In Vitro Hepatotoxicity of Routinely Used Opioids and Sedative Drugs.

A hepatocyte cell line was used to determine the hepatotoxicity of sedatives and opioids, as the hepatotoxicity of these drugs has not yet been well characterized. This might pose a threat, especially to critically ill patients, as they often receive high cumulative doses for daily analgosedation and often already have impaired liver function due to an underlying disease or complications during treatment. A well-established biosensor based on HepG2/C3A cells was used for the determination of the hepatotoxicity of commonly used sedatives and opioids in the intensive care setting (midazolam, propofol, s-ketamin, thiopental, fentanyl, remifentanil, and sufentanil). The incubation time was 2 × 3 days with clinically relevant (Cmax) and higher concentrations (C5× and C10×) of each drug in cell culture medium or human plasma. Afterward, we measured the cell count, vitality, lactate dehydrogenase (LDH), mitochondrial dehydrogenase activity, cytochrome P 450 1A2 (CYP1A2), and albumin synthesis. All tested substances reduced the viability of hepatocyte cells, but sufentanil and remifentanil showed more pronounced effects. The cell count was diminished by sufentanil in both the medium and plasma and by remifentanil only in plasma. Sufentanil and remifentanil also led to higher values of LDH in the cell culture supernatant. A reduction of mitochondrial dehydrogenase activity was seen with the use of midazolam and s-ketamine. Microalbumin synthesis was reduced in plasma after its incubation with higher concentrations of sufentanil and remifentanil. Remifentanil and s-ketamine reduced CYP1A2 activity, while propofol and thiopental increased it. Our findings suggest that none of the tested sedatives and opioids have pronounced hepatotoxicity. Sufentanil, remifentanil, and s-ketamine showed moderate hepatotoxic effects in vitro. These drugs should be given with caution to patients vulnerable to hepatotoxic drugs, e.g., patients with pre-existing liver disease or liver impairment as part of their underlying disease (e.g., hypoxic hepatitis or cholestatic liver dysfunction in sepsis). Further studies are indicated for this topic, which may use more complex cell culture models and global pharmacovigilance reports, addressing the limitation of the used cell model: HepG2/C3A cells have a lower metabolic capacity due to their low levels of CYP enzymes compared to primary hepatocytes. However, while the test model is suitable for parental substances, it is not for toxicity testing of metabolites.

[Risk factors for postoperative hypoxemia during transport to the postanesthesia care unit and influence of transport monitoring : A retrospective propensity score-matched databank analysis]. / Risikofaktoren für postoperative Hypoxämie während des Transportes in den Aufwachraum und Einfluss von Transport-Monitoring : Eine retrospektive Propensity-Score-gematchte Datenbankanalyse.

BACKGROUND: Within a central operating room area, after general anesthesia (GA) patients are at risk of hypoxemia during transport to the postanesthesia care unit (PACU); however, specific risk factors have not been conclusively clarified and uniform recommendations for monitoring vital signs during transport within a central operating room area complex do not exist. The purpose of this retrospective database analysis was to identify risk factors for hypoxemia during this transport and to determine whether the use of transport monitoring (TM) affects the initial value of peripheral venous oxygen saturation (SpO2) in the PACU. MATERIAL AND METHODS: This analysis was performed on a retrospectively extracted dataset of procedures in GA within a central operating room area of a tertiary care hospital from 2015 to 2020. The emergence from GA was conducted in the operating room with subsequent transport to the PACU. The transport distance was between 31 and 72 m. Risk factors for initial hypoxemia in the PACU, defined as peripheral oxygen saturation (SpO2) below 90%, were determined using multivariate analysis. After splitting the dataset into patients without TM (group OM) and with TM (group MM) and propensity score matching, the influence of TM on initial SpO2 and the Aldrete score after arrival in the PACU were examined. RESULTS AND DISCUSSION: From a total of 22,638 complete datasets included in the analysis, 8 risk factors for initial hypoxemia in PACU were identified: age > 65 years, body mass index (BMI) > 30 kg/m2, chronic obstructive pulmonary disease (COPD), intraoperative airway driving pressure (∆p) > 15 mbar and positive endexpiratory pressure (PEEP) > 5 mbar, intraoperative administration of a long-acting opioids, first preoperative SpO2 < 97%, and last SpO2 < 97% measured after emergence from anesthesia before transport. At least 1 risk factor for postoperative hypoxemia was present in 90% of all patients. After propensity score matching, 3362 datasets per group remained for analysis of the influence of TM. Patients transported with TM revealed a higher SpO2 at PACU arrival (MM 97% [94; 99%], OM 96% [94; 99%], p < 0.001). In a subgroup analysis, this difference between groups remained in the presence of one or more risk factors (MM 97% [94; 99%], OM 96% [94; 98%], p < 0.001, n = 6044) but was not detectable in the absence of risk factors for hypoxemia (MM 97% [97; 100%], OM 99% [97; 100%], p < 0.393, n = 680). Furthermore, the goal of an Aldrete score > 8 at PACU arrival was achieved significantly more often in monitored patients (MM 2830 [83%], OM: 2665 [81%], p = 0.004). Critical hypoxemia (SpO2 < 90%) at PACU arrival had an overall low occurrence within propensity matched datasets and showed no difference between groups (MM: 161 [5%], OM 150 [5%], p = 0.755). According to these results, consistent use of TM leads to a higher SpO2 and Aldrete score at PACU arrival, even after a short transport distance within an operating room area. Consequently, it appears to be reasonable to avoid unmonitored transport after general anesthesia, even for short distances.

Dexmedetomidine Sedation Combined With Remifentanil in MitraClip Procedures is Feasible and Improves Hemodynamics.

OBJECTIVES: The objective of the study was to compare the overall feasibility, respiratory and hemodynamic stability, as well as process times of a dexmedetomidine-based sedative regimen compared with general anesthesia among patients undergoing MitraClip procedures. DESIGN: A retrospective cohort study. SETTING: A single tertiary care university center. PARTICIPANTS: The study included 79 patients. INTERVENTIONS: Dexmedetomidine sedation versus general anesthesia. MEASUREMENTS AND MAIN RESULTS: Seventy-nine MitraClip procedures in dexmedetomidine/remifentanil conscious sedation (DCS, n = 26) or general anesthesia (GA, n = 53), performed between 2018 and 2020 at Charité - Universitätsmedizin Berlin, were analyzed retrospectively. Patients' median age was 81 years in both groups without differences in preinterventional EuroScore I (DCS 6 [5; 8], GA 7 [6; 8]) or systolic function (left ventricular ejection fraction: DCS 50% [32; 60] v. GA 50% [36; 60]; tricuspid annular plane systolic excursion: DCS 19 mm [16; 22] v GA 19 mm [15; 22]). During MitraClip procedures, respiratory parameters revealed no differences between groups, whereas patients under DCS showed higher mean arterial pressures (DCS 64 mmHg [59; 74] v GA 58 mmHg [53; 66]) and needed less norepinephrine (DCS 0.0µg/kg/min [0.0; 0.2] v GA 0.08 µg/kg/min [0.05; 0.15]). Emergence from both anesthesia regimens to readiness for intensive care unit transfer was faster in DCS (8 min [4; 18] v GA 16 min [11; 23]); however, total process time was comparable between groups (DCS 128 min [104; 155] v GA 142 min [117; 190]). Two patients required a switch from DCS to GA due to oral bleeding or prolonged procedure time. Both were excluded from the analysis. There was no switch to open surgery and no differences in postoperative complications between DCS and GA. CONCLUSION: Dexmedetomidine/remifentanil sedation appears to be feasible and a safe option for MitraClip procedures, and provides better hemodynamic stability with faster emergence times compared with general anesthesia.

Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro.

(1) Antibiotics are an important weapon in the fight against serious bacterial infections and are considered a common cause of drug-induced liver injury (DILI). The hepatotoxicity of many drugs, including antibiotics, is poorly analyzed in human in vitro models. (2) A standardized assay with a human hepatoma cell line was used to test the hepatotoxicity of various concentrations (Cmax, 5× Cmax, and 10× Cmax) of antibiotics. In an ICU, the most frequently prescribed antibiotics, ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, meropenem, rifampicin, tigecycline, and vancomycin, were incubated with HepG2/C3A cells for 6 days. Cell viability (XTT assay, LDH release, and vitality), albumin synthesis, and cytochrome 1A2 activity were determined in cells. (3) In vitro, vancomycin, rifampicin, and tigecycline showed moderate hepatotoxic potential. The antibiotics ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, and meropenem were associated with mild hepatotoxic reactions in test cells incubated with the testes Cmax concentration. Rifampicin and cefuroxime showed significantly negative effects on the viability of test cells. (4) Further in vitro studies and global pharmacovigilance reports should be conducted to reveal underlying mechanism of the hepatotoxic action of vancomycin, rifampicin, tigecycline, and cefuroxime, as well as the clinical relevance of these findings.

Two-year outcome of repeat trabeculectomy with mitomycin C in primary open-angle and PEX glaucoma.

PURPOSE: To evaluate the effectiveness of repeat trabeculectomy with risk factor-adjusted mitomycin C (MMC) application in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) over 2 years. METHODS: A total of 58 patients (43 with POAG, 15 with PEXG) who had undergone repeat trabeculectomy with MMC were included in this retrospective study. Exposure time of MMC 0.3 mg/mL was adjusted according to a standardized protocol. Main outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP) reduction, surgical success rate (criteria were defined as A: IOP ≤21 mm Hg and a reduction of IOP ≥20%; B: IOP ≤18 mm Hg and a reduction of IOP of ≥30%; C: IOP ≤15 mm Hg and a reduction of IOP of ≥40% from baseline), and number of medications at baseline, 3 months, and 2 years postoperatively. RESULTS: The BCVA remained stable for 2 years after surgery (0.47 ± 0.47 at baseline, 0.49 ± 0.64 logMAR units after 2 years, respectively). Mean IOP decreased from 22.2 ± 7.0 mm Hg at baseline to 12.7 ± 3.1 mm Hg at 3 months and 12.9 ± 4.3 mm Hg 2 years after surgery. The qualified success rate for criterion A was 75.4%, for criterion B 66.6%, and for criterion C45.6%. Complete success rates were 42.9%, 37.5%, and 32.1%, respectively. Two years after repeat trabeculectomy, the mean IOP was reduced by 38.8%, and the number of medications was reduced significantly. CONCLUSIONS: Repeat trabeculectomy with MMC is successful at lowering IOP in POAG and PEXG and permits a significant and safe reduction of antiglaucomatous medication for at least 2 years after surgery.

Recovery of visual function after administration of dabigatran etexilate.

A 46-year-old Caucasian female underwent pars plana vitrectomy (ppv) for retinal detachment. After the procedure, the patient could only distinguish hand movements; the condition was tentatively diagnosed as nonarteritic anterior ischemic optic neuropathy. Conventional treatment with systemic corticosteroids and acetylsalicylic acid was ineffective and yielded substantial steroid-related side effects. Additional administration of 2 × 110 mg dabigatran etexilate (Pradaxa(®)), a novel direct thrombin inhibitor, resulted in a prompt and marked improvement of visual acuity, which indicated improved blood flow in the central vessels of the optic nerve. Dabigatran etexilate may provide a promising alternative for the treatment of postprocedural vision loss after ppv.

Delayed macular hole closure.

PURPOSE: The presented case raises questions regarding the favorable scheduling of planned postoperative care and the ideal observation interval to decide for reoperations in macular hole surgery. Furthermore a discussion about the use of short- and long-acting gas tamponades in macular hole surgery is encouraged. METHODS: We present an interventional case report and a short review of the pertinent literature. RESULTS: We report a case of spontaneous delayed macular hole closure after vitreoretinal surgery had been performed initially without the expected success. A 73-year-old male Caucasian patient presented at our clinic with a stage 2 macular hole in his left eye. He underwent 23-gauge pars plana vitrectomy and internal limiting membrane peeling with a 20% C2F6-gas tamponade. Sixteen days after the procedure, an OCT scan revealed a persistent stage 2 macular hole, and the patient was scheduled for reoperation. Surprisingly, at the date of planned surgery, which was another 11 days later, the macular hole had resolved spontaneously without any further intervention. CONCLUSIONS: So far no common opinion exists regarding the use of short- or long-acting gas in macular hole surgery. Our case of delayed macular hole closure after complete resorption of the gas tamponade raises questions about the need and duration of strict prone positioning after surgery. Furthermore short-acting gas might be as efficient as long-acting gas. We suggest to wait with a second intervention at least 4 weeks after the initial surgery, since a delayed macular hole closure is possible.