Sedation for adult ICU patients: A narrative review including a retrospective study of our own data.

The optimization of patients' treatment in the intensive care unit (ICU) needs a lot of information and literature analysis. Many changes have been made in the last years to help evaluate sedated patients by scores to help take care of them. Patients were completely sedated and had continuous intravenous analgesia and neuromuscular blockades. These three drug classes were the main drugs used for intubated patients in the ICU. During these last 20 years, ICU management went from fully sedated to awake, calm, and nonagitated patients, using less sedatives and choosing other drugs to decrease the risks of delirium during or after the ICU stay. Thus, the usefulness of these three drug classes has been challenged. The analgesic drugs used were primarily opioids but the use of other drugs instead is increasing to lessen or wean the use of opioids. In severe acute respiratory distress syndrome patients, neuromuscular blocking agents have been used frequently to block spontaneous respiration for 48 hours or more; however, this has recently been abolished. Optimizing a patient's comfort during hemodynamic or respiratory extracorporeal support is essential to reduce toxicity and secondary complications.

Existing and emerging therapies for the treatment of invasive candidiasis and candidemia.

INTRODUCTION: Invasive candidiasis or candidemia is a severe infection affecting more than 250,000 people worldwide every year. It is present in up to 16% of ICU patients. The prognosis of these infections is unfavorable, with global death estimated around 50,000 per year, which corresponds to up to 40% depending on patient severity and comorbidities. Therapeutic failure is not rare due to the emergence of multiresistant strains and of new species poorly responsive to current therapies like Candida auris. AREAS COVERED: We first review the positioning of antifungal drugs used to treat candidiasis, namely polyenes, azoles, echinocandins and pyrimidine analogues. We then discuss the progresses brought by new formulations, new derivatives within these classes, compounds acting on new targets or repurposed drugs in terms of pharmacokinetic profile, spectrum of activity, potency, safety or risk of drug-drug interactions. EXPERT OPINION: While new formulations (amphotericin B cochleate) improve oral bioavailability of the corresponding drugs, new azoles or echinocandins offer higher potency including against strains resistant to former generations of drugs. Repurposed drugs show synergism with current therapies in vitro. Results from ongoing and future clinical trials will be decisive to establish the interest for these drugs in our arsenal.

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

Effects of Acute Hypobaric Hypoxia Exposure on Cardiovascular Function in Unacclimatized Healthy Subjects: A "Rapid Ascent" Hypobaric Chamber Study.

Background: This study aimed to observe the effects of a fast acute ascent to simulated high altitudes on cardiovascular function both in the main arteries and in peripheral circulation. Methods: We examined 17 healthy volunteers, between 18 and 50 years old, at sea level, at 3842 m of hypobaric hypoxia and after return to sea level. Cardiac output (CO) was measured with Doppler transthoracic echocardiography. Oxygen delivery was estimated as the product of CO and peripheral oxygen saturation (SpO2). The brachial artery's flow-mediated dilation (FMD) was measured with the ultrasound method. Post-occlusion reactive hyperemia (PORH) was assessed by digital plethysmography. Results: During altitude stay, peripheral oxygen saturation decreased (84.9 ± 4.2% of pre-ascent values; p < 0.001). None of the volunteers presented any hypoxia-related symptoms. Nevertheless, an increase in cardiac output (143.2 ± 36.2% of pre-ascent values, p < 0.001) and oxygen delivery index (120.6 ± 28.4% of pre-ascent values; p > 0.05) was observed. FMD decreased (97.3 ± 4.5% of pre-ascent values; p < 0.05) and PORH did not change throughout the whole experiment. Τhe observed changes disappeared after return to sea level, and normoxia re-ensued. Conclusions: Acute exposure to hypobaric hypoxia resulted in decreased oxygen saturation and increased compensatory heart rate, cardiac output and oxygen delivery. Pre-occlusion vascular diameters increase probably due to the reduction in systemic vascular resistance preventing flow-mediated dilation from increasing. Mean Arterial Pressure possibly decrease for the same reason without altering post-occlusive reactive hyperemia throughout the whole experiment, which shows that compensation mechanisms that increase oxygen delivery are effective.

Creatinine correction to account for fluid overload in children with acute respiratory distress syndrome treated with extracorporeal membrane oxygenation: an initial exploratory report.

BACKGROUND: Creatinine is distributed between the intracellular and extracellular compartments, and as a result, the measurement of its concentration is strongly related to the fluid status of the patient. An interest has been shown in correcting measured serum creatinine levels according to the fluid balance in order to better specify the degree of acute kidney injury (AKI). METHODS: We conducted a retrospective observational study of 33 children, aged 0 to 5 years, admitted to the pediatric intensive care unit for acute respiratory distress syndrome treated by extracorporeal membrane oxygenation. We compared measured and corrected creatinine and assessed the degree of agreement between these values using both Cohen's kappa and Krippendorff's alpha coefficient. RESULTS: In our cohort, 37% of the classifications made according to measured creatinine levels were erroneous and, in the majority of cases, the degree of AKI was underestimated. CONCLUSION: Correction of the measured creatinine value according to the degree of fluid overload may result in more accurate diagnosis of AKI. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.