2004project61White

Request for Funding

Medical Student Research Fellowship for Summer 2004

Mentor: Kendall Tongier, MD/Paul F. White, PhD, MD
Department: Anesthesiology & Pain Management
Room number: PM
Mail Code: 9068
Phone number: 214-590-7278
E-mail: dolly.tutton@utsouthwestern.edu

Four Projects

Project title: Multi-center, double-blind, randomized, placebo-controlled, multiple dose study of the analgesic efficacy and safety of acetaminophen injection 1 g vs placebo for pain following primary total hip arthroplasty

Human subjects IRB approved project number (where applicable): 1203-759

Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): Patient-based research

Brief Description of Project:

The efficacy of intravenously (IV) acetaminophen has been tested in two clinical trials in Europe, namely dental (oral) surgery and hip/knee replacement surgery. Results from these studies showed that IV acetaminophen was an effective pain reliever. In addition, the orthopedic study demonstrated a significantly reduced morphine consumption for subjects taking acetaminophen compared to placebo. There were no unexpected adverse events observed and the general safety profile was similar to that seen with oral acetaminophen.

This is a Phase III, multi-center, double-blind, randomized, placebo controlled study conducted in 200 subjects (100 per group) who will undergo elective primary total unilateral hip or knee arthroplasty. Patients will receive multiple doses of IV acetaminophen (or saline) in the postoperative period as an adjunct to patient-controlled analgesia (PCA) with morphine.

Mentor: Babatunde Ogunnaike/Paul F. White, PhD, MD
Department: Anesthesiology & Pain Management
Room number: F2.208
Mail Code: 9068
Phone number: 214-648-6424
E-mail: dolly.tutton@utsouthwestern.edu
Project title: A randomized, double-blind active comparator-controlled, parallel-group study conducted under in-house blinding conditions, to examine the safety, tolerability, and efficacy of two doses of aprepitant (Emend ) for the prevention of postoperative nausea and vomiting

Human subjects IRB approved project number (where applicable): 1003-602

Animal subjects IRB approved project number (where applicable): N/A

Brief Description of Project:

Postoperative nausea and vomiting (PONV) are among the most frequent complications of surgery. The most commonly used antiemetic for prophylaxis of PONV is a 5-HT3-receptor antagonist administered intravenous (IV) (e.g., ondansetron [Zofran ]). Despite prophylactic treatment with a 5-HT3-receptor antagonist, 30-40% of the high-risk patients continue to experience nausea or vomiting during the first 24 hours after surgery. Hence, there is a need for new therapies with broader antiemetic efficacy. Aprepitant (Emend ) is NK-1 receptor (brain stem) antagonist which has been shown to have potent, and usually long-lasting, antiemetic activity against a broad spectrum of both central and peripheral emetogens. It is currently approved for the treatment and prevention of chemotherapy-induced nausea and vomiting.

This study is designed to compare two doses of oral aprepitant (125 mg and 40 mg) with one dose of ondansetron (4 mg IV) with respect to their antiemetic efficacy and safety in patients undergoing "open" abdominal surgery.

Request for Funding
Medical Student Research Fellowship for Summer 2004

Mentor: Paul F. White, PhD, MD
Department: Anesthesiology & Pain Management
Room number: CS02.202
Mail Code: 9068
Phone number: 214-648-6424
E-mail: dolly.tutton@utsouthwestern.edu
Project title: Two prospective, randomized, double-blinded, placebo-controlled studies were designed to evaluate the pre-emptive analgesic efficacy of oral celecoxib (Celebrex ) and rofecoxib (Vioxx™) in patients undergoing elective surgery procedures

Human subjects IRB approved project number (where applicable): 0502-279 (Rofecoxib)
1003-629 (Celecoxib)

Animal subjects IRB approved project number (where applicable): N/A

Brief Description of Project:

The nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for treating non-surgically related pain because of their well-known antiinflammatory, antipyretic and analgesic properties. With the introduction of parenteral NSAIDs (e.g., ketorolac, diclofenac), these drugs have become more popular in the management of pain associated with surgery. Early reports suggested that NSAIDs possessed analgesic properties comparable to opioid analgesics without opioid-related side effects. However, concerns have been raised regarding operative site bleeding and gastrointestinal and renal complications associated with the use of the classical, non-selective NSAIDs. In an effort to minimize the potential for the side effects associated with the traditional NSAIDs, more specific COX-2 inhibitors are postoperatively increasingly being utilized as non-opioid adjuvants for minimizing pain during the perioperative period. The early clinical studies evaluated the use of celecoxib and rofecoxib for preventative analgesia when administered for oral premedication. Further studies are in indicated to evaluate these COX-2 inhibitor analgesics with respect to their efficacy and safety when administered both preoperatively and postoperatively as an adjuvant to current standard opioid analgesic therapy.

The purpose of this study is to evaluate the preemptive pain-relieving effects of oral celecoxib (Celebrex®) or rofecoxib (Vioxx®) when given before and after surgery (for up to 3 days) on the patient's recovery profile and surgical outcome. Specific endpoints will include pain control, recovery of bowel and bladder function, resumption of normal physical activities and patient satisfaction with their recovery from surgery.

Request for Funding
Medical Student Research Fellowship for Summer 2004

Mentor: Louis Stool, MD/Paul F. White, PhD, MD
Department: Anesthesiology & Pain Management
Room number: CS02.116
Mail Code: 9068
Phone number: 214-648-7818
E-mail: dolly.tutton@utsouthwestern.edu
Project title: A randomized, double-blind, controlled study of nicardipine (Cardene ) infusion for improving control acute autonomic response during surgery

Human subjects IRB approved project number (where applicable): 1003-598

Animal subjects IRB approved project number (where applicable): N/A

Brief Description of Project:

Nicardipine (Cardene ), a dihydropyridine calcium antagonist was introduced into clinical practice for use by intravenous (IV) infusion. Previous studies have shown the effects of nicardipine IV bolus on controlling hemodynamic response during surgical procedures. When administered IV bolus 1 mg, 2 min before tracheal intubation, nicardipine was found to maintain hemodynamic stability during the intraoperative period. Another study indicated that nicardipine 2.5 mg IV bolus in combination with labetolol 10 mg IV was the most effective pretreatment regimen for preventing the acute hyperdynamic response to electroconvulsive therapy. Nicardipine IV infusion was equally effective to sodium nitroprusside in the therapy of postoperative hypertension. However, the optimal infusion rate of nicardipine during surgery has not been studied.

We propose to study the effect of four different nicardipine infusion rates (1.25 mg/hr, 2.5 mg/hr, 5 mg/hr and 10 mg/hr vs placebo [saline]) during surgery for providing intraoperative hemodynamic stability and facilitating recovery in patients under general anesthesia.

Previous Research Activities or Publications with Medical Students:

Song D, Singh H, White PF, Gadhiali M, Griffin, JD, Klein KW: Optimal dose of nicardipine for maintenance of hemodynamic stability after tracheal intubation and skin incision. Anesth Analg 1997; 85: 1247-51.

Song D, Heise DA, White PF: Facial electromyography correlates with the level of sedation and pain in outpatients undergoing lithotripsy. Anesthesiology 1998; 89: A928.

Fredman B, d'Etienne BA, Taylor E, Smith I, White PF: Use of low-dose propofol vs methohexital for electroconvulsive therapy. Anesth Analg 1994; 78: S120.

Zarate E, Watcha MF, White PF, Klein KW, Sá Rêgo M, Stewart DG: A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis. Anesth Analg 2000 90: 1352-8.

Shao X, Li H, White PF, Klein KW, Kulstad C, Owens A: Bisulfite-containing propofol: is it a cost-effective alternative to Diprivan for induction of anesthesia?. Anesth Analg 2000; 91: 871-5.

Coloma M, Markowitz SD, White PF, Whitten CW, Berrisford SB: Effect of dexamethasone on the prophylactic antiemetic activity of dolasetron. Anesthesiology 2001; 95: A-40.

Kadar AG, Ing CH, White PF, Wakefield CA, Kramer BA, Clark K: Anesthesia for electroconvulsive therapy in obese patients. Anesth Analg 2002; 94: 360-1.

Issioui T, Klein KW, White PF, Watcha MF, Skrivanek GD, Jones SB, Hu J, Marple BF, Ing C: Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. Anesthesiology 2002; 97: 931-7.

Coloma M, White PF, Markowitz SD, Whitten CW, Macaluso A, Berrisford S, Thornton K: Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting: effect on outcome after laparoscopic cholecystectomy. Anesthesiology 2002; 97: 1387-92.

White PF, Issioui T, Hu J, Jones SB, Coleman JE, Waddle JP, Markowitz SD, Coloma M, Macalusco AD, Ing CH: Comparative efficacy of acustimulation (ReliefBand ) and ondansetron (Zofran ) in combination with droperidol for preventing nausea and vomiting. Anesthesiology 2002; 97: 1075-81.

Coloma M, White PF, Ogunnaike BO, Markowitz SD, Brown PM, Lee AQ, Berrisford SB, Wakefield CA, Jones SB, Jones DB: Comparison of acustimulation and ondansetron for the treatment of established postoperative nausea and vomiting. Anesthesiology 2002; 97: 1387-92.

Issioui S, Jones B, White PF, Hu J, Rawal S, Ing C: Comparative efficacy of ondansetron and the Reliefband for antiemetic prophylaxis in outpatients undergoing plastic surgery. Anesth Analg 2002; 94: S3.
Issioui T, Klein KW, White PF, Rawal S, Skrivanek GD, Ing C: Comparison of ibuprofen, celecoxib and rofecoxib as premedication prior to outpatient orthopedic surgery. Anesth Analg 2002; 94: S4.
Coloma M, White PF, Markowitz SD, Jones SB, Wakefield CA, Berrisford SB: Comparison of the acustimulation ReliefBand device to ondansetron for treatment of PONV after ambulatory surgery. Anesth Analg 2002; 94: S12.

Coloma M, Ogunnaike BO, White PF, Lee AQ, Brown PM, Wakefield CA: Comparative analgesic efficacy of ibuprofen, ketorolac and rofecoxib in preventing pain after ambulatory surgery. SAMBA annual meeting May, 2002, poster 10.

White PF, Rawal S, Latham P, Markowitz S, Issioui T, Chi L, Dellaria S, Shi C, Morse L, Ing C: Use of a continuous local anesthetic infusion for pain management after median sternotomy. Anesthesiology 2003; 99: 918-23.

White PF, Issioui T, Skrivanek GD, Early JS, Rawal S, Ing C, Wakefield C: Use of a continuous popliteal sciatic nerve block for the management of pain after major podiatric surgery: does it improve quality of recovery? Anesth Analg 2003; 97: 1303-9.

Recart A, White PF, Wang A, Gasanova I, Byerly S, Jones SB: Effect of evoked potential index monitoring on anesthetic drug requirements and recovery profile after laparoscopic surgery: A clinical utility study. Anesthesiology 2003; 99: 813-8.

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 practice. Anesth Analg 2003; 97: 1667-74.

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