability to prevent, detect, and treat SA-AKI. Despite these advances, SA-AKI remains an important concern and clinical burden, and further study is needed to reduce the acute and chronic consequences. This review summarizes the relevant evidence, with a focus on the risk factors, early recognition and diagnosis, treatment, and long term consequences of SA-AKI. In addition to literature pertaining to SA-AKI specifically, pertinent sepsis and acute kidney injury literature relevant to SA-AKI was included.

Sepsis associated acute kidney injury

Background
Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial.

Methods
In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.

Results
The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).

Conclusions
Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1803213

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

Background: Assessment and management of septic shock associated adrenal function remain controversial. The aim of this study was to explore the prognostic value of adrenal gland volume in adults with septic shock. Methods: A short cosyntropin test and determination of adrenal volume by computed tomography were performed within 48 h of shock in patients with septic shock (n = 184) and in 2 control groups: 40 ambulatory patients and 15 nonseptic critically ill patients. The primary endpoint was intensive care unit mortality. Results: At intensive care unit discharge, 59 patients with septic shock died. Adrenal volume was 12.5 cm 3 [95% CI, 11.3-13.3] and 8 cm 3 [95% CI, 6.8-10.1] in the nonseptic group (P < 0.05 with both septic cohorts) and 7.2 cm 3 [95%CI, 6.3-8.5] in the ambulatory patient group (P < 0.05 in patients with septic shock). In patients with septic shock, adrenal volume less than 10 cm 3 was associated with higher 28-day mortality rates with an area under the receiver operating curve of 0.84 [95% CI, 0.78-0.89]. Adrenal volume above 10 cm 3 was an independent predictor of intensive care unit survival (hazard ratio = 0.014; 95% CI [0.004-0.335]). Conclusion: A total adrenal gland volume less than 10 cm 3 during septic shock was associated in univariate and multi-variate analysis with mortality at day 28 in patients with septic shock. Whether adrenal gland volume can be a surrogate of adrenal gland function and used to guide hydrocortisone therapy in septic shock patients needs to be further investigated.

The absence of adrenal gland enlargement during septic shock predicts mortality: a computed tomography study of 239 patients.

The Absence of Adrenal Gland Enlargement During Septic Shock Predicts Mortality: A Computed Tomography Study of 239 Patients

Critical illness is characterized by redistribution of energy and anabolic processes toward favoring vital functions and self-defense against danger. Prolonged critical illness is associated with uncompensated catabolism with major nitrogen loss, muscle wasting, and decreased endocrine responses. If the whole endocrine system takes part in the acute and chronic responses to critical illness, androgens, insulin, growth hormone, and thyroid hormone are the most important players in the anabolic/catabolic balance. Levels of sulfate-dehydroepiandrosterone and testosterone are commonly inappropriately low in critically ill patients, with lower levels in sickest patients. These findings have formed the rationale for several trials on replacement therapy with various androgens. Albeit conflicting conclusions from these trials, synthetic androgens such as oxandrolone may be considered as adjunct treatment in selected critically ill patients. Insulin has become a routine treatment in ICU patients to maintain blood glucose levels of less than 180 mg/dL. During the chronic phase of critical illness, growth hormone (GH) and insulin growth factor (IGF)-1 levels decrease partly as the result of decreased ghrelin levels. Yet so far, trials of GH supplementation have suggested that critically ill patients may not benefit from this treatment. Likewise, albeit promising findings in animal models of critical illness, there is no evidence from clinical trial to supplement ICU patients with thyroid hormones.

Djillali Annane

Papers

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

The absence of adrenal gland enlargement during septic shock predicts mortality: a computed tomography study of 239 patients.

The Absence of Adrenal Gland Enlargement During Septic Shock Predicts Mortality: A Computed Tomography Study of 239 Patients

Is there a place for anabolic hormones in critical care