[Normoglycaemic ketoacidosis induced by the use of sglt2 inhibitors : impact of intense physiological stress and fasting]. / Acidocétose normoglycémique induite par la prise de gliflozines en cas de stress physiologique intense et de jeûne.

Ketoacidosis is a serious complication of diabetes that only occurs in cases of absolute or severe relative insulin deficiency. This condition is rare in type 2 diabetes. The use of gliflozin during intense physiological stress associated with fasting can lead to the development of ketoacidosis without severe hyperglycaemia. The diagnosis of this normoglycaemic or euglycaemic diabetic ketoacidosis in the context of type 2 diabetes may be challenging. The treatment of metabolic acidosis cannot rely solely on symptomatic measures such as bicarbonate infusion. The demonstration of metabolic acidosis necessitates the search for an etiological diagnosis. The calculation of the anion gap is the cornerstone of the pathophysiological diagnosis of metabolic acidosis. In the context of diabetes, the occurrence of metabolic acidosis of unknown etiology requires its calculation and systematic measurement of ketones, even in the absence of severe hyperglycaemia. Only the etiological treatment of diabetic ketoacidosis, which is insulin therapy, allows for the lasting restoration of acid-base balance. Normoglycaemic ketoacidosis induced by the use of gliflozin during intense physiological stress associated with fasting should therefore be a recognized situation by healthcare providers.

L'acidocétose est une complication grave du diabète qui ne survient qu'en cas de déficit en insuline, absolu ou relatif sévère. Cette condition est rare dans le diabète de type 2. La prise de gliflozines en cas de stress physiologique intense, notamment associé à un jeûne, peut induire la survenue d'une acidocétose sans hyperglycémie sévère. Cette acidocétose diabétique dite normoglycémique ou euglycémique dans le cadre d'un diabète de type 2 est source d'errance diagnostique. Le traitement d'une acidose métabolique ne peut pas se satisfaire de l'instauration de mesures symptomatiques comme la perfusion de bicarbonates. La démonstration d'une acidose métabolique impose la recherche d'un diagnostic étiologique. Le calcul du trou anionique est la pierre angulaire du diagnostic physiopathologique d'une acidose métabolique. Dans le cadre du diabète, la survenue d'une acidose métabolique d'étiologie inconnue impose son calcul et le dosage systématique de la cétonémie, même en l'absence d'hyperglycémie sévère, a fortiori en cas de traitement par gliflozine. Seul le traitement étiologique d'une acidocétose diabétique, l'insulinothérapie, permet la restitution durable de l'équilibre acido-basique. L'acidocétose normoglycémique induite par la prise de gliflozines en cas de stress physiologique intense associé à un jeûne doit donc être une situation connue.

Prevention of ventilator-associated pneumonia and ventilator-associated conditions: a randomized controlled trial with subglottic secretion suctioning.

OBJECTIVES: Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use. DESIGN: Randomized controlled clinical trial conducted in five ICUs of the same hospital. PATIENTS: Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2). MAIN RESULTS: During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory days, ventilator-associated pneumonia rates were 9.6 of 1,000 ventilatory days and 19.8 of 1,000 ventilatory days, respectively (p = 0.0076). Ventilator-associated condition prevalence was 21.8% in group 1 and 22.5% in group 2 (p = 0.84). Among the 47 patients with ventilator-associated pneumonia, 25 (58.2%) experienced a ventilator-associated condition. Neither length of ICU stay nor mortality differed between groups; only ventilator-associated condition was associated with increased mortality. The total number of antibiotic days was 1,696 in group 1, representing 61.6% of the 2,754 ICU days, and 1,965 in group 2, representing 68.5% of the 2,868 ICU days (p < 0.0001). CONCLUSIONS: Subglottic secretion suctioning resulted in a significant reduction of ventilator-associated pneumonia prevalence associated with a significant decrease in antibiotic use. By contrast, ventilator-associated condition occurrence did not differ between groups and appeared more related to other medical features than ventilator-associated pneumonia.

Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients.

OBJECTIVES: To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients. DESIGN: Single-center, prospective, randomized controlled study. SETTING: Five intensive care units from a tertiary teaching hospital. PATIENTS: All consecutive adult patients hospitalized for >48 hrs in the intensive care unit during a 9-month period. INTERVENTIONS: Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist. MEASUREMENTS AND MAIN RESULTS: There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6±34.4% and 57.7±34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p=.11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value>1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels<0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve=0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician. CONCLUSIONS: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.

The Role of Imaging in the Detection of Non-COVID-19 Pathologies during the Massive Screening of the First Pandemic Wave.

During the COVID-19 pandemic induced by the SARS-CoV-2, numerous chest scans were carried out in order to establish the diagnosis, quantify the extension of lesions but also identify the occurrence of potential pulmonary embolisms. In this perspective, the performed chest scans provided a varied database for a retrospective analysis of non-COVID-19 chest pathologies discovered de novo. The fortuitous discovery of de novo non-COVID-19 lesions was generally not detected by the automated systems for COVID-19 pneumonia developed in parallel during the pandemic and was thus identified on chest CT by the radiologist. The objective is to use the study of the occurrence of non-COVID-19-related chest abnormalities (known and unknown) in a large cohort of patients having suffered from confirmed COVID-19 infection and statistically correlate the clinical data and the occurrence of these abnormalities in order to assess the potential of increased early detection of lesions/alterations. This study was performed on a group of 362 COVID-19-positive patients who were prescribed a CT scan in order to diagnose and predict COVID-19-associated lung disease. Statistical analysis using mean, standard deviation (SD) or median and interquartile range (IQR), logistic regression models and linear regression models were used for data analysis. Results were considered significant at the 5% critical level (p < 0.05). These de novo non-COVID-19 thoracic lesions detected on chest CT showed a significant prevalence in cardiovascular pathologies, with calcifying atheromatous anomalies approaching nearly 35.4% in patients over 65 years of age. The detection of non-COVID-19 pathologies was mostly already known, except for suspicious nodule, thyroid goiter and the ascending thoracic aortic aneurysm. The presence of vertebral compression or signs of pulmonary fibrosis has shown a significant impact on inpatient length of stay. The characteristics of the patients in this sample, both from a demographic and a tomodensitometric point of view on non-COVID-19 pathologies, influenced the length of hospital stay as well as the risk of intra-hospital death. This retrospective study showed that the potential importance of the detection of these non-COVID-19 lesions by the radiologist was essential in the management and the intra-hospital course of the patients.

Overall Survival Rate in Allogeneic Stem Cell Transplanted Patients Requiring Intensive Care Can Be Predicted by the Prognostic Index for Critically Ill Allogeneic Transplantation Patients (PICAT) and the Sequential Organ Failure Assessment (SOFA) Scores.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients requiring intensive care unit (ICU) have high mortality rates. Methods. In the current study, we retrospectively assessed whether the Prognostic Index for Critically Ill Allogeneic Transplantation patients (PICAT) score predicted overall survival in a cohort of 111 consecutive allo-HCT recipients requiring ICU. Results. Survival rates at 30 days and 1 year after ICU admission were 57.7% and 31.5%, respectively, and were significantly associated with PICAT scores (p = 0.036). Specifically, survival at 30-day for low, intermediate, and high PICAT scores was 64.1%, 58.1%, and 31.3%, respectively. At one-year, the figures were 37.5%, 29%, and 12.5%, respectively. In multivariate analyses, high PICAT score (HR = 2.23, p = 0.008) and relapse prior to ICU admission (HR = 2.98, p = 0.0001) predicted higher mortality. We next compared the ability of the PICAT and the Sequential Organ Failure Assessment (SOFA) scores to predict mortality in our patients using c-statistics. C statistics for the PICAT and the SOFA scores were 0.5687 and 0.6777, respectively. Conclusions. This study shows that while the PICAT score is associated with early and late mortality in allo-HCT recipients requiring ICU, it is outperformed by the SOFA score to predict their risk of mortality.

Ceftriaxone-induced Encephalopathy: A Pharmacokinetic Approach.

We report a case of ceftriaxone-induced encephalopathy correlated with a high concentration of the drug in cerebrospinal fluid (CSF). Cephalosporin neurotoxicity is increasingly reported, especially in association with fourth-generation cephalosporins. The factors influencing CSF concentration are plasma concentration, liposolubility, ionization, molecular weight, protein binding and efflux. In our patient, high levels of ceftriaxone (27.9 mg/l) were found in CSF. ß-Lactam-associated neurotoxicity is mainly due to similarities between GABA and the ß-lactam ring. Because of differences in CSF/plasma ratios and blood-brain barrier efflux among patients, plasma drug monitoring cannot be used to estimate CSF concentration. As far as we know, this is the first reported case of ceftriaxone-induced encephalopathy associated with a high CSF concentration. LEARNING POINTS: Ceftriaxone dose adjustment and clinical surveillance are strongly recommended in patients with renal failure.Measuring ceftriaxone cerebrospinal fluid concentration could be useful for confirming ceftriaxone-induced encephalopathy.

SAPS 3 admission score: an external validation in a general intensive care population.

OBJECTIVES: To validate the SAPS 3 admission score in an independent general intensive care case mix and to compare its performances with the APACHE II and the SAPS II scores. DESIGN: Cohort observational study. SETTING: A 26-bed general ICU from a Tertiary University Hospital. PATIENTS AND PARTICIPANTS: Eight hundred and fifty-one consecutive patients admitted to the ICU over an 8-month period. Of these patients, 49 were readmissions, leaving 802 patients for further analysis. INTERVENTION: None. MEASUREMENTS AND RESULTS: APACHE II, SAPS II and SAPS 3 variables were prospectively collected; scores and their derived probability of death were calculated according to their original manuscript description. The discriminative power was assessed using the area under the ROC curve (AUROC) and calibration was verified with the Hosmer-Lemeshow goodness-of-fit test. The AUROC of the APACHE II model (AUROC = 0.823) was significantly lower than those of the SAPS II (AUROC = 0.850) and SAPS 3 models (AUROC = 0.854) (P = 0.038). The calibration of the APACHE II model (P = 0.037) and of the SAPS 3 global model (P = 0.035) appeared unsatisfactory. On the contrary, both SAPS II model and SAPS 3 model customised for Central and Western Europe had a good calibration. However, in our study case mix, SAPS II model tended to overestimate the probability of death. CONCLUSION: In this study, the SAPS 3 admission score and its prediction model customised for Central and Western Europe was more discriminative and better calibrated than APACHE II, but it was not significantly better than the SAPS II.

Metachronous type III and type II acute aortic dissections in puerperium.

The case of a 30-year-old non-Marfan woman who developed a type III acute aortic dissection 5 days after delivery, followed within 16 h by an independent type II dissection, is reported. Preoperative CT scan imaging and TEE suggested metachronous type II and type III dissection. This was confirmed at surgery, where limited dissection of the aortic root without communication with the isthmic area via the aortic arch was evidenced. The patient underwent repair of the aortic root and adjacent ascending aorta and was medically treated for her type III dissection. This is the first report of metachronous acute aortic dissections in puerperium.

Prolonged anhepatic state after early liver graft removal.

Two-stage liver transplantation, i.e. salvage emergent total hepatectomy with prolonged anhepatic state, and subsequent liver transplantation, has been described as a life-saving procedure in selected cases. The principal drawback of two-stage liver transplantation is the fact that anhepatic patient survival only depends on the future availability of a liver graft. The pathophysiologic alterations induced by total hepatectomy are not fully known, as it is not known how long a patient may be anhepatic before it is too late for hope of survival. In this report the authors describe the cases of three liver recipients who had to undergo salvage liver graft removal early during or after liver transplantation as a life-saving maneuver. All were afterwards registered for emergent liver retransplantation. Mean anhepatic period was 20 hours (Range: 17-24 hours). Two patients survived and fully recovered. From this experience and from other cases reported in the literature, the authors concluded that total hepatectomy may be life-saving in some cases if a liver graft is available in a timely manner.

Selection of resistance during sequential use of preferential antibiotic classes.

OBJECTIVE: To determine the effect of antibiotic class pressure on the susceptibility of bacteria during sequential periods of antibiotic homogeneity. DESIGN AND SETTING: Prospective study in a mixed ICU with three separated subunits of eight, eight, and ten beds. PATIENTS AND PARTICIPANTS: The study examined the 1,721 patients with a length of stay longer than 2 days. INTERVENTIONS: Three different antibiotic regimens were used sequentially over 2 years as first-choice empirical treatment: cephalosporins, fluoroquinolone, or a penicillin-beta-lactamase inhibitor combination. Each regimen was applied for 8 months in each subunits of the ICU, using "latin square" design. RESULTS: We treated 731 infections in 546 patients (32% of patients staying more than 48 h). There were 25.5 ICU-acquired infections per 1,000 patient-days. Infecting pathogens and colonizing bacteria were found in 2,739 samples from 1,666 patients (96.8%). No significant change in global antibiotic susceptibility was observed over time. However, a decrease in the susceptibility of several species was observed for antibiotics used as the first-line therapy in the unit. Selection pressure of antibiotics and occurrence of resistance during treatment was documented within an 8-month rotation period. CONCLUSIONS: Antibiotic use for periods of several months induces bacterial resistance in common pathogens.

Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779].

INTRODUCTION: Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy. METHODS: Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter. RESULTS: Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed. CONCLUSION: Antibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.

Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study.

OBJECTIVE: To compare the efficacy and safety of adjusted-dose unfractionated heparin with that of regional citrate anticoagulation in intensive care patients treated by continuous venovenous hemofiltration (CVVH). DESIGN AND SETTING: Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a university teaching hospital. PATIENTS: ICU patients with acute renal failure requiring continuous renal replacement therapy, without cirrhosis, severe coagulopathy, or known sensitivity to heparin. INTERVENTIONS: Before the first CVVH run patients were randomized to receive anticoagulation with heparin or trisodium citrate. Patients eligible for another CVVH run received the other study medication in a cross-over fashion until the fourth circuit. MEASUREMENTS AND RESULTS: Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and 26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range 44-140) with citrate anticoagulation and 40 h (17-48) with heparin (p=0.0007). One major bleeding occurred during heparin anticoagulation and one metabolic alkalosis (pH=7.60) was noted with citrate after a protocol violation. Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2 (0.0-0.4) with citrate and 1.0 (0.0-2.0) with heparin (p=0.0008). CONCLUSIONS: Regional citrate anticoagulation seems superior to heparin for the filter lifetime and transfusion requirements in ICU patients treated by continuous renal replacement therapy.

High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial.

PURPOSE: Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI. METHODS: This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period. RESULTS: Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups. CONCLUSIONS: In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.

Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation.

PURPOSE: Sepsis induces hypercoagulability, hypofibrinolysis, microthrombosis, and endothelial dysfunction leading to multiple organ failure. However, not all studies reported benefit from anticoagulation for patients with severe sepsis, and time courses of coagulation abnormalities in septic shock are poorly documented. Therefore, the aim of this prospective observational cohort study was to describe the coagulation profile of patients with septic shock and to determine whether alterations of the profile are associated with hospital mortality. METHODS: Thirty-nine patients with septic shock on ICU admission were prospectively included in the study. From admission to day 7, analytical coagulation tests, thrombin generation (TG) assays, and thromboelastometric analyses were performed and tested for association with survival. RESULTS: Patients with septic shock presented on admission prolongation of prothrombin time, activated partial thromboplastin time (aPTT), increased consumption of most procoagulant factors as well as both delay and deficit in TG, all compatible with a hypocoagulable state compared with reference values (P < 0.001). Time courses revealed a persistent hypocoagulability profile in non-survivors as compared with survivors. From multiple logistic regression, prolonged aPTT (P = 0.007) and persistence of TG deficit (P = 0.024) on day 3 were strong predictors of mortality, independently from disease severity scores, disseminated intravascular coagulation score, and standard coagulation tests on admission. CONCLUSIONS: Patients with septic shock present with hypocoagulability at the time of ICU admission. Persistence of hypocoagulability assessed by prolonged aPTT and unresolving deficit in TG on day 3 after onset of septic shock is associated with greater hospital mortality.

Cyclic appearance of left ventricular outflow tract dynamic obstruction during mechanical ventilation: evidence for a preload dependent phenomenon.

The cyclic appearance of dynamic left ventricular outflow tract obstruction during mechanical ventilation, according to the phasic changes in preload, is described in this article. Hemodialysis-induced fluid removal resulted in preload dependence as evidenced by the pulse pressure variation in a 56-year-old critically ill patient. The clinical picture was suggestive of myocardial failure. Transthoracic echocardiography disclosed dynamic left ventricular outflow tract obstruction associated with systolic anterior motion of the mitral valve. Progressive fluid restitution resulted in a parallel decrease in both the degree of dynamic obstruction and pulse pressure variation. During fluid loading, dynamic obstruction disappeared at first during the inspiratory phase of intermittent positive pressure ventilation corresponding to the phasic increase in left ventricular preload. Further fluid loading resulted in the disappearance of dynamic obstruction during both inspiratory and expiratory phase of intermittent positive pressure ventilation. This is the first reported case clearly relating left ventricular outflow tract dynamic obstruction to preload dependence during mechanical ventilation in a critically ill patient without predisposing anatomical factor.