Hemodynamic Effects of Ketamine Infusion in the Intensive Care Unit for Maintenance Sedation Compared With Propofol and Midazolam: A Retrospective Cohort Study.

Background: Sedation and analgesia in the intensive care unit (ICU) are major clinical challenges, and several continuous infusion medications have been used for these purposes. The use of these sedative medications has been associated with hemodynamic effects that complicate the patient's critical illness. Continuous ketamine infusion is an emerging sedative option that has been used more frequently in the ICU since 2017. The purpose of this study was to characterize the hemodynamic differences between 3 continuous sedative infusions: ketamine, propofol, and midazolam. Methods: For this single-center retrospective cohort study, we collected data for patients hospitalized between January 2015 and April 2020 at Saint Luke's Health System in Kansas City, Missouri. Adult patients in the ICU requiring a norepinephrine infusion and sedation were included. The change in norepinephrine requirement from baseline at 1 hour was the primary outcome. The change in vasopressor requirement at 3 and 30 hours after initiation of the infusion was also tabulated. Results: Sixty-eight critically ill patients with several types of shock requiring vasopressor support with norepinephrine were enrolled in our study. Patients who received ketamine had an increase in norepinephrine requirement compared to midazolam and propofol, although this difference was not statistically significant. Conclusion: In our study, continuous ketamine infusion did not reveal a statistically significant favorable hemodynamic effect compared with propofol and midazolam because of the small sample size. A trend toward an unfavorable hemodynamic effect is not expected, but large randomized trials are needed to further evaluate the hemodynamic effects of continuous ketamine infusion in the ICU.

The C-terminus of ribosomal protein uS4 contributes to small ribosomal subunit biogenesis and the fidelity of translation.

Ribosomal protein uS4 is an essential ribosomal component involved in multiple functions, including mRNA decoding. Structural analyses indicate that during decoding, the interface between the C-terminus of uS4 and protein uS5 is disrupted and in agreement with this, C-terminal uS4 truncation mutants are readily isolated on the basis of their increased miscoding phenotypes. The same mutants can also display defects in small subunit assembly and 16S rRNA processing and some are temperature sensitive for growth. Starting with one such temperature sensitive Escherichia coli uS4 mutant, we have isolated temperature insensitive derivatives carrying additional, intragenic mutations that restore the C-terminus and ameliorate the ribosomal defects. At least one of these suppressors has no detectable ribosome biogenesis phenotype, yet still miscodes, suggesting that the C-terminal requirements for ribosome assembly are less rigid than for mRNA decoding. In contrast to the uS4 C-terminal mutants that increase miscoding, two Salmonella enterica uS4 mutants with altered C-termini have been reported as being error-restrictive. Here, reconstruction experiments demonstrate that contrary to the previous reports, these mutants have a distinct error-prone, increased misreading phenotype, consistent with the behavior of the equivalent E. coli mutants and their likely structural effects on uS4-uS5 interactions.