Manuel Gonzalez

Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients: a double-blind, randomized, placebo-controlled study.

OBJECTIVE To document the action of erythromycin on gastric emptying and motility in mechanically ventilated patients. DESIGN Crossover, double-blind, randomized, placebo-controlled study. SETTING General intensive care unit in a university hospital. PATIENTS Ten patients, mechanically ventilated, in a stable hemodynamic condition. INTERVENTIONS Erythromycin (200 mg i.v. over 30 mins) and placebo were infused at mid-morning, on two consecutive days, in a random order. Pressure changes in the gastric antrum were recorded by means of a multi-lumen manometric tube (perfused catheter technique) over a period of 300 mins, beginning with the institution of the erythromycin or placebo infusion. Gastric emptying was simultaneously assessed by the kinetics of the absorption of acetaminophen delivered into the stomach (1 g with 20 mL of water) immediately before the infusion. MEASUREMENTS AND MAIN RESULTS Motility was quantified by determining the number of contractions, the amplitude of contractions, and the Motility Index (Motility Index = natural logarithm [sum of amplitude x number of contractions] + 1). Comparison between placebo and erythromycin was made for the first hour after the infusion and for the whole recording session. The maximal acetaminophen concentration, the time to reach the peak acetaminophen concentration, and the area under the concentration-time curve at 60 mins were obtained from serial determinations of plasma acetaminophen concentrations. Compared with placebo, the mean number of contractions (104 +/- 34 vs. 5 +/- 8; p = .003), the mean amplitude of contractions (52 +/- 16 vs. 20 +/- 17 mm Hg; p = .005), and the Motility Index (13.06 +/- 0.95 vs. 4.45 +/- 3.54; p = .004) were significantly increased during the first hour after erythromycin infusion compared with placebo. Number of contractions (p = .017) and Motility Index (p < .001) after erythromycin infusion remained significantly higher when values throughout the whole recording session were considered. The following data were noted after erythromycin was infused: a) the time to reach the peak acetaminophen concentration was shorter (32 +/- 8 vs. 171 +/- 93 mins; p = .007); b) the maximal acetaminophen concentration was higher (22.09 +/- 6.23 vs. 5.38 +/- 3.80 micrograms/mL; p = .007); and c) the area under the concentration-time curve at 60 mins increased markedly (730 +/- 269 vs. 72 +/- 42 micrograms/min/mL; p = .002) as compared with placebo. CONCLUSION In mechanically ventilated patients, intravenous erythromycin (200 mg over 30 mins) increases indices of antral motility and accelerates gastric emptying as assessed by the kinetics of acetaminophen absorption.

Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery.

OBJECTIVES The present study was aimed to evaluate the efficacy of a specific algorithm with continuous atrial dynamic overdrive pacing to prevent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. BACKGROUND Atrial fibrillation occurs in 30% to 40% of patients after cardiac surgery with a peak incidence on the second day. It still represents a challenge for postoperative prevention and treatment and may have medical and cost implications. METHODS Ninety-six consecutive patients undergoing CABG for severe coronary artery disease and in sinus rhythm without antiarrhythmic therapy on the second postoperative day were randomized to have or not 24 h of atrial pacing through temporary epicardial wires using a permanent dynamic overdrive algorithm. Holter ECGs recorded the same day in both groups were analyzed to detect AF occurrence. RESULTS No difference was observed in baseline data between the two study groups, particularly for age, male gender, history of AF, ventricular function, severity of coronary artery disease, preoperative beta-adrenergic blocking agent therapy or P-wave duration. The incidence of AF was significantly lower (p = 0.036) in the paced group (10%) compared with control subjects (27%). Multivariate analysis showed AF incidence to increase with age (p = 0.051) but not in patients with pacing (p = 0.078). It decreased with a better left ventricular ejection fraction only in conjunction with atrial pacing (p = 0.018). CONCLUSIONS We conclude that continuous atrial pacing with an algorithm for dynamic overdrive reduces significantly incidence of AF the second day after CABG surgery, particularly in patients with preserved left ventricular function.

Combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients.

The aim of this study was to evaluate the safety and diagnostic yield of bedside bronchoalveolar lavage (BAL) combined with fibrescopic transbronchial lung biopsy (TBLB) in determining the aetiology of pulmonary infiltrates in mechanically ventilated patients. The records of 38 mechanically ventilated patients who underwent BAL/TBLB to investigate unexplained pulmonary infiltrates were retrospectively reviewed. Patients were divided into two groups: immunocompetent (group 1: n=22; group 1a: n=11, late acute respiratory distress syndrome (ARDS); group 1b: n=11, no ARDS) and immunocompromised (group 2, n=16). The procedure allowed a diagnosis in 28 patients (74%), inducing therapeutic modification in 24 (63%) and confirmation of clinical diagnosis in four (11%). In groups 1a, 1b and 2, diagnosis was obtained in 11 out of 11 (fibroproliferation), seven out of 11 and 10 out of 16 patients, and therapy changed in 11 out of 11 (administration of steroids), six out of 11 and seven out of 16 patients, respectively. Pneumothorax occurred in nine patients (four of group 1a), bleeding in four (<35 mL), and transient hypotension in two. No fatalities were procedure-related. Combined bronchoalveolar lavage/transbronchial lung biopsy is of diagnostic and therapeutic value in mechanically ventilated patients with unexplained pulmonary infiltrates, excluding those with late acute respiratory distress syndrome. Although complications are to be expected, the benefits of the procedure appear to exceed the risks in patients in whom a histological diagnosis is deemed necessary.

Duodenal motor response to continuous enteral feeding is impaired in mechanically ventilated critically ill patients.

In order to investigate the duodenal motor response to continuous enteral feeding during critical illness, we recorded the duodenal contractions of 12 mechanically ventilated critically ill patients during a 4 h fasting period immediately followed by another 4 h period of continuous (100 kcal/h) nasogastric feeding with a polymeric diet. Duodenal motility was recorded by manometry (perfused catheter technique) and the migrating motor complexes (MMC) were identified by their activity front (period of high frequency, regular contractions). The incidence and the mean duration of activity fronts as well as the mean duration of the MMC (time interval separating two successive activity fronts) recorded during both periods were compared. The incidence of activity fronts (fasting: median: 2.5, interquartile range: 5.5; feeding: median: 2, interquartile range: 3.5), their duration (fasting: 6.2 +/- 1.6 min; feeding: 5.8 +/- 1.6 min), and the mean duration of the MMC (fasting: 50.9 +/- 24.7 min; feeding: 49.1 +/- 20.3 min) were similar during both periods. We conclude that in these patients, the fasting pattern of motility is not interrupted by the continuous nasogastric administration of a polymeric diet. Since the activity fronts of the MMCs are highly propulsive, we suggest that their abnormal persistence during feeding may play a role in the pathophysiology of unexplained diarrhoea in some critically ill patients.

Efficacy of enoximone in the management of refractory low-output states following cardiac surgery.

Fifteen consecutive patients with post-cardiac surgery low-output states refractory to catecholamine inotropic support and intra-aortic balloon counter-pulsation (seven patients), were given enoximone (MDL 17,043, a phosphodiesterase inhibitor), 1 to 2 mg/kg, as a slow intravenous bolus injection, followed by a continuous infusion of 3 to 10 microg/kg/min. Enoximone resulted in a marked improvement in clinical and hemodynamic conditions. Despite the severity of their initial status, all the patients survived their acute circulatory failure and all but two were discharged from the hospital. Hemodynamic improvement was observed as early as 15 minutes after the drug administration and reflected the previously reported inotropic and vasodilatory properties of enoximone. No serious adverse effects were observed. Enoximone thus appears safe and effective in the management of post-cardiac surgery low-output states. Its effects are additive to those of high-dose catecholamines.

A Dose-response Study of Intravenous Enoximone in Congestive-heart-failure

Previous clinical studies with intravenous enoximone have used cumulative dosing to quantify enoximones hemodynamic effects. The magnitude and duration of the hemodynamic effects of single intravenous doses of enoximone were evaluated in patients with congestive heart failure. Sixty patients, who were in New York Heart Association functional classes III and IV, received single intravenous doses of enoximone, either 0.25 (12 patients), 0.5 (13 patients), 1 (14 patients), 1.5 (10 patients) or 2 mg/kg (11 patients). Cardiac index was increased by 20% with the 0.25 mg/kg dose and by 48% and 42% with the 1.5 and 2 mg/kg doses, respectively. These increases were statistically significant (Students paired t test with Bonferronis correction, p less than 0.007) for 1 hour after 0.25 and 0.5 mg/kg, for 2 hours after 1 mg/kg and for 4 hours after 1.5 and 2 mg/kg. Enoximone also reduced pulmonary artery diastolic pressure by 19% with 0.25 mg/kg and by 29% with 2 mg/kg. The duration of effect varied from 1 hour with 0.25 mg/kg to 4 hours with 2 mg/kg. Enoximone produced no consistent or dose-related effects on heart rate or blood pressure. Eighteen adverse reactions were reported by 15 patients, of which 11 were minor and transient (vein pain, flushes, nausea). In 5 patients ventricular or supraventricular arrhythmias were observed, including nonsustained ventricular tachycardia and extrasystoles; 3 of these patients had evidence of arrhythmias before enoximone. Laboratory studies before and after treatment showed no drug-related effects. Dose-related effects on the magnitude and duration of hemodynamic responses to intravenous enoximone were evident within the dose range of 0.25 to 2 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Operation for unstable angina pectoris : factors influencing adverse in-hospital outcome

Coronary artery bypass grafting for the treatment of unstable angina is still associated with increased operative risk and postoperative morbidity. The impact of the extended use of arterial grafts on early results is incompletely defined. In a 7-year period (1986 to 1993), 474 patients (average age, 65 years; range, 34 to 85 years) underwent coronary artery bypass grafting for the treatment of unstable angina. Sixty-eight patients were operated on emergently and 406 urgently. They received an average of 3.0 distal anastomoses (range, 1 to 6). Seventy-nine patients had exclusively venous grafts, 316 had one internal thoracic artery graft, 79 had bilateral internal thoracic artery grafts, and 20 had inferior epigastric artery grafts. Sequential internal thoracic artery grafting was performed in 70 patients. Redo operations were performed in 26 patients. Thirty-four patients (7.2%) experienced a new myocardial infarction. Eighty-nine patients (18.8%) had an intraaortic balloon pump inserted preoperatively, intraoperatively, or postoperatively. Eight patients (1.7%) died intraoperatively and 24 patients (5.1%) died postoperatively. Seventy-seven patients (16.2%) had an adverse outcome, as shown by the need for an intraaortic balloon pump (intraoperatively or postoperatively) or hospital death, or by both. Forty variables were examined by multivariate analysis for their influence on the occurrence of an adverse outcome. Aortic cross-clamp time (p = 0.0004), transfer from the intensive care unit (p = 0.0023), female sex (p = 0.0023), operation performed in early years (p = 0.0041), left ventricular aneurysm (p = 0.0068), the number of diseased coronary vessels (p = 0.0312), and reoperation (p = 0.0318) were all found to be significant independent predictors of increased risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects on hemodynamics of enoximone (MDL 17,043), dobutamine and nitroprusside in severe congestive heart failure

To assess their comparative effects on hemodynamics, nitroprusside, dobutamine and enoximone were sequentially administered to 10 patients with severe congestive heart failure. Nitroprusside, dobutamine (at 10 micrograms/kg/min) and enoximone (at 2 mg/kg) increased stroke volume index to a similar extent (31%, 34% and 36%, respectively). Enoximone produced less tachycardia than dobutamine and, consequently, a smaller improvement in cardiac index. Mean arterial pressure was not altered by dobutamine but was reduced 9% by enoximone, 2 mg/kg. This finding accounts for the larger (although not significant) increase in left ventricular stroke work index observed with dobutamine compared with enoximone. Ventricular filling pressures and vascular resistances were significantly decreased by all 3 drugs (p = 0.001). All 3 drugs improved cardiac pump function when assessed by the increase in stroke index to a similar extent; however, enoximone (2 mg/kg) resulted in less hypotension than nitroprusside (mean arterial pressure -9% vs -22%, p = 0.0001) and in less tachycardia than dobutamine 10 micrograms/kg/min. Those differences in mode of action account for the variations observed in the heart rate-blood pressure product (dobutamine 10 micrograms/kg/min, +18%, enoximone 2 mg/kg, -5%, p = 0.003). Enoximone thus appears to be of great value in the management of severe congestive heart failure by its combination of vasodilatory and inotropic properties. Enoximone (2 mg/kg) provides a clinically significant increase in cardiac index, a clear reduction of ventricular filling pressures, a moderate reduction of mean arterial pressure and only minor changes of heart rate and of rate pressure product.

Off-pump coronary artery bypass grafting: a case-matched comparison of hemodynamic outcome.

OBJECTIVE The objective of this study was to assess improved myocardial protection by performing coronary artery bypass grafting (CABG) on the beating heart. A case-matched study was conducted among patients who underwent CABG either on-pump (group 1), or off-pump (group 2). METHODS Forty-five pairs of patients, having a similar clinical profile, were selected on the basis of five variables: age, gender, body surface area, ejection fraction, extent of coronary disease. Operative risk predicted by the The Society of Thoracic Surgeons national database was 1.80+/-0.35% in group 1, and 1.89+/-0.37% in group 2 (NS). Cold blood cardioplegia and 28 degrees C cardiopulmonary bypass were used in group 1. In group 2, beating heart coronary grafting was achieved with the Octopus 1 and 2 stabilizers. The average number of distal anastomoses was 2.8+/-0.1 in group 1 and 2.3+/-0.1 in group 2 (P=0.015). RESULTS There was no significant difference among the groups regarding the trend in cardiac index, left and right ventricular stroke work indexes, and systemic and pulmonary vascular resistance indexes. However, heart rate trend was slower in group 2 (P=0.05). Pharmacological support was required in 65% of the patients in group 1, and in 33% in group 2 (P<0.001). The total amount of Dobutamine and/or Dopamine administered during the first 48 h was 3914+/-1306 gamma/kg in group 1 and 1645+/-697 gamma/kg in group 2 (P=0.049). Release of creatine kinase MB mass isoenzyme (CK-MB mass) was markedly reduced in group 2 (P<10(-4)). CONCLUSIONS Hemodynamic outcome following off-pump CABG is similar to on-pump CABG but the need for inotropic support is significantly reduced and CPK-MB mass release is markedly lower.

Patent foramen ovale: a cause of significant post-coronary artery bypass grafting morbidity.

We describe two patients who underwent coronary artery bypass grafting complicated by postoperative hypoxemia due to a patent foramen ovale with right-to-left shunting. We discuss different hypotheses to explain the shunt: decreased right ventricular compliance, right atrial geometric changes due to septal distension or ischemia, exceeding filling pressure and localised haemorragic pericardial tamponade and low atrial pressure when correcting aortic stenosis. We emphasize the close interplay of pericardectomy and the four cardiac chambers including the distortion of the heart axis. The contrast echo produced by microbubbles of air is the safest and the most accurate procedure to detect the shunt. The two patients progressed positively with an extracorporeal circulation of short duration and without complications linked to the intervention. We conclude that postoperative unexplained hypoxemia must always exclude diagnosis of right-to-left shunting due to a patent foramen ovale (PFO).