Comparison of cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition in critically III, mechanically ventilated adults.

BACKGROUND: Placebo-controlled studies have indicated that both cisapride and metoclopramide promote gastric motility in critically ill patients. OBJECTIVE: This study was conducted to compare cisapride and metoclopramide for facilitating gastric emptying and improving tolerance to intragastric enteral nutrition (EN) and to evaluate the relationship between aspirated gastric residual volume and gastric emptying function in this patient population. METHODS: In this double-blind study, critically ill, mechanically ventilated patients with an aspirated gastric residual volume > or = 150 mL while receiving intragastric EN were randomized to receive enteral cisapride 10 mg or metoclopramide 10 mg every 6 hours for a total of 7 doses. The acetaminophen-absorption method was used to assess gastric emptying at baseline and 30 minutes after the seventh dose by determining the area under the plasma concentration-time curve at 240 minutes (AUC240), maximum concentration (Cmax), and time to Cmax (Tmax). Gastric residual volume was measured every 6 hours before dosing. RESULTS: Fourteen patients were included in the study, 7 in each group. Patient characteristics were similar in the 2 groups. Compared with baseline, metoclopramide significantly accelerated Tmax (39.00 +/- 15.56 min with metoclopramide vs 103.71 +/- 47.35 min at baseline; P = 0.018) and increased Cmax (12.94 +/- 6.68 mg/L vs 6.97 +/- 4.78 mg/L; P = 0.018) and AUC240 (1,421.43 +/- 780.31 mg/L x min vs 839.00 +/- 545.58 mg/L x min; P = 0.043). Cisapride increased Cmax from baseline (12.27 +/- 8.95 mg/L vs 4.53 +/- 2.37 mg/L, respectively), but the difference was not statistically significant. Gastric residual volume was significantly reduced from baseline after 3 doses of metoclopramide (from 268.7 +/- 112.3 mL to 57.0 +/- 23.1 mL; P < 0.05) and was significantly lower after the seventh dose of metoclopramide than after the seventh dose of cisapride (5.3 +/- 8.2 mL vs 41.4 +/- 39.7 mL, respectively; P = 0.05). Cmax at baseline and residual volume at study entry were inversely correlated (r = -0.50; P = 0.049). CONCLUSIONS: Both cisapride and metoclopramide enhanced gastric motility and improved tolerance to intragastric EN. Metoclopramide reduced gastric residual volume to a significantly greater extent than did cisapride. Only Cmax at baseline was inversely associated with residual volume.

A prospective evaluation of empiric versus protocol-based sedation and analgesia.

STUDY OBJECTIVE: To compare empiric and protocol-based therapies of sedation and analgesia in terms of pharmacologic cost, effects on mechanical ventilation and intensive care unit (ICU) stay, and quality of sedation and analgesia. DESIGN: Prospective study. SETTING: A 24-bed medical-surgical-neurologic ICU. PATIENTS: Seventy-two patients evaluated during empiric therapy and 86 during protocol-based therapy. INTERVENTION: Assessment of data collected for 4 months before and 5 months after an evidence-based sedation and analgesia protocol was implemented. MEASUREMENTS AND MAIN RESULTS: Protocol adherence rate was 83.7%. The hourly cost (Canadian dollars) of sedation was less with protocol-based therapy ($5.68 +/- 4.27 vs $7.69 +/- 5.29, p<0.01) likely due to increased lorazepam use. Pharmacologic cost savings may be negated since sedation duration tended to be longer (122.7 +/- 142.8 vs 88.0 +/- 94.8 hrs, p<0.1) and extubation may have been delayed (61.6 +/- 97.4 vs 39.1 +/- 54.7 hrs, p=0.13) with protocol use. Duration of ICU stay after sedation was discontinued was not significantly different before and after protocol implementation. With the protocol, however, the percentage of modified Ramsay sedation scores representing discomfort decreased from 22.4 to 11% (p<0.001) and the percentage at a score of 4 increased from 17.2% to 29.6% (p<0.01). The percentage of modified visual analog measurements representing pain decreased from 9.6 to 5.9% (p<0.05) with the protocol. When data were stratified according to duration of sedation, the benefits and delayed extubation associated with protocol-based therapy were limited to patients requiring long-term sedation. CONCLUSION: Compliance with this protocol reduced drug costs and enhanced the quality of sedation and analgesia for patients requiring long-term sedation. Protocol-based therapy with lorazepam may have delayed extubation but did not delay ICU discharge.

A randomized, double-blind comparison of methoxamine and epinephrine in human cardiopulmonary arrest.

The beneficial effect of epinephrine has been attributed to its alpha-adrenergic properties. The present study was designed to compare the effects of epinephrine and methoxamine in witnessed cardiac arrests. Consecutive, witnessed cardiac-arrest victims presenting to the emergency room or from the inpatient population of our institution were enrolled in this study. Patients were randomized to receive either epinephrine (2 mg bolus followed by 2 mg every 4 min) or methoxamine (40 mg bolus followed after 4 min by 40 mg) in a blind design. Patients were followed prospectively for survival and neurologic outcome. A total of 199 patients were randomized into the study, but 54 had to be retrospectively dropped from analysis for failure to comply with the study protocol. Of the 145 patients remaining, 77 received methoxamine (M) and 68 epinephrine (E). There was no difference in rate of successful resuscitation (42% versus 53%, M versus E, respectively), or in neurologic outcome as measured by the Glasgow-Pittsburgh Coma Score (GPCS). This study failed to demonstrate any difference in the rate of initial resuscitation, survival to discharge from the hospital, or neurologic status with methoxamine as opposed to epinephrine in the setting of cardiac arrest.

Lack of in vitro inactivation of tobramycin by imipenem/cilastatin.

OBJECTIVE: Inactivation of aminoglycosides by beta-lactam antimicrobials both in vitro and in vivo has been documented. Such an interaction has not previously been documented between carbapenems and aminoglycosides. Examination of serum concentrations of tobramycin in a patient receiving both agents suggested that this interaction might exist. The purpose of this study was to look at this question in an in vitro model. METHODS: Low concentrations of tobramycin (10 micrograms/mL) were incubated with imipenem/cilastatin (concentrations of 10, 20, and 40 micrograms/mL) in human serum at 37 degrees C. Aliquots of these solutions were withdrawn at 0, 6, 24, 72, and 120 hours and assayed for tobramycin concentrations using a fluorescence polarization immunoassay. Aliquots of tobramycin 10 micrograms/mL and carbenicillin 200 micrograms/mL were analyzed in the same manner, as a positive control. High concentrations of tobramycin (800 micrograms/mL) and imipenem (5000 micrograms/mL)/cilastatin were incubated together at 21 degrees C and sampled at 0, 6, 24, and 72 hours for tobramycin concentrations. RESULTS: The degradation rates for low-concentration tobramycin and the various concentrations of imipenem/cilastatin were not statistically different from those of the controlled incubations. In contrast, carbenicillin significantly enhanced the degradation rate of tobramycin at this concentration (half-life 72 hours and a 34 percent loss at 24 hours, p = 0.0028). Higher in vitro concentrations of imipenem (5000 micrograms/mL)/cilastatin and tobramycin (800 micrograms/mL) resulted in significant, but moderate degradation over controlled incubations (half-life 80 hours and 10 percent loss at 12 hours, p = 0.0031). CONCLUSIONS: These results suggest that inactivation of tobramycin is not a problem at common clinically achievable imipenem serum concentrations in patients.

Infective endocarditis due to Eikenella corrodens: Case report and review of the literature.

Eikenella corrodens is an uncommon cause of bacterial endocarditis. In the 11 reported cases in the literature, the disease was associated with predisposing factors and was clinically indolent or subacute. A case is reported which in contrast to the reported literature was acute in onset with severe heart failure, requiring urgent valve replacement.