Please select the eligibility criteria that correspond to the clinical trial below.
Title: Delirium in the ICU: a Prospective, Randomized, Trial of Placebo vs. Haloperidol vs. Ziprasidone
Brief Summary: Delirium is associated with increased risk of death, prolonged stay, higher cost of care, and likely long-term brain deficits in survivors. This form of brain dysfunction occurs in intensive care unit (ICU) patients in epidemic proportions, and the scope of this problem is likely to worsen in upcoming years due to the aging of our population and increased utilization of the ICU. Currently, delirium goes unrecognized and untreated in the vast majority of circumstances in the ICU unless the patient presents with hyperactive delirium and agitation. In the latter circumstance, a commonly used typical antipsychotic called haloperidol is considered the principal agent for treating delirium based largely on anecdotal evidence to support its usefulness, though no placebo controlled trials exist. There are no FDA approved medications for delirium. The atypical antipsychotics provide a promising alternative for the treatment of delirium due to their enhanced beneficial effects on positive (agitated) and negative (quiet) symptoms proven in mania and schizophrenia, reduced risk for side effects common to haloperidol such as extrapyramidal symptomatology, and less potentially lethal heart rhythm disturbances. It is imperative that well-designed phase II studies to determine proof of principle be conducted. A pilot study of feasibility to begin assessing the role of antipsychotics in the management of ICU delirium.


Options:
A: Inclusion Criteria:

* Male or female age 18 -75 years
* Was admitted in Maharaj Nakhon Chiang Mai hospital
* Was diagnosed by the diagnostic criteria for DSM-IV-TR delirium due to a general medical condition or delirium due to multiple etiologies
* Delirious state (delirium) of the patients was confirmed by using name-assess confusion assessment method (CAM) and assessment of severity with delirium rating scale-revised-98 (DRS-R-98)
* Have a written consent from the legal representatives

Exclusion Criteria:

* Was diagnosed substance withdrawal delirium
* Having a history drug allergy either from quetiapine or haloperidol
* Female patients who are pregnant or breastfeeding
* No written consent from the legal representatives
* Received other anti-psychotic drug before attend the study
* Being ill with renal or hepatic failure
B: Inclusion Criteria:

* Medical or surgical ICU patients on mechanical ventilation who are receiving sedatives or analgesics or displaying an abnormal level of consciousness (delirium or coma).

Exclusion Criteria:

* Subjects expected to have a short time on mechanical ventilation. That is, those in whom the likelihood for the need for mechanical ventilation is less than 24 hours.
* Subjects who have been on mechanical ventilation for more than 72 hours.
* Subjects in whom gastric access is not available (i.e., no enteral feeding tube or NG/OG tube)and is not anticipated to be available for 48 hours.
* Subjects younger than 18 years old.
* Subjects who are pregnant (a pregnancy test will be performed on all women of child bearing age) or breastfeeding.
* Inability to obtain informed consent from the subject or the subject's authorized representative.
* Documented history of allergic reaction to ziprasidone or haloperidol.
* Subjects admitted to the ICU for drug/alcohol overdose, suicide attempts, alcohol withdrawal/delirium tremens.
* Subjects with active seizures or cerebrovascular accident within the last 2 weeks.
* Subjects who are benzodiazepine dependent at the time of index hospitalization (i.e., patients on benzodiazepines as outpatient and whose attending judges it unsafe to withhold these medications due to risk for withdrawal syndrome).
* Subjects with chronic pain syndromes or who are on maintenance narcotics.
* Subjects with a history of torsades de pointes, known history of QT prolongation (e.g., congenital long QT syndrome), a QTc at baseline of 500 ms or over in the absence of bundle branch block, documented myocardial infarction within the previous 2 weeks, or uncompensated NYHA IV heart failure (dyspnea or anginal syndrome present at rest due to CHF). \[NOTE: ICU patients who have an incidental rise in troponin in the absence of definitive ischemic ECG changes remain eligible\]
* Subjects who are on neuroleptic therapy as an outpatient maintenance drug (e.g., haloperidol, mesoridazine, thorazine, chlorpromazine, trifluoperazine, droperidol, risperidone, quetiapine, olanzapine, or ziprasidone).
* Subjects who are receiving and will continue to receive other drugs that prolong the QT interval such as sotalol, quinidine, other Class Ia or III anti-arrhythmics, dofetilide (Tikosyn for arrhythmias), pimozide (for Tourette's), gatifloxacin, moxifloxacin (levofloxacin permissible), pentamidine, tacrolimus (Prograf), dolasetron (Anzemet). Azithromycin is an acceptable medication for study patients, and anyone slated to receive (or receiving) either clarithromycin or erythromycin can be switched to azithromycin by their primary team and be enrolled into the study the following day. Patients receiving clindamycin or clotrimazole will be excluded from the study.
* Subjects who have a history of neuroleptic malignant syndrome.
* Subjects with potassium levels below 3.0 mg/dl or magnesium levels below 1.8 mg/dl. NOTE: If the patient is receiving replacement of K+ or Mg+, then he/she would be eligible unless there is reason to suspect that these electrolyte abnormalities will be refractory.
* Subjects with moderate/severe dementia (e.g., Alzheimer's type, vascular origin, or HIV-related) as documented by medical history or modified Blessed dementia rating scale (mBDRS) 4 or more or Informant Questionnaire of Cognitive Dysfunction in the Elderly (IQCODE) over 3.6.
* Subjects who have suspected anoxic brain injury or documented cerebral edema at the time of screening.
* Subjects who are moribund and not expected to survive 24 hours from the time of study enrollment, or who have a "Do Not Resuscitate" order, or whose family or medical team have not committed to aggressive support (e.g., not going to use vasopressors or mechanical ventilation or likely to have withdrawal of support within 24 hours).
C: Inclusion Criteria:

* Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible.

Exclusion Criteria:

* Patients who could not be extubated even if delirium or agitation were corrected. This will include:

  * Patients receiving high dose opioid analgesia (\>20 m/morphine/day)
  * Patients shortly to return to the operating theatre
  * Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation.
  * Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity)
* Known allergy to haloperidol or alpha2 agonists
D: Inclusion Criteria:

Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible, AND in the opinion of their treating intensivist their agitation is so severe as to make lessening their sedation unsafe.

These criteria will be objectively quantified as follows:

* they have required either mechanical restraint and/or anti-delirium or sedative medication in the 4 hours prior to seeking consent AND
* their Confusion Assessment Method for the ICU (CAM-ICU) test is positive for delirium in the 4 hours prior to seeking consent AND
* their Motor Activity Assessment Scale (MAAS) score is 5 or more in the 4 hours prior to seeking consent, confirming psychomotor agitation AND
* their SOFA score is less than or equal to 5 in the 4 hours prior to seeking consent, predicting a mortality or around 5%.

Exclusion Criteria:

* Age less than 18 years old
* Pregnancy or breastfeeding
* Advanced dementia (in the premorbid state requiring professional nursing care)
* Open or closed head injury
* Death is deemed imminent and inevitable
* The patient has previously been enrolled in the DahLIA study
* Patients who could not be extubated, or who would be intubated within the following 48 hours, even if delirium or agitation were corrected. This will include:

  * Patients receiving high dose opioid for analgesia (not sedation) ( \> 40 mg/morphine/day)
  * Patients shortly to return to the operating theatre
  * Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation
  * Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity)
* Known allergy to haloperidol or alpha 2 agonists

Answer: B