Platelets Are Critical Key Players in Sepsis Vardon-Bounes, Fanny; Ruiz, Stéphanie; Gratacap, Marie-Pierre ...
International journal of molecular sciences,
07/2019, Letnik:
20, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Host defense against infection is based on two crucial mechanisms: the inflammatory response and the activation of coagulation. Platelets are involved in both hemostasis and immune response. These ...mechanisms work together in a complex and synchronous manner making the contribution of platelets of major importance in sepsis. This is a summary of the pathophysiology of sepsis-induced thrombocytopenia, microvascular consequences, platelet-endothelial cells and platelet-pathogens interactions. The critical role of platelets during sepsis and the therapeutic implications are also reviewed.
Abstract
The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for the treatment of refractory cardiogenic shock has increased significantly. Nevertheless, early weaning may be ...advisable to reduce the potential for severe complications. Only a few studies focusing on ECMO weaning predictors are currently available. Our objective was to evaluate factors that may help predict failure during VA ECMO weaning. We included 57 patients on VA ECMO support previously considered suitable for weaning based on specific criteria. Clinical, haemato-chemical and echocardiographic assessment was considered before and after a “weaning test” (ECMO flow < 2 L/min for at least 60 min). ECMO removal was left to the discretion of the medical team blinded to the results. Weaning failure was defined as a patient who died or required a new VA ECMO, heart transplant or LVAD 30 days after ECMO removal. Thirty-six patients (63.2%) were successfully weaned off VA ECMO, of whom 31 (54.4%) after the first weaning test. In case of first test failure, 3 out of 7 patients could be weaned after a 2nd test and 3 out of 4 patients after a 3rd test. Pre-existing ischemic heart disease (OR 9.6 1.1–83), pre-test left ventricular ejection fraction (LVEF) ≤ 25% and/or post-test LVEF ≤ 40% (OR 11 0.98–115), post-test systolic blood pressure ≤ 120 mmHg (OR 33 3–385), or length of ECMO support > 7 days (OR 24 2–269) were predictors of weaning failure. The VA ECMO weaning test failed in less than 40% of patients considered suitable for weaning. Clinical and echocardiographic criteria, which are easily accessible by a non-expert intensivist, may help increase the probability of successful weaning.
In the intensive care unit, patients are subject to discomforts and pain. Their management is essentially based on pharmacologic approaches. Immersive virtual reality could represent an adjunctive ...non-invasive and non-pharmacological pain control technique. It is based on real-time interaction with an artificial 360° immersive world using interfaces that enable physical and emotional perceptions to make the user feel better trying to reduce pain perception and to limit anxiety. Evaluation of virtual reality in intensive care unit is lacking and further studies are necessary before to introduce this alternative method for critical patients.
Fiberoptic intubation for a difficult airway requires significant experience. Traditionally only normal airways were available for high fidelity bronchoscopy simulators. It is not clear if training ...on difficult airways offers an advantage over training on normal airways. This study investigates the added value of difficult airway scenarios during virtual reality fiberoptic intubation training. A prospective multicentric randomized study was conducted 2019 to 2020, among 86 inexperienced anesthesia residents, fellows and staff. Two groups were compared: Group N (control, n = 43) first trained on a normal airway and Group D (n = 43) first trained on a normal, followed by three difficult airways. All were then tested by comparing their ORSIM® scores on 5 scenarios (1 normal and 4 difficult airways). The final evaluation ORSIM® score for the normal airway testing scenario was significantly higher for group N than group D: median score 76% (IQR 56.5-90) versus 58% (IQR 51.5-69, p = 0.0039), but there was no difference in ORSIM® scores for the difficult intubation testing scenarios. A single exposure to each of 3 different difficult airway scenarios did not lead to better fiberoptic intubation skills on previously unseen difficult airways, when compared to multiple exposures to a normal airway scenario. This finding may be due to the learning curve of approximately 5-10 exposures to a specific airway scenario required to reach proficiency.
Purpose:
Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely ...monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)—a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population.
Methods:
All patients treated by venoarterial or venovenous ECMO in our intensive care unit between January 2014 and December 2015 were prospectively included. A concomitant measurement of the anti-Xa activity and ACT was performed on the same sample collected twice a day (morning–evening) for unfractionated heparin adaptation with an ACT target range of 180 to 220 seconds.
Results:
One hundred and nine patients (men 69.7%, median age 54 years) treated with ECMO (70.6% venoarterial) were included. Spearman analysis found no correlation between anti-Xa and ACT (ρ < 0.4) from day 1 and worsened over time. Kappa analysis showed no agreement between the respective target ranges of ACT and anti-Xa.
Conclusions:
We demonstrate that concomitant measurement of ACT and anti-Xa activity is irrelevant in ECMO patients. Since ACT is poorly correlated with heparin dosage, anti-Xa activity appears to be a more suitable assay for anticoagulation monitoring.
The French phase 3 trial (OS 2006) testing zoledronic acid, an osteoclast inhibitor, with chemotherapy and surgery did not improve the outcome of patients with osteosarcoma (OS). To understand this ...unexpected result, the presence of infiltrating immune cells was investigated in 124 pre-therapeutic biopsies of patients enrolled in the trial. The percentage of CD68/CD163 tumor-infiltrating macrophages (TAMs), CD8
+
lymphocytes, osteoclasts, and the PD1/PDL-1 checkpoint were assessed by immunohistochemistry. M1/M2 macrophage polarization was characterized by pSTAT1/CMAF staining. The expression of these biomarkers was correlated with clinical outcome. No statistical correlations were found with response to chemotherapy. High CD163 levels (>50% of cells per core; 43.8% of patients) were associated with CMAF nuclear expression and significantly correlated with better overall survival (p = 0.0025) and longer metastasis progression-free survival (MPFS, p = 0.0315) independently of metastatic status (p = 0.002). Only a trend was observed for patients with high CD68-positive cells (p = 0.0582). CD8
+
staining was positive in >50% of cases with a median staining of 1%. Lower CD8
+
levels were associated with metastatic disease at diagnosis and the presence of CD8-positive cells significantly correlated with improved overall survival in zoledronate-treated patients (p = 0.0415). PD1/PDL-1 staining was negative in >80% of cases and was not correlated with outcome. Finally, CD163-positive TAMs and CD8 positive cells are crucial prognostic biomarkers in OS, whereas PD1/PDL-1 checkpoint plays a minor role. For the first time, we described a correlation between CD8 positive cells and survival in zoledronate-treated patients. The immunohistochemical analysis of the microenvironment in biopsies may represent a novel tool for therapeutic stratification.
Thrombocytopenia is well recognized as a poor prognosis sign associated with increased mortality and prolonged Intensive Care Unit (ICU) stay, particularly in septic patients. Mean platelet volume ...(MPV) could represent a relevant predictive marker of mortality. Here we investigated whether MPV kinetics during the first 15 days after hospital admission has a potential prognostic value for clinical outcome in septic shock.
We performed a retrospectively analysis of a cohort of 301 septic patients admitted in ICU. Three-month mortality was the primary endpoint. The prognostic value of the covariates of interest was ascertained by multidimensional analysis. We proposed a classification and regression trees analysis to predict survival probability.
MPV kinetics was significantly different between 90-day survivors and non-survivors when followed during 15 days (except on day 3). 10-day MPV >11.6fL was an independent predictive factor of 90-day mortality (Hazard Ratio (HR) 3.796, 95% Confidence Interval (CI) 1.96-7.35, p = 0.0001) in multivariate analysis. Base excess on day 4 <1.9mmol/L was also a predictive factor of mortality (HR 2.972, 95%CI 1.38-6.40, p = 0.0054.
MPV increase during the first 15 days after ICU admission in non-survivors was observed during septic shock and 10-day MPV >11.6fL was an independent predictive factor of 90-day mortality. This could be explained by the emergent response to acute platelet loss during septic shock, leading to megakaryocyte rupture to produce new but potentially immature platelets in the circulation. Therefore, continuous monitoring of MPV may be a useful parameter to stratify mortality risk in septic shock.
Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess ...the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting.
This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis.
A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO
(R = 0.270, p = 0.03), age (R = 0.574, p < 0.0001), diastolic arterial pressure (DAP) (R = - 0.368, p = 0.0028), and SaO
(R = - 0.284, p = 0.0231). Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267).
The interpretation of renal arterial RI should take into account thresholds for PaCO
, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70-0914, received approval from local Ethical Committee of Toulouse University Hospital.
Background
This study was design to investigate the prognostic value for death at day-28 of lactate course and lactate clearance during the first 24 hours in Intensive Care Unit (ICU), after initial ...resuscitation.
Methods
Prospective, observational study in one surgical ICU in a university hospital. Ninety-four patients hospitalized in the ICU for severe sepsis or septic shock were included. In this septic cohort, we measured blood lactate concentration at ICU admission (H0) and at H6, H12, and H24. Lactate clearance was calculated as followed: (lactate
initial
- lactate
delayed
)/ lactate
initial
x 100%.
Results
The mean time between severe sepsis diagnosis and H0 (ICU admission) was 8.0 ± 4.5 hours. Forty-two (45%) patients died at day 28. Lactate clearance was higher in survivors than in nonsurvivors patients for H0-H6 period (13 ± 38% and −13 ± 7% respectively,
p
= 0.021) and for the H0-H24 period (42 ± 33% and −17 ± 76% respectively,
p
< 0.001). The best predictor of death at day 28 was lactate clearance for the H0-H24 period (AUC = 0.791; 95% CI 0.6-0.85). Logistic regression found that H0-H24 lactate clearance was independently correlated to a survival status with a
p
= 0.047 odds ratio = 0.35 (95% CI 0.01-0.76).
Conclusions
During the first 24 hr in the ICU, lactate clearance was the best parameter associated with 28-day mortality rate in septic patients. Protocol of lactate clearance-directed therapy should be considered in septic patients, even after the golden hours.