Subsyndromal Delirium | Preventing ICU Subsyndromal Delirium Conversion to Delirium With Haloperidol
Subsyndromal Delirium research study
What is the primary objective of this study?
About one-third of the patients who develop mild, acute confusion (i.e., subsyndromal delirium) will go on to develop a severe acute confusional state (i.e. delirium). Delirium refers to a temporary change in the way a person thinks about things. Delirium occurs in patients admitted to the hospital particularly those patients that are very sick, who are given a number of medications, and who are not able to sleep normally. It affects their behavior, their understanding of the people and things around them, and their ability to make decisions. While ICU doctors do everything possible to eliminate the factors that may cause delirium, delirium may cause a person to become very agitated which if not controlled is dangerous to their safety as well as the safety of those around them. As well, if delirium develops in patients in the ICU, it may increase the risk for death, keep patients in both the ICU and hospital for longer and send patients to a long term care facility rather than home after they are discharged from the hospital. A recent medical report found that patients in the ICU who develop subsyndromal delirium have a mortality rate, a length of stay in both the ICU and the hospital, and a transfer rate to a long term care facility that is nearly as great as patients with delirium and greater than patients who develop neither subsyndromal delirium or delirium. Recent studies in non-ICU patients suggest that if a patient who is at high risk for developing delirium receives a medication called an antipsychotic (e.g. haloperidol) they may not be as likely to develop delirium or if they do develop delirium it will not last as long. No studies have evaluated the effect of administering an antipsychotic in patients in the ICU who have subsyndromal delirium. Another study completed in the ICUs at Tufts Medical Center found that there may be an association between the development of delirium in patients with subsyndromal delirium and the use of haloperidol. However, this small study had many limitations and thus it is not currently known whether using haloperidol in patients with subsyndromal delirium will actually cause fewer of these patients to develop delirium. Haloperidol makes a person sleepy and helps control behavior like agitation. Haloperidol is the drug that is used most often to help control delirium in the ICU. This prospective, double-blind, randomized controlled study will determine if haloperidol administered through the vein four times daily (1mg IV q6h) to patients who have subsyndromal delirium, and who are on a breathing machine and being cared for by the Medical ICU service at Tufts Medical Center, will help prevent patients from developing delirium. A total of 68 participants will be enrolled. Exclusion criteria are extensive and include conditions that could affect the ability to determine if delirium is present or increase the risk for side effects related to the administration of haloperidol. Patients older than 80 will be excluded from the study. Study medication (i.e. haloperidol) will be administered until one the following occurs: 1) delirium develops (that is confirmed by a staff psychiatrist or his designate, 2) the patient is discharged from the ICU at Tufts Medical Center, 3) the patient has received haloperidol or placebo for 10 days or 4) an adverse event potentially attributable to the study drug is experienced by a patient that is deemed, in the opinion of a pulmonologist member of the investigative team to warrant discontinuation of therapy. Haloperidol may cause unwanted side effects such as low blood pressure, twitching, and an unsafe abnormal heart rhythm. Patients with chronic confusion (e.g., a dementia such as Alzheimer's Disease) should not receive haloperidol and will not be included in this study. Patients will be carefully monitored for side effects that are potentially related to haloperidol. Patients who become confusion-free in the ICU before they leave the ICU (i.e., have no subsyndromal delirium) will be asked to provide consent for all research activities that occured in the ICU. If patients where cognition is regained (ie. no subsyndromal delirium or delirium) are not willing to provide consent then any study data collected from them while they were in the ICU will be destroyed and they will not be approached to participate in the post-ICU component of the study. This study also seeks to understand how the use of haloperidol in the ICU in patients with subsyndromal delirium may have affect memory, emotional status, happiness, ability to function, and quality of sleep in patients after they leave the ICU. Patients (that do not have delirium based on CAM screening at the time the 3-10 day and 6 month assessments are attempted) will be approached to participate in this post-ICU component of the study.
Who is eligible to participate?
Inclusion Criteria: - Age 18-84 years old - Subsyndromal delirium (ICDSC of 1-3) - Mechanically ventilated - No objection from the MICU, CCU, or SICU service attending MD for enrollment - Admitted to the MICU, CCU, or SICU service at Tufts Medical Center - Patients is expected by their ICU attending physician to require admission to the ICU for ≥ 24 hours Exclusion Criteria: - Pregnancy - Delirium (ICDSC ≥ 4) - History of severe dementia or an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)) score ≥ 4 - IQCODE is not able to be completed. - Current treatment with donepezil (aricept), tacrine (cognex), rivastigmine (exelon), or memantine (namenda) - Admitted with a neurologic diagnosis (e.g., CVA) - Past diagnosis of schizophrenia or a formal thought disorder as defined by DSM IV criteria. - Treatment with an antipsychotic agent in the 30 days prior to ICU admission - Current treatment with a neuromuscular blocker or dexmedetomidine - A patient requiring a level of sedation equivalent to a sedation-agitation scale (SAS) score ≤ 2 - Inability to conduct valid ICDSC assessment (e.g., coma, deaf) - Acute alcohol or drug withdrawal - Acute drug overdose - Severe encephalopathy - History of end stage liver failure (based on presence of ≥ 1 or more of the following: AST/ALT ≥ 2 times ULN, INR ≥ 2, total bilirubin ≥ 1.5 - Patients with a baseline QTc interval >/= 500 msec or an elevation >/= 60mmHg above baseline - Current drug therapy with a class Ia, Ic or III antiarrhythmic other than amiodarone. - History of haloperidol allergy - History of neuroleptic malignant syndrome. - Patients expected to die within 24 hours - Inability to obtain informed consent - Current participation in another research study. - Lack of permission of the patient's primary MICU service attending physician for participation in the study. - Current employment at Tufts Medical Center. - Age ≥ 85 years.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Haloperidol decanoateIV q6h. Study drug will be continued until one of the following study withdrawal/termination criteria is met: Delirium (ICDSC ≥ 4) develops. The diagnosis of delirium will be confirmed in all instances by the Psychiatric Consultation Service, Division of Psychiatry, Tufts Medical Center using DSM-IV criteria. The patient is discharged from the ICU at Tufts MC. 10 days of study drug administration occurs. The subject experiences an adverse event potentially attributable to the study drug that is deemed, in the opinion of one of the physicians on the study team or the MICU team, to warrant discontinuation of therapy.
Drug:PlaceboD5W 0.2mL IV q6h Study drug will be continued until one of the following study withdrawal/termination criteria is met: Delirium (ICDSC ≥ 4) develops. The diagnosis of delirium will be confirmed in all instances by the Psychiatric Consultation Service, Division of Psychiatry, Tufts Medical Center using DSM-IV criteria. The patient is discharged from the ICU at Tufts MC. 10 days of study drug administration occurs. The subject experiences an adverse event potentially attributable to the study drug that is deemed, in the opinion of one of the physicians on the study team or the MICU team, to warrant discontinuation of therapy.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Haloperidol 1mg IV q6h
D5W 0.2mL IV q6h
Start Date: September 2010
Completed Date: March 2014
Phase: Phase 4
Primary Outcome: Conversion from subsyndromal delirium to delirium during the period of study drug administration (up to 10 days).
Secondary Outcome: The number of hours spent agitated (SAS >/=5) as percent of time study drug administered (up to 10 days).
Study sponsors, principal investigator, and references
Principal Investigator: John W Devlin, PharmD
Lead Sponsor: Northeastern University
Collaborator: National Institute on Aging (NIA)
Ouimet S, Riker R, Bergeron N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med. 2007 Jun;33(6):1007-13. Epub 2007 Apr 3. Erratum in: Intensive Care Med. 2007 Sep;33(9):1677. Bergeon, Nicolas [corrected to Bergeron, Nicolas].