Pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To determine the pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery. DESIGN: Prospective, multigroup study. SETTING: University-affiliated hospital. PARTICIPANTS: Patients with good left ventricular function undergoing elective surgery (n = 103). INTERVENTIONS: Sufentanil was administered by target-controlled infusion, with target effect-site concentrations ranging from 0.4 to 4.5 ng/mL. Isoflurane was administered as required to maintain stable hemodynamics. Sufentanil pharmacokinetics were determined by population modeling. The potential effects of gender, weight, different premedications (lorazepam, morphine-scopolamine, or clonidine), and coinduction with propofol on sufentanil pharmacokinetics were explored. MEASUREMENTS AND MAIN RESULTS: The first model determined was a simple 3-compartment model, without any covariates, which had these parameters: V(1) = 5.7 L, V(2) = 18.1 L, V(3) = 225 L, Cl(1) = 0.69 L/min, Cl(2) = 3.1 L/min, and Cl(3) = 1.4 L/min. The overall predictive ability during the entire pre-cardiopulmonary bypass period of this model was excellent, with virtually no bias (median prediction error, -0.4%) and good precision (median absolute prediction error, 18.4%). More complex models with the various premedications used or coinduction with propofol as covariates did not improve the predictive accuracy or precision compared with the simple 3-compartment model. Similarly, including either gender or weight as a covariate did not improve predictive ability. CONCLUSION: The authors have determined a pharmacokinetic model for sufentanil that can be used to maintain desired target concentrations of sufentanil before cardiopulmonary bypass, with a high degree of accuracy and acceptable variability. Concomitantly administered medications (lorazepam, morphine-scopolamine, clonidine, or propofol) do not appear to have any clinically important effects on distribution-phase sufentanil pharmacokinetics.

Concentration-response relationships for fentanyl and sufentanil in patients undergoing coronary artery bypass grafting.

BACKGROUND: Concentration-response relationships for sufentanil and fentanyl are undefined in patients undergoing coronary artery bypass grafting. METHODS: Separate studies of sufentanil and fentanyl were performed in lorazepam-premedicated patients undergoing coronary artery bypass grafting. Patients were assigned randomly to groups with different prebypass effect-site opioid concentrations targeted by computer-assisted infusion. The target sufentanil concentrations were 0.4 ng/ml (group LS, n = 11), 0.8 ng/ml (group MS, n = 10), and 1.2 ng/ml (group HS, n = 11); the target fentanyl concentrations were 5 ng/ml (group LF, n = 7), 10 ng/ml (group MF, n = 7), and 15 ng/ml (group HF, n = 6). Propofol at a dose of 1 mg/kg was administered at induction of anesthesia and isoflurane was used for hemodynamic control Hemodynamics, end-tidal isoflurane concentration, and opioid concentration in arterial blood were measured at specific intervals. RESULTS: Intraoperative opioid concentrations were constant, averaging 0.71 +/- 0.13, 1.25 +/- 0.21, and 2.03 +/- 0.46 ng/ml for groups LS, MS, and HS, respectively, and 7.3 +/- 1.1, 13.2 +/- 2.2, and 24.4 +/- 5.8 ng/ml for groups LF, MF, and HF, respectively (all mean +/- SD). Isoflurane requirements were significantly greater in group LS than in groups MS and HS and greater in group LF than in groups MF and HF. The serum opioid and end-tidal isoflurane concentrations were correlated significantly. There were no intergroup differences in hemodynamics. CONCLUSIONS: Serum sufentanil and fentanyl concentrations of 0.71 +/- 0.13 ng/ml and 7.3 +/- 1.3 ng/ml, respectively, are on the steep parts of the concentration-response relationships and facilitate prebypass hemodynamic control in patients undergoing coronary artery bypass grafting with opioid-isoflurane anesthesia. Concentrations of sufentanil > or = 1.25 +/- 0.21 ng/ml and of fentanyl > or = 13.3 +/- 2.2 ng/ml minimize isoflurane requirements but do not improve hemodynamic control.

Brain implants in man do not break down the blood-brain barrier to dopamine and domperidone.

We have evaluated the blood-brain barrier (BBB) in 8 Parkinsonian patients before and after stereotactic implantation of foetal mesencephalon (STIM) and one patient with an adrenal medullary implant. Parenteral administration of dopamine did not reverse Parkinsonism pre-operatively or at 5 days, 1, 2, 3, 4 months and 1 year post-operatively. Apomorphine and domperidone reversed Parkinsonism and produced dyskinesia in all patients pre- and post-operatively. We conclude that the BBB remains intact to dopamine following implantation.

Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease.

Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome.

A comparative evaluation of clinical rating scales and quantitative measurements in assessment pre and post striatal implantation of human foetal mesencephalon in Parkinson's disease.

Six patients with advanced Parkinson's Disease were evaluated before and after implantation of human fetal ventral mesencephalic tissue to the head of the right caudate nucleus. The results of clinical assessment indicate that attempts to characterise patient fluctuations requires a combination of clinical rating scales and timing of specific limb tasks.

A series of experimental surgery for advanced Parkinson's disease by foetal mesencephalic transplantation.

12 patients with advanced Parkinson's Disease who had right caudate implantations of late stage foetal mesencephalon have been followed up for 1 to 2 years with extensive clinical and physiological assessments. Three patients failed to comply and were excluded. Seven of the remaining 9 patients showed substantial initial improvement which was well maintained in 4. Two of the 3 remaining patients of this group maintained lesser improvement. One returned to pre-operative state. Two patients with greatly advanced disease had only slight but brief improvement. A series of 24 matched patients have been treated and continue under investigation.

Stereotactic implantation of fetal mesencephalon.

Twelve patients with advanced Parkinson's disease have been improved by transplantation of fetal mesencephalon into the caudate nucleus. No immunosuppression had been used. The human allogeneic transplantation window is wide.

Giant cell tumor of the skull: case report.

The case of a 16-year-old girl with giant cell tumor involving the occipital bone is described. The radiological and pathological findings are detailed, followed by a discussion of the literature.

The Freeman-Swanson ICLH total knee arthroplasty. Complications and problems.

Seventy Freeman-Swanson ICLH total-knee arthroplasties were performed in fifty-eight patients. Five major prosthetic problems and complications were encountered: (1) instability, (2) abnormal prosthetic insertion, (3) prosthetic loosening, (4) patellofemoral abnormalities, and (5) cement debris. These major problems and other complications resulted in an over-all reoperation rate of 28.5 per cent. Instability and abnormal prosthetic insertion seemed to be the primary factors that led to loosening. Eight knees were revised with other prostheses while three were fused because of gross loosening and instability. Two additional knees required an arthrodesis because of deep infection, resulting in a failure rate of 18.5 per cent. Clinical and roentgenographic abnormalities appeared to correlate with the failures of this total knee replacement. Modifications in the prosthetic design and improved surgical technique could obviate many of these complications and problems.