Use of 1,3-Beta-D-Glucan concentration in peritoneal fluid for the diagnosis of intra-abdominal Candidiasis in Critically-ill patients.

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401.

Intra-Abdominal Candidiasis (IAC) is associated with a high mortality in Intensive Care Unit (ICU) patients. 1,3-Beta-D-Glucan (BDG), a component of Candida cell wall, was prospectively measured in peritoneal fluid from ICU patients Low peritoneal BDG concentrations may be used to rule out IAC.

Pharmacokinetic/Pharmacodynamic Dosage Individualization of Cefepime in Critically Ill Patients: A Case Study.

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.

PIPAC versus HIPEC: cisplatin spatial distribution and diffusion in a swine model.

Purpose: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach for delivering intraperitoneal chemotherapy and offers perspective in the treatment of peritoneal carcinomatosis. Concept is based on a 12 mmHg capnoperitoneum loaded with drug changed in microdoplets. It was postulated to guarantee a more homogeneous drug distribution and tissular uptake than hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to compare cisplatin peritoneal distribution and pharmacokinetic between HIPEC and PIPAC procedures in a healthy swine model.Methods: Two groups of eight pigs underwent either HIPEC with cisplatin (70 mg/m2) at 43 °C for 60 min, or PIPAC with cisplatin (7.5 mg/m2) for 30 min. Postoperatively, peritoneal areas were biopsied allowing peritoneal cavity cartography. Tissular and plasmatic cisplatin concentrations were analyzed.Results: Cisplatin distribution was heterogeneous in both the groups with higher concentrations obtained closed to the delivery sites. Median total platinum peritoneal concentration by pig was higher in the HIPEC group than in the PIPAC group (18.0 µg/g versus 4.3 µg/g, p < .001) but the yield was 2.2 times better with PIPAC. Platinum concentrations were higher in the HIPEC group in all stations. At each time-point, cisplatin plasmatic concentrations were higher in the HIPEC group (p < .001) but beneath the toxicity threshold.Conclusions: With doses used in clinical practice, HIPEC guaranteed a higher cisplatin peritoneal uptake than PIPAC in this swine model. Spatial drug distribution was heterogeneous with both technics, with hotspots closed to the drug delivery sites. Nevertheless, considering the dose ratio, IP drug uptake yield was better with PIPAC.

Immune hemolysis secondary to injection of contrast medium.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare but sometimes severe side effect. CASE REPORT: We describe the case of a 32-year-old patient who presented a cardiovascular collapse and a severe hemolysis secondary to the injection of iomeprol, a contrast medium, after a carcinologic surgery. RESULTS: The evolution was favorable after blood transfusion and short catecholamine support. The biology showed drug-dependent antibodies after incubation with iomeprol. CONCLUSION: This case is the second report of DIIHA with iomeprol.

Relaxation before Debriefing during High-fidelity Simulation Improves Memory Retention of Residents at Three Months: A Prospective Randomized Controlled Study.

BACKGROUND: High-fidelity simulation is known to improve participant learning and behavioral performance. Simulation scenarios generate stress that affects memory retention and may impact future performance. The authors hypothesized that more participants would recall three or more critical key messages at three months when a relaxation break was performed before debriefing of critical event scenarios. METHODS: Each resident actively participated in one scenario and observed another. Residents were randomized in two parallel-arms. The intervention was a 5-min standardized relaxation break immediately before debriefing; controls had no break before debriefing. Five scenario-specific messages were read aloud by instructors during debriefings. Residents were asked by telephone three months later to recall the five messages from their two scenarios, and were scored for each scenario by blinded investigators. The primary endpoint was the number of residents participating actively who recalled three or more messages. Secondary endpoints included: number of residents observing who recalled three or more messages, anxiety level, and debriefing quality. RESULTS: In total, 149 residents were randomized and included. There were 52 of 73 (71%) residents participating actively who recalled three or more messages at three months in the intervention group versus 35 of 76 (46%) among controls (difference: 25% [95% CI, 10 to 40%], P = 0.004). No significant difference was found between groups for observers, anxiety or debriefing quality. CONCLUSIONS: There was an additional 25% of active participants who recalled the critical messages at three months when a relaxation break was performed before debriefing of scenarios. Benefits of relaxation to enhance learning should be considered for medical education.

Comparison of cardiac output optimization with an automated closed-loop goal-directed fluid therapy versus non standardized manual fluid administration during elective abdominal surgery: first prospective randomized controlled trial.

An intraoperative automated closed-loop system for goal-directed fluid therapy has been successfully tested in silico, in vivo and in a clinical case-control matching. This trial compared intraoperative cardiac output (CO) in patients managed with this closed-loop system versus usual practice in an academic medical center. The closed-loop system was connected to a CO monitoring system and delivered automated colloid fluid boluses. Moderate to high-risk abdominal surgical patients were randomized either to the closed-loop or the manual group. Intraoperative final CO was the primary endpoint. Secondary endpoints were intraoperative overall mean cardiac index (CI), increase from initial to final CI, intraoperative fluid volume and postoperative outcomes. From January 2014 to November 2015, 46 patients were randomized. There was a lower initial CI (2.06 vs. 2.51 l min-1 m-2, p = 0.042) in the closed-loop compared to the control group. No difference in final CO and in overall mean intraoperative CI was observed between groups. A significant relative increase from initial to final CI values was observed in the closed-loop but not the control group (+ 28.6%, p = 0.006 vs. + 1.2%, p = 0.843). No difference was found for intraoperative fluid management and postoperative outcomes between groups. There was no significant impact on the primary study endpoint, but this was found in a context of unexpected lower initial CI in the closed-loop group.Trial registry number ID-RCB/EudraCT: 2013-A00770-45. ClinicalTrials.gov Identifier NCT01950845, date of registration: 17 September 2013.

Risk factors for intraoperative allogeneic blood transfusion during craniotomy for brain tumor removal in children.

BACKGROUND: Several clinical and surgical factors can influence the occurrence of allogeneic blood transfusion (ABT) during oncologic neurosurgery. OBJECTIVES: To identify the potential predictive factors of ABT during craniotomy for the removal of brain tumors in children and the potential impact of intraoperative ABT on early postoperative outcome. METHODS: A retrospective study was performed in all pediatric patients younger than 18 years who underwent craniotomy for brain tumor removal from December 2009 to December 2012 in our institution. Pre-, intra-, and postoperative data were collected from medical and stored electronic anesthesia records. The predictors of intraoperative ABT were determined using multivariate logistic regression. RESULTS: A total of 110 patients were included. Twenty-seven patients (25%) received intraoperative ABT with a volume of 16 ± 8 ml·kg(-1) . On multivariate analysis, an age <4 years, a duration of surgery >270 min, and a preoperative hemoglobin <12.2 g·dl(-1) were independently associated with the need for intraoperative ABT. We did not show any significant difference concerning postoperative early outcome and length of stay between the transfused and non-transfused patients except for the duration of postoperative mechanical ventilation that was significantly higher in the transfused group (P = 0.04). CONCLUSION: In children, craniotomy for brain tumor removal is at risk of intraoperative ABT. An age <4 years, a duration of surgery >270 min, and a preoperative hemoglobin <12.2 g·dl(-1) are the main factors associated with intraoperative ABT during this surgery.

A new device for continuous assessment of gut perfusion: proof of concept on a porcine model of septic shock.

INTRODUCTION: We evaluate an innovative device consisting of an enteral feeding tube equipped with a photoplethysmography (PPG) sensor in contact with the duodenal mucosa. This study aims to determine if the PPG signal, composed of a continuous (PDC) and a pulsatile part (PAC), is a reliable method to assess gut perfusion in a porcine model of septic shock. METHOD: Fourteen piglets were anesthetized and mechanically ventilated. They were randomly assigned to two groups: the nonseptic (NS) group received an infusion of Ringer's lactate solution (RL) alone, the septic (S) group received in addition a suspension of live Pseudomonas aeruginosa. Heart rate (HR), pulse oximetry (SpO2), mean arterial pressure (MAP), cardiac index (CI) and serum lactates were recorded and gut microcirculation (GM) was monitored with a laser Doppler probe applied on the duodenal serosa. PDC and PAC were given by the PPG probe inserted in the duodenum. Data was collected every 15 minutes (t0, t15…) during 150 minutes (t150). After administration of the bacteria suspension (t0), resuscitation maneuvers were performed following a defined algorithm. GM PAC, and PDC were expressed as variation from baseline (GMvar, PACvar, PDCvar). Analysis of variance (ANOVA) with repeated measures was performed to compare hemodynamic variables, with Bonferroni correction as post hoc analysis on t0, t60 and t150. RESULTS: One piglet was withdrawn from analysis due to a defective probe. S group (six piglets) received resuscitation therapy while NS group (seven piglets) did not. A significant group effect was found for the all parameters except HR. Post hoc analysis found a significant decrease for GM and PAC at t60. The correlation between PAC, PDC and microcirculatory parameters were as follows: rPACvar-GMvar = 0.496, P <0.001, rPDCvar-GMvar = 0.244; P = 0.002. In the septic group, correlations were as follows: rPAC-lactate = -0.772, P <0.001; rPDC-lactate = -0.681, P <0.01). At the onset of shock, a decrease of PAC, PDC and GM occurred before the alteration of MAP. CONCLUSIONS: PAC and PDC decreased at the onset of shock and were correlated with GM and lactate. These results confirm that PPG signal reliably reflects the early perfusion alteration of the gut. Further studies should assess the clinical use of this device.

Eliminating the need for preoperative intravenous hyperhydration: Sodium thiosulfate as nephrotoxicity prevention in HIPEC-treated patients - A retrospective analysis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal metastases. However, HIPEC with cisplatin is associated with renal toxicity. Sodium thiosulfate (ST) has been shown to prevent cisplatin-induced toxicity. METHODS: A retrospective, single-center analysis of patients treated curatively for peritoneal surface malignancy, who underwent cytoreductive surgery with cisplatin-based HIPEC between 2015 and 2020. Patients were categorized into three groups based on the management of cisplatin-induced renal toxicity: preoperative hyperhydration alone (PHH), preoperative hyperhydration with ST (PHH + ST), and ST alone. Renal function and complications, in terms of Acute (AKI) and chronic kidney injury (CKI), were monitored and analyzed during 3 postoperative months. RESULTS: This study included 220 consecutive patients. Mean serum creatinine levels were 95, 57 and 61 mmol/L, for PHH, PHH + ST and ST groups, respectively (p < 0.001). Glomerular Filtration Rate (GFR) were 96, 94 and 78 ml/min/1.73 m2, respectively (p < 0.001). AKI and CKI are respectively for PHH, PHH + ST and ST groups were 21 % (n = 46), 1 % (n = 2) and 0 % vs 19 % (n = 42), 0 % and 0 % (p < 0.001), for pairwise analysis did not show any difference between PHH + ST and ST alone combination, regarding nephrological outcomes. All patients were followed 3 months postoperatively. CONCLUSION: There is no need for preoperative hyperhydration when sodium-thiosulfate is used to prevent cisplatin-induced nephrotoxicity in patients undergoing cytoreductive surgery with HIPEC. These findings have implications for improving and simplifying the management of patients with peritoneal metastases undergoing HIPEC with cisplatin.

Fatal Community-Acquired Peritonitis Due to Invasive Necrotizing Intestinal Mucormycosis: Case Report and Review of the Literature.

We report here a rare case of fatal rapidly progressive necrotizing gastrointestinal mucormycosis due to Mucor circinelloides f. circinelloides in the setting of community-acquired peritonitis, in an immunocompromised adult patient. Diagnosis was established by direct examination of peritoneal fluid showing hyphae consistent with mucormycosis confirmed by the culture.

Which injured patients with moderate fibrinogen deficit need fibrinogen supplementation?

BACKGROUND: In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L-1, but some teams have suggested to use higher thresholds (fibrinogenemia < 2.0 g L-1 or FIBTEM clot amplitude at 5 min (A5) values < 11 mm). The goal of this study was to specify in patients with a moderate fibrinogen deficit (MFD) whether some admission characteristics would be associated with fibrinogen administration at 24 h. METHODS: Prospective analysis of retrospectively collected data from a trauma registry (01/2011-12/2019). MFD-C was defined by a fibrinogenemia 1.51-1.99 g L-1 or the corresponding FIBTEM-A5 values (MFD-A5) that were determined from linear regression and ROC curve analysis. Administration of fibrinogen were described according to the following admission parameters: shock index (SI) > 1, hemoglobin level < 110 g L-1 (HemoCue®), and base deficit > 5 mEq L-1. Data are expressed as count (%), median [IQR]. RESULTS: 1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19-36] vs. 24 [17-29]) and had more impaired vital signs (base deficit: 5.4 [3.6-7.8] vs. 3.8 [2.0-6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level < 1.5 g L-1 and < 2.0 g L-1, FIBTEM-A5 thresholds were 6 mm (sensitivity 85%, specificity 83%, AUC: 0.934) and 9 mm (sensitivity 84%, specificity 69%, AUC: 0.874), respectively. MFD-A5 values (185 (27%) patients) were defined as a FIBTEM-A5 between 7 and 9 mm. More than 50% of MFD-C patients presenting a SI > 1, a hemoglobin level < 110 g L-1, or a base deficit > 5.0 mEq L-1 received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06-1.82] for MFD-C, and 2.17 [1.48-3.19] for MFD-A5. Results were not modified after adjustment on the ISS. CONCLUSIONS: We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.

Effects of modification of trauma bleeding management: A before and after study.

OBJECTIVE: We hypothesised that the association of tranexamic acid (TXA) administration and thromboelastometry-guided haemostatic therapy (TGHT) with implementation of Damage Control Resuscitation (DCR) reduced blood products (BP) use and massive transfusion (MT). METHODS: Retrospective comparison of 2 cohorts of trauma patients admitted in a university hospital, before (Period 1) and after implementation of DCR, TXA (first 3-hours) and TGHT (Period 2). Patients were included if they received at least 1 BP (RBC, FFP or platelet) or coagulation factor concentrates (fibrinogen or prothrombin complex) during the first 24-hours following the admission. RESULTS: 380 patients were included. Patients in Period 2 (n = 182) received less frequently a MT (8% vs. 33%, P < 0.01), significantly less BP (RBC: 2 units [1-5] vs. 6 [3-11]; FFP: 0 units [0-2] vs. 4 [2-8]) but more fibrinogen concentrates (3.0 g [1.5-4.5] vs. 0.0 g [0.0-3.0], P < 0.01). Multivariate logistic regression analysis identified Period 1 as being associated with an increased risk of receiving MT (OR: 26.1, 95% CI: 9.7-70.2) and decreased survival at 28 days (OR: 2.0, 95% CI: 1.0-3.9). After propensity matching, the same results were observed but there was no difference for survival and a significant decrease for the cost of BP (2370 ± 2126 vs. 3284 ± 3812 €, P: 0.036). CONCLUSION: Following the implementation of a bundle of care including DCR, TGHT and administration of TXA, we observed a decrease to the use of blood products, need for MT and an improvement of survival.