The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial (PODCAST)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01690988 |
|
Recruitment Status :
Completed
First Posted : September 24, 2012
Results First Posted : May 2, 2018
Last Update Posted : June 6, 2018
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Delirium | Drug: Ketamine (0.5 mg/kg) Drug: Normal Saline (placebo) Drug: Ketamine (1 mg/kg) | Phase 3 |
Postoperative delirium is one of the most common complications of major surgery, affecting between 10% and 70% of all elderly surgical patients. Delirium manifests as poor attention and inability to think logically, and is associated with longer intensive care unit and hospital stay, long lasting cognitive deterioration, and increased mortality rate. Studies have shown that a low sub-anesthetic dose of ketamine, an anesthetic drug, has the potential to decrease several postoperative complications, including delirium, pain, opioid consumption, and nausea and vomiting. Low dose ketamine would be particularly appealing as a drug to prevent delirium and other postoperative complications, as it is inexpensive and extremely safe. However, these proposed benefits of ketamine in the perioperative setting have not yet been tested in a large clinical trial. The investigators are therefore proposing a pragmatic, exploratory clinical trial to support or refute the contention that low dose ketamine decreases the incidence of postoperative delirium, with the possibility of conducting a larger randomized clinical trial pending the results of this study. At the time of enrollment, patients will undergo the same delirium and pain evaluation that will be used postoperatively. Additionally patients will be screened for functional dependence using the Barthel Index of Activities of Daily Living, for depression using the Geriatric Depression Scale - Short Form, and for obstructive sleep apnea using the STOP-Bang criteria. They will also be asked about any falls they have experienced in the six months prior to surgery. Comorbid conditions, including the components of the Charlson Comorbidity Index, will be obtained by reviewing the patients' medical records. Any available preoperative lab results, including electrolytes and blood counts, will also be recorded.
Patients will be randomized to receive low dose ketamine or placebo following induction of anesthesia and prior to surgical incision. Blinded observers will assess delirium on the afternoon/evening of postoperative day 0 (if feasible) and twice daily (morning and afternoon/evening with at least six hours between assessments) on postoperative days 1-3 using the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Unit. Acute pain will be assessed via the observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of the patient-reported Visual Analog Scale from postoperative days 0-3. Postoperative opioid consumption will be assessed from the patients' medical charts for postoperative days 0-3. Postoperative nausea and vomiting will be assessed via a patient-reported section of the Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) for postoperative days 0-3. ICU and/or hospital length of stay will be assessed from the patients' medical charts. Adverse outcomes (e.g. hallucinations and nightmares) will be assessed via the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Unit for postoperative days 0-3.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 746 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Prevention |
| Official Title: | The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial |
| Actual Study Start Date : | February 1, 2014 |
| Actual Primary Completion Date : | June 26, 2016 |
| Actual Study Completion Date : | July 2017 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Ketamine (0.5 mg/kg)
Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
|
Drug: Ketamine (0.5 mg/kg)
Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
Other Name: Ketalar |
|
Placebo Comparator: Normal saline (placebo)
Intravenous normal saline
|
Drug: Normal Saline (placebo)
Normal saline IV following induction of anesthesia or administration of sedative medications
Other Name: Normal saline |
|
Experimental: Ketamine (1 mg/kg)
Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
|
Drug: Ketamine (1 mg/kg)
Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
Other Name: Ketalar |
- Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3 [ Time Frame: Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients ]
According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.
To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS <-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.
The primary comparison will be between the combined ketamine groups and the placebo group.
- Daily Maximum Pain Recorded [ Time Frame: Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments ]Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.
- Median Opioid Consumption [ Time Frame: Postoperative days 0-3 ]
Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively
Opioid Drugs included:
* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)
- Number of Patients With Postoperative Nausea and Vomiting [ Time Frame: Postoperative days 1-3 ]
Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they "currently have nausea/vomiting" AM & PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3
The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.
- ICU and/or Hospital Length of Stay [ Time Frame: Postoperative period ]Assessed from patients' medical charts
- Adverse Outcomes (Number of Patients With Hallucinations) [ Time Frame: Postoperative days 1-3 ]Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit
- Adverse Outcomes (Number of Patients With Nightmares) [ Time Frame: Postoperative days 1-3 ]Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 60 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients 60 and older
- Competent to provide informed consent
- Undergoing major surgery (e.g., open cardiac surgery, open or thoracoscopic thoracic surgery, abdominal surgery, open urological surgery, open gynecological surgery, major orthopedic surgery, major vascular surgery including endovascular procedures, major ear, nose and throat surgery).
Exclusion Criteria:
- Patients with an allergy to ketamine
- Those in whom a significant elevation of blood pressure would constitute a serious hazard (e.g., pheochromocytoma, aortic dissection)
- Unable to provide informed consent
- Patients with drug misuse history (e.g., ketamine, cocaine, heroin, amphetamine, methamphetamine, MDMA, phencyclidine, lysergic acid, mescaline, psilocybin)
- Patients taking anti-psychotic medications (e.g., chlorpromazine, clozapine, olanzapine, risperidone, haloperidol, quetiapine, risperidone, paliperidone, amisulpride, sertindole)
- Patients with a weight outside the range 50 kg - 200 kg (110 lbs - 440 lbs)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01690988
| United States, Missouri | |
| Washington University School of Medicine | |
| Saint Louis, Missouri, United States, 63110 | |
| Principal Investigator: | George A Mashour, MD PhD | University of Michigan | |
| Study Director: | Daniel A Emmert, MD PhD | Washington University School of Medicine | |
| Study Director: | Kane Pryor, MBBS | Cornell | |
| Study Director: | Eric Jacobsohn, MB ChB | University of Manitoba | |
| Study Director: | Judith Hudetz, PhD | Medical College of Wisconsin | |
| Study Chair: | Hilary P Grocott, MD | University of Manitoba | |
| Principal Investigator: | Michael S Avidan, MBBCh | Washington University School of Medicine | |
| Study Director: | Sharon Inouye | Harvard Medical School (HMS and HSDM) | |
| Study Director: | Robert Veselis | Memorial Sloan Kettering Medical Center | |
| Study Director: | Jayant Aveek | Postgraduate Institute of Medical Education and Research | |
| Study Director: | Heiko Kaiser | University of Bern | |
| Study Chair: | Stephen Choi | University of Toronto | |
| Study Chair: | Ryan Pong | Virginia Mason Medical Center | |
| Study Director: | Gyujeong Noh | Asan Medical Center |
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Michael Avidan, Director, Institute of Quality Improvement, Research & Informatics, Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT01690988 |
| Other Study ID Numbers: |
201206071 |
| First Posted: | September 24, 2012 Key Record Dates |
| Results First Posted: | May 2, 2018 |
| Last Update Posted: | June 6, 2018 |
| Last Verified: | November 2017 |
|
Delirium ketamine surgery neurological complications |
|
Delirium Confusion Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Neurocognitive Disorders Mental Disorders Ketamine Analgesics Sensory System Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Anesthetics, Dissociative Anesthetics, Intravenous Anesthetics, General Anesthetics Central Nervous System Depressants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action |