Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Long-term quality of life in necrotizing soft-tissue infection survivors: a monocentric prospective cohort study.

BACKGROUND: Compared to other life-threatening infection survivors, long-term health-related quality of life (QOL) of patients surviving necrotizing soft-tissue infections (NSTI) and its determinants are little known. In this monocentric prospective cohort including NSTI survivors admitted between 2014 and 2017, QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36), the Hospital Anxiety and Depression (HAD), the activity of daily living (ADL), instrumental ADL (IADL) scales and the Impact of Event Scale-Revised (IES-R). The primary outcome measure was the SF-36 physical component summary (PCS). NSTI patients were compared according to intensive care unit (ICU) admission status. ICU survivors were matched on SAPS II with non-NSTI related septic shock survivors. RESULTS: Forty-nine NSTI survivors were phone-interviewed and included in the study. Median PCS was decreased compared to the reference population [- 0.97 (- 2.27; - 0.08) SD]. Previous cardiac disease was the only variable associated with PCS alteration [multivariate regression coefficient: - 8.86 (- 17.64; - 0.07), p = 0.048]. Of NSTI survivors, 15.2% had a HAD-D score ≥ 5 and 61.2% an IES-R score ≥ 33. ICU admission was not associated with lower PCS [35.21 (25.49-46.54) versus (vs) 41.82 (24.12-51.01), p = 0.516], but with higher IES-R score [14 (7.5-34) vs 7 (3-18), p = 0.035] and a higher proportion of HAD-D score ≥ 5 (28.6 vs 4.0%, p = 0.036). Compared to non-NSTI septic shock-matched controls, NSTI patients had similar PCS [33.81 (24.58; - 44.39) vs 44.87 (26.71; - 56.01), p = 0.706] but higher HAD-D [3.5 (1-7) vs 3 (1.5-6), p = 0.048] and IES-R scores [18 (8-35) vs 8 (3-19), p = 0.049]. CONCLUSIONS: Long-term QOL in NSTI survivors is severely impaired, similarly to that of non-NSTI septic shock patients for physical compartments, but with more frequent depressive and/or post-traumatic stress disorders. Only ICU admission and previous cardiac disease were predictive of QOL impairment.

Successful Use of Extracorporeal Membrane Oxygenation Postpartum as Rescue Therapy in a Woman With COVID-19.

Clinical manifestations of coronavirus disease 2019 in pregnant women, in contrast to previous outbreaks, seem to be similar to those of nonpregnant women. During severe acute respiratory syndrome (SARS), SARS influenza A, and Middle East respiratory syndrome outbreaks, an increased severity of disease among pregnant women was observed. In some pregnant women, respiratory failure can occur and progress quickly to acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO) as a rescue therapy. Despite a lack of current guidelines on the use of ECMO in pregnant or postpartum women, this support therapy is an effective salvage therapy for patients with cardiac and/or respiratory failure, and is associated with favorable maternal and fetal outcomes. Herein, the authors report a case of severe COVID-19 disease in a pregnant patient after urgent cesarean delivery, who was treated successfully with ECMO during the postpartum. Extracorporeal membrane oxygenation should be considered early when conventional therapy is ineffective, and it is essential to refer to ECMO expert centers.

Management and prevention of anemia (acute bleeding excluded) in adult critical care patients

Anemia is very common in critical care patients, on admission (affecting about two thirds ofpatients), but also during and after their stay, due to repeated blood loss, the effects of inflammation onerythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated withseverity of illness and length of stay.Methods: A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT,evaluated three fields: (1) anaemia prevention, (2) transfusion strategies and (3) non-transfusiontreatment of anaemia. Population, Intervention, Comparison, and Outcome (PICO) questions werereviewed and updated as needed, and evidence profiles were generated. Analysis of the literature andformulation of recommendations were then conducted according to the GRADE1methodology.Results: The SFAR-SRLF guideline panel provided ten statements concerning the management of anemiain adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope ofthese recommendations. After two rounds of discussion and various amendments, a strong consensuswas reached for ten recommendations. Three of these recommendations had a high level of evidence(GRADE 1) and four had a low level of evidence (GRADE 2). No GRADE recommendation could be providedfor two questions in the absence of strong consensus.Conclusions: The experts reached a substantial consensus for several strong recommendations foroptimal patient management. The experts recommended phlebotomy reduction strategies, restrictivered blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless ofstorage time, treatment of anemic patients with erythropoietin, especially after trauma, in the absence ofcontraindications and avoidance of iron therapy (except in the context of erythropoietin therapy). C2020 The Author(s). Published by Elsevier Masson SAS on behalf of Socie ́te ́franc ̧aise d'anesthe ́sie et dere ́animation (Sfar).

Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study.

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).

Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical Ventilation: An Ancillary Study of a Weaning Trial.

BACKGROUND: Delirium is frequent in patients in the ICU, but its association with the outcome of weaning from mechanical ventilation has not been assessed. Circadian rhythm alteration may favor delirium. In the current study, we assessed the impact of delirium during weaning and associated alterations in the circadian rhythm of melatonin excretion. METHODS: This was a substudy of 70 participants of the B-type Natriuretic Peptide for the Fluid Management of Weaning trial, comparing two fluid management strategies during weaning. Patients with or without delirium (as assessed using the Confusion Assessment Method for the ICU) were compared in terms of baseline characteristics and outcomes and the circadian rhythm of melatonin excretion using the 24-h excretion of its urinary metabolite 6-sulfatoxymelatonin (aMT6s). RESULTS: Among the 70 patients included, 43 (61.4%) experienced delirium at the initiation of weaning. Delirium at the initiation of weaning was associated with more alcohol consumption, a greater severity of illness, and medication use before weaning (including neuromuscular blockade, antibiotics, sedatives, and narcotics). Delirium at the initiation of weaning was associated with more respiratory and neurologic complications and a reduced probability of successful extubation (Cox multivariate model hazard ratio of successful extubation = 0.54; 95% CI, 0.30-0.95; P = .03). Delirium was also associated with a significant reduction in peak, mean, amplitude, and total values of aMT6s urinary excretion during the first 24 h of weaning (general linear model F statistic = 5.81, P = .019). CONCLUSIONS: Delirium is frequent at the initiation of ventilator weaning. It is associated with a prolongation of weaning and an alteration in the circadian rhythm of melatonin excretion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov.

Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome.

The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with F-fluorodeoxyglucose [18F-fluorodeoxyglucose (F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS.Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with F-FDG emission scans for quantification of regional F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed.Seventeen patients with ACS (mean age 28.3 ±â€Š6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1-2.9] vs 0.8 [0.6-1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6-11] vs 4 [3-6] days; P = 0.016).Lungs of patients with ACS exhibited higher F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower F-FDG uptake than lung bases, but higher F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung F-FDG uptake had longer ICU stay than others.