Objective
Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of ...inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay.
Methods
A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE
®
methodology.
Results
The SFAR–SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus.
Conclusions
The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy).
To evaluate if the increase in chloride intake during a continuous infusion of 20% hypertonic saline solution (HSS) is associated with an increase in the incidence of acute kidney injury (AKI) ...compared to standard of care in traumatic brain injury patients.
In this post hoc analysis of the COBI trial, 370 patients admitted for a moderate-to-severe TBI in the 9 participating ICUs were enrolled. The intervention consisted in a continuous infusion of HSS to maintain a blood sodium level between 150 and 155 mmol/L for at least 48 h. Patients enrolled in the control arm were treated as recommended by the latest Brain Trauma foundation guidelines. The primary outcome of this study was the occurrence of AKI within 28 days after enrollment. AKI was defined by stages 2 or 3 according to KDIGO criteria.
After exclusion of missing data, 322 patients were included in this post hoc analysis. The patients randomized in the intervention arm received a significantly higher amount of chloride during the first 4 days (intervention group: 97.3 ± 31.6 g vs. control group: 61.3 ± 38.1 g; p < 0.001) and had higher blood chloride levels at day 4 (117.9 ± 10.7 mmol/L vs. 111.6 ± 9 mmol/L, respectively, p < 0.001). The incidence of AKI was not statistically different between the intervention and the control group (24.5% vs. 28.9%, respectively; p = 0.45).
Despite a significant increase in chloride intake, a continuous infusion of HSS was not associated with AKI in moderate-to-severe TBI patients. Our study does not confirm the potentially detrimental effect of chloride load on kidney function in ICU patients.
The COBI trial was registered on clinicaltrial.gov (Trial registration number: NCT03143751, date of registration: 8 May 2017).
Abstract
Background
Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to ...describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes.
Methods
This prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18–24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensitivity analyses were conducted in patients with and without haematology malignancy and chemotherapy.
Results
Poor platelet transfusion response occurred in 349 of the 472 (73.9%) prophylactic platelet transfusions and in 141/181 (77.9%) patients. The mixed-effect model identified haemoglobin at ICU admission (odds ratio (OR): 0.79 95% confidence interval (CI) 0.7–0.89) and body mass index (BMI) (OR: 0.93 0.89–0.98) being positively and independently associated with platelet transfusion response, while a haematological malignancy (OR 1.93 1.09–3.43), sepsis as primary ICU admission diagnosis (OR: 2.81 1.57–5.03), SOFA score (OR 1.10 1.03; 1.17) and maximum storage duration of platelet (OR: 1.24 1.02–1.52) were independently associated with a suboptimal platelet increment. Clinical outcomes did not differ between groups, nor the requirement for red blood cells. Poor platelet transfusion response was found in 93.5% of patients with haematology malignancy and chemotherapy.
Conclusions
In this study of critically ill patients, of whom more than half had bone marrow failure, almost three quarters of prophylactic platelet transfusions led to suboptimal platelet increment measured 18 to 24 h following platelet transfusion. Platelet storage duration was the only factor associated with poor platelet response that may be accessible to intervention.
Trial registration
in October 2017: ClinicalTrials.gov: NCT03325140.
Septic shock results from the dysregulation of the innate immune response following infection. Despite major advances in fundamental and clinical research, patients diagnosed with septic shock still ...have a poor prognostic outcome, with a mortality rate of up to 50%. Indeed, the reasons leading to septic shock are still poorly understood. First postulated 30 years ago, the general view of septic shock as an acute and overwhelming inflammatory response still prevails today. Recently, the fact that numerous clinical trials have failed to demonstrate any positive medical outcomes has caused us to question our fundamental understanding of this condition. New and sophisticated technologies now allow us to accurately profile the various stages and contributory components of the inflammatory response defining septic shock, and many studies now report a more complex inflammatory response, particularly during the early phase of sepsis. In addition, novel experimental approaches, using more clinically relevant animal models, to standardize and stratify research outcomes are now being argued for. In the present review, we discuss the most recent findings in relation to our understanding of the underlying mechanisms involved in septic shock, and highlight the attempts made to improve animal experimental models. We also review recent studies reporting promising results with two vastly different therapeutic approaches influencing the renin-angiotensin system and applying mesenchymal stem cells for clinical intervention.
Norepinephrine administration is controversial during hemorrhagic shock resuscitation to stabilize mean arterial pressure (MAP) level because it could have deleterious effects on local circulations. ...The authors investigated the effect of norepinephrine on intestinal microcirculation during fluid resuscitation in uncontrolled hemorrhagic shock.
Mice (n = 6 per group) submitted to an uncontrolled hemorrhagic shock by tail section were randomly assigned to a resuscitation with fluid but without norepinephrine to target a MAP level of 50 mmHg (FR50) or 60 mmHg (FR60) or a resuscitation with fluid and norepinephrine to target a MAP level of 50 mmHg (FRNE50) or 60 mmHg (FRNE60). Intestinal microcirculation was observed by intravital microscopy.
Fluid requirements were lower in groups resuscitated with fluid and norepinephrine than in groups resuscitated with fluid without norepinephrine (74.6 ± 45.1 in FR50 vs. 28.1 ± 10.0 µl/g in FRNE50; P = 0.004 and 161.9 ± 90.4 in FR60 vs. 44.5 ± 24.0 µl/g in FRNE60; P = 0.041). Blood loss was not statistically different between FR50 and FRNE50 (14.8 ± 8.3 vs. 8.5 ± 2.9 µl/g; P = 0.180) but was significantly lower in FRNE60 than in FR60 (10.1 ± 4.2 vs. 22.6 ± 9.6 µl/g; P = 0.015). This beneficial effect was associated with the restoration of intestinal microcirculation to the same extent in fluid resuscitated groups without norepinephrine (FR50 and FR60) and fluid resuscitated groups with norepinephrine (FRNE50 and FRNE60).
During MAP-directed resuscitation of uncontrolled hemorrhagic shock, the administration of norepinephrine decreased blood loss and fluid requirements while preserving intestinal villi microcirculation.
Background
Acute kidney injury (AKI) in traumatic brain injury (TBI) is poorly understood and it is unknown if it can be attenuated using erythropoietin (EPO).
Methods
Pre‐planned analysis of ...patients included in the EPO‐TBI (ClinicalTrials.gov NCT00987454) trial who were randomized to weekly EPO (40 000 units) or placebo (0.9% sodium chloride) subcutaneously up to three doses or until intensive care unit (ICU) discharge. Creatinine levels and urinary output (up to 7 days) were categorized according to the Kidney Disease Improving Global Outcome (KDIGO) classification. Severity of TBI was categorized with the International Mission for Prognosis and Analysis of Clinical Trials in TBI.
Results
Of 3348 screened patients, 606 were randomized and 603 were analyzed. Of these, 82 (14%) patients developed AKI according to KDIGO (60 10% with KDIGO 1, 11 2% patients with KDIGO 2, and 11 2% patients with KDIGO 3). Male gender (hazard ratio HR 4.0 95% confidence interval CI 1.4‐11.2, P = 0.008) and severity of TBI (HR 1.3 95% CI 1.1‐1.4, P < 0.001 for each 10% increase in risk of poor 6 month outcome) predicted time to AKI. KDIGO stage 1 (HR 8.8 95% CI 4.5‐17, P < 0.001), KDIGO stage 2 (HR 13.2 95% CI 3.9‐45.2, P < 0.001) and KDIGO stage 3 (HR 11.7 95% CI 3.5‐39.7, P < 0.005) predicted time to mortality. EPO did not influence time to AKI (HR 1.08 95% CI 0.7‐1.67, P = 0.73) or creatinine levels during ICU stay (P = 0.09).
Conclusions
Acute kidney injury is more common in male patients and those with severe compared to moderate TBI and appears associated with worse outcome. EPO does not prevent AKI after TBI.
Full text
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated.
We performed a prospective multicentric study in ...patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain.
Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 4-12 days (median interquartile). At 3 months, the median intensity of pain symptoms was 2 1-5 in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI 1.1-2.1), prior use of anti-depressive agents (OR 2.2 95% CI 1.3-4), prone positioning (OR 3 95% CI 1.4-6.4) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI 1.7-3.4) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI 2.1-6) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months.
Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain.
NCT04817696. Registered March 26, 2021.
Septic shock is the consequence of a conflict between a pathogenic agent and the immune system of the host. This conflict induces an immune-mediated cytokine storm, with a whole-body inflammatory ...response often leading to multiple organ failure. Although extensively studied, the pathophysiology of sepsis-associated multiorgan failure remains unknown. One postulated mechanism is changes in mitochondrial function with an inhibition of mitochondrial respiratory chain and a decrease of oxygen utilization.
Mitochondrion is a key organelle in supplying energy to the cell according to its metabolic need. Hypoxia and a number of the mediators implicated in sepsis and in the associated systemic inflammatory response have been demonstrated to directly impair mitochondrial function. A large body of evidence supports a key role of the peroxynitrite, which can react with most of the components of the electron transport chain, in the mitochondrial dysfunction.
A pivotal role is suggested for mitochondrial dysfunction during the occurrence of multiorgan failure. Understanding the precise effect of sepsis on the mitochondrial function and the involvement of mitochondria in the development of multiple organ failure is fundamental. More human studies are thus necessary to clarify the mitochondrial dysfunction in the various phases of sepsis (early and late phase) before testing therapeutic strategies targeting mitochondria.
Background and Purpose
Angiotensin AT2 receptors are upregulated in disease states such as atherosclerosis and blockade of the AT2 receptors exacerbates plaque formation. Direct stimulation of these ...receptors is anti‐atherogenic but the mechanisms and pathways involved remain unknown. We examined the effect of direct AT2 receptor stimulation with Compound 21 (C21) on the leukocyte adhesion cascade in vitro, right through to plaque formation in vivo.
Experimental Approach
Effects of C21 on TNFα‐induced inflammation were assessed in human umbilical vein endothelial cells (HUVECs), activation of monocytes, polarisation of monocyte‐derived macrophages and in intact mouse aortae.
Key Results
C21 attenuated TNFα‐induced: monocyte adhesion to cultured HUVECs, adhesion molecule expression and abolished TNFα‐induced ROS production. TNFα‐induced NFκB translocation from the cytoplasm to the nucleus, essential for cytokine production, was prevented by C21. C21 did not influence monocyte activation or macrophage polarisation but did reduce TNFα and IL‐6 mRNA expression in M1 macrophages. The anti‐inflammatory effects of C21 were abolished by an AT2 receptor antagonist confirming that the effects of C21 were AT2 receptor‐mediated. Also, leukocyte adhesion and cytokine gene expression, induced by high‐fat diet (HFD), was attenuated in ApoE‐/‐ mice treated with C21. Plaque size and stability were improved with C21 treatment with increased smooth muscle cell composition and decreased lipid size, compared with HFD‐saline treated mice.
Conclusion and Implications
C21 prevented TNFα‐induced and HFD‐induced vascular inflammation in vitro and in vivo. Our data provide strong evidence that the anti‐atherosclerotic actions of C21 were due to vascular anti‐inflammatory effects, mediated by AT2 receptors.
Linked Articles
This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Fluid infusion represents one of the cornerstones of resuscitation therapies in order to increase oxygen delivery during septic shock. Fluid overload as a consequence of excessive fluid ...administration seems to be linked to worse long-term outcome. However, its immediate effect on patient's clinical state is poorly described. The goal of this study was to assess the impact of FO on SOFA score kinetics as a surrogate marker of organ dysfunction from day 0 to day 5.
Retrospective, multicenter, investigator-initiated study. All adult patients (> 18 years old) admitted from January 2012 to April 2017 in one of the three ICUs for septic shock, secondary to peritonitis or pulmonary infection and mechanically ventilated, were included. Univariate analysis was performed with Student's
and chi-square test, for continuous and categorical variables, respectively. A multivariate linear regression model evaluated the impact of FO on delta SOFA score from day 0 to day 5. Secondly, a multivariate mixed-model accounting for repeated measures analyzed the impact of FO on SOFA score kinetics.
One hundred twenty-nine patients met the inclusion criteria and were assigned into FO and no FO groups. FO occurred in 39% of the patients. The difference between SOFA score at day 0 and day 5 was more than twofold higher in the no FO group than in the FO group with a difference of 2.37 between the two groups (4.52 vs. 2.15;
= 0.001). Cumulative fluid intake at day 5 was higher in the FO group (2738 vs. 8715 ml,
< 0.001). In multivariate analysis, FO was associated with delta SOFA score: aRR = 0.15 (95% CI 0.03-0.63;
= 0.009). In mixed model, the regression coefficient for fluid overload status (
= 1.16;
= 0.014) indicated that the slope for SOFA score kinetic was less pronounced for patients with FO than for patients without FO.
FO patients had a more prolonged multi-organ failure according to SOFA score kinetics during septic shock from resuscitation phase to day 5.
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