The coronavirus pandemic continues to challenge global healthcare. Severely affected patients are often in need of high doses of analgesics and sedatives. The latter was studied in critically ill coronavirus disease 2019 (COVID-19) patients in this prospective monocentric analysis. COVID-19 acute respiratory distress syndrome (ARDS) patients admitted between 1 April and 1 December 2020 were enrolled in the study. A statistical analysis of impeded sedation using mixed-effect linear regression models was performed. Overall, 114 patients were enrolled, requiring unusual high levels of sedatives. During 67.9% of the observation period, a combination of sedatives was required in addition to continuous analgesia. During ARDS therapy, 85.1% (n = 97) underwent prone positioning. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) was required in 20.2% (n = 23) of all patients. vv-ECMO patients showed significantly higher sedation needs (p < 0.001). Patients with hepatic (p = 0.01) or renal (p = 0.01) dysfunction showed significantly lower sedation requirements. Except for patient age (p = 0.01), we could not find any significant influence of pre-existing conditions. Age, vv-ECMO therapy and additional organ failure could be demonstrated as factors influencing sedation needs. Young patients and those receiving vv-ECMO usually require increased sedation for intensive care therapy. However, further studies are needed to elucidate the causes and mechanisms of impeded sedation.

Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during ECMO treatment due to pathophysiological changes in the drug metabolism of the critically ill and/or the ECMO therapy itself. This study investigates the latter aspect for commonly used anti-infective drugs in an ex vivo setting. A fully functional ECMO device circulated an albumin–electrolyte solution through the ECMO tubes and oxygenator. The antibiotic agents cefazolin, cefuroxim, cefepime, cefiderocol, linezolid and daptomycin and the antifungal agent anidulafungin were added. Blood samples were taken over a period of four hours and drug concentrations were measured via high-pressure liquid chromatography (HPLC) with UV detection. Subsequently, the study analyzed the time course of anti-infective concentrations. The results showed no significant changes in the concentration of any tested anti-infectives throughout the study period. This ex vivo study demonstrates that the ECMO device itself has no impact on the concentration of commonly used anti-infectives. These findings suggest that ECMO therapy does not contribute to alterations in the concentrations of anti-infective medications in severely ill patients.

Remote ischaemic preconditioning (RIPC) might reduce acute kidney injury after cardiac surgery. Protective effects appear to be restricted to patients with early and transient increases in two cell cycle arrest markers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), in urine. Studies suggest that propofol can attenuate the preconditioning effect on the myocardium. This study investigated whether propofol diminishes the renoprotective effect associated with the early transient increases in TIMP-2 and IGFBP7. This was a single-centre, prospective randomised double-blind 2×2 factorial clinical trial of high-risk patients undergoing cardiac surgery. Patients were randomised to receive either propofol+sham-RIPC, propofol+RIPC, sevoflurane+sham-RIPC, or sevoflurane+RIPC. The primary outcome measure was the change in the product of urinary concentrations of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]) from before to after the intervention. We enrolled 160 participants in the trial (propofol+sham-RIPC: n=20, propofol+RIPC: n=60, sevoflurane+sham-RIPC: n=20, sevoflurane+RIPC: n=60). The median change in [TIMP-2]·[IGFBP7] as an indicator of response to RIPC was greater in participants receiving sevoflurane (0.070; interquartile range, -0.120 to 0.418) compared with those receiving propofol (-0.015; interquartile range, -0.138 to 0.068; P=0.022). Conversely, elevated [TIMP-2]·[IGFBP7] as a sign of renal stress in response to surgery was detected in all groups except for sevoflurane+RIPC (P=0.001). There were no statistically significant differences in patient-centred outcomes between groups. Transient increases in [TIMP-2]·[IGFBP7] induced by RIPC, which were associated with renoprotective effects, were only seen with sevoflurane anaesthesia, but not when propofol was used. The association of biomarker concentrations and choice of anaesthetic agent suggests that propofol can attenuate the renoprotective effects of remote ischaemic preconditioning. DRKS00014989.

Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) therapy has become increasingly used and established in many hospitals as a routine treatment. With ECMO-therapy being a resource-demanding procedure, it is of interest whether a more prolonged VV-ECMO treatment would hold sufficient therapeutic success. Our retrospective study included all VV-ECMO runs from 1 January 2020 to 31 June 2022. We divided all runs into four groups (<14 days, 14–27, 28–49, 50+) of different durations and looked for differences overall in hospital survival. Additionally, corresponding treatments and therapeutic modalities, as well as laboratory results, were analyzed. We included 117 patients. Of those, 97 (82.9%) received a VV-ECMO treatment longer than two weeks. We did not find a significant association between ECMO duration (p = 0.15) and increased mortality though a significant correlation between the patients’ age and their probability of survival (p = 0.02). Notably, we found significantly lower interleukin-6 levels with an increase in therapy duration (p < 0.01). Our findings show no association between the duration of ECMO therapy and mortality. Thus, the treatment duration alone may not be used for making assumptions about the prospect of survival. However, attention is also increasingly focused on long-term outcomes, such as post-intensive care syndrome with severe impairments.

The scope of extracorporeal membrane oxygenation (ECMO) is expanding, nevertheless, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This study aims to evaluate the pharmacokinetics (PK) of cefazolin in patients undergoing ECMO treatment. Total and unbound plasma cefazolin concentration of critically ill patients on veno-arterial ECMO were determined. Observed PK was compared to dose recommendations calculated by an online available, free dosing software. Concentration of cefazolin varied broadly despite same dosage in all patients. The mean total and unbound plasma concentration were high showing significantly (p = 5.8913 E−09) greater unbound fraction compared to a standard patient. Cefazolin clearance was significantly (p = 0.009) higher in patients with preserved renal function compared with CRRT. Based upon the calculated clearance, the use of dosing software would have led to lower but still sufficient concentrations of cefazolin in general. Our study shows that a “one size fits all” dosing regimen leads to excessive unbound cefazolin concentration in these patients. They exhibit high PK variability and decreased cefazolin clearance on ECMO appears to compensate for ECMO- and critical illness-related increases in volume of distribution.

Introduction: Operating suites are multidisciplinary units par excellence, and mostly they are the most expensive units in hospitals. Interdisciplinary workflow and efficiency are therefore crucial, which is influenced by floor plans varying from hospital to hospital. Most operating rooms are equipped with adjacent induction rooms, allowing preparation and anesthesia induction of the next patient, while the previous patient is still in the operating room. Parallelizing the working steps is thought to improve turn-over time, thus increasing throughput, number of cases and finally revenue. However, this assumption has never been challenged. Methods: We analyzed workflow during regular working hours in an operating suite equipped with a mixture of operating rooms (OR) with next door induction rooms and operating rooms without induction rooms. This allows a direct comparison of both structural elements for efficiency using utilization data over a 24-months period. Both settings were used for gynecological operations. Results: Key result is that induction rooms do not improve perioperative workflow including turn-over time. Instead, ORs without adjacent induction rooms have a significantly shorter turn-over time and OR occupancy duration per case, although surgical time and staffing were similar. Discussion: Adjacent induction rooms require extra space, funding, and high maintenance costs, but they do not speed up peri-operative processes. Modern anesthetic techniques allow for fast induction of and emergence from anesthesia. Induction rooms adjacent to the OR are no longer needed if general anesthesia without extended monitoring is used for the majority of cases.