Clinical trial NCT02604459
Conditions: Hip Fractures Anesthesia Delirium
Sponsor: University of Missouri-Columbia
Start date: 2015-06-01; Completion date: 2018-02-28
Enrollment: 145 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Subjects will have their general anesthetic management directed at the discretion of the anesthesia provider.

General anesthesia with be maintained with propofol, fentanyl, sevoflurane arm 2: 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. arm 3: Subjects will have their general anesthetic management directed at the discretion of the anesthesia provider.

General anesthesia with be maintained with propofol, fentanyl, sevoflurane arm 4: Subjects will have their general anesthetic management directed at the discretion of the anesthesia provider.

General anesthesia with be maintained with propofol, fentanyl, sevoflurane
Interventions: intervention 1: cerebral oximeter (Fore-Sight) intervention 2: depth of anesthesia monitor (BIS) intervention 3: BP management intervention 4: General anesthesia intervention 5: propofol intervention 6: fentanyl intervention 7: sevoflurane
Intervention descriptions: intervention 1: The cerebral oximeter will be monitored in the optimized care group and cerebral oxygenation will be maintained at 60% or higher. intervention 2: The depth of anesthesia will be maintained between 40 and 60 in the optimized care group. intervention 3: The systolic blood pressure will be maintained within 20% of preoperative levels in the optimized care group. intervention 4: General anesthesia will be used in both groups intervention 5: propofol per protocol intervention 6: fentanyl per protocol intervention 7: maintenance of anesthesia with inhaled sevoflurane

Protocol documents:
Prot_SAP_000.pdf: 
 
 
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Date:    February 20, 2017  
Version Number:   11___________ 
Principal Investigator: _Quinn Johnson, MD_____ 
Application Number: __1212915____ 
Application Title:  
 
Does Optimized General Anesthesia Care Reduce Postoperative Delirium In Older Patients 
Undergoing Hip Fracture Repair? 
 
Protocol 
 
*************************************************************************************************** 
 
 
1. 
Abstract 
 
          The overall objective of this proposal is to determine if optimized general anesthesia care of elderly 
patients undergoing hip fracture surgery will minimize postoperative delirium (POD) and improve 
postoperative outcomes. A proactive geriatric consultation using a multifactorial bundle of pharmacological 
and non-pharmacological strategies in the perioperative period has been shown to effectively reduce POD, 
but even with these perioperative medical interventions, more than 30% of patients undergoing hip fracture 
surgery experience POD.1,2   
             There is tantalizing preliminary evidence suggesting that intraoperative interventions may also 
have the potential to further decrease POD. 3-6  This prospective randomized clinical trial (RCT) will focus 
on the intraoperative optimization of:  1. blood pressure, 2. depth of anesthesia, 3. cerebral oxygenation, 
and 4. postoperative pain management in an effort to further reduce POD.  All of these interventions can 
easily be managed by anesthesia providers during surgery.  A total of 160 patients will be randomized to 
optimal versus usual anesthesia care for hip fracture surgery to determine the impact of this targeted 
anesthesia care bundle on the severity and incidence of POD.  The results of our proposed study are 
intended to enhance patient safety by developing a relatively easily implemented, generalizable anesthesia 
management strategy that can be used by anesthesia providers in both academic and private settings. This 
proposal has the potential to further reduce POD, thereby decreasing patient morbidity and mortality.   
 
 


 
 
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2. 
Objectives (include all primary and secondary objectives) 
 
The primary objective of this proposal is to develop an optimized general anesthetic plan, focusing on 
anesthetic depth, blood pressure control, and cerebral oxygenation for elders undergoing hip fracture 
surgery. This protocol will compare usual care to optimal general anesthesia care to test the following 
hypotheses:  
The use of an optimized general anesthetic technique for elders undergoing hip fracture surgery will: 
• Primary hypothesis:  decrease the severity of POD 
• Secondary hypothesis 1:  decrease the incidence and duration of POD  
• Secondary hypothesis 2:  decrease the length of stay in the hospital  
• Secondary hypothesis 3: to determine if poor performance on preoperative cognitive tests 
or preoperative depression identify patients at high-risk for POD 
• Secondary hypothesis 4:  to determine if the level of preoperative inflammation predicts 
patients at risk for POD 
3. 
Background  
Postoperative delirium (POD) is common in elderly patients and is reported to occur in 35 to 65% 
of patients undergoing hip fracture surgery.8  Despite the fact that delirium is a temporary condition, it is a 
medical and societal stressor from an economic and healthcare standpoint.  POD is independently 
associated with increased morbidity, mortality, length of hospital stay, and placement in long-term care 
institutions.  It increases the cost of hospitalization by $4000 for each patient who develops this 
complication and the total costs attributed to the treatment of delirium in the US are estimated to be as 
high as $152 billion each year.9,10   
The etiology of POD is multifactorial and involves a complex interaction between a vulnerable 
patient with preoperative risk factors who is exposed to numerous precipitating factors in the perioperative 
period.11  Most of the preoperative risk factors such as age, comorbidities and cognitive status are fixed and 
cannot be modified during the perioperative period.  However, there are perioperative factors that are 
directly under the control of the anesthesia provider that could potentially be modified to minimize POD.   


 
 
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     At the present time, only multi-component medical interventions have shown to consistently reduce 
POD.1,12,13  Although it makes sense that neuraxial anesthesia would be associated with less POD than 
general anesthesia (GA), there is no evidence to support this theory, possibly because sedation levels were 
not controlled in these studies.14 There is, however, limited evidence that minimizing anesthetic exposure 
during hip fracture surgery might decrease POD.  Sieber et al.3 randomized elderly patients undergoing hip 
fracture repair with spinal anesthesia to light versus deep propofol sedation for the procedure and found 
that light propofol sedation (BIS  > 80) decreased the incidence of POD by 50% compared with deep 
sedation (BIS =50).  Despite the promising results of this study, the study results have been questioned 
because the two treatment groups were not matched with respect to cognitive and functional status.12  A 
more important issue is that spinal anesthesia is rarely used for patients undergoing hip fracture surgery. A 
large retrospective study of 56,729 patients having hip fracture surgery in the US found that only 28% of 
patients received regional anesthesia and that GA was much more common (72%).15  There are a multitude 
of reasons that anesthesia providers prefer to administer GA for hip fracture surgery including patient 
preference, avoidance of pain during positioning of the patient, difficulty with block placement in elderly 
patients with arthritic spines, and the use of anticoagulation in many elders.  An optimized general 
anesthetic technique is, therefore, needed to improve postoperative outcomes in elders receiving GA for 
this hip fracture surgery.  
Modifiable Intraoperative Factors  
     There is growing evidence that limiting the amount of anesthesia during GA may decrease the 
incidence of POD.  Chan et al.5 prospectively randomized elderly patients undergoing elective major 
surgery to either BIS-guided or routine care anesthesia and found that patients in the BIS-guided group 
received less anesthetic and had a 35% decrease in the incidence of POD.  A second prospective study 
randomized elders undergoing elective surgery and found that intraoperative monitoring with BIS was 
associated with a lower incidence of delirium, “possibly by reducing extreme low BIS values.”6  In a third 
study, a retrospective analysis of patients undergoing general anesthesia found a trend toward less POD 
with BIS-guided compared to end-tidal anesthetic concentration guided protocols.16   


 
 
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     Near-infrared spectroscopy (NIRS) can be used to monitor the balance between cerebral oxygen 
delivery and consumption.17   There is moderate to close correlation between regional cerebral oxygen 
saturation (rScO2) and mixed venous saturation (SvO2) in awake and anesthetized patients, indicating that 
rScO2 is reflective of not only cerebral, but also systemic oxygen balance.18,19 A longitudinal study of 
healthy elderly patients undergoing abdominal surgery found that intraoperative cerebral desaturations 
occurred in 25% of patients and was associated with a higher incidence of early postoperative cognitive 
decline and longer hospital stays.20  Murkin et al.7 randomized 200 patients undergoing coronary artery 
bypass to either NIRS monitoring with active treatment of cerebral desaturations or usual care and found 
that active treatment significantly decreased mortality and major organ morbidity (stroke, myocardial 
infarction, ventilation > 48 hours).  There are no studies evaluating outcomes with the use of NIRS 
monitoring with a predetermined treatment protocol on outcomes after noncardiac surgery. 
         There is conflicting literature as to the relationship between intraoperative hypotension and POD.21,22  
A recent abstract found that nearly half of elderly patients had intraoperative mean arterial BP (MAP) 
decreases of 20% or more from baseline.22  While these investigators did not find a relationship between 
intraoperative hypotension and POD, their findings suggest that intraoperative blood pressure variance may 
have an impact on the occurrence of POD.   
4. 
Study Procedures 
a. Study Design: prospective, randomized, clinical trial with a parallel arm including patients who sign 
the consent to be enrolled in the study but are not randomized because they have a Mini-Mental 
State examination score < 15.  
b. Patient Population: This study will include 160 adults, aged ≥ 65 years, scheduled for surgery to 
repair a hip fracture at the University of Missouri-Columbia hospital.  We plan to recruit 250  
subjects to allow for  90 subjects to be excluded if their surgery is moved to another site or they 
fail the MMSE  prior to completion of the study.  The subjects will be recruited for the study 
after they are admitted to the University hospital for care of their hip fracture.  They will be 
visited during the hospitalization.  After discharge from the hospital, they will be called at home 


 
 
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at 1 year after surgery and this will be the final subject contact during the study.  They will not 
be required to return to the hospital for the purposes of this study.   
c. Intraoperative care – All patients will be monitored with standard ASA monitors and normocarbia 
and normothermia will be maintained during surgery.  None of the patients will be given 
benzodiazepine premedication.  All patients will receive a fascia iliaca compartment block in 
the holding area prior to surgery unless contraindicated (patient refusal, anticoagulation).  
Patients will be randomized to one of two intraoperative anesthesia care groups.  The patients, 
surgeons, and research personnel performing the confusion assessments will be blinded to the 
study group.  The anesthesia providers will be aware of the study group.  For the remainder of 
their intraoperative anesthesia care, patients will be randomized to: 
1. Usual care – General anesthesia will be induced with the medications commonly used for general 
anesthesia for this type of surgery namely, iv propofol or etomidate, iv fentanyl, and iv neuromuscular 
blocking agents to facilitate endotracheal intubation.  Patients will be ventilated with air/oxygen 
mixtures during surgery and anesthesia will be maintained with sevoflurane.  Anesthetic administration 
will be titrated on the basis of clinical judgment. A BIS® (Covidien) monitor and Fore-Sight® cerebral 
oximeter (CASMED) will be placed on the patients in the usual care arm, but the anesthesia team will 
be blinded to this monitoring data.  This data will not be used to treat the patient, but it will be analyzed 
to determine differences in intraoperative hemodynamics, cerebral oxygenation, and depth of anesthesia 
between groups.    
2. Optimized general anesthesia care (OP Care) – The anesthesia providers will be trained on the OP 
care protocol prior to the start of the study.  The same anesthetic agents will be used for induction and 
maintenance as in the usual care group, but the maintenance anesthesia will be titrated to achieve a BIS 
value between 40 and 60.  Non-invasive cerebral oximetry (Fore-Sight) will be placed before the 
induction of anesthesia and resting baseline rScO2 and BIS levels will be obtained on room air prior to 
sedation.  Intraoperative interventions will be performed for: 


 
 
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a. Cerebral desaturations - defined as an rScO2 < 50% or a 15% bilateral or unilateral reduction from 
baseline values.  If a desaturation occurs, patients will be treated using an algorithm developed by 
Denault et al.23   This algorithm brings BP to baseline values, increases oxygen delivery, and 
corrects head position, hypoventilation, and anemia.  
b. BP aberrations – any intraoperative systolic BP change greater than 20% from preoperative values 
and/or systolic BP < 90 mm Hg will be treated.  The initial treatment of hypotension will include 
fluid bolus followed by vasoactive agents (phenylephrine, ephedrine, glycopyrrolate) if needed.  
Vasoactive drugs (hydralazine, beta blockers) will be used to treat hypertension.  The 
anesthesiologist will use clinical judgment to determine the treatment regimen.  
IV. Perioperative assessments 
1. Hip Fracture Management Protocol – all patients will be managed by the Hip Fracture Improvement 
Team according to the hip fracture management protocol.  Postoperative pain management is 
outlined in this protocol. 
2. Cognitive and functional assessments – at baseline prior to surgery (This is a research procedure) 
a. 
Mini-Mental State Examination (MMSE-2)24 - a widely used screening tool for 
assessing global cognition (maximum score is 30);  Controlled Oral Word Association 
(COWA)25 –a brief measure of lexical fluency in which the subject must generate words 
beginning with specific letters; and Trails Making Test25 –a cognitive flexibility task. 
b. 
Depression will be measured using the Geriatric Depression – Short Form.26 
c. 
Pre-injury functional status will be evaluated using 7 instrumental and 7 basic activities 
of daily living (ADL).27 
d. 
Fragility Risk Analysis Index (RAI)28 - The RAI is a novel frailty index for use in 
surgical populations.   It is a 14-item questionnaire that takes less than 2 minutes to complete 
and generates scores ranging from 0 to 81. 


 
 
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e. 
Grip strength measured by the JAMAR handgrip dynamometer29 – an instrument for 
measuring the maximal isometric strength of the hand and forearm muscles.  The subjects 
are verbally encouraged to produce their maximal grip strength for 2-4 seconds for a total of 
3 trials.  This measurement can be completed in one minute or less. The maximal value will 
be used for analysis.Pain assessments –  
3. 
Patients will be asked to verbally rate their pain at each delirium assessment using a 
numerical rating scale from 0 (no pain) to 10 (worst imaginable pain).  (This is a research 
procedure).  Patients will also be assessed using the Critical-Care Pain Observation Tool (CPOT).  
This assessment can be used in intubated or delirious patients who cannot verbally rate their pain 
and will be performed by the member of the research team during the research visits.   
4. 
Delirium assessments - During the preoperative interview, the presence of delirium will 
be measured using the Confusion Assessment Method (CAM) and observation (appendix).  The 
CAM 30 uses 4 clinical criteria to diagnose delirium: acute onset and fluctuating course, inattention, 
disorganized thinking, and altered level of consciousness. The CAM was developed to be 
administered by nonpsychiatric clinicians and, across studies, has a pooled sensitivity of 86% and 
specificity of 93%, a positive and negative predictive accuracy of greater than 90%, and high inter-
rater reliability (kappa = .81 to 1.0.28 If the subject has a positive CAM at preoperative testing, 
he/she will be excluded from the study. For the first five postoperative days, subjects will be visited 
daily by a trained research technician.  The patients will be assessed daily using the CAM, the 
CAM-ICU and the 3D-CAM.  If the CAM is positive, the diagnosis of delirium will be confirmed 
by a second investigator who has specialty training in evaluating delirium and is unaware of the 
treatment assignment for the subject and the baseline cognitive test scores.  The specialist will 
administer the Delirium Rating Scale-Revised-98 (DSR-R98) daily until the delirium resolves or the 
patient is discharged.34  The severity and duration of delirium will be recorded.  (This is a research 
procedure.) 


 
 
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5. Systemic Inflammatory Response (SIRS) markers: 
The subjects will undergo venipuncture on the morning of surgery (prior to the start of 
anesthesia) and a total of 6 ml blood will be collected (for whole blood, serum, plasma). Blood 
will also be drawn at the end of surgery and on postoperative day 2 so a total of 18 ml of blood 
will be collected for study purposes.  All blood will be treated as follows: whole blood will be 
stimulated ex vivo with LPS for 24 hours at 37 °C, as described by Riyaz with 10 ng/ml (final 
concentration) Escherichia coli lipopolysaccharide (Difco, Detroit, MI).  Serum and plasma 
samples will be spun at 3000 rpm for 15 minutes and the supernatant stored at -80 °C until 
analyses are performed.  After 24 hours, the TruCulture incubation will be terminated, as 
described and samples stored until analyses.  The resulting plasma samples (+/- LPS) will be 
used for cytokine analyses.  These blood samples will be stored until funding is obtained for 
analysis of the inflammatory response. (This is a research procedure to obtain pilot data on the 
relationship between preoperative inflammatory state and POD. 
6. Postoperative follow up:  patients will be contacted at 3 months and 1 year after surgery to 
determine postoperative complications, functional status, and living environment (independent 
versus assisted living or nursing home).   
5. 
Inclusion/Exclusion Criteria 
Inclusion Criteria: a. Subject or legal representative has voluntarily signed the informed consent 
approved by the IRB, b. hip fracture surgery scheduled under general anesthesia, c. subject is 65 
years or older on the day of surgery 
Exclusion Criteria: a. Inability to follow directions or comprehend the English language, b. Severe 
uncorrected visual or auditory handicaps, c. delirium at screening or baseline, , d. emergency 
surgery in which the preoperative care of the patient is not optimized by the hip fracture or primary 
care team.   
Parallel arm 1:  During the initial hospital visit, we ask the patient to state his/her name and the 
year.  If they can correctly answer these questions, we explain the protocol and attempt to obtain 


 
 
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informed consent.  If the patient is unable to answer these two questions, we do not attempt to enroll 
the patient because he/she would not be able to follow directions to take the preoperative cognitive 
tests.  The nurses caring for these patients do CAM screening several times each day to assess the 
patient for delirium.  After the patient is discharged from the hospital, we will perform a 
retrospective chart review to determine the incidence of postoperative delirium (as assessed by the 
nursing staff) in this patient population.    
Parallel arm 2: If a patient is enrolled in the study, but scores < 15 on the MMSE, they will remain 
in the study but will not be randomized to one of the treatment groups.  They will be given the 
depression (GDS) and activities of daily living (ADL) questionnaires, but will not be administered 
the COWA or the Trail-making tests. However, they will receive the same type of general 
anesthesia for their hip fracture surgery and will be assessed for pain and delirium after surgery as 
described in 3 and 4 above. They will not be monitored with BIS or cerebral oximetry during the 
surgical procedure.    
6. 
Drugs/ Substances/ Devices 
 
a. Drug selection:  We are using the anesthetic agents routinely used during anesthesia care for hip 
fracture in both study groups.  The anesthetic management is routine care.  The only difference 
is that in the optimized anesthesia care group, the amount of intraoperative anesthetic given will 
be titrated using a depth of anesthesia (BIS) monitor.  All of the drugs used in this protocol are 
being administered in approved dosages for FDA approved indications.  The use of the BIS and 
Fore-Sight monitors are for the purposes of the research.  
b. Device selection:  We are using the depth of anesthesia device (BIS) that is already available in 
the University Hospital operating rooms.  However, most clinicians prefer to follow clinical 
signs such as BP and heart rate to adjust the anesthetic depth and the anesthesia providers at the 
University Hospital do not routinely use the BIS for this purpose.  The BIS is a FDA approved 
monitor intended depth of anesthesia monitoring, but it is not a standard of care.  The cerebral 
oxygenation monitor (Fore-Sight) is often used to monitor oxygenation of the brain during 


 
 
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cardiac surgery.  It is a FDA approved monitor and has an indication linking its’ use to 
improved patients outcomes after surgery.  
7. 
Study Statistics 
 
Outcome Variables: 
 
     To assess the primary hypothesis, the DRS-R98, a 16-item clinician-rated scale with 13 severity items 
and 3 diagnostic items (maximum total score of 46 and a maximum severity score of 39 points) will be 
utilized.31   The DRS-R98 is widely utilized in clinical and research situations when a sensitive, valid 
standardized measurement of delirium is needed.  For the secondary hypotheses, we will collect data on 
the incidence of POD which will be a dichotomous outcome.  The duration of delirium episodes and length 
of stay in the hospital will be measured in days and analyzed as a continuous variable.   
Statistical Analysis:  Group comparisons on the delirium severity score and length of stay will be made 
using the Wilcoxon Rank Sum Test (WRST).  The WRST is a nonparametric alternative to the two sample 
t-test.  The standard assumptions of the t-test are normality and equal variances, neither of which is 
required for the WRST.  Hospital length of stay (LOS) is typically a highly skewed outcome due to a 
relatively few patients having atypically long LOS.  Thus the WRST will also be used for a simple two-
group comparison and results reported in terms of median LOS.  Log-transformed LOS will be the 
dependent variable if regression analysis is needed for covariate adjustment. 
Randomization only guarantees homogeneous groups when randomizing a very large number of 
subjects.  Thus, preliminary comparison of the baseline characteristics of the usual care and study group 
will be performed to confirm that randomization did indeed produce similar groups with respect to 
demographics and initial cognitive status.  Any statistically significant (p < 0.05) differences that are also 
judged to be clinically meaningful will shift the analytical approach to an analysis of covariance using 
either parametric or non-parametric regression methods most appropriate to the specific outcome.  
We will also collect data on intraoperative variables including the average BIS and BP as well as 
the proportion of time that the BP and BIS is in the recommended range.  This information will be analyzed 
as a quality control measure to ensure compliance with the treatment protocol in the optimal care group.  


 
 
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Data for the treatment group (OP Care) will be analyzed after the first 5 patients and then after each 
additional 15 patients are treated to ensure compliance with the treatment protocol (BP and BIS in 
recommended range).  Patients will be followed daily during the hospitalization and charts reviewed to 
determine transfusion requirements and prevalence and types of postoperative complications.   
Power Analysis: The primary hypothesis states that optimized anesthesia care will decrease the severity of 
POD compared to usual care.  We expect that the severity score in the optimized group will be 14 ± 3 
versus 18 ± 4 in the usual care group similar to that seen in previous treatment studies.35 To have 80% 
power to detect such a difference when testing a two sided alternative and alpha of 0.05 will require 22 
subjects per group.  This is the number of subjects that qualify as confused.   Only patients with POD 
contribute to the DRS severity sample, so if 30% of subjects are expected to experience delirium, then the 
total sample size for the study would have to be 44/.3 = 148, or 74 per group. We plan to enroll 80 patients 
per group for a total sample size of 160.   
Interim Analysis:  There will be no interim analyses and no safety monitoring board so there are no early 
stopping rules. 
Data management 
The data collected on the data collection forms developed for this study, will be obtained 
specifically for research purposes.  Research data will be stored in a locked research office in the 
Department of Anesthesiology at the University Hospital.  All patient identifiable information will be 
stored in a locked file cabinet in this locked research office or stored on a secure server in this locked 
office.  Only research personnel listed on the IRB proposal will know the log in and password information 
for this server.  The demographic, hemodynamic, laboratory and historical data that are collected at the 
time of the intraoperative study are part of the routine medical record documenting the patient’s care in the 
perioperative period.  The patient’s identity will be specifically protected and confidentiality will be 
maintained in any publication of data.   
 
8. 
Risks 
 


 
 
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         This study will enroll 160 patients scheduled for surgery for repair of a hip fracture.  All subjects will 
have an injury requiring surgery and general anesthesia is routinely used at the University of Missouri-
Columbia for repair of a hip fracture. The anesthesia used in the protocol is routine care and does not add 
additional risk to the patients.  In the optimized care group, we will apply two additional monitors, a 
cerebral oximeter and a depth of anesthesia monitor.  Both of these monitors are non-invasive and FDA 
approved for use in the operating room so the additional risk of using these monitors is minimal.  Both 
devices use a bandage-like sensor applied to the forehead.  There are no reports of allergies or rashes from 
these sensors.   
          The Hip Fracture Improvement Team evaluates all patients who are admitted to the University 
Hospital with this type of injury and they will evaluate all of the patients in the study and adhere to the Hip 
Fracture Management Protocol in the perioperative period.  Thus, the perioperative care of the patient will 
be unchanged for patients enrolled in this study.     
          Elderly patients with hip fractures may have cognitive impairment and ensuring informed consent 
can be a challenge in this type of patients.  Patients will not be enrolled in the study if they are delirious 
when approached and will be excluded from the study if they exhibit significant cognitive impairment as 
evidenced by a score < 18 on the baseline MMSE.  However, inclusion of older adults with cognitive 
impairment in research studies in necessary because preoperative cognitive impairment is one of the 
primary risk factors for POD.32,31   We will request IRB approval to obtain consent from a legally 
authorized representative (as outlined in a Missouri statute) if a subject’s decision-making capacities are in 
question.  If the subject agrees to the research protocol, but we are unsure of his/her ability to fully 
understand the research, we will obtain additional informed consent from a family member or legal 
representative.   
           The baseline cognitive and functional tests and questionnaires are brief and are not adverse.  These 
tests, however, can be frustrating for older subjects.  To prevent this problem, the test battery is limited to 
approximately 15 min and we will ask the subject if he/she needs a break during testing.  We will also have 


 
 
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water, soda and snacks available for the subjects during testing.  If a subject wants to stop the testing at any 
time, we will not continue testing him/her. 
     There are always risks associated with the breach of a subject’s confidentiality.  To minimize this risk, 
research data will be stored in a locked research office in the Department of Anesthesiology at the 
University Hospital.  All patient identifiable information will be stored in a locked file cabinet in this 
locked research office or stored on a secure server in this locked office.  Only research personnel listed on 
the IRB proposal will know the log in and password information for this server.  The demographic, 
hemodynamic, laboratory and historical data that are collected at the time of the intraoperative study are 
part of the routine medical record documenting the patient’s care in the perioperative period.  The patient’s 
identity will be specifically protected and confidentiality will be maintained in any publication of data.   
9. 
Benefits 
 
          In general, the research procedures will not benefit the individual participant.  Subjects in both 
groups will be monitored closely and will receive the type of general anesthesia that would be used if they 
were not enrolled in the study.  It is possible that patients in the optimized anesthesia care group will have 
better outcomes, but this is not known. The primary benefit of this project is to society as a whole, from the 
new information that will be obtained regarding the role of optimized anesthesia care in preventing POD 
and improving postoperative outcomes. 
10. 
Payment and Remuneration 
 
      There will be no compensation or payments to participants in this study.  
 
11. 
Costs 
   
 
 
         The subjects in the study will not be responsible for any of the additional costs associated with the 
research procedures.  The additional costs in the study include the costs of the sensors for the BIS and Fore-
Sight monitors.  These sensors will be paid for by research funds in the Department of Anesthesiology at 
the University of Missouri.  Funding will be sought for analysis of the blood samples for the inflammatory 
response.  The blood samples will be stored until this funding is obtained. 
 
12. 
References 


 
 
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1. 
Marcantonio ER, Flacker JM, Wright RJ, Resnick NM: Reducing delirium after hip fracture: a 
randomized trial. J Am Geriatr Soc 2001; 49: 516-22 
 
2. 
Lundstrom M, Olofsson B, Stenvall M, Karlsson S, Nyberg L, Englund U, Borssen B, Svensson O, 
Gustafson Y: Postoperative delirium in old patients with femoral neck fracture: a randomized intervention 
study. Aging Clin Exp Res 2007; 19: 178-86 
 
3. 
Sieber FE, Zakriya KJ, Gottschalk A, Blute MR, Lee HB, Rosenberg PB, Mears SC: Sedation depth 
during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip 
fracture repair. Mayo Clin Proc 2010; 85: 18-26 
 
4. 
Palmbergen WA, van Sonderen A, Keyhan-Falsafi AM, Keunen RW, Wolterbeek R: Improved 
perioperative neurological monitoring of coronary artery bypass graft patients reduces the incidence of 
postoperative delirium: the Haga Brain Care Strategy. Interact Cardiovasc Thorac Surg 2012; 15: 671-7 
 
5. 
Chan MT, Cheng BC, Lee TM, Gin T, Group CT: BIS-guided anesthesia decreases postoperative 
delirium and cognitive decline. J Neurosurg Anesthesiol 2013; 25: 33-42 
 
6. 
Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD: Monitoring depth of 
anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative 
cognitive dysfunction. Br J Anaesth 2013; 110 Suppl 1: i98-105 
 
7. 
Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, 
Irwin B, Fox S: Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, 
prospective study. Anesth Analg 2007; 104: 51-8 
 
8. 
Rudolph JL, Marcantonio ER: Review articles: postoperative delirium: acute change with long-term 
implications. Anesth Analg 2011; 112: 1202-11 
 
9. 
Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK: One-year health care costs 
associated with delirium in the elderly population. Arch Intern Med 2008; 168: 27-32 
 
10. 
Franco K, Litaker D, Locala J, Bronson D: The cost of delirium in the surgical patient. 
Psychosomatics 2001; 42: 68-73 
 
11. 
Inouye SK, Charpentier PA: Precipitating factors for delirium in hospitalized elderly persons. 
Predictive model and interrelationship with baseline vulnerability. JAMA 1996; 275: 852-7 
 
12. 
Shim JJ, Leung JM: An update on delirium in the postoperative setting: prevention, diagnosis and 
management. Best Pract Res Clin Anaesthesiol 2012; 26: 327-43 
13. 
Bjorkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D: Reducing 
delirium in elderly patients with hip fracture: a multi-factorial intervention study. Acta Anaesthesiol Scand 
2010; 54: 678-88 
 
14. 
Zhang H, Lu Y, Liu M, Zou Z, Wang L, Xu FY, Shi XY: Strategies for prevention of postoperative 
delirium: a systematic review and meta-analysis of randomized trials. Crit Care 2013; 17: R47 
 
15. 
Neuman MD RP, Ludwig JM, Zubizarreta JR, Silber JH: Anesthesia technique, mortality and length 
of stay after hip fracture surgery. JAMA 2014; 311: 2508-2517 
 


 
 
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16. 
Whitlock EL, Torres BA, Lin N, Helsten DL, Nadelson MR, Mashour GA, Avidan MS: 
Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG-RECALL clinical trial. 
Anesth Analg 2014; 118: 809-17 
 
17. 
Murkin JM: Cerebral oximetry: monitoring the brain as the index organ. Anesthesiology 2011; 114: 
12-3 
 
18. 
Paarmann H, Heringlake M, Heinze H, Hanke T, Sier H, Karsten J, Schon J: Non-invasive cerebral 
oxygenation reflects mixed venous oxygen saturation during the varying haemodynamic conditions in 
patients undergoing transapical transcatheter aortic valve implantation. Interact Cardiovasc Thorac Surg 
2012; 14: 268-72 
 
19. 
Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe M, Berger KU: Preoperative regional 
cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: a 
prospective observational trial. Crit Care 2011; 15: R218 
 
20. 
Casati A, Fanelli G, Pietropaoli P, Proietti R, Tufano R, Montanini S, Collaborative Italian Study 
Group on Anaesthesia in Elderly P, Danelli G, Nuzzi M, Mentegazzi F, Torri G, Martani C, Spreafico E, 
Fierro G, Pugliese F, De Cosmo G, Aceto P, Servillo G, Monaco F: Monitoring cerebral oxygen saturation 
in elderly patients undergoing general abdominal surgery: a prospective cohort study. Eur J Anaesthesiol 
2007; 24: 59-65 
 
21. 
Williams-Russo P, Sharrock NE, Mattis S, Liguori GA, Mancuso C, Peterson MG, Hollenberg J, 
Ranawat C, Salvati E, Sculco T: Randomized trial of hypotensive epidural anesthesia in older adults. 
Anesthesiology 1999; 91: 926-35 
 
22. 
Hirsch J DG, Tsai TL, Sands LP, Leung JM: Intraoperative blood pressure variance, not 
hypotension impacts early postoperative delirium. Anesthesiology 2013: A3015 
 
23. 
Denault A, Deschamps A, Murkin JM: A proposed algorithm for the intraoperative use of cerebral 
near-infrared spectroscopy. Semin Cardiothorac Vasc Anesth 2007; 11: 274-81 
 
24. 
Folstein MF, Folstein SE, McHugh PR: "Mini-mental state". A practical method for grading the 
cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-98 
 
25. 
Spreen O SE: A compendium of neuropsychological tests, 2nd edition. New York, Oxford, Oxford 
University Press, 1998 
 
26. 
Bass DS, Attix DK, Phillips-Bute B, Monk TG: An efficient screening tool for preoperative 
depression: the Geriatric Depression Scale-Short Form. Anesth Analg 2008; 106: 805-9, table of contents 
 
27. 
George LK, Fillenbaum GG: OARS methodology. A decade of experience in geriatric assessment. J 
Am Geriatr Soc 1985; 33: 607-15 
 
28.  
Melin AA, Schmid KK, Lynch TG, et al. Preoperative frailty Risk Analysis Index to stratify patients undergoing 
carotid endarterectomy. Journal of vascular surgery. 2015;61:683-89. 
 
29.  
Hamilton GF, McDonald C, Chenier TC. Measurement of grip strength: validity and reliability of 
the sphygmomanometer and JAMAR grip dynamometer. JOSPT 1992; 16: 215-19 
 
30. 
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI: Clarifying confusion: the 
confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990; 113: 941-8 


 
 
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Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N: Validation of the Delirium 
Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J 
Neuropsychiatry Clin Neurosci 2001; 13: 229-42 
 
32. 
Greene NH, Attix DK, Weldon BC, Smith PJ, McDonagh DL, Monk TG: Measures of executive 
function and depression identify patients at risk for postoperative delirium. Anesthesiology 2009; 110: 788-
95 
 
33. 
Smith PJ, Attix DK, Weldon BC, Greene NH, Monk TG: Executive function and depression as 
independent risk factors for postoperative delirium. Anesthesiology 2009; 110: 781-7 
 
 
 
 
 
 

ICF_001.pdf: 
 
 
 
 
MU IRB: CONSENT  
 
 
 
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HS IRB USE ONLY 
Approval Date: 11/15/2017 
Expiration Date: 12/10/2018 
 
CONSENT FORM TO PARTICIPATE IN A RESEARCH STUDY 
 
INVESTIGATOR’S NAME:  QUINN JOHNSON, MD 
 
 
PROJECT # 1212915 
 
STUDY TITLE:  
DOES OPTIMIZED GENERAL ANESTHESIA CARE REDUCE POSTOPERATIVE 
DELIRIUM IN OLDER ADULTS UNDERGOING HIP FRACTURE REPAIR? 
 
 
 
 
 
 
INTRODUCTION 
This consent may contain words that you do not understand.  Please ask the investigator or the 
study staff to explain any words or information that you do not clearly understand. 
 
This is a research study.  Research studies include only people who choose to participate.  As a study 
participant you have the right to know about the procedures that will be used in this research study so that 
you can make the decision whether or not to participate.  The information presented here is simply an 
effort to make you better informed so that you may give or withhold your consent to participate in this 
research study.   
 
Please take your time to make your decision and discuss it with your family and friends. 
 
You are being asked to take part in this study because you have A HIP FRACTURE THAT REQUIRES SURGERY 
UNDER GENERAL ANESTHESIA AND YOU ARE 65 YEARS OR OLDER.  
 
This study is being sponsored by the Anesthesia Patient Safety Foundation. 
In order to participate in this study, it will be necessary to give your written consent. 
 
 
WHY IS THIS STUDY BEING DONE? 
The purpose of this study is to determine if careful management of blood pressure, oxygen levels in the 
brain, and the amount of general anesthesia during surgery decreases mental confusion and improves 
recovery after surgery.   
 
We are going to compare the effects (good and bad) of the strict control of blood pressure, the amount of 
anesthesia, and oxygen levels in the brain during general anesthesia for hip fracture surgery.  We will 
compare general anesthesia administered in the normal way with general anesthesia administered using 
two monitors to adjust the amount of anesthesia and oxygen in the brain to see which is better.  This 
research is being done because these two monitors are not routinely used during hip fracture surgery and 
we are trying to determine if patients will do better after surgery if these two monitors are used.   
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
We plan to enroll 250 patients to ensure that 160 patients will complete this entire study at the University 
Hospital at the University of Missouri. 


 
 
 
 
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Expiration Date: 12/10/2018 
 
WHAT IS INVOLVED IN THE STUDY? 
If you agree to be in the study, you will receive the same medical care before and after surgery.   
If you have a high score on the memory test prior to surgery, you will be “randomized” into one of the 
two study groups described below on the day of surgery.  Randomization means that you are put into a 
group by chance.  It is like flipping a coin.  Neither you nor the researcher will choose what group you 
will be in.  You will have an equal chance of being placed in any group.  The two study groups are: 
 
● Routine care group – you will receive general anesthesia during surgery and the amount of anesthesia 
you are given will be determined by the anesthesia provider using your blood pressure and heart rate to 
adjust the anesthesia during the surgery. 
 
● Study care group – you will receive general anesthesia during surgery using the same medications as in 
the routine care group.  Two monitors will be used to measure the amount of anesthesia being given and 
the amount of oxygen in the brain during surgery.  These monitors will be used to determine the amount 
of anesthesia and oxygen you are given during surgery.   Your blood pressure will also be kept within 20 
percent of its preoperative level. 
 
If you enroll in the study but do not have a high score on the memory test prior to surgery, you will not be 
randomized to a study group.  You will have the same type of anesthesia that will be used in both study 
groups and the amount of anesthesia given will be determined by the anesthesia provider taking care of 
you in the operating room. 
 
If you do not enroll in the study, you will have the same type of anesthesia that will be given in both study 
groups and the amount of anesthesia given will be determined by the anesthesia provider taking care of 
you in the operating room. 
 
  
If you take part in this study, you will have the following tests and procedures: 
 
●  a short memory test prior to surgery - this memory test will take about 15 minutes. 
 
●  a short questionnaire to determine what you can do at home and if you are depressed – these 
questionnaires will take about 5 minutes 
 
● a short questionnaire to review your medical history and activities at home 
 
● a measurement of your grip strength in your dominant hand 
 
● a daily visit by the research team after surgery to determine if you are confused 
 
● a telephone call at 3 months and 1 year after surgery to find out how you are doing 
 
If you are in the study care group, you will have two additional monitors used in surgery 
 
●  a Band-Aid type sticker placed on your forehead during surgery to measure the amount of anesthesia 
you are receiving.  The amount of anesthesia will be adjusted using this monitor. 
 


 
 
 
 
MU IRB: CONSENT  
 
 
 
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Approval Date: 11/15/2017 
Expiration Date: 12/10/2018 
●   a Band-Aid type of sticker placed on your forehead during surgery to measure the amount of oxygen 
in your brain.  The anesthesia will be adjusted to keep the oxygen level in your brain at the same level that 
it was at prior to surgery. 
 
HOW LONG WILL I BE IN THE STUDY? 
We think you will be in the study for the entire time you are in the hospital.  After you leave the hospital, 
we will call you at 3 months and 1 year after surgery to find out how you are doing. 
Furthermore, we would greatly appreciate being able to contact you in the future about other studies by 
our research team. 
 
□  Do you agree to allow us to contact you in the future about our next study? 
 
 
The investigator and/or your doctor may decide to take you off this study if you become confused before 
you have surgery to repair the hip fracture.   
 
You can stop participating at any time.  Your decision to withdraw from the study will not affect in 
any way your medical care and/or benefits.   If you decide to stop participating in the study, you are 
encouraged to discuss your decision with your doctor.  There are no consequences of withdrawing 
from the study.   
 
WHAT ARE THE RISKS OF THE STUDY? 
While on the study, you are at risk for the side effects described below.  You should discuss these with the 
investigator and/or your doctor.  There may also be other side effects that we cannot predict.   
 
The risks associated with the procedures or monitors used in this study are not very likely but include: 
 
● Performing the questionnaires and memory tests for the study will require approximately 15 to 20 
minutes of your time at each of the three visits for these exams.  While performing these questionnaires 
and memory exams, you may become frustrated or tired.  The research person giving these tests will assist 
you in completing them.  You may also ask for a break during this time if you need to rest before 
completing all of the exams.   
 
● If you are in the group that has the monitors placed on your forehead, it is possible that you could 
develop a rash, but this has never been reported with these monitors. 
 
For the reasons stated above the investigator will observe you closely while giving the treatment described 
and, if you have any worrisome symptoms or symptoms that the investigator or his associates have described 
to you, notify the investigator immediately.  Dr. Johnson’s telephone number is (573)-882-2568.  For more 
information about risks and side effects, ask the investigator or contact Dr. Johnson at (573)-882-2568. 
 
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
There is no direct medical benefit to you for participating in this study; however, you will be contributing 
to medical knowledge.  We hope the information learned from this study will benefit other patients who 
need general anesthesia for their surgery in the future. 


 
 
 
 
MU IRB: CONSENT  
 
 
 
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Approval Date: 11/15/2017 
Expiration Date: 12/10/2018 
 
There is no guarantee that taking part in this research will result in any improvement in your condition. 
 
WHAT OTHER OPTIONS ARE THERE? 
Instead of being in this study, you have these options: 
An alternative is to not participate in this research study.  You can have your hip fracture repaired using 
general or spinal anesthesia. You will receive the best medical care possible even if you are not in the 
study.  Please discuss these and other options with the investigator and your doctor. 
 
WHAT ABOUT CONFIDENTIALITY? 
A copy of this consent will be placed in the medical record.  Anyone accessing your record will be able to 
view the document and see that you have agreed to participate in the study.  Medical information 
produced by this study will become part of your hospital medical record.  Information that does not 
become part of your medical record will be stored in the investigator’s file and identified by a code 
number only.  The code key connecting your name to specific information about you will be kept in a 
separate, secure location.  Information contained in your records may not be given to anyone unaffiliated 
with the University Hospital in a form that could identify you without your written consent, except as 
required by law.  If the investigator conducting this study is not your primary, or regular doctor, the 
investigator must obtain your permission before contacting your regular doctor for information about your 
past medical history or to inform them that you are in this trial. 
 
It is possible that your medical and/or research record, including sensitive information and/or identifying 
information, may be inspected and/or copied by the study sponsor (and/or its agent), the Food and Drug 
Administration (FDA), federal or state government agencies, or hospital accrediting agencies, in the 
course of carrying out their duties.  If your record is inspected or copied by the study sponsor (and/or its 
agents), or by any of these agencies, the University Hospital will use reasonable efforts to protect your 
privacy and the confidentiality of your medical information. 
 
The results of this study may be published in a medical book or journal or used for teaching purposes.  
However, your name or other identifying information will not be used in any publication or teaching 
materials without your specific permission.   
 
WHAT ARE THE COSTS? 
There is no cost to you for your involvement in the study itself.  However, you will be paying for the 
normal cost of anesthesia and surgery for repair of your hip fracture and your routine medical care.  Any 
procedure related solely to research that would not otherwise be necessary will be explained.  Some of 
these procedures may result in added costs and the additional costs will be paid with research funds. 
 
You will not be charged for the memory tests that are part of this research study.  You or your insurance 
company will, however, be charged for any other portion of your care that is considered standard care.   
 
You or your insurance company will be charged for continuing medical care and/or hospitalization. 
 
WILL I BE PAID FOR PARTICIPATING IN THE STUDY? 
You will receive no payment for taking part in this study. 


 
 
 
 
MU IRB: CONSENT  
 
 
 
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HS IRB USE ONLY 
Approval Date: 11/15/2017 
Expiration Date: 12/10/2018 
 
WHAT IF I AM INJURED? 
It is not the policy of the University of Missouri to compensate human subjects in the event the research 
results in injury.  The University of Missouri, in fulfilling its public responsibility, has provided medical, 
professional and general liability insurance coverage for any injury in the event such injury is caused by the 
negligence of the University of Missouri, its faculty and staff.  The University of Missouri also will provide, 
within the limitations of the laws of the State of Missouri, facilities and medical attention to subjects who 
suffer injuries while participating in the research projects of the University of Missouri.  In the event you 
have suffered injury as the result of participation in this research program, you are to contact the Risk 
Management Officer, telephone number (573) 882-1181, at the Health Sciences Center, who can review the 
matter and provide further information.  This statement is not to be construed as an admission of liability. 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
Participation in this study is voluntary.  You do not have to participate in this study.  Your present 
or future care will not be affected should you choose not to participate.  If you decide to participate, 
you can change your mind and drop out of the study at any time without affecting your present or future 
care in the University Hospital at the University of Missouri.  Leaving the study will not result in any 
penalty or loss of benefits to which you are entitled.  In addition, the investigator of this study may decide 
to end your participation in this study at any time after he has explained the reasons for doing so and has 
helped arrange for your continued care by your own doctor, if needed.   
 
You will be informed of any significant new findings discovered during the course of this study that 
might influence your health, welfare, or willingness to continue participation in this study.  
 
“A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. law. 
This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time.” 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
If you have any questions regarding your rights as a participant in this research and/or concerns about the 
study, or if you feel under any pressure to enroll or to continue to participate in this study, you may 
contact the University of Missouri Institutional Review Board (which is a group of people who review the 
research studies to protect participants’ rights) at (573) 882-3181.   
 
You may ask more questions about the study at any time.  For questions about the study or a research-
related injury, contact Dr. Quinn Johnson at (573)-882-2568. 
 
A copy of this consent form will be given to you to keep. 
 
 


 
 
 
 
MU IRB: CONSENT  
 
 
 
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HS IRB USE ONLY 
Approval Date: 11/15/2017 
Expiration Date: 12/10/2018 
SIGNATURE 
 
I confirm that the purpose of the research, the study procedures, the possible risks and discomforts as well 
as potential benefits that I may experience have been explained to me.  Alternatives to my participation in 
the study also have been discussed.  I have read this consent form and my questions have been answered.  
My signature below indicates my willingness to participate in this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject/Patient* 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Legal Guardian/Advocate/Witness (if required)**  
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional Signature (if required) (identify relationship to subject)*** 
Date 
 
*A minor’s signature on this line indicates his/her assent to participate in this study.  A minor’s signature is not 
required if he/she is under 7 years old.  Use the “Legal Guardian/Advocate/Witness” line for the parent’s signature, 
and you may use the "Additional Signature" line for the second parent’s signature, if required. 
 
**The presence and signature of an impartial witness is required during the entire informed consent discussion if 
the patient or patient’s legally authorized representative is unable to read.   
 
***The "Additional Signature" line may be used for the second parent’s signature, if required.  This line may also 
be used for any other signature which is required as per federal, state, local, sponsor and/or any other entity 
requirements. 
 
“If required” means that the signature line is signed only if it is required as per federal, state, local, sponsor and/or 
any other entity requirements. 
 
 
SIGNATURE OF STUDY REPRESENTATIVE 
I have explained the purpose of the research, the study procedures, identifying those that are 
investigational, the possible risks and discomforts as well as potential benefits and have answered 
questions regarding the study to the best of my ability. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Representative**** 
 
 
 
 
 
Date 
 
****Study Representative is a person authorized to obtain consent.  Per the policies of the University of Missouri 
Health Care, for any 'significant risk/treatment' study, the Study Representative must be a physician who is either 
the Principal or Co-Investigator.  If the study is deemed either 'significant risk/non-treatment' or 'minimal risk,' the 
Study Representative may be a non-physician study investigator.   


 
 
 
 
MU IRB: CONSENT  
 
 
 
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HS IRB USE ONLY 
Approval Date: 11/15/2017 
Expiration Date: 12/10/2018 
IF THE PATIENT IS INCOMPETENT TO GIVE CONSENT, COMPLETE THE FOLLOWING: 
 
I,                                                            , hereby certify that I am                                 
 
 
 
 
 
 
 
 
 
 
 
 
(Relationship to Patient) 
of               
 
                              and duly authorized to execute the foregoing. 
 
(Name of Patient) 
 
I consent to the     research study, experimental treatment, test, drug, etc.     as described in the attached 
consent form.  
 
 
 
 
 
 
 
 
 
___________________________ 
Legal Guardian/Patient Representative           
 
Date 
 
 
 
 
 
 
 
 
 
___________________________ 
Study Representative* 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
___________________________ 
Witness (if required)** 
 
 
 
 
Date    
 
*Study Representative is a person authorized to obtain consent.  Per the policies of the University of Missouri 
Health Care, for any 'significant risk/treatment' study, the study representative must be a physician who is either the 
Principal or Co-Investigator.  If the study is deemed either 'significant risk/non-treatment' or 'minimal risk,' the 
study representative may be a non-physician study investigator.   
 
**Regulations do not require the signature of a witness when the patient or patient’s legally authorized 
representative is able to read and is capable of understanding the consent form document. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
THE FOLLOWING REGULATION ONLY APPLIES WHEN AN ADULT PERSON, BECAUSE OF A MEDICAL CONDITION, IS 
TREATED AT A TEACHING HOSPITAL FOR A MEDICAL SCHOOL ACCREDITED BY THE AMERICAN OSTEOPATHIC 
ASSOCIATION OR THE AMERICAN MEDICAL ASSOCIATION AND SUCH PERSON IS INCAPABLE OF GIVING INFORMED 
CONSENT.   
 
Persons authorized to consent when a patient is incapable of consenting to an experimental treatment, test or drug. 
 
1. 
Legal guardian or 
 
2. 
Attorney in fact (person appointed by durable power of attorney) or 
 
3. 
A family member in the following order of priority: 
 
 
a. 
Spouse unless the patient has no spouse, or is separated, or the spouse is physically or 
mentally incapable of giving consent, or the spouse's whereabouts is unknown or the 
spouse is overseas; 
 
 
b. 
Adult child; 
 
 
c. 
Parent; 
 
 
d. 
Brother or sister; 
 
 
e. 
Relative by blood or marriage. 
 
Such legal guardian, attorney in fact, or family member is not authorized to consent to treatment in contravention to 
such incapacitated person's expressed permission regarding such treatment. 
 
If the patient is competent to consent but cannot write, do not use this proxy consent form.  Please contact the IRB 
for directions in this situation.