Albumin in Sepsis

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial

Summary

Background

Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients.

Methods

We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125–250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253.

Findings

Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate −5·5%, 95% CI −15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40–54] vs 55% [49–63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (63% [95% CI 52–72] vs 46% [35–55]; p=0·0283). Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported.

Interpretation

In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury.

Funding

French Ministry of Health and the Société Française d'Anesthésie Réanimation.

Fewer Episodes of Atrial Fibrillation When Vasopressin Is Combined with Norepinephrine

Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive ShockA Systematic Review and Meta-analysis

Alexandra P. Lengyel¹; Ludhmila Hajjar, MD²; Anthony C. Gordon, MD^3,4; François Lamontagne, MD, MSc⁵; Jeff S. Healey, MD, MSc¹; Richard P. Whitlock, MD, PhD¹; Emilie P. Belley-Côté, MD, MSc¹

JAMA. 2018;319(18):1889-1900. doi:10.1001/jama.2018.4528

Results  Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], −0.06 [95% CI, −0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, −0.04 [95% CI, −0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, −0.07 [95% CI, −0.12 to −0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes.

Conclusions and Relevance  In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied.

Alternatives to the Swan–Ganz catheter

While the pulmonary artery catheter (PAC) is still interesting in specific situations, there are many alternatives. A group of experts from different backgrounds discusses their respective interests and limitations of the various techniques and related measured variables. The goal of this review is to highlight the conditions in which the alternative devices will suffice and when they will not or when these alternative techniques can provide information not available with PAC. The panel concluded that it is useful to combine different techniques instead of relying on a single one and to adapt the “package” of interventions to the condition of the patient. As a first step, the clinical and biologic signs should be used to identify patients with impaired tissue perfusion. Whenever available, echocardiography should be performed as it provides a rapid and comprehensive hemodynamic evaluation. If the patient responds rapidly to therapy, either no additional monitoring or pulse wave analysis (allowing continuous monitoring in case potential degradation is anticipated) can be applied. If the patient does not rapidly respond to therapy or complex hemodynamic alterations are observed, pulse wave analysis coupled with TPTD is suggested

Several articles are attached regarding volume management, revoiew of clinical parameters, as well as still a small role for CVP ( as long as the physiology of what CVP means is understood)monitoring, and critical role echocardiography appears to play in early management of septic shock .

Articles:

1) Alternatives to the Swan -Ganz Catheter

2) Expert Statement for the Management of Hypovolemia in Sepsis

3) Should we measure the CVP to guide fluid management: Ten answers to 10 questions

4) TTE and Mortality in Sepsis

5) Lactate Guided ResuscitationSaves Lives: no ( Editorial)

Please see my next entry in this blog for an extended discussion and the problems with lactate guided therapy in sepsis.

Links to Noninvasive and Minimally Invasive Devices mentioned in the above articles

ClearSight system

Flotrac on EV1000 clinical platform

EV1000 Brochure

The relationship between ICU hypotension and in-hospital mortality and morbidity in septic patients

The Surviving Sepsis Guidelines suggest keeping mean arterial pressure initially above 65 mmHg, followed by individualized treatment to optimize tissue perfusion. In our analysis, risks for mortality, AKI and myocardial injury were apparent by 85  mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Until randomized trials show that the relationship between hypotension and serious complications is not causal, it would probably be prudent to keep mean arterial pressure well above 65  mmHg in septic ICU patients.


The relationship between ICUhypotension and in-hospital mortalityand morbidity in septic patients

Kamal Maheshwari1,7*, Brian H. Nathanson2 , Sibyl H. Munson3 , Victor Khangulov3 , Mitali Stevens4 , Hussain Badani3 , Ashish K. Khanna5 and Daniel I. Sessler6

Author details 1 Department of Outcomes Research, Center for Perioperative Intelligence, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA. 2 OptiStatim, LLC, Longmeadow, MA, USA. 3 Department of Health Economics and Outcomes Research, Boston Strategic Partners, Inc., Boston, MA, USA. 4 Edwards Lifesciences, Irvine, CA, USA. 5 Department of Outcomes Research, Center for Critical Care, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA. 6 Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA. 7 Department of General Anesthesiology, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Avenue, E-31, Cleveland, OH 44195, USA.

Transthoracic echocardiography and mortality in sepsis

The performance of TTE is associated with a 28-day mortality beneft in a general population of septic, critically ill patients. The mechanism of this beneft remains to be explored but may be related to the increased use of fuids and vasoactive agents as indicated and guided by TTE results. Given that for most of ICU practice, randomized controlled trial (RCT)-based data are lacking and no RCT will likely be performed to provide evidence in the future, the application of the real-world data that is captured in EHRs is necessary to assess the clinical efectiveness of interventions such as TTE. While these investigations must be performed with full awareness of and attention to the complexity, and possible confounding by indication, of such data applications, they are now quite feasible and, we feel, absolutely necessary in the future development and evolution of optimal clinical care.


Transthoracic echocardiographyand mortality in sepsis: analysis of the MIMIC-IIIdatabase

Mengling Feng1 , Jakob I. McSparron2*, Dang Trung Kien1 , David J. Stone3 , David H. Roberts4 , Richard M. Schwartzstein4 , Antoine Vieillard‑Baron5 and Leo Anthony Celi4,6 © 2018 Springer-Verlag GmbH Germany, part of Springer Nature and ESICM

Fluids in Septic Shock

Fluid Management in Septic Shock

The 4D's

Expert Statement for the Management of Hypovolemia in Sepsis

Hypovolemia is frequent in patients with sepsis and may contribute to worse outcome. The management of these patients is impeded by the low quality of the evidence for many of the specifc components of the care.This paper discusses  recent advances and controversies in this field and give expert statements for the management of hypovolemia in patients with sepsis including triggers and targets for fuid therapy and volumes and types of fuid to be given.