Background: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock. Results: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38–65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1–3) days, the number of doses was 2 (1–2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5–43.5) h. TDM of C _max and C _min was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a C _max /MIC > 8 and 353 (71%) having concentrations above C _min recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes. Conclusion: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov

Neuromuscular blocking agents (NMBAs) have been shown to improve the outcome of the most severely hypoxemic, acute respiratory distress syndrome (ARDS) patients. However, the recommended dosage as well as the necessity of monitoring the neuromuscular block is unknown. We aimed to evaluate the efficiency of a nurse-directed protocol of NMBA administration based on a train-of-four (TOF) assessment to ensure a profound neuromuscular block and decrease cisatracurium consumption compared to an elevated and constant dose regimen. A prospective open labeled study was conducted in two medical intensive care units of two French university hospitals. Consecutive ARDS patients with a PaO2/FiO2 ratio less than 120 with a PEEP ≥5 cm H2O were included. Cisatracurium administration was driven by the nurses according to an algorithm based on TOF monitoring. The primary endpoint was cisatracurium consumption. The secondary endpoints included the quality of the neuromuscular block, the occurrence of adverse events, and the evolution of ventilatory and blood gas parameters. Thirty patients were included. NMBAs were used for 54 ± 30 h. According to this new algorithm, the initial dosage of cisatracurium was 11.8 ± 2 mg/h, and the final dosage was 14 ± 4 mg/h, which was significantly lower than in the ACURASYS study protocol (37.5 mg/h with a constant infusion rate (p < 0.001). The overall cisatracurium dose used was 700 ± 470 mg in comparison with 2040 ± 1119 mg for patients had received the ACURASYS dosage for the same period (p < 0.001). A profound neuromuscular block (TOF = 0, twitches at the ulnar site) was obtained from the first hour in 70% of patients. Modification of the cisatracurium dosage was not performed from the beginning to the end of the study in 60% of patients. Patient–ventilator asynchronies occurred in 4 patients. A nurse-driven protocol based on TOF monitoring for NMBA administration in ARDS patients was able to decrease cisatracurium consumption without significantly affecting the quality of the neuromuscular block.

Introduction: Immune checkpoint inhibitors (ICIs) are a major breakthrough in cancer treatment. Their increasingly frequent use leads to an uprising incidence of immune-related adverse events (irAEs). Among those, myocarditis is the most reported fatal cardiovascular irAE, frequently associated with ICI-related myositis. Case series: Here, we report three cases of ICI-induced myocarditis/myositis with an extremely severe myasthenia gravis-like (MG-like) presentation, highlighting the main challenges in irAEs management. These patients were over 60 years old and presented an ongoing melanoma, either locally advanced or metastatic, treated with ICI combinations. Shortly after the first or second ICI infusion, they were admitted in an intensive care unit (ICU) for grade 3 ICI-induced MG-like symptoms leading to acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV). The initial misdiagnosis was later corrected to severe ICI-induced seronegative myocarditis/myositis upon biological results and histopathology from muscular/endomyocardial biopsies. All of them received urgent high-dose corticosteroids pulses. The oldest patient died prematurely, but the two others received targeted therapies leading to complete recovery for one of them. Discussion: These cases highlight the four main challenges of irAEs, encompassing the lack of knowledge among physicians, the risk of misdiagnosis due to numerous and non-specific symptoms, the frequent overlapping forms of irAEs, and the extremely rare MG-like misleading presentation of myocarditis/myositis. The exact pathophysiology of irAEs remains unclear, although a major involvement of the lymphoid compartment (specifically T lymphocytes) was evidenced. Therapeutic management is based on urgent high-dose corticosteroids. For the severest forms of irAEs, case-by-case targeted immunosuppressive therapies should be urgently administered upon multidisciplinary meetings. Conclusion: These cases highlight the lack of knowledge of irAEs among physicians, aggravated by misleading overlapping forms, requiring specific management in trained units and multidisciplinary care. Severe MG-like presentation of irAEs constitutes an absolute therapeutic emergency with high-dose corticosteroids and targeted immunosuppressive therapy.

Background: Several randomized clinical trials have shown that non-invasive ventilation (NIV) applied immediately after extubation may prevent reintubation in patients at high-risk of extubation failure. However, most of studies included patients with chronic respiratory disorders as well as patients without underlying respiratory disease. To date, no study has shown decreased risk of reintubation with prophylactic NIV after extubation among patients with chronic obstructive pulmonary disease (COPD). We hypothesized that prophylactic NIV after extubation may decrease the risk of reintubation in COPD patients as compared with high-flow nasal oxygen. We performed a post hoc subgroup analysis of COPD patients included in a multicenter, randomized, controlled trial comparing prophylactic use of NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone immediately after extubation. Results: Among the 651 patients included in the original study, 150 (23%) had underlying COPD including 86 patients treated with NIV alternating with high-flow nasal oxygen and 64 patients treated with high-flow nasal oxygen alone . The reintubation rate was 13% (11 out of 86 patients) with NIV and 27% (17 out of 64 patients) with high-flow nasal oxygen alone [difference, − 14% (95% CI − 27% to − 1%); p = 0.03]. Whereas reintubation rates were significantly lower with NIV than with high-flow nasal oxygen alone at 72 h and until ICU discharge, mortality in ICU did not differ between groups: 6% (5/86) with NIV vs. 9% (6/64) with high-flow nasal oxygen alone [difference − 4% (95% CI − 14% to 5%); p = 0.40]. Conclusions: In COPD patients, prophylactic NIV alternating with high-flow nasal oxygen significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial registration The study was registered at http://www.clinicaltrials.gov with the trial registration number NCT03121482 (20 April 2017)

Background: In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. Methods: Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. Results: Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, − 11% [95% CI, − 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, − 28% [95% CI, − 54 to − 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). Conclusions: In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.