Abstract Background Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic ...support (i.e., fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-thrombotic properties (i.e., inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction. Methods The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e., skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6 h and later 24 h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7 days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28 days post-randomization, number of renal replacement therapy-free survival days in the 28 days post-randomization, number of vasopressor-free survival days in the 28 days post-randomization, and mottling score at day 1 after randomization. Discussion The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders. Trial registration NCT NCT03788837 . Registered on 28 December 2018
Dipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial ...depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients.
In this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3
) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI).
One hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5-63) years, with a median total body surface area burned of 35% (25-53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7-11). Ninety-day mortality was 32%. The median DPP3
was significantly higher in non-survivors versus survivors (53.3 ng/mL IQR 28.8-103.5 versus 27.1 ng/mL IQR 19.4-38.9; p < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3
but decreased levels on day 3. Patients with circulatory failure had higher DPP3
(39.2 ng/mL IQR 25.9-76.1 versus 28.4 ng/mL IQR 19.8-39.6; p = 0.001) as well as patients with AKI (49.7 ng/mL IQR 30.3-87.3 versus 27.6 ng/mL IQR 19.4-41.4; p = 0.001). DPP3
added prognostic value on top of ABSI (added chi
12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi
4.9, p = 0.0268), and plasma lactate at admission (added chi
6.9, p = 0.0086) to predict circulatory failure within the first 48 h.
Plasma DPP3 concentration at admission was associated with an increased risk of death, circulatory failure, and AKI in severely burned patients. Whether DPP3 plasma levels could identify patients who would respond to alternative hemodynamic support strategies, such as intravenous angiotensin II, should be explored.
Acute kidney injury (AKI) has been associated with both short- and long-term outcomes. To date, there is still a debate whether the increase risk of morbidity and mortality is directly due to AKI ...occurrence. There is, however, a potential causal impact of AKI on outcome, but evidence of this association is yet lacking. The hypothesis of remote organ damage and dysfunction (heart, lung, liver, brain, etc.) has emerged over the last decade and may explain the reason for the potential negative impact of AKI on outcome. The aim of this review was to describe findings concerning the remote effect of AKI in animal models and human studies.
The metabolic consequences in vivo of various balanced solutions are poorly known in critically ill patients. The main objective of this study was to describe the metabolic consequences of Plasmalyte ...versus Ringer lactate (RL) in critically ill burn patients, with a special focus on the plasma clearance of buffer anions (i.e., gluconate, acetate, and lactate). We conducted a randomized trial between August 2017 and October 2018 in a tertiary teaching hospital in Paris, France. Patients with burn total body surface area >30% were randomized to receive Plasmalyte or RL. The primary end point was the base excess 24 h after inclusion. The secondary end points were acetate, gluconate, and lactate plasma concentration, the strong ion difference (SID). Twenty-eight patients were randomized. Twenty-four hours after inclusion, plasma BE was not significantly different in the Plasmalyte and RL groups {-0.9 95% confidence interval (95% CI): -1.8-0.9 vs. -2.1 95% CI: -4.6-0.6 mmol/L, respectively,
= 0.26}. Plasma gluconate concentration was higher in the Plasmalyte group (
< 0.001), with a maximum level of 1.86 (95% CI: 0.98-4.0) mmol/L versus 0 (95% CI: 0-0.15) mmol/L. Plasma acetate and lactate were not significantly different. Ionized calcium level was lower in the Plasmalyte group (
= 0.002). Hemodynamics did not differ between groups. To conclude, the alkalinizing effect of Plasmalyte was less important than expected with no difference in base excess compared with RL, in part due to gluconate accumulation. Acetate and lactate did not significantly accumulate. Plasmalyte led to significantly lower ionized calcium levels.
During fluid resuscitation in burns the alkalinizing effect of Plasmalyte was less important than expected, with no difference in base excess compared with Ringer lactate (RL), in part due to gluconate accumulation. Acetate and lactate did not significantly accumulate. Plasmalyte led to significantly lower ionized calcium levels.
OBJECTIVES:To assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by esophageal Doppler.
...DESIGN:Prospective, monocentric study.
SETTING:Medical ICU.
PATIENTS:Twenty-eight adult patients with acute circulatory failure and a decision of the clinicians in charge to administer fluids.
INTERVENTIONS:Before and after infusing 500 mL of saline, we measured cardiac index estimated by esophageal Doppler before and during the last 5 seconds of successive 15-second end-inspiratory occlusion and end-expiratory occlusion, separated by 1 minute. Patients in whom volume expansion increased cardiac index measured by transpulmonary thermodilution greater than or equal to 15% were defined as “fluid responders.” Cardiac index measured by the Pulse Contour Cardiac Output device (from pulse contour analysis or transpulmonary thermodilution) was used as the reference.
MEASUREMENTS AND MAIN RESULTS:End-expiratory occlusion increased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (8% ± 2% vs 3% ± 1%, respectively; p < 0.0001) and end-inspiratory occlusion decreased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (–8% ± 5% vs –4% ± 2%, respectively; p = 0.0002). Fluid responsiveness was predicted by the end-expiratory occlusion induced percent change in cardiac index estimated by esophageal Doppler with an area under the receiver operating characteristic curve of 1.00 (95% CI, 0.88–1.00) and a threshold value of 4% increase in cardiac index estimated by esophageal Doppler. It was predicted by the sum of absolute values of percent changes in cardiac index estimated by esophageal Doppler during both occlusions with a similar area under the receiver operating characteristic curve (0.99 0.86–1.00) and with a threshold of 9% change in cardiac index estimated by esophageal Doppler, which is compatible with the esophageal Doppler precision.
CONCLUSIONS:If the absolute sum of the percent change in cardiac index estimated by esophageal Doppler induced by two successive end-inspiratory occlusion and end-expiratory occlusion maneuvers is greater than 9%, it is likely that a 500 mL fluid infusion will increase cardiac output. This diagnostic threshold is higher than if only end-expiratory occlusion induced percent changes in cardiac index estimated by esophageal Doppler are taken into account.
•A retrospective single-centre study was undertaken including 147 samples from 92 patients.•The overall percentage agreement was 98% for detection of typical bacteria.•Significant thresholds in ...culture were compared with nucleic acid copy number.•Median turnaround time was significantly shorter for the FilmArray Pneumonia Panel Plus than for culture.
This study aimed to evaluate the performance of FilmArray Pneumonia Panel Plus (FA-PP) for the detection of typical bacterial pathogens in respiratory samples from patients hospitalized in intensive care units (ICUs).
FA-PP was implemented for clinical use in the microbiology laboratory in March 2020. A retrospective analysis on a consecutive cohort of adult patients hospitalized in ICUs between March 2020 and May 2020 was undertaken. The respiratory samples included sputum, blind bronchoalveolar lavage (BBAL) and protected specimen brush (PSB). Conventional culture and FA-PP were performed in parallel.
In total, 147 samples from 92 patients were analysed; 88% had coronavirus disease 2019 (COVID-19). At least one pathogen was detected in 46% (68/147) of samples by FA-PP and 39% (57/147) of samples by culture. The overall percentage agreement between FA-PP and culture results was 98% (93–100%). Bacteria with semi-quantitative FA-PP results ≥105 copies/mL for PSB samples, ≥106 copies/mL for BBAL samples and ≥107 copies/mL for sputum samples reached clinically significant thresholds for growth in 90%, 100% and 91% of cultures, respectively. FA-PP detected resistance markers, including mecA/C, blaCTX-M and blaVIM. The median turnaround time was significantly shorter for FA-PP than for culture.
FA-PP may constitute a faster approach to the diagnosis of bacterial pneumonia in patients hospitalized in ICUs.
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