Gentamicin intrapatient pharmacokinetics variations were studied in 40 critically ill medical patients, suffering gram-negative sepsis. These patients were studied in two phases throughout gentamicin treatment: firstly, on the second day of treatment, when aggressive fluid therapy was required, and secondly, five days later, when patients had achieved a more stable clinical condition. Pharmacokinetic parameters were determined using least squares linear regression analysis assuming a one-compartment model using the Sawchuk-Zaske method. The apparent volume of distribution (Vd) in the first phase of the study was 0.43 +/- 0.12 L/kg, while on the seventh day of treatment it was 0.29 +/- 0.17 L/kg (p less than 0.001). Statistically significant differences were also observed for peak serum concentration (p less than 0.001), total dosage recommended (p less than 0.001) and half-life (p less than 0.05), whilst differences were not found for trough levels. From the analysis of the results obtained, we recommend increasing the initial dosage and monitoring plasma levels within the first days of therapy in critically ill patients treated with gentamicin, since important variations in aminoglycoside Vd related to disease, fluid balance and renal function, commonly occur in these patients.

Background Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. Methods In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. Results Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58–0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80–1.83] for non-invasive mechanical ventilation. Conclusion In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.

The influence of controlled mechanical ventilation (CMV) on the pharmacokinetic profile of gentamicin has been examined in 23 patients after elective open heart surgery. A parallel design was adopted in two groups of patients; 13 patients requiring CMV for at least 32 h after surgery, all of whom were able to breath spontaneously (SB) after 72 h (study group), and 10 patients who required CMV for only a brief period and who showed SB at 32 h postsurgery. Haemodynamic parameters remained stable throughout the study. Apparent volume of distribution (VZ), half-life (t1/2), total clearance (CL), peak (Cmax") and trough (Cmin") plasma levels at steady-state for target levels (6-8 microgram/ml), were measured. In the study group significant differences between CMV and SB conditions were found in VZ (mean 0.36 and 0.25 l/kg). t1/2 (mean 3.63 and 2.90 h) and Cmax" (mean 4.30 and 5.53 microgram/ml) while Cmin" (mean 1.06 microgram.ml-1 and 0.92 microgram.ml-1) did not change significantly. In contrast, the pharmacokinetics in the control group showed no differences. It appears that CMV leads to an increase in gentamicin Vz which accounts for the fall in Cmax" below the therapeutic dose range (less than 5 microgram/ml) recommended for gentamicin. It seems advisable to use a large dose of gentamicin in patients receiving CMV, even before the level is assessed.

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