Anesthesia, Delirium, Hip Fractures
Conditions
Brief summary
Postoperative delirium occurs in up to 65% of elders undergoing surgery for repair of a hip fracture and this complication is independently associated with increased morbidity, mortality, length of hospital stay, and placement in long-term care institutions. To date, the only intervention shown to be effective at minimizing postoperative delirium is a proactive geriatric consultation. This prospective randomized clinical trial will randomize 160 adults, aged 65 years or older, to either optimized general anesthesia or usual general anesthesia care for hip fracture surgery to determine if the optimized anesthesia management reduces the severity of postoperative delirium.
Detailed description
Subjects will be randomized to one of two intraoperative anesthesia treatment groups: 1.) Usual care - the anesthetic management will be at the discretion of the anesthesia provider; or 1.) Optimal care - the intraoperative depth of anesthesia will be directed using a BIS monitor, blood pressure will be maintained within 20% of preoperative levels, and cerebral oxygenation will be maintained \> 60% during anesthesia. Subjects will be evaluated using the Confusion Assessment Method (CAM) for the first 5 postoperative days to determine if they experience postoperative delirium.
Interventions
DEVICEcerebral oximeter (Fore-Sight)
The cerebral oximeter will be monitored in the optimized care group and cerebral oxygenation will be maintained at 60% or higher.
DEVICEdepth of anesthesia monitor (BIS)
The depth of anesthesia will be maintained between 40 and 60 in the optimized care group.
PROCEDUREBP management
The systolic blood pressure will be maintained within 20% of preoperative levels in the optimized care group.
PROCEDUREGeneral anesthesia
General anesthesia will be used in both groups
DRUGpropofol
propofol per protocol
DRUGfentanyl
fentanyl per protocol
DRUGsevoflurane
maintenance of anesthesia with inhaled sevoflurane
Sponsors
University of Missouri-Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The individuals assessing the patients for delirium after surgery will be unaware of the treatment in the operating room.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject or legal representative has voluntarily signed the informed consent approved by the Institutional Review Board, * Hip fracture surgery scheduled under general anesthesia * Subject is 65 years or older on the day of surgery
Exclusion criteria
* Inability to follow directions or comprehend the English language * Severe uncorrected visual or auditory handicaps * Delirium at screening or baseline * Emergency surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Postoperative Delirium | 5 postoperative days | Delirium Rating Scale-Revised-98 (DRS-R-98) is a 16-item clinician-rated scale with 13 severity items and 3 diagnostic items (maximum severity score of 39 points). Higher scores indicate more severe delirium; score of 0 indicates no delirium. Only the number of patients who had high scores on the DRS-R-98 are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Presented With Postoperative Delirium | 5 postoperative days | Confusion Assessment Method (CAM) with delirium scored as 'present' (1) or 'absent' (0) based on question responses; CAM is considered positive based on the CAM algorithm: presence of acute onset or fluctuating course, inattention, and disorganized thinking or altered level of consciousness. |
| Perioperative Inflammatory Response | preoperative, day of surgery, and postoperative day 2 | Blood will be drawn for analysis of inflammatory markers including interleukin 6 (IL6), interleukin 10 (IL10), tumor necrosis factor (TNF) alpha on the day prior to surgery, at the end of surgery and on the second postoperative day. |
| Number of Patients Who Experienced Postoperative Complications | 3 months and 1 year | The investigators will make a telephone call to the subjects at 3 months and 1 year after surgery to determine if the subject has experienced any complications. We will ask the subjects about the occurrence of infections, strokes, cardiac problems, or respiratory problems since discharge from the hospital. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator: Usual General Anesthesia Care Subjects will have their general anesthetic management directed at the discretion of the anesthesia provider.
General anesthesia with be maintained with propofol, fentanyl, sevoflurane | 56 |
| Experimental: Optimized General Anesthesia Care The subjects will have general anesthesia with propofol, fentanyl, sevoflurane. In addition the subjects will be monitored with a depth of anesthesia monitor (BIS) and a cerebral oximeter (Foresight). These additional monitors will be used to direct care. BP management: Systolic BP will be maintained within 20% of baseline systolic BP variables. | 53 |
| Mini Mental State Exam Subjects will have their general anesthetic management directed at the discretion of the anesthesia provider.
General anesthesia with be maintained with propofol, fentanyl, sevoflurane | 22 |
| Tested and Excluded Subjects will have their general anesthetic management directed at the discretion of the anesthesia provider.
General anesthesia with be maintained with propofol, fentanyl, sevoflurane | 14 |
| Total | 145 |
Baseline characteristics
| Characteristic | Experimental: Optimized General Anesthesia Care | Total | Tested and Excluded | Mini Mental State Exam | Active Comparator: Usual General Anesthesia Care |
|---|---|---|---|---|---|
| Age, Continuous | 77.8 years STANDARD_DEVIATION 9.3 | 78 years STANDARD_DEVIATION 8.9 | 81 years STANDARD_DEVIATION 7.9 | 86.6 years STANDARD_DEVIATION 6.8 | 78.1 years STANDARD_DEVIATION 8.4 |
| American Society of Anesthesiologists (ASA) Physical Status Classification System 2 | 10 Participants | 25 Participants | 6 Participants | 1 Participants | 8 Participants |
| American Society of Anesthesiologists (ASA) Physical Status Classification System 3 | 33 Participants | 94 Participants | 6 Participants | 16 Participants | 39 Participants |
| American Society of Anesthesiologists (ASA) Physical Status Classification System 4 | 10 Participants | 24 Participants | 1 Participants | 4 Participants | 9 Participants |
| American Society of Anesthesiologists (ASA) Physical Status Classification System 5 | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 53 Participants | 142 Participants | 13 Participants | 21 Participants | 55 Participants |
| Sex: Female, Male Female | 36 Participants | 105 Participants | 9 Participants | 17 Participants | 43 Participants |
| Sex: Female, Male Male | 17 Participants | 40 Participants | 5 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 56 | 6 / 53 | 10 / 22 | 0 / 0 |
| other Total, other adverse events | 25 / 56 | 20 / 53 | 0 / 22 | 0 / 0 |
| serious Total, serious adverse events | 26 / 56 | 28 / 53 | 11 / 22 | 0 / 0 |
Outcome results
Primary
Severity of Postoperative Delirium
Delirium Rating Scale-Revised-98 (DRS-R-98) is a 16-item clinician-rated scale with 13 severity items and 3 diagnostic items (maximum severity score of 39 points). Higher scores indicate more severe delirium; score of 0 indicates no delirium. Only the number of patients who had high scores on the DRS-R-98 are reported.
Time frame: 5 postoperative days
Population: Number of patients who presented with postoperative delirium and had high scores on the delirium test measures per group are indicated here. Patients who were excluded were not assessed for postoperative delirium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Comparator: Usual General Anesthesia Care | Severity of Postoperative Delirium | 0.14 score on a scale | Standard Deviation 0.35 |
| Experimental: Optimized General Anesthesia Care | Severity of Postoperative Delirium | 0.06 score on a scale | Standard Deviation 0.23 |
| Mini Mental State Exam | Severity of Postoperative Delirium | 0.63 score on a scale | Standard Deviation 0.49 |
Secondary
Number of Patients Who Experienced Postoperative Complications
The investigators will make a telephone call to the subjects at 3 months and 1 year after surgery to determine if the subject has experienced any complications. We will ask the subjects about the occurrence of infections, strokes, cardiac problems, or respiratory problems since discharge from the hospital.
Time frame: 3 months and 1 year
Population: Number analyzed in rows differs due to loss to follow-up. Patients who were excluded from the study were not followed op post operatively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Cardiac arrest requiring cardiopulmonary resuscitation | 1 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Myocardial infarction | 1 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Both cardiac arrest requiring cardiopulmonary resuscitation and myocardial infarction | 0 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Deep incisional surgical site infection | 0 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Organ/space surgical site infection | 1 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Cardiac arrest requiring cardiopulmonary resuscitation | 2 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Myocardial infarction | 0 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Both cardiac arrest requiring cardiopulmonary resuscitation and myocardial infarction | 1 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Deep incisional surgical site infection | 1 Participants |
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Organ/space surgical site infection | 0 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Deep incisional surgical site infection | 1 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Cardiac arrest requiring cardiopulmonary resuscitation | 0 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Cardiac arrest requiring cardiopulmonary resuscitation | 0 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Organ/space surgical site infection | 2 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Myocardial infarction | 1 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Organ/space surgical site infection | 2 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Both cardiac arrest requiring cardiopulmonary resuscitation and myocardial infarction | 0 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Both cardiac arrest requiring cardiopulmonary resuscitation and myocardial infarction | 0 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 1 Year: Myocardial infarction | 1 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Experienced Postoperative Complications | 3 Months: Deep incisional surgical site infection | 1 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 1 Year: Both cardiac arrest requiring cardiopulmonary resuscitation and myocardial infarction | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 3 Months: Deep incisional surgical site infection | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 3 Months: Organ/space surgical site infection | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 1 Year: Cardiac arrest requiring cardiopulmonary resuscitation | 2 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 1 Year: Deep incisional surgical site infection | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 1 Year: Myocardial infarction | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 3 Months: Cardiac arrest requiring cardiopulmonary resuscitation | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 1 Year: Organ/space surgical site infection | 0 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 3 Months: Myocardial infarction | 1 Participants |
| Mini Mental State Exam | Number of Patients Who Experienced Postoperative Complications | 3 Months: Both cardiac arrest requiring cardiopulmonary resuscitation and myocardial infarction | 0 Participants |
Secondary
Number of Patients Who Presented With Postoperative Delirium
Confusion Assessment Method (CAM) with delirium scored as 'present' (1) or 'absent' (0) based on question responses; CAM is considered positive based on the CAM algorithm: presence of acute onset or fluctuating course, inattention, and disorganized thinking or altered level of consciousness.
Time frame: 5 postoperative days
Population: Number of patients who presented with postoperative delirium are reported. The patients who where tested and then excluded were not included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Comparator: Usual General Anesthesia Care | Number of Patients Who Presented With Postoperative Delirium | 8 Participants |
| Experimental: Optimized General Anesthesia Care | Number of Patients Who Presented With Postoperative Delirium | 4 Participants |
| Mini Mental State Exam | Number of Patients Who Presented With Postoperative Delirium | 0 Participants |
Secondary
Perioperative Inflammatory Response
Blood will be drawn for analysis of inflammatory markers including interleukin 6 (IL6), interleukin 10 (IL10), tumor necrosis factor (TNF) alpha on the day prior to surgery, at the end of surgery and on the second postoperative day.
Time frame: preoperative, day of surgery, and postoperative day 2
Population: Lack of funding prevented the analysis of blood to obtain inflammatory markers.