Evolution, control and success of combination therapy with Ampicilin-sulbactam/Ceftazidime-Avibactam during a Carbapenem-Resistant Acinetobacter baumannii outbreak in burn Intensive Care Unit.

We present our findings on interpatient transmission, epidemic control measures, and the outcomes of a series of ten critically ill burn patients who were either colonized or infected with carbapenem-resistant Acinetobacter baumannii (CRAB). None of the five infected patients achieved clinical cure, and all experienced relapses. Microbiological failure was observed in 40% of the infected patients. The isolated CRAB strains were found to carry blaOXA-23 and armA resistance genes. Despite the lack of clinical cure, all five infected patients survived and were discharged from the Burn Intensive Care Unit.

Usefulness of lactate albumin ratio at admission to predict 28-day mortality in critically ill severely burned patients: A retrospective cohort study.

INTRODUCTION: 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. METHODS: A retrospective cohort study including all burn patients hospitalized in intensive care unit. The primary endpoint was the 28-day mortality. RESULTS: 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)). CONCLUSION: 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.

Characteristics and prognosis of Herpesviridae-related pneumonia in critically ill burn patients.

BACKGROUND: The aim of this study was to describe the prevalence, characteristics and outcome of critically burn patients with pulmonary HSV reactivation. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Continuous Lower Abdominal Compression as a Therapeutic Intervention in COVID-19 ARDS.

We report the case of a patient with severe COVID-19 ARDS, suggesting a possible therapeutic intervention by applying a continuous lower abdominal compression. In order to assess ventilation distribution, a lung CT scan was performed with and without lower abdominal compression.

Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

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.

Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients.

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 < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3admin 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.

Physiological response to fluid resuscitation with Ringer lactate versus Plasmalyte in critically ill burn patients.

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.

PenKid measurement at admission is associated with outcome in severely ill burn patients.

BACKGROUND: 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. METHODS: A prospective observational study in two centers with severely ill adult burn patients was conducted. The inclusion criteria were total body surface area (TBSA) burns >15%, with burn injury occurring <72 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. RESULTS: 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, p < 0.001). 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]; p < 0.001). 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; p < 0.001). CONCLUSIONS: 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.

Early hypoalbuminemia is associated with 28-day mortality in severely burned patients: A retrospective cohort study.

BACKGROUND: Hypoalbuminemia is a frequent condition in the first 24 h after a severe burn injury and is associated with worse outcomes. METHODOLOGY: 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. RESULTS: 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. CONCLUSION: 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.

Contributing factors and outcomes of burn-associated cholestasis.

BACKGROUND & AIMS: Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients. METHODS: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN. RESULTS: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge. CONCLUSION: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis. LAY SUMMARY: Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis.

Risk Factors for Acute Mesenteric Ischemia in Critically Ill Burns Patients-A Matched Case-Control Study.

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.

Outcome and potentially modifiable risk factors for candidemia in critically ill burns patients: A matched cohort study.

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.

Prediction of major adverse kidney events in critically ill burn patients.

OBJECTIVE: 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. MATERIAL AND METHODS: Single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface >20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI). MEASUREMENTS AND RESULTS: 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, p<0.001). 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. CONCLUSIONS: 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.

Undetectable haptoglobin is associated with major adverse kidney events in critically ill burn patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Measurement of Oxygen Consumption Variations in Critically Ill Burns Patients: Are the Fick Method and Indirect Calorimetry Interchangeable?

OBJECTIVES: To evaluate the interchangeability of oxygen consumption variations measured with the Fick equation (ΔVO2Fick) and indirect calorimetry (ΔVO2Haldane) in critically ill burns patients. METHODS: Prospective observational single-center study conducted in a university hospital. Twenty-two consecutive burns patients with circulatory insufficiency and hyperlactatemia (>2 mmol/L) who required a fluid challenge (FC) were included. All patients had cardiac output monitoring (transpulmonary thermodilution technique) and were ventilated and sedated. Simultaneous measurements of VO2Fick and VO2Haldane were performed before and immediately after the FC, at rest, and in hemodynamic conditions stabilized for at least 1 h. VO2Fick and VO2Haldane were measured, respectively, with the standard formulae (using arterial and central venous saturation measured with a blood gas analyzer) and with a metabolic monitor. RESULTS: Forty-four paired measurements of VO2 were obtained. At each timepoint, the median (interquartile range, 25-75) VO2Haldane values were significantly higher than the median VO2Fick values (126 (103-192) vs. 90 (66-149) mL O2/min/m (P = 0.004) before FC and 129 (105-189) vs. 80 (54-119) mL O2/min/m (P = 0.001) after FC). Correlation between the ΔVO2Fick and the ΔVO2Haldane (%) measurements was poor, with an r = 0.06, (P = 0.77). The mean bias was 8.6% [limits of agreement (LOA): -75.7%, 92.9%]. CONCLUSIONS: Analysis of agreement showed poor concordance for the ΔVO2Haldane and the ΔVO2Fick (%) with a low mean bias but large and clinically unacceptable LOA. ΔVO2Haldane and ΔVO2Fick (%) are not interchangeable in these conditions.