Differences in plaque composition and distribution in stable coronary artery disease versus acute coronary syndromes; non-invasive evaluation with multi-slice computed tomography.

BACKGROUND: Plaque composition rather than degree of luminal narrowing may be predictive of acute coronary syndromes (ACS). The purpose of the study was to compare plaque composition and distribution with multi-slice computed tomography (MSCT) between patients presenting with either stable coronary artery disease (CAD) or ACS. METHODS: MSCT was performed in 22 and 24 patients presenting with ACS or stable CAD, respectively. Coronary lesions were classified as calcified, non-calcified or mixed while signal intensity (SI) was measured. RESULTS: In patients with stable CAD, the majority of lesions were calcified (89%). In patients with ACS, less calcifications were observed with a greater proportion of non-calcified (18%) or mixed (36%) lesions (P<0.001). Accordingly, mean SI of plaques was significantly less in ACS (320+/-201 HU versus 620+/-256 HU in stable CAD, P<0.001). Dividing lesions in the ACS group according to culprit versus non-culprit vessel location resulted in no significant difference in average SI between these two groups while still lower as compared to stable CAD (P<0.001). CONCLUSIONS: In patients with ACS, significantly less calcifications were present as compared to stable CAD. Moreover, even in non-culprit vessels, multiple non-calcified plaques were detected, indicating diffuse rather than focal atherosclerosis in ACS.

Detection of malignant right coronary artery anomaly by multi-slice CT coronary angiography.

Coronary artery anomalies occur in 0.3-0.8% of the population and infer a high risk for sudden cardiac death in young adults. Diagnosis is usually established during coronary angiography, which is hampered by poor spatial visualization. Magnetic resonance imaging is an alternative, but it is not feasible in the presence of metal objects or claustrophobia. In this report, a 15-year-old boy experienced ventricular fibrillation and was successfully resuscitated. Cardiac catheterization was inconclusive, and pacemaker implantation prohibited the use of MR imaging. Multi-slice CT coronary angiography revealed a malignant anomalous right coronary artery.

Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients.

The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated. A large variation was observed in the plasma concentration of midazolam and between the plasma concentration of midazolam and its metabolite 1-hydroxymethylmidazolam glucuronide. The plasma albumin concentration governs the volume of distribution of midazolam. Decreased plasma albumin concentration (25 gm/L) results in an increased volume of distribution and a decreased elimination rate of midazolam. The observed plasma concentration ratio between the parent drug and its metabolite 1-hydroxymethylmidazolam glucuronide is governed by the variables of protein binding, the metabolic rate of midazolam, and the renal clearance of the glucuronide metabolite itself (which can be considered as a measure of the kidney function of the patient).

Continuous infusion of midazolam during anaesthesia and postoperative sedation after maxillofacial surgery.

The clinical effects and pharmacokinetics of 24 h infusion of midazolam (MDZ) during major maxillofacial surgery and postoperative observation in an Intensive Care Unit (ICU) were studied in 20 patients. During anaesthesia, infusion of MDZ at 5 mg/h combined with 67% nitrous oxide, 1.8 (s.d. = 0.8) mg of fentanyl, and 26.5 (s.d. = 11.4) mg of vecuronium, adequately suppressed clinical responses to surgical nociceptive stimuli. Postoperatively, infusion of MDZ was continued in the ICU at 5 mg/h until 9 a.m. of the first postoperative day for sedation of the intubated but spontaneously breathing patients. The depth of sedation in the ICU was scored from 1-5 (1 = "awake and tense", 5 = "unable to communicate"). During infusion the sedation score decreased from 3.8 after ICU arrival to 2.2 at 8 a.m. of the first postoperative day. Neither ventilatory nor circulatory depression were observed. After cessation of MDZ, recovery from sedation was fast. The degree of amnesia was low. During constant rate infusion no increase in plasma concentration of either MDZ or metabolites occurred. T1/2 beta of MDZ after cessation was 125 min (range 90-320) and its total body clearance was 10.5 ml/kg/min (s.d. = 3.1). The volume of distribution, clearance and T1/2 beta were significantly longer in women than in men. It was concluded that 24 h of MDZ infusion at 5 mg/h caused satisfactory ICU sedation with fast recovery, but that individual tailoring of the infusion rate may still improve the quality of sedation.

Clinical pharmacokinetics of long-term infusion of midazolam in critically ill patients--preliminary results.

Seven intensive care patients were sedated with prolonged infusion of midazolam. One patient received a continuous infusion of midazolam for the treatment of status epilepticus. A bolus injection of 5 mg was administered, followed by infusion of 4-14 mg/hour depending on the required level of sedation. The length of infusion varied between 80 and 360 hours. The plasma concentrations of the midazolam during infusion were between 500-1000 ng/ml. All the patients were adequately sedated. The plasma elimination half-life of midazolam and its main metabolite, 1-OH-midazolam glucuronide, after stopping the infusion varied from 4-12 hours.

Imipenem as monotherapy in the treatment of intensive care patients with severe infections.

In an open study, 24 intensive care patients were treated with imipenem/cilastatin as monotherapy for serious bacterial infections. Twenty-one patients were treated for bronchopulmonary infection, two patients for septicaemia, and one patient for an empyema. Initially all strains were susceptible to imipenem. Gram-negative bacilli accounted for 80% of these isolates. The most frequently isolated species were Proteus mirabilis, Escherichia coli and Pseudomonas aeruginosa. All 24 patients were considered clinically cured. Sixteen of these patients (67%) were both clinically and microbiologically cured. In eight of the 24 patients (33%), the strains isolated initially persisted. In eight of the 24 patients (33%), colonization of the respiratory tract developed. Two of the five Ps. aeruginosa isolates developed resistance during therapy but in none of these patients was therapy considered to have failed. In 12 patients (50%), transient elevations in hepatic function tests were observed and these were probably drug-related. The present study supports the view that imipenem/cilastatin may be useful as monotherapy in the treatment of severe infections in intensive care patients.

Pharmacokinetics of intravenously administered ciprofloxacin in intensive care patients with acute renal failure.

The pharmacokinetics of ciprofloxacin after a single intravenous administration of 100 mg were studied in intensive care patients with an acute renal impairment. There was no correlation found between the creatinine clearance and the renal clearance of ciprofloxacin. This applies to the entire group of patients. The decrease in renal clearance of ciprofloxacin was, however, more pronounced than the change in the elimination half-life, suggesting an important extra-renal elimination of the drug.