multipaRameter mOnitoring systeM for sedAtion iNThe ICu

Official title

Sistema de monitorización multiparámetros Para sedación de Pacientes críticos en UCI (ROMANTIC: multipaRameter mOnitoring systeM for sedAtion iNThe ICu)

Overview

The administration of sedation in Intensive Care Units (ICU) is a vital and complex task, essential for the well-being of critically ill patients. Proper dosing is crucial, as both under-dosing and overdosing have adverse consequences for patients, including risks such as accidental extubation, ventilator disconnections, delirium, prolonged ventilation, ICU stays, and even increased mortality. Monitoring sedation levels is essential to maintain a balance in sedative administration. Clinical scales (RASS/SAS) are currently used as the reference method, but they have limitations. These scales may be inadequate when the patient is unresponsive or when neuromuscular blockers are used. An alternative is electroencephalography (EEG)-based monitors, though they also have limitations in accurately representing the level of hypnosis. The proposal is to develop an advanced multiparameter system called ROMANTIC, which utilizes machine learning algorithms to monitor sedation status continuously. The aim is for this system to surpass current techniques and provide a more accurate determination of sedation levels. ROMANTIC would incorporate a variety of variables, demographic, pharmacological, hemodynamic, respiratory, and EEG data, to predict sedation status in three categories: under-dosing, appropriate dosing, and overdosing. With ROMANTIC, clinical staff (users) are expected to be able to determine sedation levels more quickly and accurately, reducing patients' wake-up times and possibly decreasing the incidence of delirium. In the long term, this could result in fewer ICU bed days, less time on mechanical ventilation, cost savings, and reduced complications. At the end of the project, the goal is to have a prototype model or software that allows non-specialized staff (users) to quickly determine sedation levels in the ICU. This machine learning-based model targets hospitals with ICUs and mechanical ventilation to offer more efficient and cost-effective clinical care. ROMANTIC seeks to innovate in sedation monitoring, providing a more advanced and precise tool for the care of critically ill patients (beneficiaries) in the ICU.

Detailed description

The project is characterized by incorporating multiple clinical, demographic, and pharmacological variables, along with prediction methods based on machine learning, to classify the level of sedation of critically ill patients into three broad categories: underdosage, appropriate dosage, and overdosage. The investigators will compare the performance of this approach against the current gold standard, which is the use of validated clinical sedation scales (RASS/SAS).

The design of this project is divided into two phases. The first phase involves a prospective observational cohort study where demographic, vital signs, ventilatory, pharmacological, and EEG variables will be collected from ICU patients. The second phase involves using the data obtained to create a multiparameter model with machine learning tools that informs ICU staff about the depth of sedation or the degree of hypnosis of each patient. Data will be collected from two national intensive care units: Hospital Clinico Red UC-CHRISTUS (associated entity) and Dr. Sótero del Río Hospital (associated entity). A technical team specialized in data collection and analysis, clinical research, and algorithm development from Pontificia Universidad Católica de Chile (beneficiary entity) will use this information to create a retrospective classifier that categorizes patients into one of three groups: underdosed, appropriately dosed, and overdosed.

Upon admission, comprehensive patient data will be collected, including age, sex, cause of connection to mechanical ventilation, comorbidities, and educational level. The researchers will also record the drugs and doses used for sedation, neuromuscular relaxants, and vasopressor drugs. Sedation will be administered with Fentanyl plus Propofol or Midazolam, according to usual clinical practices at both participating centers. Data from the RASS and SAS clinical sedation rating scales will be collected every hour during two time windows, providing a detailed picture of the patient's sedation levels.

There will be two or three data recording windows per patient. Time zero will be when the patient is intubated and connected to mechanical ventilation. The first collection window will be between 18 to 60 hours after intubation, for a period of 6 hours during business hours, aiming to obtain a record of data once the chosen sedation strategy is established and has presumably stable blood levels of drugs. The second window will start once the patient's sedation is suspended and will last for at least 6 hours or until the patient awakens, defined as SAS 4 and RASS 0, with eyes open to verbal command or if the patient presents agitation and/or delirium according to CAM-ICU. The suspension time will be recorded, along with the day and time all sedatives are stopped in the continuous infusion pump. If for any reason it is necessary to sedate the patient again, a third window similar to the second will be performed.

Demographic (age, previous educational level, SOFA, Charlson, APACHE II), hemodynamic (systolic and diastolic blood pressure, heart rate, electrocardiography), ventilatory (oxygen saturation, respiratory rate, ventilatory mode, PEEP, tidal volume, plateau pressure, peak pressure), electroencephalographic (EEG signal in time domain), pain (hourly behavioral pain scale), neuromuscular blockade (hourly TOF), and pharmacological (total mass of sedative drugs used at the time of suspending infusions and plasma samples of sedative drug concentration at the beginning of both windows) data will be collected. Once patients wake up, the onset of delirium will be assessed with the CAM-ICU tool twice a day (AM/PM) by appropriately trained nursing staff.

Interventions

• Drug Sedative
  Patients admitted to intensive care units who require sedation and mechanical ventilation for more than 24 hours.

Primary outcome measures

• Time to extubation [Time frame: From the start of last window up to extubation (assessed up to 72 hours)]

Secondary outcome measures (4)

• Length of Intensive Care Unit stay [Time frame: During intensive care unit hospitalization (assessed up to 100 days)]
• Length of mechanical ventilation [Time frame: During intensive care unit hospitalization (assessed up to 100 days)]
• Intensive Care Unit Delirium incidence [Time frame: From extubation to discharge from Intensive Care Unit, CAM-ICU assessed twice daily (AM/PM) for the first 5 post extubation days]
• Serum concentration of sedative drugs [Time frame: At baseline of all data extraction windows (assessed at the first hour of the respective window)]

Eligibility criteria

Inclusion criteria

• Patients admitted to adult critical care units
• Individuals over 18 years old
• Requiring sedation for more than 24 hours
• Patients needing mechanical ventilation for more than 24 hours

Exclusion criteria

• Patients with neurological pathology as the cause of mechanical ventilation (including recovered cardiocirculatory arrest, fulminant liver failure, and neurocritical conditions, except subdural hematomas or subarachnoid hemorrhages).
• Pregnancy
• Presence of psychiatric or intellectual disability prior to hospitalization
• Drug dependency
• History of chronic liver damage with hepatic encephalopathy
• Second period of mechanical ventilation during hospitalization
• Early limitation of therapeutic effort
• Patients under 18 years old

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Chile · 2 centers

• Hospital Dr. Sotero del Rio — Santiago
• Hospital Clínico Pontificia Universidad Católica de Chile — Santiago

Publications

• Erstad BL, Puntillo K, Gilbert HC, Grap MJ, Li D, Medina J, Mularski RA, Pasero C, Varkey B, Sessler CN. Pain management principles in the critically ill. Chest. 2009 Apr;135(4):1075-1086. doi: 10.1378/chest.08-2264. PMID 19349403
• Rotondi AJ, Chelluri L, Sirio C, Mendelsohn A, Schulz R, Belle S, Im K, Donahoe M, Pinsky MR. Patients' recollections of stressful experiences while receiving prolonged mechanical ventilation in an intensive care unit. Crit Care Med. 2002 Apr;30(4):746-52. doi: 10.1097/00003246-200204000-00004. PMID 11940739
• Jackson DL, Proudfoot CW, Cann KF, Walsh T. A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety. Crit Care. 2010;14(2):R59. doi: 10.1186/cc8956. Epub 2010 Apr 9. PMID 20380720
• Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med. 2014 Jan 30;370(5):444-54. doi: 10.1056/NEJMra1208705. No abstract available. PMID 24476433
• Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, C PMID 30113379
• Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med. 1999 Jul;27(7):1325-9. doi: 10.1097/00003246-199907000-00022. PMID 10446827
• Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138. PMID 12421743
• Balzer F, Weiss B, Kumpf O, Treskatsch S, Spies C, Wernecke KD, Krannich A, Kastrup M. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care. 2015 Apr 28;19(1):197. doi: 10.1186/s13054-015-0929-2. PMID 25928417

Identifiers

NCT: NCT06667869 · 230926014 · FONDEF ID24I10057

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗