Intra-operative anesthetic induced myocardial protection during cardiothoracic surgery: a literature review.

Background and Objective: Myocardial protection involves limiting the metabolic activity and oxygen consumption of the heart, thus enabling surgery to proceed with minimal blood loss while reducing the level of ischemic injury. It was this concept that allowed for the development of the open-heart surgical technique. We know myocardial ischemia and reperfusion injury are both detrimental, thus developing strategies to mitigate this can help reduce peri-operative morbidity and mortality. In this review, we will mainly be addressing the anesthetic considerations for myocardial protection, along with discussing potential future research which can help expand the field. Methods: We searched the PubMed database for relevant studies dating from 2004-2022. In total, 18 studies were deemed suitable for this literature review. Key Content and Findings: Studies have demonstrated cardioprotective effects with use of the volatile agents and propofol, mainly with respect to lower levels of inflammatory markers such as creatine kinase (CK)-MB and troponin I (TnI)/troponin T (TnT). The data is lacking regarding protective effects of dexmedetomidine and lidocaine, hence we cannot recommend either agent at present. Conclusions: Myocardial protection with respect to the anesthetic agents have been extensively studied over the past two decades, some routinely used drugs such as the volatile agents, propofol and opiates have demonstrated a cardioprotective role. The ideal dosing regimen and duration are areas of research that can be studied further. The data for the other anesthetic adjuncts such as lidocaine, dexmedetomidine along with use of regional anesthesia is still equivocal. Alongside advances in anesthesia, we believe surgical research looking into optimal cardioplegia solutions will also help improve myocardial protection in the future.

Quetiapine for delirium prophylaxis in high-risk critically ill patients.

BACKGROUND: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. METHODS: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. RESULTS: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). CONCLUSIONS: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Open-source discovery of chemical leads for next-generation chemoprotective antimalarials.

To discover leads for next-generation chemoprotective antimalarial drugs, we tested more than 500,000 compounds for their ability to inhibit liver-stage development of luciferase-expressing Plasmodium spp. parasites (681 compounds showed a half-maximal inhibitory concentration of less than 1 micromolar). Cluster analysis identified potent and previously unreported scaffold families as well as other series previously associated with chemoprophylaxis. Further testing through multiple phenotypic assays that predict stage-specific and multispecies antimalarial activity distinguished compound classes that are likely to provide symptomatic relief by reducing asexual blood-stage parasitemia from those which are likely to only prevent malaria. Target identification by using functional assays, in vitro evolution, or metabolic profiling revealed 58 mitochondrial inhibitors but also many chemotypes possibly with previously unidentified mechanisms of action.

A high throughput screen for next-generation leads targeting malaria parasite transmission.

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2-1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male-female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population.