Medical Student Research Fellowship for Summer 2007
Mentor: Babatunde Ogunnaike, MD
Department: Anesthesiology and Pain Management
Room number: A 33
Mail Code: 9068
Phone number: 214 590 8536
E-mail: babatunde.ogunnaike@utsouthwestern.edu
Project I title: Effects of Oral Pregabalin versus Placebo on Postoperative
Pain and Morphine Consumption after Mastectomy
Human subjects IRB approved project number (where applicable): 022006-010
Animal subjects IRB approved project number (where applicable):
Project Type: Patient-based
Brief Description of Project:
Eighty female patients between the ages of 18 and 70 with ASA physical status
I to III and undergoing unilateral mastectomy are enrolled in this study. Patients
with known allergy to pregabalin or morphine and those unable to cooperate are
excluded. Also patients with a history of drug or alcohol abuse, chronic pain
or history of daily intake of analgesics or steroids, and those with diabetes
or impaired kidney function are all excluded. Oral pregabalin 300mg (or placebo)
will be administered to all patients 1-2 hours before surgery followed by 150mg
(or placebo) 12 hours later. Thereafter, 150mg of oral pregabalin (or placebo)
will be administered twice daily until day 14. Patients will then be followed-up
for 3 months during which time they will be visited while still in the hospital
or contacted by telephone at home. This study will require 1 visit after the
operation while still in hospital, and subsequent visits in clinic on day 7,
14, 30 and 90. Anesthetic technique will be a standardized general anesthetic.
All patients will receive intravenous (IV) patient controlled analgesia (PCA)
morphine as rescue pain medication in the immediate postoperative period while
oral opioids will be administered for this purpose after discontinuation of
IV-PCA. Patient follow-up and pain assessments will begin on postoperative day
1 to contiune daily for 7 days and will be repeated on days 14, 30, and 90 during
which time patients are contacted by telephone and asked to keep a diary.
Past and present medical history, current medications and side effects, demographic
information (age, sex, weight, and height), and a physical examination will
be performed including vital signs (heart rate, blood pressure, respiration).
Also pain scores (VAS and categorical), morphine consumption (IV-PCA and oral
opioid dosage), side effects, adverse effects and patient activity will all
be monitored prior to discharge from hospital and subsequently during follow-up.
Laboratory tests including hematology and chemistry analysis will be performed
perioperatively to rule out patients with significant coexisting diseases that
will not be eligible for the study. A serum or urine pregnancy test will be
done to exclude pregnant women from the study. Approximately 20-30 ml of blood
will be collected preoperatively.
Project II title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Two Arm Parallel, Multicenter Study Evaluating the Efficacy and Safety of Dexmedetomidine in the Prevention of Postoperative Delirium in Subjects Undergoing Surgery for Fractured Hip with General Anesthesia
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable):
Project Type: Patient-based
Brief Description of Project:
This is a phase III, randomized, double-blind, placebo-controlled, two-arm parallel,
multicenter study. An estimated 310 subjects (155 in each of the two treatment
groups: DEX and Placebo) will be enrolled at approximately 35 investigative
sites. Subjects undergoing hip fracture surgery with general anesthesia will
be screened for eligibility to participate in the study. Subjects must be screened
and randomized within 3 days of hospital admission for hip fracture. Eligible
subjects will be randomized to one of the two treatment groups in a 1:1 ratio
to receive either DEX or matching placebo (PBO; 0.9% sodium chloride). The study
drug will be given via continuous intravenous (IV) infusion beginning prior
to anesthesia induction and ending two hours after arrival in the Post Anesthesia
Care Unit (PACU). The initial dose will be fixed at 0.4 mcg/kg/hr DEX (or matching
placebo) prior to and during surgery. Upon arrival in the PACU the dose will
be titrated from 0.2 to1.4 mcg/kg/hr DEX (or matching placebo) to maintain Richmond
Agitation and Sedation Scale (RASS) between -2 to +1. Study drug will be discontinued
two hours after arrival in the PACU. At least 15 minutes after starting the
study drug infusion, a RASS score will be obtained. Rescue midazolam will be
given for sedation if RASS >0 at this time. Once a RASS score of <0 has
been obtained, induction of anesthesia will be performed, and the surgery will
commence.
During the Intraoperative Period rescue fentanyl will be given if systolic blood
pressure (SBP) or and/or heart rate (HR) increase in response to painful stimuli
to >20% of the baseline values at allowed maximum end-tidal concentration
of sevoflurane (2%). While in the PACU, all subjects who do not have adequate
pain control will receive rescue fentanyl as indicated by a Numeric Pain Rating
Scale (NPRS) score ? 4 or upon subjects' request. After study drug infusion
has been completed, the presence of postoperative delirium will be assessed
using the Confusion Assessment Method for the ICU (CAM-ICU). The CAM-ICU will
be administered postoperatively twice daily, in the morning between 6:00-9:00
AM and in the evening between 5:00-8:00 PM, for 72 hours after the end of study
drug infusion. The first CAM-ICU assessment will not be performed less than
4 hours after study drug has been discontinued. Therefore, subjects whose study
drug was discontinued after 4:00 PM must have their first scheduled CAM-ICU
performed the following morning between 6:00-9:00 AM. Subjects whose study drug
was discontinued prior to 4:00 PM should have their first scheduled CAM-ICU
performed later that same day (at least four hours after study drug was stopped,
but no later than 8:00 PM).
Standard protocol-defined environmental and supportive interventions (e.g. placement
of a calendar and large-face clock within sight of the subject, provision of
hearing aids and/or glasses as needed) will be employed during the 72-Hour Follow-up
Period by all study sites. Other study-specific assessments will be performed
during the study drug infusion period (Pre- and Intraoperative Periods and PACU
Period), the 72-Hour Follow-up Period post end of study drug infusion, at Hospital
Discharge, and Day 30 after the end of study drug infusion.
Project III title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Pregabalin in the Treatment of Subjects with Post-operative Pain Following Total Knee Arthroplasty (TKA)
Human subjects IRB approved project number (where applicable): 032007-019
Animal subjects IRB approved project number (where applicable):
Project Type: Patient-based
Brief Description of Project:
This study is being conducted to investigate the benefits of pregabalin in treating
postoperative pain after total knee replacement. In addition, pregabalin treatment
will be evaluated during the rehabilitative and physical therapy phase. It will
compare the effects of oral pregabalin with placebo on postoperative pain after
Total Knee Arthroplasty. Pregabalin is an anticonvulsant agent approved by the
United States Food and Drug Administration (FDA) for the treatment of neuropathic
pain associated with post-herpetic neuralgia and diabetic neuropathy.
Fifty patients between 18 and 80 years of age will be recruited to participate
in the study. Those with known allergy to pregabalin and those with a history
of alcohol abuse, chronic pain, history of daily intake of analgesics or steroids,
and patients with a hostory of malignancy, inflammatory arthritides, lyme disease,
fibromyalgia, neurologucal disorder will be excluded from the study. Blood tests
will be performed before surgery to determine if a patient qualifies for enrollment
in the study. A pregnancy test will also be performed to exclude pregnant women
from the study. About 20 to 30 ml of blood will be collected for the tests.
All treatments of either Pregablin 150mg, 75mg or palcebo will start pre-operatively
(with 2 single doses at approximately 12 and 2 hours pre-surgery) and continue
twice a day for up to 6 weeks post-surgery. The study duration will be approximately
6 months:
· 1-2 week screening,
· A baseline visit 1-2 weeks prior to surgery,
· 2 to 6 weeks of post-operative dosing period including 3-5 days post
operative hospitalization
· 1-week taper.
· Post discharge, site visits will occur on post-op weeks 2, 4, 6 and
7 (post taper) and phone call follow-up will be done at 3 and 6 months.
Subjects will be washed out of any prohibited medication, including NSAIDs and
COX-2 selective inhibitors.
Anesthesia will be provided by epidural, spinal, or combined spinal/epidural
analgesia with local anesthetic and hydromorphone or fentanyl. The use of peripheral
nerve block is also allowed for the first 36 hours post-surgery. At 36 hours
post-op, continuous infusion of peripheral nerve blocks/neuroaxial blocks should
be removed and patients switched to oral analgesia
An institutionally defined rehabilitation protocol for total knee arthroplasty
will be initiated immediately post surgery under the supervision of a physical
medicine and rehabilitation investigator or physical therapist. All physical
therapy protocols should be applied at least once daily during the hospital
stay and 3 times weekly for at least 4 weeks post-discharge.
Potential adverse effects of pregabalin include dizziness, somnolence, peripheral
edema, weight gain, headache, dry mouth, blurry vision, and ataxia. The incidence
of these side effects has been reported on 10% (10 in 100) or more participants.
Investigators will closely monitor all patients for the occurrence of these
side effects.
Previous Research Activities or Publications with Medical Students:
1. White PF, Sacan O, Tufanogullari, Eng M, Nuangchamnong N, Ogunnaike B. Effect
of short-term postoperative celecoxib administration on patient outcome after
outpatient laparoscopic surgery. Can J Anesth 2007 (in press)
2. Recart A, Gasanova I, White PF, Thomas T, Ogunnaike B, Hamza M, Wang A: Effect
of cerebral monitoring on recovery after general anesthesia: comparison of AEP
vs BIS devices vs standard clinical practice. Anesth Analg 2003; 97: 1667-74.
3. Coloma M, White PF, Ogunnaike BO, Markowitz SD, Brown PM, Lee AQ, Berrisford
SB, Wakefield CA, Issioui T, Jones SB, Jones DB,: Comparison of acustimulation
and ondansetron for the treatment of established postoperative nausea and vomiting.
Anesthesiology 2002: 97:1387-92.
4. White PF, Tang J, Hamza MA, Ogunnaike B, Lo M, Wender RH, Naruse R, Sloninsky
A, Kariger R. The use of oral granisetron versus intravenous ondansetron for
antiemetic prophylaxis in patients undergoing laparoscopic surgery: the effect
on emetic symptoms and quality of recovery. Anesth Analg 2006; 102: 1387-93.
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