Sedation is necessary in the management of critically ill patients, both to alleviate suffering and to cure patients with diseases that require admission to the intensive care unit. Such sedation ...should be appropriate to the patient needs at each timepoint during clinical evolution, and neither too low (undersedation) nor too high (oversedation). Adequate sedation influences patient comfort, safety, survival, subsequent quality of life, bed rotation of critical care units and costs. Undersedation is detected and quickly corrected. In contrast, oversedation is silent and difficult to prevent in the absence of management guidelines, collective awareness and teamwork. The Zero Oversedation Project of the Sedation, Analgesia and Delirium Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units aims to offer a practical teaching and collective awareness tool for ensuring patient comfort, safety and management with a view to optimizing the clinical outcomes and minimizing the deleterious effects of excessive sedation. The tool is based on a package of measures that include monitoring pain, analgesia, agitation, sedation, delirium and neuromuscular block, keeping patients pain-free, performing dynamic sedation according to clinical objectives, agreeing upon the multidisciplinary protocol to be followed, and avoiding deep sedation where not clinically indicated.
La sedación es necesaria en el tratamiento de los pacientes críticos, tanto para aliviar el sufrimiento como para curar a los pacientes con enfermedades que precisan el ingreso en unidades de cuidados intensivos. Esta sedación debe ser la adecuada a las necesidades del paciente en cada momento de su evolución clínica, ni por debajo (infrasedación) ni por encima (sobresedación). Una sedación adecuada influye en la comodidad, la seguridad, la supervivencia, la calidad de vida posterior, la rotación de camas de las unidades de críticos y los costes. La infrasedación se detecta y corrige rápidamente. Sin embargo, la sobresedación es silente y difícil de prevenir sin unas pautas de actuación, una concienciación colectiva y un trabajo en equipo. El proyecto «Sobresedación Zero» del Grupo de Trabajo de Sedación, Analgesia y Delirium de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias pretende ser una herramienta docente, práctica y de concienciación colectiva de comodidad, seguridad y gestión para maximizar el resultado clínico y minimizar los efectos perjudiciales de la sedación excesiva. Se basa en un paquete de medidas que se incluye monitorizar el dolor, la analgesia, la agitación, la sedación, el delirium y el bloqueo neuromuscular, mantener a los pacientes sin dolor, realizar una sedación dinámica según objetivos clínicos, consensuar el protocolo multidisciplinar a seguir y evitar la sedación profunda no indicada clínicamente.
To assess the epidemiology and outcome at discharge of cancer patients requiring admission to the Intensive Care Unit (ICU).
A descriptive observational study was made of data from the ENVIN-HELICS ...registry, combined with specifically compiled variables. Comparisons were made between patients with and without neoplastic disease, and groups of cancer patients with a poorer outcome were identified.
Intensive Care Units participating in ENVIN-HELICS 2018, with voluntary participation in the oncological registry.
Subjects admitted during over 24 h and diagnosed with cancer in the last 5 years.
The general epidemiological endpoints of the ENVIN-HELICS registry and cancer-related variables.
Of the 92 ICUs with full data, a total of 11,796 patients were selected, of which 1786 (15.1%) were cancer patients. The proportion of cancer patients per Unit proved highly variable (1%–48%). In-ICU mortality was higher among the cancer patients than in the non-oncological subjects (12.3% versus 8.9%; p < .001). Elective postoperative (46.7%) or emergency admission (15.3%) predominated in the cancer patients. Patients with medical disease were in more serious condition, with longer stay and greater mortality (27.5%). The patients admitted to the ICU due to nonsurgical disease related to cancer exhibited the highest mortality rate (31.4%).
Great variability was recorded in the percentage of cancer patients in the different ICUs. A total of 46.7% of the patients were admitted after undergoing scheduled surgery. The highest mortality rate corresponded to patients with medical disease (27.5%), and to those admitted due to cancer-related complications (31.4%).
Conocer la epidemiología y evolución al alta de los pacientes oncológicos que precisan ingreso en UCI.
Estudio descriptivo observacional de datos del registro ENVIN-HELICS combinado con variables registradas específicamente. Se comparan pacientes con y sin neoplasia. Se identifican grupos de pacientes neoplásicos con peor evolución.
UCI participantes en ENVIN-HELICS del año 2018 con participación voluntaria en el registro oncológico.
Ingresados más de 24 horas. Entre estos aquellos diagnosticados de neoplasia en los últimos 5 años.
Las generales epidemiológicas del registro ENVIN-HELICS y variables relacionadas con la neoplasia.
En las 92 UCI con datos completos se seleccionaron 11.796 pacientes, de los que 1.786 (15,1%) son pacientes con neoplasia. La proporción de pacientes con cáncer por unidad fue muy variable (rango: 1–48%). La mortalidad en UCI de los pacientes oncológicos fue superior a los no oncológicos (12,3% versus 8,9%; p < 0,001). En pacientes oncológicos predominaron los ingresados en el postoperatorio programado (46,7%) o urgente (15,3%). Los pacientes con proceso patológico médico fueron más graves, con mayor estancia y mortalidad (27,5%). Aquellos ingresados en UCI por enfermedad no quirúrgica relacionada con el cáncer tuvieron la mortalidad más alta (31,4%).
Existe una gran variabilidad en el porcentaje de pacientes oncológicos en las diferentes UCI. El 46,7% de los pacientes ingresa tras someterse a cirugía programada. La mayor mortalidad corresponde a pacientes con enfermedad médica (27,5%) y a los ingresados por complicaciones relacionadas con el cáncer (31,4%).
Cedazuridine (CED), a cytidine deaminase (CDA), inhibitor allows oral availability of decitabine (DEC); 5 daily doses of the fixed-dose combination (FDC) of 35 mg DEC/100 mg CED standard dose (SD) ...provides equivalent exposure to an IV DEC regimen of 20 mg/m2 D1-5 (Garcia-Manero et al, 2020). Attenuated HMA regimens (e.g., 3 days IV DEC) have shown activity in LR-MDS (Jabbour, et al. 2017).
This Phase 1/2 study explores lower dose oral DEC/CED regimens in LR-MDS patients.
Phase 1/2 study in lower-risk-MDS (IPSS low risk and lntermediate-1) subjects requiring treatment. Phase 1: explored 28-day regimens, dose ranges 5-20 mg DEC/100mg CED; duration ranges 5-10 days. Primary endpoints: recommended Phase 2 dose (RP2D) based on safety and dose-limiting toxicity (DLT). Secondary endpoints: clinical activity per 2006 IWG (transfusion independence TI, LFS, OS). Phase 2: randomized 81 LR-MDS 1:1 to receive Phase 1 RP2D vs 35 mg DEC/100 mg CED (SD) for 3days (SD-3Day) (reflecting attenuated HMA regimen for LR-MDS). Similar efficacy and safety endpoints as Phase 1.
Phase 1: 47 patients treated with five different DEC/CED regimens. DLT (myelosuppression-associated) increased with higher treatment doses and longer duration. Hematologic improvement (HI) % across dosing regimens: 30% (14/47), 8-week RBC transfusion-independent rate: 33% (7/21); mOS: 31 months (95%Cl:19,NE); mLFS 23 months (95%Cl:14,32). Based on clinical efficacy and safety, 10mg DEC/100mgCED D1-5 every 28D (LD-5Day) was selected as RP2D. Phase 2: Baseline: Int-1 (65-73%), 48% prior MDS treatment (21%ESA, 26% luspatercept), 46% RBC transfusion-dependent (TD); 14% platelet TD. At cutoff, 80 subjects had received a median of 4.5 treatment cycles, ~10 patients received subsequent transplant. PK data showed LD-5Day exposure about half SD-3Day exposure. Reported adverse event terms with LD-5Day were similar to SD-5day, with most common grade ≥3 from myelosuppression. By cycle 8, average neutrophil counts were higher in LD-5Day regimen vs SD-3Day regimen; platelet changes were similar. Of 8 all-cause deaths at data cutoff, only 1 was within 30 days (in SD-3Day group).
This Phase 1/2 study suggests LD-5Day regimen is tolerable (less neutropenia) and potentially an optimal regimen for LR-MDS (longer term efficacy analysis vs SD-3Day regimen pending).
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