Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients.

Hydroxychloroquine (HCQ) appears to be a promising treatment for COVID-19. However, all ongoing clinical trials with HCQ use different dosing regimens, resulting in various concentrations. Pharmacokinetic studies are therefore needed to define the optimal dosing regimen.

Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study.

INTRODUCTION: Urinary indices have limited effectiveness in separating transient acute kidney injury (AKI) from persistent AKI in ICU patients. Their time-course may vary with the mechanism of AKI. The primary objective of this study was to evaluate the diagnostic value of changes over time of the usual urinary indices in separating transient AKI from persistent AKI. METHODS: An observational prospective multicenter study was performed in six ICUs involving 244 consecutive patients, including 97 without AKI, 54 with transient AKI, and 93 with persistent AKI. Urinary sodium, urea and creatinine were measured at ICU admission (H0) and on 6-hour urine samples during the first 24 ICU hours (H6, H12, H18, and H24). Transient AKI was defined as AKI with a cause for renal hypoperfusion and reversal within 3 days. RESULTS: Significant increases from H0 to H24 were noted in fractional excretion of urea (median, 31% (22 to 41%) and 39% (29 to 48%) at H24, P<0.0001), urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40), P<0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57 (29 to 104), P=0.01). Fractional excretion of sodium did not change significantly during the first 24 hours in the ICU (P=0.13). Neither urinary index values at ICU admission nor changes in urinary indices between H0 and H24 performed sufficiently well to recommend their use in clinical setting (area under the receiver-operating characteristic curve≤0.65). CONCLUSION: Although urinary indices at H24 performed slightly better than those at H0 in differentiating transient AKI from persistent AKI, they remain insufficiently reliable to be clinically relevant.

Weaning from mechanical ventilation with pressure support in patients failing a T-tube trial of spontaneous breathing.

OBJECTIVE: Evidence that PS may facilitate weaning from mechanical ventilation (MV), although not confirmed by randomized trials, prompted us to investigate whether patients could be weaned with PS after failing a T-tube trial. DESIGN AND SETTING: This was a prospective, non-randomized study in two French intensive care units. PATIENTS AND PARTICIPANTS: One hundred eighteen patients were enrolled and underwent a T-tube trial, after which 87 were extubated. Thirty-one underwent a further trial with PS, after which 21 were extubated. INTERVENTIONS: All patients under MV >24 h meeting the criteria for a weaning test underwent a 30-min T-tube trial. If this was successful, they were immediately extubated. Otherwise, a 30-min trial with +7 cm H2O PS was initiated with an individualized pressurization slope and trigger adjustment. If all weaning criteria were met, the patients were extubated; otherwise, MV was reinstated. MEASUREMENTS AND RESULTS: The extubation failure rate at 48 h did not differ significantly between the groups: 11/87 (13%) versus 4/21 (19%), P=0.39. The groups were comparable with regard to endotracheal tube diameter, MV duration, the use of non-invasive ventilation (NIV) after extubation, initial severity score, age and underlying pathology, except for COPD. A significantly higher percentage of patients with COPD was extubated after the trial with PS (8/21-38%) than after a single T-tube trial (11/87-13%) (P=0.003). CONCLUSIONS: Of the patients, 21/118 (18%) could be extubated after a trial with PS, despite having failed a T-tube trial. The reintubation rate was not increased. This protocol may particularly benefit patients who are most difficult to wean, notably those with COPD.

Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation.

INTRODUCTION: In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting. METHOD: Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m2 AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography. RESULTS: The mean (+/- standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 +/- 1 hours, 19 +/- 6 l, 2514 +/- 212 mg/h per l, and 62 +/- 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8-36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 +/- 0.11 and 33.6 +/- 4 mg/l, respectively. CONCLUSION: We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF.

Prognostic factors in acute respiratory distress syndrome: a retrospective multivariate analysis including prone positioning in management strategy.

OBJECTIVE: To investigate the prognostic factors in acute respiratory distress syndrome (ARDS) patients focusing on the use of prone positioning (PP). DESIGN AND SETTING: Retrospective study conducted in an intensive care unit of a university hospital. PATIENTS: All consecutive mechanically ventilated ARDS patients surviving on day 7 after the diagnosis of ARDS. METHODS: The study included all ARDS patients who survived more than 7 days after ARDS diagnosis between January 1995 and December 2002. Demographic and respiratory variables were collected on day 1, and the management of ARDS was analyzed during the first 7 days ( n=125). We performed a univariate analysis and a stepwise logistic regression analysis comparing survivors and nonsurvivors on day 28 and at 2 and 6 months. RESULTS: Mortality rates on day 28 and at 2 and 6 months were 21.6%, 32%, and 44% respectively. A SAPS II score less than 49, McCabe score, and the use of PP introduced in the first 7 days of ARDS management appeared to be independently correlated with a decrease in mortality. CONCLUSIONS: The SAPS II score, the McCabe score, and use of PP are independently correlated with the outcome in ARDS patients.