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The aim of this study was to describe the prevalence, characteristics and outcome of critically burn patients with pulmonary HSV reactivation.Retrospective, single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients with bronchoalveolar lavage performed for pneumoniae suspicion and screened for HSV from January 2013 and April 2017. We used logistic regression to identify factors associated with HSV reactivation and outcomes.94 patients were included, mean age was 51 (39-64) years; median total body surface area burned was 36 (25-54)% and ICU mortality 38%. Fifty-five patients (59%) had pulmonary HSV reactivation and 30 (55%) were treated with acyclovir. Patients with HSV reactivation were more severely ill with higher SOFA score at admission compared to patient without HSV reactivation (6 [3-8] vs. 2 [1-4], p0.0001 respectively). In multivariate analysis, sex, SOFA score at admission and smoke inhalation were significantly associated with HSV reactivation. Only septic shock was associated with 90-day mortality when HSV reactivation was not.Pulmonary HSV reactivation is frequent among severely ill burn patients. Initial severity and smoke inhalation are risk factors. Antiviral treatment was not associated with outcome.

Hypoalbuminemia is a frequent condition in the first 24 h after a severe burn injury and is associated with worse outcomes.We investigated the relation between very early hypoalbuminemia (6 h after admission) and clinical outcome in a retrospective cohort admitted to our unit for severe burn injuries between 2012 and 2017.73 severely burned patients were included, with a delay of admission of 3 (2-4) h. In a context of early exogenous supply of albumin, admission and 4H Albuminemia (Alb4 h) were significantly lower in deceased patients (respectively, 34 (29-37) vs 27 (23-30) g/l; p = 0.009 and 27 (24-32) vs 21 (17-27) g/l; p = 0.022) whereas albuminemia ≥6 h were not. The best threshold value of Alb4 h to discriminate 28-day mortality was 23 g/l. Patients with an Alb4 h 23 g/l had a higher 28-day mortality than patients with an Alb4 h ≥ 23 g/l (42% vs 11%; p = 0.003); adjusted OR = 4.47 (95% CI 1.15-17.36); p = 0.03.In severely burned patients receiving early albumin supply, early hypoalbuminemia is associated with higher mortality whereas later albuminemia (≥6 h) is not. Exploration of whether early albumin infusion (8-12 h post injury) may alter clinical outcome is warranted.

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, P = 0.26}. Plasma gluconate concentration was higher in the Plasmalyte group ( P < 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 ( P = 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. NEW & NOTEWORTHY 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.

Lactate albumin ratio (LAR) has been used as a prognostic marker associated with organ failure in critically ill septic patients. LAR and its association with outcomes has never been studied in burned patients. The aim of this study was to evaluate the ability of LAR to predict 28-day mortality.A retrospective cohort study including all burn patients hospitalized in intensive care unit. The primary endpoint was the 28-day mortality.One thousand three hundred thirty four patients were screened, and 471 were included between June 2012 and December 2018. Briefly, the population study was mainly composed by men (249, 59.1%), the median age, TBSA burned, full thickness, ABSI and IGS2 were 52 [34-68], 20 [10-40], 8 [1-23], 7 [5-9] and 25 [15-40] respectively. Fifty-two patients (12.4%) died at day 28 after admission. At admission, the LAR level was lower in 28-day survivors compared non-survivors (0.05 [0.04, 0.08] vs 0.12 [0.07, 0.26], p 0.001 respectively). In multivariate analysis accounting for ABSI, LAR levels at admission 0.13 was independently associated with 28-day mortality (adjusted OR = 3.98 (IC95 1.88-8.35)). The ability of LAR at admission to discriminate 28-day mortality showed an AUC identical when compared to SOFA and ABSI scores (0.81 (IC95 0.74-0.88), 0.80 (IC95 0.72-0.85) and (0.85 (IC95 0.80-0.90), p 0.05, respectively). Patients with LAR levels ≥ 0.13 at admission had higher 28-day mortality (40.6% vs 6.8%, p 0.001, HR 7.39 (IC95 4.28-12.76)).At admission, LAR is an easy and reliable marker independently associated to 28-day mortality in patients with severe burn injury, but prediction by LAR does not perform better than lactate level alone.

Proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of renal function. This study evaluated the association of concentrations of plasma penKid with death and risk of acute kidney injury (AKI) in severely ill burn patients.A prospective observational study in two centers with severely ill adult burn patients was conducted. The inclusion criteria were total body surface area (TBSA) burns15%, with burn injury occurring72 h before intensive care unit (ICU) admission and plasma sample taken at admission. The primary endpoint was 90-day mortality. The secondary endpoints were AKI and a combined endpoint of 90-day mortality and/or AKI. Mortality was also evaluated in the sub-group of patients with sub-clinical AKI, defined as a patient without AKI but with elevated penKid.A total of 113 consecutive patients were enrolled. The median age was 48 years (Interquartile range [IQR] 33-64), the median burn TBSA was 35% (IQR 25-53), and 90-day mortality was 31.9%. Thirty-one percent of the patients had AKI, and 41.6% of patients had the combined endpoint. There was a stepwise decrease in survival from patients without AKI, sub-AKI, and with AKI (survival rate 90.0% [95% CI 82.7-97.9], 66.7% [95% CI 48.1-92.4], and 31.4% [95% CI 19.3-51.3], respectively, p0.001). Plasma penKid concentration was significantly higher in non-survivors compared to survivors (86.9 pmol/L [IQR 53.3-166.1] versus 52.9 pmol/L [IQR 37.1-70.7]; p = 0.0001) and in patients with AKI compared to patients without AKI (86.4 pmol/L [IQR 56.5-153.4] versus 52.5 pmol/L [IQR 35.5-71.2]; p0.001). Penkid provided added value on top of serum creatinine (Screat) and Sepsis Related Organ Failure Assessment (SOFA) scores to predict 90-day mortality (combined c-index of 0.738 versus 0.707; p = 0.024 and 0.787 versus 0.752; p0.001).Plasma penKid concentration at admission was associated with an increased risk of death in burn patients. PenKid has additional prognostic value on top of Screat and SOFA to predict 90-day mortality.

Background We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). Methods This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. Results Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38–56%) in the intervention group and 42% (IQR, 25–53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5–14 days) in the control group and 9 days (IQR, 5–20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69–2.01; P = .10). Conclusions The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. Clinical Trials Registration NCT03348579.

Background 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. Methods 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 (DPP3admin) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI). Results 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 DPP3admin 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 admin but decreased levels on day 3. Patients with circulatory failure had higher DPP3admin (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). DPP3admin added prognostic value on top of ABSI (added chi2 12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi2 4.9, p = 0.0268), and plasma lactate at admission (added chi2 6.9, p = 0.0086) to predict circulatory failure within the first 48 h. Conclusions 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.

BACKGROUND Patients with extensive burns are at risk of developing candidemia. OBJECTIVES To identify potentially modifiable risk factors and outcomes of candidemia in critically ill burns patients. PATIENTS AND METHODS Retrospective matched cohort study including adult burns patients. Patients who developed candidemia were matched with burns patients with Candida spp colonisation and sepsis or septic shock without candidemia in a ratio of 1:3 (same severity scores and colonisation index). Univariate and multiple regression analyses were performed. RESULTS Of 130 severely burned patients with Candida spp colonisation and at least one episode of sepsis or septic shock, 14 were diagnosed with candidemia. In the candidemia group, patients had a median (IQR) total burns surface area (TBSA) of 57 (38-68)%, SAPSII of 43 (36-58) and ABSI of 11 (8-13). Multiple regression analysis showed that only duration of prior antibiotic therapy was independently associated with candidemia. ICU mortality was higher in the candidemia group (71% vs 35% [P = 0.02]). The log-rank test for 28-day mortality comparing patients with candidemia treated with an empirical strategy vs a curative strategy did not reach significance (P = 0.056). CONCLUSIONS Burns patients having received recent antibiotherapy have a higher risk of candidemia. Antifungal strategies did not influence outcome in this series.

Objective Burn-induced shock can lead to tissue hypoperfusion, including the gut. We performed this study to describe burn patients at risk of acute mesenteric ischemia (AMI) with the aim to identify potential modifiable risk factors. Methods Retrospective case-control study including adult severely burned patients between August 2012 and March 2017. Patients who developed AMI were matched to severely burned patients without AMI at a ratio of 1:3 (same year of admission, Abbreviated Burn Severity Index [ABSI], and Simplified Acute Physiology Score II [SAPSII]). Univariate and multiple regression analyses were performed. Results Of 282 severely burned patients, 15 (5%) were diagnosed with AMI. In the AMI group, patients had a median (interquartile range) total body surface area (TBSA), SAPSII, and ABSI of 55 (25-63)%, 53 (39-70), and 11 (8-13), respectively. The AMI mechanism in all patients was nonocclusive. Decreased cardiac index within the first 24 h (H24 CI), higher sequential organ failure assessment score on day 1 (D1 SOFA), and hydroxocobalamin use were associated with AMI. Odds ratios were 0.18 (95% confidence interval [CI], 0.03-0.94), 1.6 (95% CI, 1.2-2.1), and 4.6 (95% CI, 1.3-15.9), respectively, after matching. Multiple regression analysis showed that only decreased H24 CI and higher D1 SOFA were independently associated with AMI. Ninety-day mortality was higher in the AMI group (93% vs. 46% [P = 0.001]). Conclusions Burns patients with initial low cardiac output and early multiple organ dysfunction are at high risk of nonocclusive AMI.

We aimed at assessing the predictive value of plasmatic Neutrophil Gelatinase Associated Lipocalin (pNGAL) at admission and severity scores to predict major adverse kidney events (MAKE, defined as death and/or need for renal replacement therapy (RRT) and/or non-renal recovery at day 90) in critically ill burn patients.Single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI).87 patients were included. Mean age was 47.7 (IQ 25-75: 33.4-65.2) years; total burn body surface area was 40 (IQ 25-75: 30-55) % and ICU mortality 36%. 39 (44.8%) patients presented a MAKE, 32 (88.9%) patients died at day 90. pNGAL was higher in the MAKE group (423 [IQ 25-75: 327-518]pg/mL vs 184 [IQ 25-75: 147-220]pg/mL, p0.001). In multivariate analysis, pNGAL and abbreviated burn severity index (ABSI) remained associated with MAKE (OR 1.005 [CI 95% 1.0005-1.009], p=0.03 and OR 1.682 [CI95%1.038-2.726], p=0.035 respectively). Adding pNGAL to abbreviated burn severity index, simplified organ failure assessment and the simplified acute physiology score 2 did outperform clinical scores for the prediction of MAKE and AKI and for most severe forms of AKI and allowed a statistically significant reclassification of patients compared to ABSI for MAKE, RRT, AKI at Day 7 and AKI during hospitalization with a number of patients needed to screen to detect one extra episode of MAKE was 44, 13 for severe AKI and 15 for AKI.pNGAL at admission is associated with the risk of MAKE in this population, and outperform severity scores when associated. Interventional studies are now needed to assess if impact of biomarkers-guided strategies would improve outcome.