Insulin therapy and blood glucose management in critically ill patients: a 1-day cross-sectional observational study in 69 French intensive care units.

BACKGROUND: Hyperglycaemia is common in critically ill patients, but blood glucose and insulin management may differ widely among intensive care units (ICUs). We aimed to describe insulin use practices and the resulting glycaemic control in French ICUs. We conducted a multicentre 1-day observational study on November 23, 2021, in 69 French ICUs. Adult patients hospitalized for an acute organ failure, severe infection or post-operative care were included. Data were recorded from midnight to 11:59 p.m. the day of the study by 4-h periods. RESULTS: Two ICUs declared to have no insulin protocol. There was a wide disparity in blood glucose targets between ICUs with 35 different target ranges recorded. In 893 included patients we collected 4823 blood glucose values whose distribution varied significantly across ICUs (P < 0.0001). We observed 1135 hyperglycaemias (> 1.8 g/L) in 402 (45.0%) patients, 35 hypoglycaemias (≤ 0.7 g/L) in 26 (2.9%) patients, and one instance of severe hypoglycaemia (≤ 0.4 g/L). Four hundred eight (45.7%) patients received either IV insulin (255 [62.5%]), subcutaneous (SC) insulin (126 [30.9%]), or both (27 [6.6%]). Among patients under protocolized intravenous (IV) insulin, 767/1681 (45.6%) of glycaemias were above the target range. Among patients receiving insulin, short- and long-acting SC insulin use were associated with higher counts of hyperglycaemias as assessed by multivariable negative binomial regression adjusted for the propensity to receive SC insulin: incidence rate ratio of 3.45 (95% confidence interval [CI] 2.97-4.00) (P < 0.0001) and 3.58 (95% CI 2.84-4.52) (P < 0.0001), respectively. CONCLUSIONS: Practices regarding blood glucose management varied widely among French ICUs. Administration of short or long-acting SC insulin was not unusual and associated with more frequent hyperglycaemia. The protocolized insulin algorithms used failed to prevent hyperglycaemic events.

Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE]).

OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp o2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7; p = 0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

Inhaled antibiotics in critical care: State of the art and future perspectives.

Administration of inhaled antibiotics in intensive care units (ICU) remains confidential compared to bronchodilators, not withstanding extensive pre-clinical and clinical research and potential indications associated with the emergence of bacterial antibiotic resistances. Inhaled antibiotic administration enables delivery of high doses of antibiotics directly to the lung. Local antibiotic concentrations are pronouncedly higher than the minimum inhibitory concentration of causative pathogens of lung infection, and also higher than the minimal concentrations preventing resistant emergence, with low systemic passage and resulting side effects. In the available armamentarium face to multidrug-resistant bacteria spread, inhaled antibiotics may have a role, insofar they remain effective and prevent further emergence of resistance. In critically ill patients, some studies have documented the benefits of aerosolized antibiotic therapy compared to intravenous treatment. Prophylactic administration of inhaled antibiotics to prevent ventilator-associated pneumonia has yielded encouraging results. In ICUs, nebulized antibiotics may be considered for treatment of ventilator-associated pneumonia caused by resistant pathogens in patients at high risk of therapeutic failure, or as a last resort in case of uncontrolled infection with intravenous antibiotics. In this review, we address the rationale for this treatment method and provide a short technical update, followed by a discussion of potential indications for inhaled antibiotics in critically ill patients. Lastly, we present the innovations and future developments of inhaled antimicrobial therapies that could benefit ICU patients.

Inhaled antibiotics during mechanical ventilation-why it will work.

Inhaled antibiotics are a common therapy among patients suffering recurrent or chronic pulmonary infections. Their use is less frequent in acutely ill patients despite a strong theoretical rationale and growing evidence of their efficiency, safety and beneficial effect on reducing bacterial resistance emergence. Clinical trials of inhaled antibiotics have shown contradictory results among mechanically ventilated patients. The optimal nebulization setup, not always implemented in all trials, the difficulty to identify the population most likely to benefit and the testing of various therapeutic strategies such as adjunctive versus alternative to systemic antibiotics may explain the disparity in trial results. The present review first presents the reasons why inhaled antibiotics have to be developed and the benefits to be expected of inhaled anti-infectious therapy among mechanically ventilated patients. A second part develops the constraints of aerosolized therapies that one has to be aware of and the simple actions required during nebulization to ensure optimal delivery to the distal lung parenchyma. Positive and negative studies concerning inhaled antibiotics are compared to understand the discrepancies of their findings and conclusions. The last part presents current developments and perspective which will likely turn it into a fully successful therapeutic modality, and makes the link between inhaled antibiotics and inhaled anti-infectious therapy.

Kinetic Glomerular Filtration Rate Equations in Patients With Shock: Comparison With the Iohexol-Based Gold-Standard Method.

OBJECTIVES: Static glomerular filtration rate formulas are not suitable for critically ill patients because of nonsteady state glomerular filtration rate and variation in the volume of distribution. Kinetic glomerular filtration rate formulas remain to be evaluated against a gold standard. We assessed the most accurate kinetic glomerular filtration rate formula as compared to iohexol clearance among patients with shock. DESIGN: Retrospective multicentric study. SETTING: Three French ICUs in tertiary teaching hospitals. PATIENTS: Fifty-seven patients within the first 12 hours of shock. MEASUREMENTS AND MAIN RESULTS: On day 1, we compared kinetic glomerular filtration rate formulas with iohexol clearance, with or without creatinine concentration correction according to changes in volume of distribution and ideal body weight. We analyzed three static glomerular filtration rate formulas (Cockcroft and Gault, modification of diet in renal disease, and Chronic Kidney Disease-Epidemiology Collaboration), urinary creatinine clearance, and seven kinetic glomerular filtration rate formulas (Jelliffe, Chen, Chiou and Hsu, Moran and Myers, Yashiro, Seelhammer, and Brater). We evaluated 33 variants of these formulas after applying corrective factors. The bias ranged from 12 to 47 mL/min/1.73 m2. Only the Yashiro equation had a lower bias than urinary creatinine clearance before applying corrective factors (15 vs 20 mL/min/1.73 m2). The corrected Moran and Myers formula had the best mean bias, 12 mL/min/1.73 m2, but wide limits of agreement (-50 to 73). The corrected Moran and Myers value was within 30% of iohexol-clearance-measured glomerular filtration rate for 27 patients (47.4%) and was within 10% for nine patients (15.8%); other formulas showed even worse accuracy. CONCLUSIONS: Kinetic glomerular filtration rate equations are not accurate enough for glomerular filtration rate estimation in the first hours of shock, when glomerular filtration rate is greatly decreased. They can both under- or overestimate glomerular filtration rate, with a trend to overestimation. Applying corrective factors to creatinine concentration or volume of distribution did not improve accuracy sufficiently to make these formulas reliable. Clinicians should not use kinetic glomerular filtration rate equations to estimate glomerular filtration rate in patients with shock.

Paracetamol use and lowered risk of acute kidney injury in patients with rhabdomyolysis.

BACKGROUND: Mortality with rhabdomyolysis-associated acute kidney injury can be as high as 80%. Experimental data from mouse models of rhabdomyolysis showed that paracetamol reduces the expected increase in serum creatinine level. We aimed to assess the association between paracetamol use and the need for starting renal replacement therapy (RRT). METHODS: We conducted a propensity score-matched cohort study in Orléans Hospital, France (a 1136-bed, public, university-affiliated and teaching hospital). All patients with serum creatine phosphokinase (CK) level > 5000 IU/L between January 1st, 2008 and December 31st, 2017 were included. A propensity score was calculated for each included patient by using multivariable logistic regression and all available baseline characteristics. The main outcome was the incidence of RRT initiation from day 1 to day 28 in the propensity score-matched cohort between patients exposed and unexposed to paracetamol. RESULTS: Over the study period, 1065 patients with at least one CK level measurement > 5000 IU/L were included; 40 (3.8%) had at least one RRT session. Among the 343 matched pairs, 10 (2.9%) exposed and 24 (7.0%) unexposed patients underwent RRT before day 28 (P = 0.021). Primary time-to-event analysis showed that exposure to paracetamol was significantly associated with reduced absolute risk of RRT: absolute risk difference = - 3.18% (95% CI - 5.23 to - 1.20, P = 0.001). All secondary analyses showed a significantly reduced absolute risk of RRT in patients exposed to paracetamol. CONCLUSION: Our study showed a significant association between paracetamol exposure and reduced incidence of RRT among patients with rhabdomyolysis.