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.

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.

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.

Detection of Circulating Mucorales DNA in Critically Ill Burn Patients: Preliminary Report of a Screening Strategy for Early Diagnosis and Treatment.

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.

Urine sodium concentration to predict fluid responsiveness in oliguric ICU patients: a prospective multicenter observational study.

BACKGROUND: Oliguria is one of the leading triggers of fluid loading in patients in the intensive care unit (ICU). The purpose of this study was to assess the predictive value of urine Na(+) (uNa(+)) and other routine urine biomarkers for cardiac fluid responsiveness in oliguric ICU patients. METHODS: We conducted a prospective multicenter observational study in five university ICUs. Patients with urine output (UO) <0.5 ml/kg/h for 3 consecutive hours with a mean arterial pressure >65 mmHg received a fluid challenge. Cardiac fluid responsiveness was defined by an increase in stroke volume >15 % after fluid challenge. Urine and plasma biochemistry samples were examined before fluid challenge. We examined renal fluid responsiveness (defined as UO > 0.5 ml/kg/h for 3 consecutive hours) after fluid challenge as a secondary endpoint. RESULTS: Fifty-four patients (age 51 ± 37 years, Simplified Acute Physiology Score II score 40 ± 20) were included. Most patients (72 %) were not cardiac responders (CRs), and 50 % were renal responders (RRs) to fluid challenge. Patient characteristics were similar between CRs and cardiac nonresponders. uNa(+) (37 ± 38 mmol/L vs 25 ± 75 mmol/L, p = 0.44) and fractional excretion of sodium (FENa(+)) (2.27 ± 2.5 % vs 2.15 ± 5.0 %, p = 0.94) were not statistically different between those who did and those who did not respond to the fluid challenge. Areas under the receiver operating characteristic (AUROC) curves were 0.51 (95 % CI 0.35-0.68) and 0.56 (95 % CI 0.39-0.73) for uNa(+) and FENa(+), respectively. Fractional excretion of urea had an AUROC curve of 0.70 (95 % CI 0.54-0.86, p = 0.03) for CRs. Baseline UO was higher in RRs than in renal nonresponders (1.07 ± 0.78 ml/kg/3 h vs 0.65 ± 0.53 ml/kg/3 h, p = 0.01). The AUROC curve for RRs was 0.65 (95 % CI 0.53-0.78) for uNa(+). CONCLUSIONS: In the present study, most oliguric patients were not CRs and half were not renal responders to fluid challenge. Routine urinary biomarkers were not predictive of fluid responsiveness in oliguric normotensive ICU patients.

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.

Impact of an Acinetobacter baumannii outbreak on kidney events in a burn unit: A targeted machine learning analysis.

BACKGROUND: Multidrug-resistant (MDR) bacteria outbreaks represent a major threat in intensive care units. Patients may then be exposed to drug-related direct toxicity during such outbreaks. The objective of this study was to explore the impact of an outbreak of imipenem-resistant Acinetobacter baumannii (IR-AB) on renal outcomes. METHODS: We performed a before-and-after observational study in a French burn intensive care unit during an IR-AB outbreak: a 13-month period before (period A, October 2013-October 2014) and a 13-month period after outbreak control (period B, December 2014-December 2015). A total of 409 patients were included, 195 during period A and 214 during period B. The main endpoint was major adverse kidney events at day 90 (MAKE 90). Secondary endpoints were acute kidney injury (AKI) and persistent renal dysfunction. RESULTS: Incidence of MAKE 90 was 15.9% during period A versus 11.2% during period B (P = .166) and AKI 28.2% versus 18.7% (P = .023). The use of colistin was associated with renal outcomes in univariate analysis. After adjustment of potential confounding factors using a targeted Machine Learning Analysis (ie, IR-AB-related infection, septic shock, severity scores, other nephrotoxics, chronic kidney disease, serum creatinine at admission, Staphylococcus aureus), colistin remained associated with the risk of MAKE and AKI (relative risk = 2.909, 95% confidence interval [CI] [1.364, 6.204], P = .006 for MAKE 90, and relative risk = 2.14, 95% CI [1.52, 3.02], P<.0001 for AKI). CONCLUSIONS: The episode of IR-AB outbreak was associated with an increased risk of kidney events, which appears to be driven by the use of colistin.

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.

Chloride toxicity in critically ill patients: What's the evidence?

Crystalloids have become the fluid of choice in critically ill patients and in the operating room both for fluid resuscitation and fluid maintenance. Among crystalloids, NaCl 0.9% has been the most widely used fluid. However, emerging evidence suggests that administration of 0.9% saline could be harmful mainly through high chloride content and that the use of fluid with low chloride content may be preferable in major surgery and intensive care patients. Administration of NaCl 0.9% is the leading cause of metabolic hyperchloraemic acidosis in critically ill patients and side effects might target coagulation, renal function, and ultimately increase mortality. More balanced solutions therefore may be used especially when large amount of fluids are administered in high-risk patients. In this review, we discuss physiological background favouring the use of balanced solutions as well as the most recent clinical data regarding the use of crystalloid solutions in critically ill patients and patients undergoing major surgery.

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.

Heart rate variability and cardiac baroreflex inhibition-derived index predicts pain perception in burn patients.

BACKGROUND: Dressing changes induce acute pain in burn patients. This pain is difficult to predict and may be therefore undertreated. Two different non-invasive electrophysiological indices from heart rate variability and baroreflex inhibition-derived indices, analgesia/nociception index (ANI) and cardiovascular depth of analgesia (CARDEAN), have been proposed to predict and better assess adequacy of anti-nociception. The aim of this study was to evaluate these techniques as early pain alert tools in conscious burnt patients during dressing changes' procedures. METHODS: Twenty adult burnt patients undergoing scheduled wound treatment procedures were included in this prospective observational study. Pain intensity was assessed using a 0-10 numerical rating scale (NRS) and was compared with both ANI and CARDEAN, during the procedures. Non parametric rank sum test and linear discriminant analysis were used for evaluating potential differences of measured variables between periods with different pain intensities. Receiver-operating characteristic (ROC) curves were built to assess their performance to detect pain within following 15s. RESULTS: The sensitivity and specificity of ANI to detect pain were 67% and 70% and those of CARDEAN were 77% and 80%, with area under the curve (AUC) values of 0.75 and 0.83, respectively. Their combination increased AUC to 0.87. CONCLUSIONS: Both ANI and CARDEAN indices during wound treatment procedures seem to discriminate periods with and without pain within 15s, serving as a potential complementary tool for early optimized pain control.

Low cardiac index and stroke volume on admission are associated with poor outcome in critically ill burn patients: a retrospective cohort study.

BACKGROUND: Impact of early systemic hemodynamic alterations and fluid resuscitation on outcome in the modern burn care remains controversial. We investigate the association between acute-phase systemic hemodynamics, timing of fluid resuscitation and outcome in critically ill burn patients. METHODS: Retrospective, single-center cohort study was conducted in a university hospital. Forty critically ill burn patients with total body surface area (TBSA) burn-injured >20 % with invasive blood pressure and cardiac output monitoring (transpulmonary thermodilution technique) within 8 h from trauma were included. We retrospectively examined hemodynamic variables during the first 24 h following admission, and their association with 90-day mortality. RESULTS: The median (interquartile range 25th-75th percentile) TBSA, Simplified Acute Physiology Score II (SAPS II) and Abbreviated Burn Severity Index of the study population were 41 (29-56), 31 (23-50) and 9 (7-11) %, respectively. 90-Day mortality was 42 %. There was no statistical difference between the median pre-hospital and 24-h administered fluid volume in survivors and non-survivors. On admission, stroke volume (SV), cardiac index (CI), oxygen delivery index and mean arterial pressure (MAP) were significantly lower in patients who died despite similar fluid resuscitation volume. ROC curves comparing the ability of initial SV, CI, MAP and lactate to discriminate 90-day mortality gave areas under curves of, respectively, 0.89 (CI 0.77-1), 0.77 (CI 0.58-0.95), 0.73 (CI 0.53-0.93) and 0.78 (CI 0.63-0.92); (p value <0.05 for all). In multivariate analysis, SAPS II and initial SV were independently associated with 90-day mortality (best cutoff value for SV was 27 mL, sensitivity 92 %, specificity 69 %). During 24 h, no interaction was found between time and outcome regarding macrocirculatory parameters changes. Hemodynamic parameters improved during the first 24-h resuscitation in all patients but patients who died had lower SV and CI on admission, which remained through the first 24 h. CONCLUSION: Low initial SV and CI were associated with poor outcome in critically ill burn patients. Very early hemodynamic monitoring may in help detecting under-resuscitated patients. Future prospective interventional studies should explore the impact of early goal-directed therapy in these specific patients.

Assessment of dyspnoea in the emergency department by numeric and visual scales: A pilot study.

OBJECTIVE(S): Dyspnoea is a common and often debilitating symptom that affects up to 50% of patients admitted to acute tertiary care hospitals. The primary purpose of this study was to compare the numeric rating scale (NRS) and the visual analogue scale (VAS) for dyspnoea evaluation in the ED setting. STUDY DESIGN AND PATIENTS: This was a cohort study of patients admitted to the ED in a university hospital, with dyspnoea as the chief complaint. METHODS: The agreement of the two dyspnoea scales was assessed using the intraclass correlation coefficient (ICC). RESULTS: One hundred and seventeen patients were included in this analysis. The median age for the whole study population was 67 years and 42% of patients were male. The aetiology of dyspnoea was acute heart failure (AHF) in 35% of patients. There was good agreement between the two scores (ICC=0.795; 95% CI=0.717-0.853; P<0.001). CONCLUSIONS: This pilot study demonstrated that numerical rating and visual analogue scales agree well when assessing the severity of dyspnoea in the ED. Further studies with larger cohorts of patients are needed to confirm these preliminary results.