Ketamine restriction correlates with reduced cholestatic liver injury and improved outcomes in critically ill patients with burn injury.

Background & Aims: Ketamine-associated cholestatic liver injury is reported in patients with severe burn injury, but its association with patient outcome is unclear. We investigated the relationship between ketamine exposure, cholestatic liver injury, and outcome of critically ill patients with burn injury. Methods: In a retrospective study, patients with severe burn injury were analysed across two periods: unrestricted ketamine prescription (ketamine-liberal) and capped ketamine dosage (ketamine-restricted). The primary endpoint was cholestatic liver injury, and the secondary endpoint was 3-month mortality. Binary logistic regression models and the revised electronic causality assessment method were used to measure the strength of associations and causality assessment, respectively. Results: Of 279 patients (median age 51 [IQR 31-67] years; 63.1% men; burned surface area 28.5%, IQR 20-45%), 155 (56%) were in the ketamine-liberal group, and 124 (44%) were in the ketamine-restricted group, with comparable clinical characteristics, except for ketamine exposure (median doses 265.0 [IQR 0-8,021] mg and 20 [IQR 0-105] mg, respectively; p <0.001). A dose- and time-dependent relationship was observed between ketamine exposure and cholestatic liver injury. Ketamine restriction was associated with a reduced risk of cholestatic liver injury (adjusted odds ratio 0.16, 95% CI 0.04-0.50; p = 0.003) and with a higher probability of 3-month survival (p = 0.035). The revised electronic causality assessment method indicated that ketamine was probably and possibly the cause of cholestatic liver injury for 14 and 10 patients, respectively. Cholangitis was not observed in the ketamine-restricted group. In propensity-matched patients, the risk of 3-month mortality was higher (adjusted odds ratio 9.92, 95% CI 2.76-39.05; p = 0.001) in patients with cholestatic liver injury and ketamine exposure ≥10,000 mg. Other sedative drugs were not associated with liver and patient outcome. Conclusions: In this cohort, ketamine restriction was associated with less cholestatic liver injury and reduced 3-month mortality. Impact and implications: In a cohort of 279 critically ill patients with burn injury, ketamine was associated with a risk of liver bile duct toxicity. The risk was found to be dependent on both the dosage and duration of ketamine use. A restriction policy of ketamine prescription was associated with a risk reduction of liver injury and 3-month mortality. These findings have implications for the analgesia and sedation of critically ill patients with ketamine, with higher doses raising safety concerns.

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.

[The missions of Biologie Sans Frontières (BSF)]. / Les missions de Biologie Sans Frontières (BSF).

« Biologie sans Frontières ¼ (BSF) is a non-governmental organisation whose mission is to develop medical biology where it is most needed, particularly in French-speaking Africa. In Guinea Conakry, with Fondation Mérieux and the Guinean Ministry of Health, BSF is in charge of training "trainers/teachers" of technicians. This training will take place at the National Health School of Kindia, a school that has been completely rehabilitated and re-equipped thanks to the support of Fondation Mérieux. This project is supported by the French Development Agency. BSF has an in-depth knowledge of the local needs in medical biology training. After an audit carried out by two BSF members, the findings were alarming: these trainers had no experience in medical biology and their theoretical knowledge was still of low level. Three training courses were then provided by BSF, the first in biochemistry, sero-immunology and immuno-hematology, the second in cyto-hematology and the last one in bacteriology-parasitology. The basic techniques have been acquired, the "student trainers" have shown great assiduity, but the level remains fragile and will require new training, which is essential to help these future teachers to provide structured, functional and above all useful practical work adapted to local practices and needs.

Activation of the renin-angiotensin-aldosterone system is associated with Acute Kidney Injury in COVID-19.

The pathophysiology of acute kidney injury (AKI) in COVID-19 patients is still poorly understood. SARS-CoV-2 has been suggested to modulate the renin-angiotensin-aldosterone system (RAAS). In this series of COVID-19 critically ill patients, we report evidence of activation of the RAAS in COVID-19 patients with AKI.

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.

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.