Post-operative Delirium
Conditions
Keywords
delirium, surgery, operation, geriatric, complication
Brief summary
Post-operative delirium is a common and deleterious complication in elderly patients. The investigators have previously found lower levels of serum tryptophan in post-operative elderly patients who developed delirium in comparison to post-operative elderly patients who did not develop delirium. The investigators hypothesize that post-operative supplementation of L-tryptophan will reduce the duration and incidence of post-operative delirium. This study is a double-blinded placebo controlled trial of L-tryptophan supplementation in post-operative ICU patients 60 years and older. The primary outcome measure is the comparison of duration of post-operative delirium in subjects who receive L-tryptophan supplementation versus a similar appearing control.
Detailed description
The sudy will compare rates and duration of postoperative delirium in groups that receive L-tryptophan supplementation compared to placebo.
Interventions
DRUGL-tryptophan supplementation
L-tryptophan 1 gram enterally TID for a maximum of nine doses or to be discontinued at the time of discharge from the ICU (whichever occurs first)
DRUGplacebo
Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Included subjects will be 60 years and older undergoing an operation with a planned ICU admission post-operatively.
Exclusion criteria
* Medications that, when combined with tryptophan, increase the risk of serotonin syndrome. The classes of medications include: * monoamine oxidase inhibitors * selective serotonin reuptake inhibitors * serotonin-norepinephrine reuptake inhibitors * triptans * opioids * central nervous system stimulants * bupropion * St. John's Wort * Patients who undergo an operation on their brain. * Factors which prevent delirium assessment with the CAM-ICU: vision impairment or non-fluent English speakers. * A lowered seizure threshold including: * history of seizure disorder * alcohol abuse defined by a high AUDIT score (\>8 females and \>13 males) * benzodiazepine or barbiturate abuse within three months of the study * OR a positive urine toxicology screen for alcohol, benzodiazepines or barbiturates. * Significant liver disease (Child's class B or greater) or significant renal disease (Creatinine ≥2.0). * History of Huntington's or Addison's disease. (As requested by the FDA) * History of bipolar disorder or a psychotic disorder (such as a psychotic major depression, schizophrenia, schizoaffective disorder, or psychosis in Alzheimer's disease or other dementia). (As requested by the FDA) * Women who are not post-menopausal. (As requested by the FDA)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Duration of Post-operative Delirium | post-operatively daily in ICU until discharged from ICU |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Post-operative Delirium | post-operatively daily in ICU until discharged from ICU | The incidence and/or duration of excitatory (hyperactive and mixed) post-operative delirium, diagnosed by the Confusion Assessment Method-ICU (CAM-ICU) with the Richmond Agitation Sedation Score (RASS), will be reduced with enteral L-tryptophan supplementation (1 gm TID for the first 3 post-op days), compared to placebo, in older patients (≥ 60 years) undergoing operations requiring ICU admission. The incidence and/or duration of all types of post-operative delirium, diagnosed by the CAM-ICU with the RASS, will be reduced with enteral L-tryptophan supplementation (1 gm TID for the first 3 post-op days), compared to placebo, in older patients (≥ 60 years) undergoing operations requiring ICU admission. |
| Level of Post-operative Serum Tryptophan | post-operative day number two blood draw | — |
| Level of Post-operative Melatonin | Blood draw on post-operative day number two | — |
| Length of Post-operative ICU and Hospital Stay | length of post-op hospital stay | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| L-tryptophan L-tryptophan 1 gm enterally TID starting the evening of the operation | 152 |
| Placebo similar appearing placebo | 149 |
| Total | 301 |
Baseline characteristics
| Characteristic | L-tryptophan | Placebo | Total |
|---|---|---|---|
| Age, Continuous Overall Study | 69 years STANDARD_DEVIATION 7 | 69 years STANDARD_DEVIATION 8 | 69 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 152 participants | 149 participants | 301 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 148 Participants | 147 Participants | 295 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 152 | 0 / 149 |
| serious Total, serious adverse events | 0 / 152 | 0 / 149 |
Outcome results
Primary
Duration of Post-operative Delirium
Time frame: post-operatively daily in ICU until discharged from ICU
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug | Duration of Post-operative Delirium | 3.3 days | Standard Deviation 1.7 |
| Placebo | Duration of Post-operative Delirium | 3.1 days | Standard Deviation 1.9 |
Secondary
Incidence of Post-operative Delirium
The incidence and/or duration of excitatory (hyperactive and mixed) post-operative delirium, diagnosed by the Confusion Assessment Method-ICU (CAM-ICU) with the Richmond Agitation Sedation Score (RASS), will be reduced with enteral L-tryptophan supplementation (1 gm TID for the first 3 post-op days), compared to placebo, in older patients (≥ 60 years) undergoing operations requiring ICU admission. The incidence and/or duration of all types of post-operative delirium, diagnosed by the CAM-ICU with the RASS, will be reduced with enteral L-tryptophan supplementation (1 gm TID for the first 3 post-op days), compared to placebo, in older patients (≥ 60 years) undergoing operations requiring ICU admission.
Time frame: post-operatively daily in ICU until discharged from ICU
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Drug | Incidence of Post-operative Delirium | 17 percentage of patient escitatorydelirium |
| Placebo | Incidence of Post-operative Delirium | 9 percentage of patient escitatorydelirium |
Secondary
Length of Post-operative ICU and Hospital Stay
Time frame: length of post-op hospital stay
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug | Length of Post-operative ICU and Hospital Stay | 10 days | Standard Deviation 8.4 |
| Placebo | Length of Post-operative ICU and Hospital Stay | 9.7 days | Standard Deviation 8.7 |
Secondary
Level of Post-operative Melatonin
Time frame: Blood draw on post-operative day number two
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug | Level of Post-operative Melatonin | 20 pg/mL | Standard Deviation 31 |
| Placebo | Level of Post-operative Melatonin | 19 pg/mL | Standard Deviation 41 |
Secondary
Level of Post-operative Serum Tryptophan
Time frame: post-operative day number two blood draw
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug | Level of Post-operative Serum Tryptophan | 65 umol/L | Standard Deviation 26 |
| Placebo | Level of Post-operative Serum Tryptophan | 41 umol/L | Standard Deviation 15 |