Ryan C. Romeo

Aprepitant plus ondansetron compared with ondansetron alone in reducing postoperative nausea and vomiting in ambulatory patients undergoing plastic surgery.

Background: Postoperative nausea and vomiting is a major challenge in the perioperative setting. The incidence can be as high as 80 percent, and the majority of the symptoms among outpatients occur after discharge. This study evaluated the efficacy of a neurokinin-1 receptor antagonist (aprepitant) in reducing postoperative symptoms for up to 48 hours in patients undergoing outpatient plastic surgery. Methods: A prospective, double-blinded, randomized, two-arm evaluation of 150 ambulatory plastic surgery patients receiving a standardized general anesthetic, including postoperative nausea and vomiting prophylaxis with ondansetron and either aprepitant or placebo, was performed. The main outcome measures were the occurrence of vomiting and the severity of nausea for up to 48 hours postoperatively. Results: Overall, 9.3 percent of patients who received aprepitant versus 29.7 percent in group B had vomiting, with the majority of vomiting episodes occurring after hospital discharge. The Kaplan-Meier plot of the hazards of vomiting revealed an increased incidence of emesis in patients receiving ondansetron alone compared with the combination of ondansetron and aprepitant (p = 0.006). The incidence of nausea was not significantly different in the two groups. Severity of nausea, however, was significantly higher in those receiving ondansetron alone compared with those receiving ondansetron and aprepitant, as measured by a peak nausea score (p = 0.014) and by multivariate analysis of variance results comparing repeated verbal rating scale scores over 48 hours after surgery (p = 0.024). Conclusion: In patients undergoing plastic surgery, the addition of aprepitant to ondansetron significantly decreases postoperative vomiting rates and nausea severity for up to 48 hours postoperatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Preemptive Analgesia With Bupivacaine for Segmental Mastectomy

Background and Objectives: Preemptive analgesia is the concept of providing analgesia before surgical incision, resulting in less postoperative pain. The purpose of this study is to determine if preemptive and/or postoperative local anesthetic infiltration of bupivacaine in patients undergoing segmental mastectomy results in less postoperative pain compared with patients receiving placebo. Methods: In this prospective, double-blinded study, 120 patients were randomized into 4 groups: group 1, preincisional (10 mL) and postoperative (10 mL) wound infiltration of 0.5% bupivicaine, (+Pre+Post); group 2, preincisional bupivacaine (10 mL) and postoperative infiltration (10 mL) of placebo (normal saline solution), (+Pre−Post); group 3, preincisional placebo (10 mL) and postoperative bupivacaine (10 mL), (−Pre+Post); or group 4, preincisional (10 mL) and postoperative infiltration of placebo (10 mL), (−Pre−Post). All patients received a standardized laryngeal mask general anesthetic. Data were recorded at the following time intervals: preoperative admission, postanesthesia care unit (PACU) admission, PACU stay, stepdown-unit admission, stepdown-unit stay, hospital discharge, and 24 hours post operation. Results: No difference was noted with respect to preoperative pain visual analog scale (VAS, 0-100 mm), surgical duration, PACU stay time, stepdown-unit stay time, incidence of postoperative nausea, or treatment for nausea in all measured time periods. The placebo group (group 4) had significantly higher mean pain VAS scores during the early postoperative period (PACU admission and PACU stay) compared to the other groups (PACU admission: group 1 = 2 ± 8, group 2 = 4 ± 11, group 3 = 3 ± 15, group 4 = 17 ± 21, P < .01; PACU stay: group 1 = 6 ± 13, group 2 = 6 ± 10, group 3 = 10 ± 21, group 4 = 20 ± 18, P < .01). Likewise, the number of patients who reported pain (pain frequency) was significantly higher in group 4 (placebo) compared with all other groups at PACU admission, PACU stay, stepdown-unit admission, and stepdown-unit stay (P ≤ .01). Conclusion: Preincisional and/or postoperative wound bupivacaine infiltration lacks preemptive analgesic effects for segmental mastectomy.

Propofol-ketamine versus propofol-fentanyl for outpatient laparoscopy: Comparison of postoperative nausea, emesis, analgesia, and recovery

STUDY OBJECTIVE To compare postoperative nausea, emesis, analgesia, and recovery between propofol-ketamine and propofol-fentanyl in outpatient laparoscopic tubal ligations with general anesthesia. STUDY DESIGN Prospective, randomized, blinded study. SETTING Tertiary-care womens hospital. PATIENTS 120 ASA physical status I and II ambulatory patients scheduled for elective laparoscopic tubal ligation. INTERVENTIONS Patients were randomized to two groups to receive either ketamine (1-1.5 mg/kg) or fentanyl (3-5 microg/kg). MEASUREMENTS Measured variables included total dose of ketamine, fentanyl, propofol, and operating time. Vital signs, pain visual analog scale scores (VAS), nausea VAS, presence of emesis, treatment for nausea and vomiting, pruritus, sedation, and presence of dreaming were recorded on postanesthesia care unit (PACU) admission, PACU discharge, stepdown unit admission, and hospital discharge. Results are expressed as means +/- SD or medians and analyzed using t-test, Chi-square, or Mann-Whitney (p < 0.05). MAIN RESULTS No differences were noted with respect to propofol dose, operating times, pain or nausea VAS scores, emesis, treatment for nausea and vomiting, pruritus, and sedation on PACU admission, PACU discharge, stepdown unit admission, and hospital discharge. The ketamine group had a higher heart rate, required more pain medication, and had a higher frequency of dreaming on PACU admission than the fentanyl group. These differences became insignificant on PACU discharge. CONCLUSIONS For outpatient laparoscopic tubal ligations with general anesthesia, propofol-ketamine does not improve postoperative nausea, emesis, analgesia or recovery compared with the propofol-fentanyl combination.

Positive inotropic effect of acetylcysteine in cardiomyopathic Syrian hamsters

Several laboratories have provided indirect evidence that the myocardium of the cardiomyopathic Syrian hamster (CMH) is chronically ischemic on the basis of microvascular spasm. We previously reported evidence supporting a defect in the ryanodine-sensitive sarcoplasmic reticulum calcium release channel (SRCRC) in CMH. A relation between alterations in SRCRC and chronic ischemia has not yet been explored. A potential mechanism could be the effects of changes in redox state on thiol groups. Thiol reagents have previously been shown to regulate calcium release from SRCRC. Accordingly, we studied the inotropic effects of the sulfhydryl donors, acetylcysteine (AC), cysteine, and cystine in CMH. AC was a positive inotrope in isolated papillary muscles prepared from CMH, but not F1B controls (F1B) (p<0.01). No significant differences were noted in inotropic responses to cysteine or cystine. AC blunted the response of CMH>F1B control papillary muscle preparations to stimulation frequency (p<0.01). The actual tension generated (in mg/mm2) by CMH was no longer different than F1B with addition of AC (10-3 M), ryanodine (10-8 M), or verapamil (5 × 10-7 M). These findings are consistent with a defect in SRCRC in CMH. This defect may be primary or may provide a novel mechanism for hibernating myocardium owing to chronic ischemia.

Verapamil regulation of a defective SR release channel in the cardiomyopathic Syrian hamster.

The Bio 14.6 Cardiomyopathic Syrian Hamster (CMH) has an autosomal recessive disease characterized by intracellular calcium overload, cardiac and skeletal myopathies and premature death from congestive heart failure. Early treatment of these animals with the calcium antagonist, verapamil (V), prevents the development of the disease. We have previously provided evidence supporting a specific defect in the ryanodine-sensitive SR calcium release channel (SRCRC) in CMH. We now provide physiologic and biochemical evidence that V modulates SRCRC. Papillary muscles prepared from F1B control hamsters (F1B) revealed an enhanced inotropic responsiveness to V and ryanodine (R) with age, not seen with CMH. CMH papillary muscles demonstrated paradoxical positive inotropic effects of V and R not shared with F1B. The positive inotropic effects of V and R were not additive. V enhanced the affinity (decreased KD) of [3H]ryanodine binding to cardiac membranes. Thus, V may prevent the overt manifestations of genetic disease in CMH by modulating a defective ryanodine-sensitive SR release channel.

Inotropic effects of calcium antagonists in the cardiomyopathic Syrian hamster

The inotropic responses of papillary muscles isolated from the BIO 14.6 cardiomyopathic Syrian hamster were compared with those of age-matched F, B controls. Length-tension curves revealed the preservation of contractile function at 1–2 months of age and significant loss of function at 4–6 months of age. Papillary muscles prepared from 4–6-month-old myopathic hamsters were significantly less sensitive to increasing frequency of stimulation than were controls (p < 0.05). There were no differences in the responses to nifedipine, Bay K 8644, diltiazem, or gallopamil. Only verapamil demonstrated a biphasic inotropic response in the cardiomyopathic hamster with a low-dose positive inotropic effect (131 ± 4% at 4 ± 2 × 10 -7 M) and a 50-fold higher IC50 for negative inotropy compared with F1B controls (200 ± 30 vs. 4.0 ± 1.0 μM). Verapamil is also a less potent negative inotrope in 1–2-month-old myopathic papillary muscles compared with controls (IC50, 280 ± 70 vs. 32 ± 10 μM; p < 0.05). These inotropic effects are not shared by the other calcium channel modulators studied (i.e., nifedipine, Bay K 8644, diltiazem, gallopamil). These findings do not support the presence of a functional defect in the sarcolem-mal L-type calcium channel in the cardiomyopathic Syrian hamster. The mechanism of action of verapamil in the cardiomyopathic Syrian hamster remains to be elucidated.

Bay K 8644 is a negative inotrope in the presence of arachidonic acid but not eicosapentaenoic acid

Summary: The inotropic and radioligand binding characteristics of arachidonic acid (AA) and the fish oil derivative, eicosapentaenoic acid (EPA), were studied. A A alone was a concentration-dependent negative inotrope in isolated hamster papillary muscles. The negative inotropic effect of AA was enhanced 500-fold by the coadministration of indomethacin (cyclo-oxygenase inhibitor) and caffeic acid (lipoxygenase inhibitor). The dihydropyridine calcium channel agonist Bay K 8644 (BK) was a concentration-dependent positive inotrope. BK in the presence of AA was a concentration-dependent negative inotrope. The negative inotropic effect of BK in the presence of AA was blocked by caffeic acid but not indomethacin. EPA alone was a concentration-dependent negative inotrope. EPA had no effect on the positive inotropic effect of BK. Scatchard analyses of [3H]nitrendipine (dihydropyridine) binding to cardiac membranes in the presence of AA or EPA resulted in a decrease in the KD (-1/slope) with no effect on Bmax (x intercept). Kinetic studies further revealed that both AA and EPA enhanced the off rate of [3H]nitrendipine binding. These data suggest that both AA and EPA mediate similar direct negative inotropic effects through cardiac sarcolemmal calcium channels. A unique effect on E-C coupling by AA, not shared by EPA, is mediated through the lipoxygenase pathway (leukotrienes). AA and its eicosanoid products may play critically important roles in regulating myocardial contractility during acute and chronic myocardial ischemia. Differences between AA and EPA may contribute to the beneficial effects of dietary fish oils enriched in EPA.