Background. Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. We describe the detection of circulating Mucorales DNA (cmDNA) for the ...early diagnosis of IWM in those patients and report the potential value of detecting cmDNA for treatment guidance. Methods. Severely ill burn patients admitted to our tertiary referral center between October 2013 and February 2016 were included. Retrospective plasma samples were tested for the presence of cmDNA by quantitative real-time polymerase chain reaction (qPCR). Patients were then prospectively screened twice a week, and liposomal amphotericin-B therapy initiated based on a positive qPCR. The primary endpoint was the time between cmDNA detection and standard diagnosis. Secondary endpoints were the time from cmDNA detection and treatment initiation and mortality. Results. Seventy-seven patients (418 samples) were included. The average age was 46 (28–60) years, abbreviated burn severity index was 8 (7–10), and simplified acute physiology score was 33 (23–46). The total body surface area was 33% (22%–52%). cmDNA was detected 11 (4.5–15) days before standard diagnosis. The in-hospital mortality was 62% for patients with IWM and 24% for those without (P = .03). The mortality due to IWM was 80% during period A and 33% during period B (P = .46). Conclusions. This study suggests that the detection of cmDNA allows earlier diagnosis of IWM in severely ill burn patients and earlier initiation of treatment. Further studies are needed to confirm the impact of earlier treatment initiation on patient outcome.
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.
Delayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post-operative lactate variation and DGF.
This was a ...single center, retrospective cohort study between February 2021 and December 2022 in Saint-Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4 h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7.
Two hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (-30 (IQR -83, -6)% vs. -15 (IQR -62, -11)%, p = .037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p = .011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR .30 .09-.79, p = .024). We did not find any association between post-operative hyperlactatemia and occurrence of complications between transplant and day 7.
DGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF.
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.
The FilmArray® Pneumonia Plus (FA-PP) panel can provide rapid identifications and semiquantitative results for many pathogens. We performed a prospective single-center study in 43 critically ill ...patients with coronavirus disease 2019 (COVID-19) in which we performed 96 FA-PP tests and cultures of blind bronchoalveolar lavage (BBAL). FA-PP detected 1 or more pathogens in 32% (31/96 of samples), whereas culture methods detected at least 1 pathogen in 35% (34/96 of samples). The most prevalent bacteria detected were Pseudomonas aeruginosa (n = 14) and Staphylococcus aureus (n = 11) on both FA-PP and culture. The FA-PP results from BBAL in critically ill patients with COVID-19 were consistent with bacterial culture findings for bacteria present in the FA-PP panel, showing sensitivity, specificity, and positive and negative predictive value of 95%, 99%, 82%, and 100%, respectively. Median turnaround time for FA-PP was 5.5 h, which was significantly shorter than for standard culture (26 h) and antimicrobial susceptibility testing results (57 h).
* Faten May, * Najouah El-Helali, * Jean-Francois Timsit and * Benoit Misset We thank Dr Chaibi et al. for their valuable and insightful comments on our report of the low evidence for an association ...between supra-therapeutic serum levels of β-lactams (BL) and clinical toxicity in ICU patients with acute renal failure (ARF) treated with intermittent hemodialysis 1. Chaibi et al. point out that neurotoxicity is common among BL, especially in at-risk patients such as those with ARF, and that some BL with a low therapeutic index may induce more neurological events. Several reports described an increased risk for penicillins, imipenem, and fourth generation cephalosporins, and suggested that neurological complications may range from confusion, depressed level of consciousness, and non-specific encephalopathy to myoclonus, non-convulsive status epilepticus (NCSE), and seizures 6. We would like to draw attention to the fact that the majority of those articles were non-human experimental studies, case series, and retrospective reviews, with assessment offering low levels of evidence 7. To establish a cause-effect relationship between a BL administration and clinical signs of encephalopathy remains a major difficulty because both clinical and electrical signs are non-specific. All the neurological symptoms of clinical encephalopathy may be observed in conditions such as metabolic abnormality, uremic disorder, ICU delirium, withdrawal syndrome, or septic encephalopathy, which are very frequent in ICU septic patients 8. In our population, while we may have missed non-convulsive signs and NCSE, we could not find an association between convulsions and BL observed at the supra-therapeutic level. Therefore, despite the comments of Chaibi et al., we consider that the BL neurotoxic threshold is not yet well identified and is still challenging. A proper diagnosis of BL neurological toxicity may be obscured by the overall clinical picture and may easily be attributed to the infectious process or to an underlying metabolic. We estimate that prospective observational studies, including pre-established and precise definitions and design, are still needed to assess BL encephalopathy and the neurotoxic threshold and to conclude on their clinical impact.
•Fluid resuscitation after burn injury is guided by biomarker.•Lactate albumin ratio (LAR) at admission is an easy and reliable marker.•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)).•Prediction by LAR does not do better than lactate level alone.
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
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, p < 0.0001 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.
Intravascular haemolysis has been associated with acute kidney injury (AKI) in different clinical settings (cardiac surgery, sickle cell disease). Haemolysis occurs frequently in critically ill burn ...patients. The aim of this study was to assess the predictive value of haptoglobin at admission to predict major adverse kidney events (MAKE) and AKI in critically ill burn patients.
We conducted a retrospective, single-centre cohort study in a burn critical care unit in a tertiary centre, including all consecutive severely burned patients (total burned body surface > 20% and/or shock and/or mechanical ventilation at admission) from January 2012 to April 2017 with a plasmatic haptoglobin dosage at admission.
A total of 130 patients were included in the analysis. Their mean age was 49 (34-62) years, their median total body surface area burned was 29% (15-51%) and the intensive care unit (ICU) mortality was 25%. Early haemolysis was defined as an undetectable plasmatic haptoglobin at admission. We used logistic regression to identify MAKE and AKI risk factors. In multivariate analysis, undetectable haptoglobin was associated with MAKE and AKI (respectively, OR 6.33, 95% CI 2.34-16.45, p < 0.001; OR 8.32, 95% CI 2.86-26.40, p < 0.001).
Undetectable plasmatic haptoglobin at ICU admission is an independent risk factor for MAKE and AKI in critically ill burn patients. This study provides a rationale for biomarker-guided therapy using haptoglobin in critically ill burn patients.
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