SUPPLEMENT
`
`Abstracts
`of
`Scientific Papers
`1996 Annual Meeting
`
`Univ. of Minn.
`Bio-Medical
`library
`
`Dr. Reddy's Laboratories, Ltd., et al.
`v.
`Helsinn Healthcare S.A., et al.
`U.S. Patent No. 8,729,094
`Reddy Exhibit 1012
`
`Publtshed for the Society by LippitlCOtt-Raven Publishers
`
`Exh. 1012
`
`

`
`Anesthesiology
`vas. No 3A, Sep 1996
`A21
`
`AMBULATORY ANESTHESIA II
`A22
`
`TITLE:
`
`AUTHORS:
`
`ORAL RS-25259 PREVENTS
`POSTOPERATIVE NAUSEA AND
`VOMITING FOLLOWING
`LAPAROSCOPIC SURGERY
`1 Chelly MD*, T Melson MD#, J Pollock
`MD", C Hantler MD@
`AFFILIATIONS: University of Texas, Houston* and San
`Antonio@, TX; Helen Keller Memorial
`Hosp#, Sheffield, AL; Mason Clinic",
`Seattle, WA
`ln.tr.o.dlic.ti.on: RS-25259 is a new highly specific 5-HT3-receptor
`antagonist being developed fpr the prevention and treatment of
`postoperative nausea and vomiting (PONV). This study was
`designed to evaluate the efficacy and safety of RS-25259
`administrated orally for PONY
`in patients undergoing
`laparoscopic procedure with a balanced anesthesia.
`Me.tlm.ds: This randomized double-blind multicenter placebo
`controlled dose ranging efficacy and safety study included Othree
`hundred fifty-one patients (308 women, and 43 men). After
`institution review board approval and written informed consent
`were obtained, these patients ASA I and II, 19-75 years old
`scheduled for elective laparoscopic surgery were enrolled to
`randomly receive oral RS-25259 (0.3, 1, 3, 10.0 and 30 Jlg/kg) or
`placebo. Exclusion criteria included: women of child bearing
`potential who did not practice an effective method of birth
`control, and patients with known hypersensitivity to HT3
`blockers. Patients received the study medication 1 to 2 hours
`prior surgery. The primary efficacy variable was defmed as the
`proportion of patients who did not develop an emetic episode and
`did not require antiemetic medication for 24 hours after recovery
`from anesthesia and surgery (complete responders; CR).
`Secondary variables included the severity of nausea using visual
`analog scale, the frequency and time course of nausea and
`vomiting episodes. The safety evaluation was based on the
`adverse events documented during the 24-hour postoperative
`observation period. Data were analyzed using the Cochran-
`Mantei-Haenszel test. P<0.05 was considered significant.
`Re,SU]ls: Compared to
`the placebo, RS-25259 increased
`significantly the percentag.e of patients who elicited CR (37%,
`58%, 52%, 59% and 53% vs 33%). RS-25259 therapeutic
`effectiveness reached a plateau at a dose of I )lglk.g. Except for
`0.3 f.lg!kg, RS-25259 induced a significant reduction in the
`frequency of severe nausea episodes as· compared to placebo.
`There was no significant difference between the adverse reactions
`repo1tcd in the placebo vs RS-25259 groups (52.4% vs 57.3%).
`In this respect, headache was the most frequent adverse reaction
`reported by the patients receivinrfthe study medication.
`Conclusions: This data demonstrates that a minimum dose of I
`)lg/kg RS-25259 orally administrated is an effective and safe
`treatment for the prevention of PONV in patients undergoing
`laparoscopy surgery.
`
`TilLE:
`
`AUTHORS:
`
`AFFILIATION:
`
`THE ANALGESIC SPARING
`EFFEC.'TS OF MUSIC: A NOVEL
`WAY TO CONTAIN COSTS
`:ME. Koch, MD; ZN. Kain, MD; C. Ayoub,
`MD; SA. Rosenbaum MD
`Departments of Anesthesiology, Surgery,
`Medicine, and Pediatrics Yale University
`School of Medicine, New Haven, Cf, 06510
`
`Introductjoo:
`Music is often used in evety day life to help us relax. It
`provides an auditory distraction from emotional, psychological
`and physical stressors. The purpose of this study was to
`determine if music is a potent enough distractant to lessen the
`amount of analgesia required for patients undergoing lithotripsy
`whose primary anesthetic was a patient controlled analgesia
`pump (PCAP).
`Methods;
`Informed consent was obtained from all participants.
`Unpremedicated ASA I or n patients undergoing lithotripsy with
`the Domier 3 or Dornier 41ithooipter were randomized into either
`a music (n=21) or a control (n=22) group and instructed on use
`of a PCAP system. Next, baseline vital signs were recorded and
`situational and baseline anxiety were noted using Spielberger's
`self-report state and trait anxiety inventory (ST AI). Subjects also
`had baseline pain and sedation scores noted using a self-report
`visual analog scale (VAS). Baseline level of sedation was
`determined by assessing responsiveness, speech, facial
`expression, and eye signs (SLOS). Next, intravenous nridazolam
`20 Jl/kg, metoclopramide 10 mg, and alfentanil 10 11/kg bolus
`were administered to all.subjects and the subjects were attached
`to an intravenous PCAP set to deliver 10 IJ/kg of alfentanil with a
`lockout period of 2 minutes. The music group had occlusive
`headphones applied and the control group listened to the ambient
`noise present in the lithotriptor suite. Blood pressure, heart rate,
`SP02, self-report VAS pain and sedation scores, and SLOS
`scores were recorded every 15 minutes as was the average power
`and frequency of the lithotriptor shock-wave generator.
`Postoperatively, total PACU time and episodes of emesis were
`noted.
`
`Resy!ts;
`Patients in the control and study group were similar in
`age, gender, weight, state and trait anxiety scores. They were
`also similar with respect to hemodynamic and respiratory
`baseline and intraoperative values, case length, and lithotriptor
`stimulus power and frequency. Patients who listened to music
`had an average 5·0% reduction in alfentanil requirements (study
`1.6 Jl/kg/min vs_ control 0.8 Jl/kg/min, p<.002) and spent an
`average of 25% less time in the P ACU (study 98±55 min vs.
`control 73±21 min, p=O.OS). The pre and mean intraoperative
`pain and sedation scores were similar as were the rate of adverse
`respiratory depression (31% vs. 28%, p=NS) and post operative
`nausea and emesis (28% vs. 27%, p=NS). All patients with
`respiratory depression responded to verbal stimulation with
`immediate increases in Sp~.
`
`Conc!usjon;
`Using musk results in less alfentanil needed to achieve
`the same level of patient controlled analgesia, with less PACU
`time needed before discharge. This decreased utilization of
`hospital resources could provide for substantial savings for both
`hospitals and patients. The relatively high incidence of
`respiratory depression, nausea, and emesis leaves room for
`future investigation and refinement
`
`Exh. 1012