Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration.

OBJECTIVES: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). DESIGN AND SETTING: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. PATIENTS: Six critically ill patients with acute renal failure on CVVHDF. INTERVENTIONS: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 l/h of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter. MEASUREMENTS AND RESULTS: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg.h l-1. CONCLUSIONS: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.

Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators.

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of maintenance oral theophylline on dipyridamole-thallium-201 myocardial imaging using SPECT and dipyridamole-induced hemodynamic changes.

To evaluate the effect of maintenance oral theophylline therapy on the diagnostic efficacy of dipyridamole-thallium-201 single photon emission computed tomography (SPECT) imaging for coronary artery disease, dipyridamole-thallium-201 SPECT imaging was performed in eight men with documented coronary artery disease before initiation of theophylline treatment and repeated while these patients were receiving therapeutic doses of oral theophylline. Before theophylline treatment, intravenous dipyridamole caused a significant increase in heart rate, decrease in blood pressure, angina in seven of eight patients, and ST segment depression in four of eight patients. While they were being treated with theophylline, none of the patients had angina or ST segment depression, and there were no hemodynamic changes with intravenous dipyridamole. Before theophylline treatment, dipyridamole-thallium-201 SPECT imaging showed reversible perfusion defects in myocardial segments supplied by stenotic coronary arteries. With theophylline treatment, dipyridamole-thallium-201 SPECT showed total absence of reversible perfusion defects. Treatment with theophylline markedly reduced the diagnostic accuracy of dipyridamole-thallium-201 imaging for coronary artery disease.

Detection of exercise induced changes in left ventricular performance by Doppler echocardiography.

A study was performed to test the hypothesis that Doppler echocardiographic measurement of ascending aortic blood flow can detect exercise induced changes in left ventricular performance during exercise in patients suspected of having ischaemic heart disease. Acceleration and peak velocity of flow and stroke volume were determined by non-imaging Doppler echocardiography in the suprasternal notch in 38 patients as they underwent simultaneous exercise radionuclide ventriculography. The patients were divided into four groups: group 1 had resting ejection fractions greater than or equal to 50% and increased their ejection fractions greater than or equal to 5% during exercise; group 2 had resting ejection fractions of greater than or equal to 50% but the ejection fraction either fell or rose less than 5% during exercise; group 3 had resting ejection fractions less than 50% but the ejection fraction rose greater than or equal to 5% during exercise; and group 4 had resting ejection fractions less than 50% and the exercise ejection fraction either fell or rose less than 5% during exercise. Acceleration, velocity, and stroke volume all rose significantly during exercise in group 1. Acceleration also increased in group 2 but to a lesser extent; velocity and stroke volume did not increase. In group 3 acceleration and velocity increased but to a lesser extent than in group 1; stroke volume did not increase. In group 4 velocity increased slightly during exercise but acceleration and stroke volume were unchanged. Doppler echocardiography thus appears capable of detecting exercise induced changes in left ventricular performance and can identify normal and abnormal responses, as defined by radionuclide ventriculography.

Catheter ablation of the atrioventricular junction and activity responsive pacing. Effect on refractory atrial fibrillation with hypertrophic cardiomyopathy.

A 50-year-old man had chronic atrial fibrillation that was refractory to conventional therapy. He was intolerant of amiodarone, but successfully managed by transcatheter atrioventricular junction ablation. Activity-initiated rate-responsive ventricular pacing resulted in a fourfold greater increase in cardiac output with exercise compared to fixed rate pacing.

Doppler echocardiographic measurement of flow velocity in the ascending aorta during supine and upright exercise.

Doppler echocardiography was used to measure stroke volume, peak flow velocity, and acceleration of flow in the ascending aorta in 10 healthy young volunteers during unlimited supine bicycle exercise and upright treadmill exercise. High quality studies were obtained in all subjects through the suprasternal notch acoustic window; there was no appreciable degradation in Doppler signal caused by interference by increased respiration or chest wall motion. Stroke volume index increased from 54 ml/m2 at rest to 63.5 ml/m2 at peak supine exercise and from 38 ml/m2 standing at rest to 63.3 ml/m2 during peak upright exercise. Mean peak flow velocity rose from 0.91 m/s at supine rest to 1.36 m/s during maximum supine exercise. In the upright position mean peak flow velocity increased from 0.75 m/s at rest to 1.39 m/s during maximum exercise. Mean peak velocities were lower in the upright position at rest but were not significantly different at peak exercise. Mean acceleration of flow in the ascending aorta increased from 12.02 m/s2 during supine rest to 21.6 m/s2 during supine exercise and from 10.8 m/s2 at rest on the treadmill to 21.9 m/s2 during peak upright exercise. This study shows that echocardiographic measurement of ascending aortic blood flow by the Doppler technique is feasible even during vigorous exercise; that stroke volume and peak flow velocity at rest are lower in the upright position than in the supine position but equalise at peak exercise; and that acceleration of flow in the ascending aorta is the same in both the supine and upright positions and increases equally at peak exercise in both positions.