Renal tolerance of a neutral gadolinium chelate (gadobutrol) in patients with chronic renal failure: results of a randomized study.

PURPOSE: To assess the renal tolerance of 1.0 mol/L gadobutrol as an electrically neutral contrast agent at magnetic resonance (MR) imaging in patients with impaired renal function. MATERIALS AND METHODS: Twenty-one patients with impaired renal function were enrolled in this prospective randomized study and classified into two subgroups according to their creatinine clearance: group 1 (n = 12), less than 80 mL/min (<1.33 mL/sec) and greater than 30 mL/min (>0.50 mL/sec); group 2 (n = 9), less than 30 mL/min (<0.50 mL/sec) and not requiring dialysis. Gadobutrol (1.0 mol/L) was injected intravenously at randomly assigned doses of either 0.1 or 0.3 mmol per kilogram of body weight. Changes in vital signs, clinical chemistry, and urinalysis results, including creatinine clearance, were monitored before, at 6 hours, and then every 24 hours until 72 hours (group 1) or 120 hours (group 2) after intravenous injection of gadobutrol. Hematologic results were checked every other day. RESULTS: No serious adverse event occurred, and no clinically relevant changes in vital signs, hematologic results, clinical chemistry, or urinalysis results were detected in the observation period. Markers for glomerular filtration (creatinine, cystatin C, beta2-microglobulin, creatinine clearance) and tubular function (N-acetyl-beta-D-glucosaminidase, alpha1-microglobulin) were unaffected by gadobutrol in both groups. CONCLUSION: Gadobutrol did not affect renal function and, therefore, proved to be a safe MR contrast agent in patients with impaired renal function. Even in patients with marginal excretory function (creatinine clearance, <30 mL/min [<0.50 mL/sec]), prehydration or treatment with diuretics or hemodialysis are not required after the administration of gadobutrol.

Cerebral MR perfusion imaging: first clinical application of a 1 M gadolinium chelate (Gadovist 1.0) in a double-blinded randomized dose-finding study.

The purpose of this study was to evaluate efficacy and safety of the 1 M gadolinium chelate Gadovist 1.0 for assessment of cerebral hemodynamics with dynamic susceptibility contrast-enhanced magnetic resonance (MR) imaging. Eighty-nine patients with carotid artery stenosis or cerebral infarcts were included in this multicenter, double-blinded study using five dose groups from 0.1 to 0.5 mmol/kg. Imaging was performed with 1-T scanners using a T2*-weighted fast low-angle shot (FLASH) sequence. Dose-dependent changes in quantitative and qualitative parameters describing signal-time curves and relative regional cerebral blood volume maps were investigated. For safety evaluation, vital signs, clinical and laboratory tests, and adverse events were assessed. The quantitative measurements revealed an optimal dose of 0.4 mmol/kg. The qualitative evaluation revealed that the required qualitative assessment for clinical purposes was already reached at a dose of 0. 3 mmol/kg. No significant changes in vital signs and laboratory tests were found. No serious adverse events were observed. The combined results revealed the dose of 0.3 mmol/kg as the diagnostically adequate dose given the gradient-echo sequence and field strength used. Gadovist 1.0 has been shown to be a safe and well-tolerated contrast agent. J. Magn. Reson. Imaging 2000;12:371-380.

Pharmacokinetics of 1M gadobutrol in patients with chronic renal failure.

RATIONALE AND OBJECTIVES: To investigate the pharmacokinetics of 1M gadobutrol as a new neutral MR contrast agent in patients with impaired renal function. METHODS: Twenty-one patients with impaired renal function and any indication for a contrast-enhanced MRI were enrolled into this prospective study and classified in two subgroups according to their creatinine clearance (group 1, 30-80 mL/ min; group 2, 30 mL/min or less, not requiring dialysis). Eleven patients were assigned to the lower dose of 0.1 mmol Gd/kg and 10 patients to the higher dose of 0.3 mmol Gd/kg. To calculate pharmacokinetic parameters, urine and venous blood samples were drawn at baseline and up to 72 hours for group 1 and 120 hours for group 2 after administration of gadobutrol. RESULTS: The predominant extracellular distribution of gadobutrol at steady state did not change according to the degree of renal impairment. The mean elimination half-life of gadobutrol increased to 7.4 +/- 2.6 hours (0.1 mmol/kg) and 5.4 +/- 1.5 hour (0.3 mmol/kg) in group 1 and to 17.9 +/- 6.2 hours (0.1 mmol/kg) and 20.4 +/- 16.9 hours (0.3 mmol/kg) in group 2, compared with 1.5 hours in healthy volunteers. The relation between serum (tbeta) and urine (t(elim)) elimination half-lives, as well as total serum and renal clearance, indicated renal elimination as the main pathway of elimination. The recovery of gadobutrol in the urine of group 1 was complete within 72 hours for both dosage levels. Patients with severe renal impairment showed a mean recovery of 80.1% (0.1 mmol/kg) and 85.3% (0.3 mmol/kg) within the observation period of 120 hours. CONCLUSIONS: The half-life of gadobutrol is prolonged in patients with impaired renal function, but elimination by means of the kidneys is the predominant route.

[Safety and use of gadobutrol in patients with brain tumors (phase III trial)]. / Sicherheit und Nutzen von Gadobutrol bei Patienten mit zerebralen Tumoren (Phase-III-Studie).

PURPOSE: The purpose of the study was to investigate the use and safety of Gadobutrol, a new low-osmolar, non-ionic contrast agent for MRI using a total dose of 0.3 mmol/kg b.w. on the basis of a clinical phase 3 study. METHODS: 30 patients with primary brain tumours (n = 15) or cerebral metastases (n = 15) were examined via MRI before and after application of a total of 0.3 mmol/kg b.w. given in two fractions (0.1 and 0.2 mmol/kg b.w.). T2-weighted images were performed before, T1-weighted images before, between and after application of contrast material. RESULTS: In this study one-molar Gadobutrol showed a good tolerance. In half of the cases the contrast between lesion and brain was improved comparing single and triple dose, but this means only a slightly improvement of information for the primary brain tumours compared with single dose. The detected metastatic lesions increased in 40% of the patients after the single dose and in 53% of the patients after cumulative triple dose. There was a consecutive change in therapy in 20% of the patients. CONCLUSION: For the differentiation of primary brain tumours the single dose was sufficient, in metastatic lesions triple dose was essential for the detection or exclusion of multifocality.

Local complications after arterial bypass grafting.

We have documented prospectively the problems occurring after 496 arterial bypass grafts (149 aortoiliac, 238 femorodistal, 65 extra-anatomic, and 44 others) implanted during the period 1987 to 1991 in a district general hospital. Postoperative bleeding occurred early in 14 (2.8%), and later (because of infection) in 3 (0.6%). Early graft occlusion (< 30 days) was seen in 2.9% aortofemoral, 10.4% femoropopliteal, and 25.3% femorotibial grafts, and amputation was required after 6.9% grafts. Wound problems were most common after femorotibial bypass--weeping of fluid in 3% and dehiscence or infection in 13.9%. Lymphatic collections occurred after 1.2% operations involving groin incisions. Graft sepsis was usually late, affecting 6% aortofemoral, 2.9% femorodistal, and 7.7% extra-anatomic grafts, but no intra-abdominal aortic grafts. These figures are probably representative of the complication rates seen by many surgeons and serve as an example for comparison and criticism.

Pertrochanteric fractures in the elderly. Is the Belgian VDP prosthesis the best treatment for unstable fractures with severe comminution?

During a ten year period (1978-1988) 565 patients, aged 70 years and over, suffering a fresh pertrochanteric fracture have been treated in the Department of Traumatology at the University Hospitals of Leuven, Belgium. According to the system of Evans and Jensen, 388 fractures were classified as unstable. Special attention was given to the 324 cases of type I C and I D fractures. The method of treating greatly changed during the period of study. All patients were followed up prospectively during one year. Our study showed that for these unstable fractures, fixation with an angled plate or Ender nails should be forsaken. The overall results of the dynamic hip screw treatment were good (reoperation rate 2%, good functional results in 64%), but as this treatment has a risk for serious collapse and pain in about 80% of all type I D fractures, one could suggest to treat these complex multifragment fractures primarily with an endoprosthesis. This treatment needs no longer to be considered as a severe intervention, as the danger of mechanical complications being very minimal (less than 1%).

Pertrochanteric fractures in the elderly: are there indications for primary prosthetic replacement?

During a 10-year period (1978-1988), 565 patients, aged greater than or equal to 70 years, who sustained a fresh pertrochanteric fracture, were treated in the Department of Traumatology at the University Hospitals of Leuven, Belgium. Three hundred eighty-eight fractures were complex and unstable, according to the Evans-Jensen system and the AO system. Special attention was given to the 324 cases of type IC and ID in Evans' system, type A2 in the AO system. The method of treatment changed greatly during the period of study. All patients were followed prospectively during 1 year. Our study showed that for these unstable fractures, fixation with an angled plate or Ender nails should be forsaken. The overall results of the compression hip screw treatment were good (reoperation rate 2%, good functional results in 64%), but as this treatment has a risk for serious collapse and pain in about 80% of all type ID fractures, one could suggest treating these complex multifragment fractures primarily with an endoprosthesis. This treatment need no longer be considered severe intervention, as the danger of mechanical complications is minimal (less than 1%).