Dexmedetomidine (DEX) is a highly selective a2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in obese patients who are at an increased risk for postoperative respiratory complications. The pharmacodynamic effects on the cardiovascular system are known; however the mechanisms that induce cardioprotection are still under study. Regarding the pharmacokinetics properties, this drug is extensively metabolized in the liver by the uridine diphosphate glucuronosyltransferases. It has a relatively high hepatic extraction ratio, and therefore, its metabolism is dependent on liver blood flow. This review shows, from a basic clinical approach, the evidence supporting the use of dexmedetomidine in different settings, from its use in animal models of ischemia-reperfusion, and cardioprotective signaling pathways. In addition, pharmacokinetics and pharmacodynamics studies in obese subjects and the management of patients subjected to mechanical ventilation are described. Moreover, the clinical efficacy of delirium incidence in patients with indication of non-invasive ventilation is shown. Finally, the available evidence from DEX is described by a group of Chilean pharmacologists and clinicians who have worked for more than 10 years on DEX.

IntroductionPatients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome, that leads to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. However, it has not been prospectively studied on these patients. A scoring system (HScore) has been validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19.Methods143 patients aged ≥18 years admitted because of COVID-19 were enrolled in a prospective, single-center, cohort study. HScore was calculated within the 72 hours since admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between HScore ≥130 points and either the requirement of mechanical ventilation or 60-days mortality was explored.ResultsThe median age of enrolled patients was 57 (21-100), and 63.6% were male. The median HScore was 96 (33-169). One patient was diagnosed with sHLH (incidence 0,7%), due to a HScore of 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥130 was independently associated with the composite clinical outcome (HR 2.13, p=0.022).ConclusionsHLH is not frequent among COVID-19 patients. HScore can efficiently predict the risk for poor outcomes.

Intensive chemotherapy with tyrosine kinase inhibitors in philadelphia-positive acute lymphoblastic leukemiaBackground: Before the advent of tyrosine kinase inhibitors (TKIs), patients with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ALL) had a poor prognosis. The association of TKIs to intensive chemotherapy (CT) improved outcome. Aim: To evaluate results of an intensive CT protocol including TKI in a public hospital in Santiago, Chile. Material and Methods: All patients with Ph+ALL diagnosed between January 2010 and February 2019, and who met inclusion criteria for intensive CT, received the Ph+ALL national protocol in association with imatinib and were included in this analysis. Results: Thirty-five patients aged 15 to 59 years received treatment. Complete response (CR) was obtained in 97%. Measurable residual disease (MRD) was negative in 61% (19/31 evaluable cases) during follow-up, and 55% (16/29) were MRD (-) before three months. Relapse was observed in 13 cases. Three patients underwent allogeneic hematopoietic stem cell transplant (HSCT), two in CR1. The overall survival (OS) and event-free survival (EFS) at three years were 52 and 34%, respectively. In patients who achieved MRD negativity before three months, no statistically significant differences in OS (64 and 42% respectively, p = 0.15) or EFS (35 and 32% respectively, p = 0.37) were observed. Conclusions: The prognosis of Ph+ALL improved with the association of imatinib to intensive CT. MRD-negative status before three months in this series was not significantly associated with better outcomes. Our series suggests that the Ph+ALL national protocol associated to TKI is a therapeutic alternative with high CR and aceptable MRD (-) rates.