The combination of kidney function variables with cell cycle arrest biomarkers identifies distinct subphenotypes of sepsis-associated acute kidney injury: a post-hoc analysis (the PHENAKI study).

BACKGROUND: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care. PATIENTS AND METHODS: In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT). RESULTS: We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92-7.42] (p < 0.001) for subphenotype B and 4.80 [1.67-13.82] (p = 0.004) for subphenotype C. CONCLUSIONS: Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates.

Protocol for fever control using external cooling in mechanically ventilated patients with septic shock: SEPSISCOOL II randomised controlled trial.

INTRODUCTION: Fever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever. METHODS AND ANALYSIS: SEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients. ETHICS AND DISSEMINATION: The study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04494074.

Sustained low-efficiency dialysis with regional citrate anticoagulation for patients with liver impairment in intensive care unit: A single-center experience.

Regional citrate anticoagulation (RCA) is a recommended method for extracorporeal circuit anticoagulation during renal replacement therapy (RRT). Increased risk of citrate accumulation by default of hepatic metabolism limits its use in liver failure patients. A Catot /Caion ratio ≥2.5 is established as an indirect control of plasma citrate poisoning. To investigate the safety of RCA in patients with liver impairment during sustained low-efficiency dialysis (SLED), we conducted a retrospective study of 41 patients with acute or chronic hepatocellular failure requiring RRT between January 2014 and June 2015 in the intensive care unit of the Groupe Hospitalier Sud Ile de France. Sixty-seven SLED sessions were performed. At admission, 32 (78%) patients had acute liver dysfunction and nine (22%) patients had cirrhosis with a median MELD score of 27 (IQR: 18.8, 42.0). Despite a majority of poor prognosis patients (SAPS-II (Simplified Acute Physiology Score II) score 71 [IQR: 58; 87]), with acute liver impairment as a part of multi-organ failure, no dosage of Catot /Caion ratio after SLED sessions exceeded the critical threshold of 2.5. Of the 63 complete sessions, neither dyscalcemia nor major dysnatremia, nor extracorporeal circuit thrombosis were noticed. Observed acid-base disturbances (16.4%) were not significantly correlated with the Catot /Caion ratio (P = .2155). In this retrospective study using RCA during intermittent RRT in ICU patients with severe liver dysfunction, we did not observe any citrate accumulation but monitoring of acid-base status and electrolytes remains necessary to ensure technique safety.

Automated vs. conventional ventilation in the ICU: a randomized controlled crossover trial comparing blood oxygen saturation during daily nursing procedures (I-NURSING).

BACKGROUND: Hypoxia is common during daily nursing procedures (DNPs) routinely performed on mechanically ventilated patients. The impact of automated ventilation on the incidence and severity of blood oxygen desaturation during DNPs remains unknown. METHODS: A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO2) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). All patients with FiO2 ≤ 60% and without prone positioning or neuromuscular blocking agents were included. Patients underwent two DNPs on the same day using AV (INTELLiVENT-ASV®) and CV (volume control, biphasic positive airway pressure, or pressure support ventilation) in a randomized order. The primary outcome was the percentage of time spent with SpO2 in the acceptable range of 90-95% during the DNP. RESULTS: Of the 265 included patients, 93% had been admitted for a medical pathology, the majority for acute respiratory failure (52%). There was no difference between the two periods in terms of DNP duration, sedation requirements, or ventilation parameters, but patients had more spontaneous breaths and lower peak airway pressures during the AV period (p <  0.001). The percentage of time spent with SpO2 in the acceptable range during DNPs was longer in the AV period than in the CV period (48 ± 37 vs. 43 ± 37, percentage of DNP period; p = 0.03). After adjustment, AV was associated with a higher number of DNPs carried out with SpO2 in the acceptable range (odds ratio, 1.82; 95% CI, 1.28 to 2.6; p = 0.001) and a lower incidence of blood oxygen desaturation ≤ 85% (adjusted odds ratio, 0.50; 95% CI, 0.30 to 0.85; p = 0.01). CONCLUSION: AV appears to reduce the incidence and severity of blood oxygen desaturation during daily nursing procedures (DNPs) in comparison to CV. TRIAL REGISTRATION: This study was registered in clinical-trial.gov ( NCT03176329 ) in June 2017.

Duration of prone position sessions: a prospective cohort study.

BACKGROUND: Prone position (PP) is highly recommended in moderate-to-severe ARDS. However, the optimal duration of PP sessions remains unclear. We searched to evaluate the time required to obtain the maximum physiological effect, and to search for parameters related to patient survival in PP. METHODS AND RESULTS: It was a prospective, monocentric, physiological study. We included in the study all prone-positioned patients in our ICU between June 2016 and January 2018. Pulmonary mechanics, data from volumetric capnography and arterial blood gas were recorded before prone positioning, 2 h after proning, before return to a supine position (SP) and 2 h after return to SP. Dynamic parameters were recorded before proning and every 30 min during the session until 24 h. 103 patients (ARDS 95%) were included performing 231 PP sessions with a mean length of 21.5 ± 5 h per session. They presented a significant increase in pH, static compliance and PaO2/FiO2 with a significant decrease in PaCO2, Pplat, phase 3 slope of the volumetric capnography, PetCO2, VD/VT-phy and ΔP. The beneficial physiological effects continued after 16 h of PP and at least up to 24 h in some patients. The evolution of the respiratory parameters during the first session and also during the pooled sessions did not find any predictor of response to PP, whether before, during or 2 h after the return in SP. CONCLUSIONS: PP sessions should be prolonged at least 24 h and be extended in the event that the PaO2/FiO2 ratio at 24 h remains below 150, especially since no criteria can predict which patient will benefit or not from it. Trial registration The trial has been registered on 28 June 2016 in ClinicalTrials.gov (NCT02816190) (https://clinicaltrials.gov/ct2/show/NCT02816190?term=propocap&rank=1).

Cabazitaxel Induced Thrombotic Microangiopathy in a Patient with Prostate Cancer.

Cancer-associated thrombotic microangiopathy (TMA) refers to a group of disorders characterized by microangiopathic haemolytic anemia, thrombocytopenia, and ischemic organ damage. TMA manifestations can be induced by cancer or by chemotherapy. We report the case of a 64-year-old man with metastatic prostate cancer who experienced a Cabazitaxel-induced TMA manifestation. TMA responds to conservative therapy, dialysis without plasmaphoresis, with progressive recovered renal function.

Urinary TIMP2 and IGFBP7 Identifies High Risk Patients of Short-Term Progression from Mild and Moderate to Severe Acute Kidney Injury during Septic Shock: A Prospective Cohort Study.

BACKGROUND: To examine whether the new urinary biomarkers TIMP2 and IGFBP7 can predict progression within 24 hours and 72 hours from mild and moderate (KDIGO 1 or 2) to severe (KDIGO 3) AKI in patients with septic shock. METHODS: A prospective, multicenter observational study performed in three French ICUs. The urinary biomarkers TIMP2∗IGFBP7 were analyzed at the early phase (<6 hours) of patients admitted for septic shock with mild and moderate AKI. RESULTS: Among the 112 patients included, 45 (40%) progressed to the KDIGO 3 level 24 hours after inclusion (KDIGO 3 H24) and 47 (42%) 72 hours after inclusion (KDIGO 3 H72). The median urinary TIMP2∗IGFBP7 at inclusion (baseline) were higher in the KDIGO 3 group than in the KDIGO<3 group at H24 and H72. All covariates with a p value < 0.1 in the univariate analysis were included in stepwise multiple logistic regression models to identify factors independently associated with the risk of KDIGO 3 at H24 and H72. TIMP2∗IGFBP7 remained independently associated with KDIGO 3 at H24 and H72. Baseline posology of norepinephrine, baseline urine output, and baseline serum creatinine remained also significantly associated with progression to KDIGO 3 at H24. Baseline TIMP2∗IGFBP7 and baseline urinary output had the best AUC ROC. A baseline TIMP2∗IGFBP7 > 2.0 (ng/ml)2/1,000 identified the population at high risk of KDIGO 3 H24 (relative risk 4.19 (1.7-10.4)) with a sensitivity of 76% (60-87) and a specificity of 81% (69-89). But the diagnostic performance at H72 of baseline TIMP2∗IGFBP7 was poor (AUC: 0.69 (0.59-0.77)). CONCLUSION: The urinary TIMP2∗IGFBP7 concentration and the urine output at the early phase of septic shock are independent factors to identify the population at high risk of progression from mild and moderate to severe AKI over the next 24 but not 72 hours. A TIMP2∗IGFBP7 concentration > 2.0 (ng/ml)2/1,000 quadruples the risk of KDIGO 3 AKI within 24 hours. This trial is registered with (NCT03547414).

Does metformin exposure before ICU stay have any impact on patients' outcome? A retrospective cohort study of diabetic patients.

BACKGROUND: Impact of metformin exposure before ICU stay remains controversial. Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce ICU mortality. We evaluated its influence on outcome in diabetic patients admitted in the ICU and then compared two different populations based on the presence of septic shock. METHODS: We conducted a retrospective cohort study in a 24-bed French ICU between October 2010 and December 2013, including all ICU-admitted diabetic patients. RESULTS: Among 635 diabetic patients admitted during the study period, 131 (21%) were admitted with septic shock. Multivariate analysis showed no difference in hospital mortality in all metformin users (OR 0.75 [95% CI 0.44-1.28]; p = 0.29), except in the septic shock subgroup (OR 0.61; 95% CI [0.37-0.99]; p = 0.04) despite higher vasopressor dosages in the first hours after shock onset. Blood lactate level was higher in metformin users than in non-metformin users in all patients (p < 0.001), in septic shock patients (p < 0.001) and in patients without kidney injury (p < 0.001). Metformin users did not have more septic shock from unknown aetiology (p = 0.65) or unknown pathogen (p = 0.99). CONCLUSIONS: Metformin use before admission to ICU did not affect in-hospital mortality. However, for patients with septic shock, mortality was lower, despite worse clinical presentation on admission. Blood lactate levels were always higher with or without septic shock and indifferent of kidney function.

Efficiency of goal-directed oxygen delivery in ICU patients.

BACKGROUND: Current clinical practice guidelines promote a goal-directed approach for oxygen delivery with respect to SpO2 objectives. We evaluated the efficiency of a strategy based on goal-directed O2 delivery in the ICU. METHODS: A group of 30 patients (Group 1) with a proven history of chronic obstructive pulmonary disease suffering from acute hypercarbic exacerbation was compared to 2 other groups of patients admitted for acute respiratory failure with no history of pulmonary disease: 30 patients requiring oxygen supply and/or non-invasive ventilation (Group 2) and 30 requiring invasive ventilation (Group 3). The delivery of oxygen was based on SpO2 measurement: 88-94% for Group 1 and 90-96% for others. The time spent with an SpO2 below, within and above the prescribed limits was collected. RESULTS: The mean time spent within the prescribed range was for Groups 1, 2 and 3, respectively as follows: 61.9% [60.5-63.2], 63.7% [62.3-65] and 56.4% [55.3-57.6] (P < 0.001 for each group). A history of chronic obstructive pulmonary disease was not correlated with better results (P = 0.11), while invasive ventilation was related to the time spent out of the prescribed range (P < 0.001; OR 1.3 [1.22-1.28]) especially in hyperoxaemia (40.7% [39.6-41.8] P < 0.001). Efficiency seems unrelated to nursing workload or night team exhaustion (r = -0.09, P = 0.77). CONCLUSIONS: Goal-directed oxygen delivery based on SpO2 objectives in ICU patients ensures that in only approximately 64% of the time, SpO2 stays within the prescribed range.