Background: Linezolid is used for the treatment of soft tissue infections in critically ill patients. However, data for characterizing the pharmacokinetics (PK) and assessing whether effective concentrations are reached at the target site are lacking. We hypothesized that current dosing regimens do not lead to effective concentrations in the plasma and interstitial fluid (ISF) of subcutaneous tissue in obese patients. Methods: As a controlled clinical model, critically ill obese and non-obese patients undergoing intra-abdominal surgery received 600 mg linezolid as a single infusion. Concentrations in the plasma and microdialysate from the ISF of subcutaneous tissue were determined up to 8 h after dosing. Pharmacokinetic analysis was performed by non-compartmental methods. As a therapeutic target, we used fAUC/MIC > 80. Results: Fifteen obese (BMI: 48.7 ± 11.2 kg/m²) and 15 non-obese (23.9 ± 2.1 kg/m²) patients were analyzed. AUC_0–8 in ISF decreased by −1.69 mg*h/L (95% CI: −2.59 to −0.79, p < 0.001) for every 10 kg increase in weight. PK in obese patients were characterized by lower maximal plasma concentrations (median 3.8 vs. 8.3 mg/L, p < 0.001) and a higher volume of distribution (41.0 vs. 30.8 L, p < 0.001), and the therapeutic target was not reached for MIC ≥ 1 mg/L in ISF and ≥ 2 mg/L in plasma. Conclusions: Increasing the weight led to a decrease of linezolid concentrations in the plasma and subcutaneous tissue. The current dosing regimen does not seem to produce sufficient concentrations to kill bacteria with MIC ≥ 2 mg/L, especially as empirical antimicrobial therapy in critically ill obese patients.

Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m²) and age-/sex-matched nonobese (18.5 kg/m² ≥ BMI ≤ 30 kg/m²) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 ± 11 kg/m²) and 15 nonobese (BMI 24 ± 2 kg/m²) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: −18.3 to −3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6–9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, −1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05–0.37) and fairly similar area under the curve (AUC)_8h (78.7 vs. 89.2 mg*h/L, −21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, −16.8 to −0.8) but not the AUC_8h (28.5 vs. 42.0 mg*h/L, −33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25–8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary.

Avoiding tidal recruitment and collapse during mechanical ventilation should reduce the risk of lung injury. Electrical impedance tomography (EIT) enables detection of tidal recruitment by measuring regional ventilation delay inhomogeneity (RVDI) during a slow inflation breath with a tidal volume (V_T) of 12 mL/kg body weight (BW). Clinical applicability might be limited by such high V_Ts resulting in high end-inspiratory pressures (P_EI) during positive end-expiratory pressure (PEEP) titration. We hypothesized that RVDI can be obtained with acceptable accuracy from reduced slow inflation V_Ts. In seven ventilated pigs with experimental lung injury, tidal recruitment was quantified by computed tomography at PEEP levels changed stepwise between 0 and 25 cmH₂O. RVDI was measured by EIT during slow inflation V_Ts of 12, 9, 7.5, and 6 mL/kg BW. Linear correlation of tidal recruitment and RVDI was excellent for V_Ts of 12 (R² = 0.83, p < 0.001) and 9 mL/kg BW (R² = 0.83, p < 0.001) but decreased for V_Ts of 7.5 (R² = 0.76, p < 0.001) and 6 mL/kg BW (R² = 0.71, p < 0.001). With any reduction in slow inflation V_T, P_EI decreased at all PEEP levels. Receiver-Operator-Characteristic curve analyses revealed that RVDI-thresholds to predict distinct amounts of tidal recruitment differ when obtained from different slow inflation V_Ts. In conclusion, tidal recruitment can sufficiently be monitored by EIT-based RVDI-calculation with a slow inflation of 9 mL/kg BW.

(1) Background: Individual PEEP settings (PEEP_IND) may improve intraoperative oxygenation and optimize lung mechanics. However, there is uncertainty concerning the optimal procedure to determine PEEP_IND. In this secondary analysis of a randomized controlled clinical trial, we compared different methods for PEEP_IND determination. (2) Methods: Offline analysis of decremental PEEP trials was performed and PEEP_IND was retrospectively determined according to five different methods (EIT-based: RVD_I method, Global Inhomogeneity Index [GI], distribution of tidal ventilation [EIT VT]; global dynamic and quasi-static compliance). (3) Results: In the 45 obese and non-obese patients included, PEEP_IND using the RVD_I method (PEEP_RVD) was 16.3 ± 4.5 cm H₂O. Determination of PEEP_IND using the GI and EIT VT resulted in a mean difference of −2.4 cm H₂O (95%CI: −1.2;−3.6 cm H₂O, p = 0.01) and −2.3 cm H₂O (95% CI: −0.9;3.7 cm H₂O, p = 0.01) to PEEP_RVD, respectively. PEEP_IND selection according to quasi-static compliance showed the highest agreement with PEEP_RVD (p = 0.67), with deviations > 4 cm H₂O in 3/42 patients. PEEP_RVD and PEEP_IND according to dynamic compliance also showed a high level of agreement, with deviations > 4 cm H₂O in 5/42 patients (p = 0.57). (4) Conclusions: High agreement of PEEP_IND determined by the RVD_I method and compliance-based methods suggests that, for routine clinical practice, PEEP selection based on best quasi-static or dynamic compliance is favorable.

Background: During the COVID-19 pandemic, Central COVID-19 Coordination Centers (CCCCs) have been established at several hospitals across Germany with the intention to assist local health care professionals in efficiently referring patients with suspected or confirmed SARS-CoV-2 infection to regional hospitals and therefore to prevent the collapse of local health system structures. In addition, these centers coordinate interhospital transfers of patients with COVID-19 and provide or arrange specialized telemedical consultations. Objective: This study describes the establishment and management of a CCCC at a German university hospital. Methods: We performed economic analyses (cost, cost-effectiveness, use, and utility) according to the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) criteria. Additionally, we conducted a systematic review to identify publications on similar institutions worldwide. The 2 months with the highest local incidence of COVID-19 cases (December 2020 and January 2021) were considered. Results: During this time, 17.3 requests per day were made to the CCCC regarding admission or transfer of patients with COVID-19. The majority of requests were made by emergency medical services (601/1068, 56.3%), patients with an average age of 71.8 (SD 17.2) years were involved, and for 737 of 1068 cases (69%), SARS-CoV-2 had already been detected by a positive polymerase chain reaction test. In 59.8% (639/1068) of the concerned patients, further treatment by a general practitioner or outpatient presentation in a hospital could be initiated after appropriate advice, 27.2% (291/1068) of patients were admitted to normal wards, and 12.9% (138/1068) were directly transmitted to an intensive care unit. The operating costs of the CCCC amounted to more than €52,000 (US $60,031) per month. Of the 334 patients with detected SARS-CoV-2 who were referred via EMS or outpatient physicians, 302 (90.4%) were triaged and announced in advance by the CCCC. No other published economic analysis of COVID-19 coordination or management institutions at hospitals could be found. Conclusions: Despite the high cost of the CCCC, we were able to show that it is a beneficial concept to both the providing hospital and the public health system. However, the most important benefits of the CCCC are that it prevents hospitals from being overrun by patients and that it avoids situations in which physicians must weigh one patient’s life against another’s.