Covid-19 severe hypoxemic pneumonia: A clinical experience using high-flow nasal oxygen therapy as first-line management.

PURPOSE: To report a French experience in patients admitted to Intensive Care Unit (ICU) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring high fractional concentration of inspired oxygen supported by high flow nasal cannula (HFNC) as first-line therapy. METHODS: Retrospective cohort study conducted in two ICUs of a French university hospital. All consecutive patients admitted during 28-days after the first admission for SARS-CoV-2 pneumonia were screened. Demographic, clinical, respiratory support, specific therapeutics, ICU length-of-stay and survival data were collected. RESULTS: Data of 43 patients were analyzed: mainly men (72%), median age 61 (51-69) years, median body mass index of 28 (25-31) kg/m2, median simplified acute physiology score (SAPS II) of 29 (22-37) and median PaO2/fraction of inspired oxygen (FiO2) (P/F) ratio of 146 (100-189) mmHg. HFNC was initiated at ICU admission in 76% of patients. Median flow was 50 (45-50) L/min and median FiO2 was 0.6 (0.5-0.8). 79% of patients presented at least one comorbidity, mainly hypertension (58%). At day (D) 28, 32% of patients required invasive mechanical ventilation, 3 patients died in ICU. Risk factors for intubation were diabetes (10% vs. 43%, P=0.04) and extensive lesions on chest computed tomography (CT) (P=0.023). Patients with more than 25% of lesions on chest CT were more frequently intubated during ICU stay (P=0.012). At ICU admission (D1), patients with higher SAPS II and Sequential Organ Failure Assessment (SOFA) scores (respectively 39 (28-50) vs. 27 (22-31), P=0.0031 and 5 (2-8) vs. 2 (2-2.2), P=0.0019), and a lower P/F ratio (98 (63-109) vs. 178 (126-206), P=0.0005) were more frequently intubated. Among non-intubated patients, the median lowest P/F was 131 (85-180) mmHg. Four caregivers had to stop working following coronavirus 2 contamination, but did not require hospitalization. CONCLUSION: Our clinical experience supports the use of HFNC as first line-therapy in patients with SARS-COV-2 pneumonia for whom face mask oxygen does not provide adequate respiratory support.

Bacterial colonization after tunneling in 402 perineural catheters: a prospective study.

BACKGROUND: Bacterial colonization of peripheral nerve catheters is frequent, although infection is relatively rare. With central venous catheters, the tunneling of the catheter into the subcutaneous tissue significantly decreases catheter colonization and catheter-related sepsis. We evaluated the incidence of bacterial colonization in adult patients with tunnelized perineural nerve catheters. METHODS: Peripheral nerve catheters placed under sterile conditions for postoperative analgesia were evaluated prospectively. After removal, they were analyzed for colonization. Quantitative culture was used as described by Brun-Buisson for intravascular catheters. The site of insertion was monitored daily for any signs of infection. RESULTS: Four-hundred-two patients were included in the study during a 2-yr period. The mean duration of peripheral nerve catheters was 48 h (47-50.4). Positive culture occurred in 25 catheters, indicating that the incidence of colonization was 6.22% (3.8-8.5). The microbiological analysis of the catheter tip cultures revealed coagulase-negative staphylococci in 72%. Twenty-two catheters of 25 catheters each had one microorganism, and for three catheters, two microorganisms were identified. No infection was found in any patient. CONCLUSION: The incidence of perineural catheter colonization is low with subcutaneous tunneling. Controlled randomized studies are warranted to determine whether this procedure decreases the risk for infection.

[Can iatrogenic air embolism related to intraoperative use of hydrogen peroxide be easily avoided?]. / Embolie gazeuse iatrogène due à l'utilisation peropératoire d'eau oxygénée: un accident facilement évitable?

Air embolism is a rare complication of intraoperative use of hydrogen peroxide. We present the case of a young girl who underwent surgery for septic nonunion of the femur and developed this complication postoperatively. Outcome was fortunately favorable. A review of the surgery and anesthesia literature revealed the pathogenic mechanism of this type of accident together with the appropriate diagnostic and therapeutic practices. We propose here a series of preventive measures based on our experience and data in the literature: inform the anesthetist before using hydrogen peroxide, use a cup instead of a syringe for administrating hydrogen peroxide and avoid use in deep highly vascularized cavities.

In vitro-in vivo correlation for modified-release formulations.

A correlation of in vitro dissolution rate measurements with in vivo pharmacokinetic results in a human study was obtained for a sustained-release formulation of bromocriptine. Different methods were applied to reach this correlation, and the various outcomes were compared.

Relevance of pH dependency on in vitro release of bromocriptine from a modified-release formulation.

Since pH profiles of the dissolution rate are thought to be predictive for the in vivo performance of oral modified-release formulations with respect to bioavailability and dose dumping with food, these pH profiles were established for a new modified-release (MR) formulation for bromocriptine (Parlodel SRO). The results show a marked decrease of bromocriptine dissolution with increasing pH of the dissolution medium. However, when measured in native human duodenal juice (pH 8.1), dissolution was significantly higher than when measured in buffer of comparable pH. In a human pharmacokinetic study, this MR formulation showed good bioavailability and no food effect on the pharmacokinetic profile. Therefore, pH profiles alone seem to have only a limited predictive power for the in vivo performance of this MR formulation for bromocriptine.

[Mucus models for investigation of intestinal absorption mechanisms. 3. A mathematical simulation model of drug diffusion through enteral mucus]. / Mucusmodelle zur Untersuchung von intestinalen Absorptionsmechanismen. 3. Mitteilung: Ein mathematisches Simulationsmodell der Wirkstoffdiffusion durch enteralen Mucus.

The diffusion of drug substance in a closed three-compartment model through a mucus layer to equilibrium is simulated by available pharmacokinetic programs. The obtained curves conform very well to the values experimentally found. If mucus is replaced by buffer solution an explicit equation from the literature, the method used and the experimental findings give the same results. Examination of the rate constants k1 for the diffusion in, kD through and k2 from the mucus shows the significance of the relation k1/k2 > 1, = 1, < 1 as a measure for the affinity of the active agent to the mucus. The discussion of the kinetic parameters shows, as in previous results, no criterion for assuming specific mucus binding. Because of its unspecifity the usual term "mucus binding" should be replaced by "mucus retention".

[Hypothermia at admission increases the risk of pulmonary contusion's infection in intubated trauma patients]. / L'hypothermie à l'admission augmente le risque d'infection des contusions pulmonaires chez les patients polytraumatisés sous ventilation invasive.

OBJECTIVES: Pulmonary contusion (PC) is common in cases of polytrauma. The aim of this study was to perform a multivariate analysis of risk factors associated with the occurrence of infection in PC and analyze the microbiological epidemiology. PATIENTS AND METHODS: All patients with PC admitted to the intensive care unit (ICU) between January 2002 and December 2006 were included in this retrospective observational study. Patients with penetrating thoracic trauma or those who died in the 48hours following admission to hospital were excluded. Diagnosis of bacterial infection in PC was performed if hyperthermia was associated with a positive quantitative culture (103 colony forming units/mL) on the bronchial sample. Univariate analysis provided statistical difference between variables that were integrated in the multivariate analysis model. Multivariate analysis was then performed to determine the risk factors of bacterial infection in PC. RESULTS: One hundred and seventeen patients were included. The incidence of bacterial infection in PC was 33.3% (39 patients). The most frequently encountered bacteria were Haemophilus sp., Staphylococcus aureus, Enterobacteriaceae, Pseudomonas sp. and Streptococcus sp. According to multivariate analysis, the existence of hypothermia at hospital admission increased the risk of PC infection (OR=2.61; IC 95% [4.2-13.3]). CONCLUSION: In conclusion, PC was infected in 33.3% of cases. The existence of hypothermia was identified as a risk factor. A prospective study is warranted to confirm these results.

[Does pulmonary contusion expose to the risk of Streptococcus pneumoniae infections? Results of an experimental study]. / La contusion pulmonaire expose-t-elle au risque de prolifération bactérienne à pneumocoque ? Résultats d'une étude expérimentale.

OBJECTIVE: To create a reliable and reproducible model of pulmonary contusion (PC) in rats in order to evaluate the influence of PC on bacterial lung proliferation. STUDY DESIGN: Experimental. ANIMALS: Male albino CD rats. METHODS: Animals were anesthetized and a PC was performed using a spring-loaded metal bar. The existence of an isolated right PC was confirmed by macroscopic, histological and radiological analysis. This model was used to compare four randomized groups of animals. These were either injured or only anesthetized and inoculated with a pneumococcal solution concentrated in 2 or 4 log(CFU/mL). The animals' lungs were collected for microbiological culture at 24 hours. The bacterial count evolution per gram of lung was the primary endpoint. RESULTS: Twelve rats were needed to validate the model, 84 to determine the morbidity and mortality and its reproducibility and 66 to assess the intra-pulmonary bacterial proliferation. The PC obtained was unilateral and isolated in 95% of cases. Mortality rate was 43%. For a low initial inoculum concentration (2 log [CFU/mL]), there is bacterial overgrowth in the PC group versus the no-PC group (P=0.0017). This difference was not found when the inoculum was more concentrated. CONCLUSION: This experimental model is reliable and reproducible. The initially high mortality seems to decrease with the experience of operators. The CP significantly increases intra-pulmonary bacterial proliferation when the inoculation is low. A high inoculum neutralizes the effect of CP. These results suggest that enhanced prevention of micro-inhalation could be beneficial in cases of CP.