Complicaciones cardiovasculares en pacientes COVID-19 hospitalizados en Unidades de Pacientes Críticos en Chile. Registro COVICAR / Cardiovascular complications in COVID-19 patients admitted to intensive care units in Chilean hospitals

BACKGROUND: Patients with a cardiovascular (CV) history may be at greater risk of becoming ill and die due to SARS-CoV-2. AIM: To assess the incidence of CV complications in COVID-19 patients, the type of complication, and their association with CV history. MATERIAL AND METHODS: The clinical course of 1,314 patients with COVID-19 admitted consecutively to critical care units of 10 Chilean hospitals was registered between April and August of 2020. RESULTS: The median age of patients was 59 years and 66% were men. One hundred-four (8%) had a CV history, namely heart failure (HF) in 53 (4.1%), coronary heart disease in 50 (3.8 %), and atrial fibrillation in 36 (2.7 %). There were CV complications in 359 patients (27.3%). The most common were venous thrombosis in 10.7% and arrhythmias in 10.5%, HF in 7.2%, type 2 acute myocardial infarction in 4.2%, arterial thrombosis in 2.0% and acute coronary syndrome (ACS) in 1.6%. When adjusted by age, sex and risk factors, only HF (Odds ratio (OR) = 7.16; 95% confidence intervals (CI), 3.96-12.92) and ACS (OR = 5.44; 95% CI, 1.50-19.82) were significantly associated with CV history. There was no association with arrhythmias, type 2 acute myocardial infarction, arterial or venous thrombosis. CONCLUSIONS: Patients with a history of CV disease are at greater risk of suffering HF and ACS when hospitalized due to COVID-19. Arrhythmias, type 2 AMI, and arterial or venous thrombosis occur with the same frequency in patients with or without CV history, suggesting that these complications depend on inflammatory phenomena related to the infection.

Experiencia en la práctica clínica real de la efectividad y la tolerabi- lidad de tapentadol de liberación prolongada para el tratamiento de dolor crónico postraumático producido por accidentes de trabajo / Real-world clinical practice experience of the effectiveness and tolerability of pro- longed-release tapentadol for the treatment of chronic post-traumatic pain caused by occupational accidents

Se llevó a cabo un estudio observacional para analizar si tapentadol de liberación prolongada (LP) puede considerarse un tratamiento de primera línea para pacientes con dolor crónico postraumático (DCPT). Métodos: Se presenta una serie de casos de la práctica clínica real de pacientes con DCPT producido por accidentes de trabajo. Antes de ingresar al estudio, todos los pacientes recibían tramadol, que se interrumpió cuando se inició la administración de tapentadol LP. Las evaluaciones de dolor incluyeron una escala de valoración numérica, el cuestionario DN4 y la escala de Impresión Global de Cambio del Paciente (PGIC, Patients' Global Impression of Change). Se recuperaron y registraron los eventos adversos. Resultados: 94 pacientes participaron en el estudio y 77 (82 %) completaron todas las visitas predefinidas. Cerca de la mitad de los pacientes informaron dolor crónico que tenía una duración de al menos 3 años; se observó un componente neuropático en el 87 % de los pacientes. El puntaje de dolor se redujo en 1,5 puntos luego del primer mes de tratamiento con tapentadol LP y en 2,48 puntos luego de 4 meses (p<0,05). También se asoció la administración de tapentadol LP con una reducción del 28,9 % de la dosis concomitante de pregabalina (p<0,01). De acuerdo con el cuestionario PGIC, el 74 % y el 77,9 % de los pacientes informó mejoría luego de uno y cuatro meses de tratamiento, respectivamente. El perfil de seguridad fue consistente con los datos actuales sobre tapentadol LP. Conclusión: El dolor osteomuscular crónico es una enfermedad prevalente que se caracteriza por tener resultados terapéuticos deficientes y se asocia a una mayor discapacidad y una mala calidad de vida. En este estudio de la práctica clínica real en pacientes que trabajan y que cuentan con un componente de dolor neuropático elevado, se observó que tapentadol LP produce efectos beneficiosos en términos del control del DCPT, y se obtuvieron índices altos de eficacia y seguridad.

An observational study was carried out to analyze whether prolonged-release (PR) tapentadol may be considered a first-line treatment for patients with chronic post-traumatic pain (PTD). Methods: A case series of cases of patients with PTFE caused by work accidents in a real clinical practice setting is described. Before entering the study, all patients were receiving tramadol, which was discontinued when PR tapentadol was started. Pain assessments included a numerical rating scale, the DN4 questionnaire, and the Patients' Global Impression of Change (PGIC) scale. Adverse events were retrieved and described. Results: 94 patients participated in the study and 77 (82%) completed all the predefined visits. About half of the patients reported chronic pain that lasted for at least 3 years. A neuropathic component was reported in 87% of patients. The pain score was reduced by 1.5 points after the first month of treatment with PR tapentadol and by 2.48 points after 4 months (p < 0.05). Administration of PR tapentadol was also associated with a concomitant reduction of pregabalin dose of 28.9% (p < 0.01). According to the PGIC questionnaire, 74% and 77.9% of patients reported improvement after one and four months of treatment, respectively. The safety profile was consistent with current data on PR tapentadol. Conclusion: Chronic musculoskeletal pain is a prevalent disease characterized by poor therapeutic results and associated with increased disability and poor quality of life. In our study in a real clinical practice setting with patients with a high neuropathic pain component, PR tapentadol produced beneficial effects in terms of DCPT control, and high efficacy and safety rates were obtained. Keywords: tapentadol, chronic pain, pain caused by work accidents, chronic post-traumatic pain, evidence from real clinical practice.

Synergism between gabapentin-tramadol in experimental diabetic neuropathic pain.

Neuropathic pain is associated with several conditions such as surgery, cancer, and diabetes and can be induced experimentally. Among the drugs used as monotherapy are gabapentin and tramadol. The purpose of this study was to evaluate the coadministration of gabapentin and tramadol, by isobolographic analysis, in three different algesiometric assays in experimental diabetic neuropathic pain induced by streptozocin in mice. In all the behavioral tests, gabapentin or tramadol produced a dose-dependent antinociception and their coadministration resulted in a positive interaction. This effect can be explained by principles of multimodal analgesia, whereby the different mechanisms of action of each drug contribute to the combined effect in a supra-additive manner. The findings of the present study suggest that the combination of gabapentin and tramadol could be a useful strategy for the treatment of pain induced by diabetic neuropathy.

Antinociception induced by rosuvastatin in murine neuropathic pain.

BACKGROUND: Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1ß, TBARS and glutathione were evaluated. METHODS: A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1ß, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models. RESULTS: PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1ß or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia. CONCLUSION: The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain.

Effect of carvedilol and nebivolol on oxidative stress-related parameters and endothelial function in patients with essential hypertension.

Oxidative stress and endothelial dysfunction have been associated with essential hypertension (EH) mechanisms. The purpose of this study was to evaluate the effect of carvedilol and nebivolol on the oxidative stress-related parameters and endothelial function in patients with EH. The studied population included 57 patients, either sex, between 30 and 75 years of age, with mild-to-moderate EH complications. Participants were randomized to receive either carvedilol (12.5 mg) (n = 23) or nebivolol (5 mg) (n = 21) for 12 weeks. Measurements included; 24-hr ambulatory blood pressure (BP), flow-mediated dilatation, levels of nitric oxide estimated as nitrite - a nitric oxide metabolite ( NO2) - in plasma, and oxidative stress-related parameters in plasma and erythrocyte. EH patients who were treated with nebivolol or carvedilol showed systolic BP reductions of 17.4 and 19.9 mmHg, respectively, compared with baseline values (p < 0.01). Diastolic BP was reduced by 13.7 and 12.8 mmHg after the treatment with ebivolol and carvedilol, respectively (p < 0.01) (fig. 2B). Nebivolol and carvedilol showed 7.3% and 8.1% higher endothelium-dependent dilatation in relation to baseline values (p < 0.05). Ferric-reducing ability of plasma (FRAP) and reduced glutathione/oxidized glutathione (GSSH) ratio showed 31.5% and 29.6% higher levels in the carvedilol group compared with basal values; however, nebivolol-treated patients did not show significant differences after treatment. On the other hand, the NO2 plasma concentration was not modified by the administration of carvedilol. However, nebivolol enhanced these levels in 62.1% after the treatment. In conclusion, this study demonstrated the antihypertensive effect of both beta-blockers. However, carvedilol could mediate these effects by an increase in antioxidant capacity and nebivolol through the raise in NO2 concentration. Further studies are needed to determine the molecular mechanism of these effects.