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PubMed1989

Apparent coagulopathy caused by infusion of shed mediastinal blood and its prevention by washing of the infusate.

We found that reinfusion of shed mediastinal blood (SMB) after a cardiac operation was associated with laboratory evidence of disseminated intravascular coagulation. In view of this, we compared the effect of infusing washed or unwashed SMB on the coagulation profiles and blood use of two serial groups of patients undergoing cardiopulmonary bypass. We found that the results of testing for fibrin degradation products converted from negative to positive in 17 of 20 patients who received unwashed SMB versus 1 of 14 patients who received washed SMB (p less than 0.0001). Other coagulation studies did not reveal disseminated intravascular coagulation in either group, nor were there differences in blood use between the two groups. The unwashed SMB contained high titers of fibrin degradation products (mean reciprocal titer = 354 +/- 161) compared with washed SMB (mean reciprocal titer = 34 +/- 18) (p less than 0.01). Based on the volume of SMB infused, the amount of fibrin degradation products in unwashed SMB was sufficient to account for the positive fibrin degradation product assays after infusion in this group. We conclude that infusion of unwashed SMB may confuse the interpretation of tests for disseminated intravascular coagulation or fibrinolysis. As this could lead to unnecessary blood component use and is preventable by washing before infusion, we recommend that the routine infusion of unwashed SMB no longer be employed.

Blood Coagulation Tests↗
PubMed2006

Comparison of a bolus of fentanyl with an infusion of alfentanil during target-controlled propofol infusion in third molar extraction under conscious sedation.

PURPOSE: This study was designed to compare hemodynamic changes, respiratory depression, and patient satisfaction between a bolus of fentanyl and an infusion of alfentanil during target-controlled propofol infusion in third molar extraction under conscious sedation. PATIENTS AND METHODS: Forty patients were randomly assigned to receive either a bolus of fentanyl (n = 24) or an infusion of alfentanil (n = 16) in combination with target-controlled propofol infusion. Hemodynamic changes, respiratory depression, sedation, and cooperation scores were recorded during surgery and patient satisfaction scores were assessed after surgery. RESULTS: Changes in mean blood pressure, heart rate, or oxygen saturation within and between the groups were not significant throughout the procedure. There were no significant differences in sedation, cooperation, and patient satisfaction scores between the 2 groups. CONCLUSION: Because there was no difference in hemodynamic variables and patient satisfaction scores between a bolus of fentanyl and an infusion of alfentanil during target-controlled propofol infusion, both combinations are suitable for conscious sedation in third molar extraction.

Adult↗
PubMed1996

Sensitization of esophageal mucosa by prior acid infusion: effect of decreasing intervals between infusions.

OBJECTIVE: To determine the effect of decreasing time intervals between acid exposures on the sensitivity of the esophageal mucosa. METHODS: Ten healthy subjects with no history of gastroesophageal reflux disease who were symptomatic during a modified Bernstein acid infusion test were recruited for the study. Hydrochloric acid solutions of pH 3, 2, and 1 were sequentially tested. The weakest pH solution that was perceived by the patient was used for the study. The same duration of acid infusions (9 ml/min for 5 min) were made but with decreasing time intervals between each subsequent acid infusion (30-0 min). Esophageal sensation during each of the infusions, the amount of distilled water required to raise intraesophageal pH > 4, and the duration of residual heartburn after pH > 4 were recorded. RESULTS: Seven of the 10 subjects (70%) were Bernstein-positive to pH 3, two to pH 2, and only one to pH 1 solution. The median time to initial heartburn was significantly reduced only between the initial infusion and the first subsequent acid exposure 30 min later (165 vs 51.5 s, p < 0.009). Subsequent reductions in the time interval between infusions did not significantly reduce the perception threshold. The water required to clear the esophagus to pH > 4 and time required for the residual esophageal sensation to disappear were not significantly altered throughout the study. CONCLUSIONS: These data suggest that some episodes of reflux may be felt sooner and perhaps more severely despite similar levels of acid burden in the esophagus when sensitization by a prior reflux episode occurs.

Adult↗
PubMed2006

The delivery of drugs to patients by continuous intravenous infusion: modeling predicts potential dose fluctuations depending on flow rates and infusion system dead volume.

IV drug infusion has the potential for dosing errors, which arise from complex interactions between carrier flows and the infusion set dead volume. We computed the steady-state mass of drug stored in the infusion set dead volume, using phenylephrine as a model compound. The mass of drug in the dead volume increases with stock drug concentration and desired dose but decreases with carrier flow rate. We also modeled the dynamic perturbations in drug delivery when a carrier is abruptly stopped. Rapid initial carrier flow rates lead to greater depression in drug delivery rate after carrier flow ceases. Rapid drug infusion rates lead to faster restoration of desired drug delivery. Finally, the time to reach a new steady-state after a change in drug delivery or carrier rate was computed. This time is longest for large stock-drug concentrations, larger dead volumes, and slower final carrier rates. These computations illustrate that (a) the dead volume may contain a large mass of drug available for inadvertent bolus, (b) cessation of carrier flow can profoundly reduce drug delivery, and (c) after a change in carrier flow or drug dosing, a significant lag is possible before drug delivery achieves steady state. Although computed for phenylephrine, the concepts are generic and valid for any drug administered by IV infusion.

Aged↗
PubMed1994

A phase I/II study of alternating constant rate infusion floxuridine with constant rate infusion vinblastine for the treatment of metastatic renal cell carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) is largely chemoresistant. The efficacy of cell cycle specific chemotherapeutic agents, particularly those with short half-lives, may be enhanced by the use of constant rate infusion schedules. Infusional floxuridine has been demonstrated to have a response rate of approximately 20%. Infusional vinblastine has not been tested extensively in patients with metastatic RCC. The sequential use of these agents was designed to increase efficacy and limit toxicity. METHODS: Fifteen patients with metastatic RCC were treated with constant rate infusion floxuridine, 0.075 mg/kg/day for 14 days, followed by a constant rate infusion of vinblastine, 0.7 mg/m2/day for 14 days. The cycle repeated every 28 days and floxuridine and vinblastine doses were incrementally increased until the maximum tolerated dose (MTD) for each patient was reached. RESULTS: Four patients had partial responses (27%), which were maintained for 3, 9, 16 and 19+ months, whereas five patients had stable disease for 3-15 months. Median survival from initiation of therapy was 379 days. Three of four responses occurred in nonpulmonary locations, and all responses occurred in patients who had a prior nephrectomy. MTD for floxuridine was 0.1 mg/kg/day and for vinblastine, 0.7 mg/m2/day. Toxic reaction to floxuridine was limited to diarrhea, whereas the principle dose-limiting toxic reaction for vinblastine was neutropenia. Catheter-related complications were also observed. CONCLUSIONS: Alternating constant rate infusion floxuridine and constant rate infusion vinblastine is active in the treatment of metastatic RCC. Whether this regimen is superior to infusional floxuridine is undetermined. Although the toxicity associated with this regimen is manageable, it appears to be more severe than that reported with infusional floxuridine alone.

Adult↗
PubMed1985

Clinical pharmacokinetics of 6-hour infusion of high-dose methotrexate. Preliminary trial of monitoring high infusion doses.

Methotrexate (MTX) in serum was measured by RIA in 12 cancer patients receiving high doses of MTX (2 to 8 g/m2) in 6 hour infusions 69 treatments were studied. The peak serum level was proportional to the dose administered and was always greater than 10(-4) M. 2 elimination phases were seen: the first had a mean half-life of 2.36 h and the second a mean half-life of 16.14 h. 24 hours after beginning the infusions there were very large variations in individual serum concentrations of MTX, from 2.4 10(-6) M to 1.9 10(-5) M by 24 h after 8 g/m2. To control these variations, a mathematical model for prediction of the individual pharmacokinetic pattern of a 6 hour-infusion of high-dose MTX by kinetic analysis of a low-test dose is proposed. A program was created for an Apple III computer using toxic and therapeutic serum levels of MTX selected by the clinician. The computer program is adaptable to any infused substance for variable infusion times, thus introducing new advances over existing methods.

Adolescent↗
PubMed1993

Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain.

Experiments were designed to examine the analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5% formalin into one hind paw. Formalin-induced pain responses were continuously recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min; the analgesia was more potent and longer-lasting when DiMe-C7 was infused after, rather than prior to, the early pain phase. In another set of experiments, rats were tested in the formalin test immediately following bilateral infusions of amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed to alter pain responses when infused into the mPFC, but both doses attenuated pain responses during 25 min when infused into the NAS. There was no evidence for pain inhibition in the tail-flick test for phasic pain following either intra-VTA DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra-NAS amphetamine produces analgesia in the formalin, but not the tail-flick test, suggests that activation of mesolimbic dopamine (DA) neurons contributes to suppression of tonic pain. Because stressors attenuate tonic pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of pain- or stress-induced pain inhibitory system.

Amphetamine↗
PubMed1981

Continuous subcutaneous insulin infusion: comparison of plasma insulin profiles after infusion or bolus injection of the mealtime dose.

To help optimize meal-time blood glucose control in diabetic patients by continuous subcutaneous insulin infusion we have studied plasma insulin profiles in six normal subjects, suppressing endogenous insulin secretion with somatostatin. Insulin was administered subcutaneously either as a bolus or by high-rate infusion. Mean infusion profiles were similar on the two occasions, with peak levels at 75 and 90 min respectively, and a linear decline to 34% and 36% of peak concentrations at 5 h. Bolus injection resulted in a faster rise in insulin concentration, more consistent with physiological requirements. It is concluded that bolus delivery would be similar in effect while mechanically simpler to achieve than infusion, when part of a dual rate subcutaneous infusion system. The dose should be given 30 min before meals, if peak insulin concentrations are to be coincident with those found physiologically. Insulin concentrations remain high in the post-absorptive phase.

Adult↗
PubMed1991

Comparison of continuous and intermittent bolus infusions of metoclopramide during 5-day continuous intravenous infusion with cisplatin.

In order to decide the administration method of metoclopramide for prevention or control of chemotherapy-induced nausea and vomiting in multidrug chemotherapy, with cisplatin 5-day continuous intravenous infusion (25 mg/m2/day) for patients with advanced lung cancer, a randomised crossover study of intermittent bolus infusion (1 mg/kg, 30 min, every 8 h, day 1-5) and continuous infusion (3 mg/kg/24 h, 120 h) of metoclopramide was performed. Both regimens included methylprednisolone and diphenhydramine given concurrently. The acute and delayed antiemetic effects were examined. 21 cases could be evaluated. There were 6 and 10 cases (P = 0.048), respectively, of no nausea and no vomiting; 14 and 18 cases (P = 0.048), respectively, of no vomiting; and vomiting episodes were seen 27 and 9 times, respectively (P = 0.042). Thus, metoclopramide continuous infusion was significantly superior in antiemetic effect compared to bolus infusion. Neither method had any serious side-effects and both were safe.

Adult↗
PubMed1992

Intravenous milrinone following cardiac surgery: I. Effects of bolus infusion followed by variable dose maintenance infusion. The European Milrinone Multicentre Trial Group.

The hemodynamic and adverse effects of intravenous milrinone were studied in 99 adult patients (66 men) following elective myocardial revascularization, mitral and/or aortic valve surgery. All patients had a low cardiac output (cardiac index [CI] mean 1.93, range, 1.11 to 2.5 L/min/m2) despite adequate cardiac filling pressure (mean pulmonary capillary wedge pressure [PCWP] 11.5 mmHg, range, 8 to 20 mmHg). Following a period of baseline stability (mean 17.8 minutes, range, 10 to 50 minutes), patients received a bolus infusion of 50 micrograms/kg over 10 minutes. A continuous maintenance infusion of 0.375 (low), 0.5 (mid) or 0.75 (high) micrograms/kg/min was administered for a minimum of 12 hours. Patients were allocated to each dosage group sequentially, not randomly. Hemodynamic measurements were made before the start of milrinone and 15 minutes after the bolus infusion. Further measurements were made at 30, 45, and 60 minutes, and at 3, 6, and 12 hours after the start of treatment. Measurements were also made at 2 and 4 hours after treatment was stopped. The bolus infusion caused significant increases in CI, heart rate (HR), and stroke index (SI), (P < 0.001), and significant falls in PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), mean arterial pressure (MAP), and systemic vascular resistance (SVR) (P < 0.001). These effects were maintained to a significant degree by each of the three maintenance infusion regimens, although the pulmonary vasodilator effects appeared less predictable and more dose dependent. Eighteen patients (19%) had arrhythmias; 16 of these were judged not to be serious events. Two were deemed serious; these were both episodes of fast atrial fibrillation (AF).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects.

BACKGROUND: Antiepileptic drugs are usually administere dorally, but alternative routes of drug delivery may be required when oral administration is not feasible. OBJECTIVE: The purpose of this study was to evaluate the single-dose bioavailability of an IV formulation of levetiracetam relative to oral tablets and the multiple-dose tolerability and pharmacokinetics of this formulation compared with placebo in healthy subjects. METHODS: This study consisted of 2 phases. Subjects entered the first phase, which was a single-dose, randomized, open-label, 2-way crossover bioavailability comparison of a 15-minute IV infusion of levetiracetam 1,500 mg and three 500-mg oral tablets. Subjects then entered the second phase, a multiple-dose, randomized, double-blind, placebo-controlled (2:1), parallel-group tolerability and pharmacokinetic study, in which they received 9 successive doses of levetiracetam 1,500 mg IV or placebo at 12-hour intervals. Plasma levetiracetam concentrations were determined by gas chromatography with nitrogen-phosphorus detection. The comparison of bioavailability was based on the 90% CIs around the geometric mean ratios for AUC and C(max) (IV/oral). RESULTS: Eighteen subjects (9 men, 9 women) participated in the study. All subjects were white. Their mean (SD) age was 35.0 (9.3) years, mean weight 73.3 (14.2) kg, and mean body mass index 23.9 (2.5) kg/m(2). After a single dose, the IV infusion and oral tablet were similar in terms of C(max) (50.5 and 47.7 microg/mL, respectively) and AUC (392.4 and 427.9 pg x h/mL). The geometric mean IV/oral ratios were 92.2 (90 % CI, 89.0-95.6) for AUC and 103.7 (90% CI, 91.6-117.4) for C(max) indicating that the IV and oral formulations were bioequivalent. After multiple twice-daily infusions, steady state was reached within 48 hours. Seventeen (94%) of 18 subjects had >or=1 treatment-emergent adverse event after single-dose administration. During the single-dose phase, the incidence of treatment-emergent adverse events was 89% (16/18) for the IV formulation and 72% (13/18) for the oral tablets; during the multiple-dose phase, the incidence of treatment-emergent adverse events was 67% (8/12) in the IV levetiracetam group and 33% (2/6) in the placebo group. The most common adverse events in the single-dose phase were somnolence (61% IV vs 28% oral) and postural dizziness (17% vs 39%, respectively). The most common adverse events with IV levetiracetam in the multiple-dose phase were also somnolence (33% vs 17% placebo) and postural dizziness (25% vs 0% placebo). CONCLUSIONS: In these healthy subjects, single doses of levetiracetam 1,500 mg administered as a 15-minute IV infusion and as oral tablets were bioequivalent. General and local tolerability during multiple dosing were good. Steady state was reached within 48 hours. Despite the limitations of a study of short duration and small size conducted in healthy subjects, the findings suggest that use of a 15-minute IV infusion of levetiracetam should be further investigated.

Administration, Oral↗
PubMed2003

A comparison between hepatic artery ligation and portal 5-Fu infusion versus 5-Fu intra arterial infusion for colorectal liver metastases.

AIM: A prospective randomized study was executed comparing two regimens of regional therapy for liver metastases from colorectal cancer. METHODS: Eighteen patients were allocated to hepatic artery occlusion for 16 h followed by intraportal 5-fluorouracil (5-Fu) infusion (1000 mg/m(2)) for 5 days every sixth week (HAO). Twenty-one patients received intra-arterial 5-Fu infusion+Leucovorin (100 mg) i.v. for 2 days every second week (HAI). The follow up every third month included CT and CEA. Thirteen patients had limited extrahepatic cancer. At tumor progression regional therapy was stopped and systemic chemotherapy or the best supportive care was administered. RESULTS: The study was discontinued after randomization of 39 patients. No significant difference in survival within patients with and without extrahepatic cancer was present. The mean survival was longer in the HAI group than for the HAO group (19 months versus 13 months, p=0.0147) (median 18 (8-37) versus 12 (2-26). PR and SD were registered in 8/18 in the HAO group and 17/21 patients in HAI group. The median time to progress was 4 (1-22) months versus 7 (1-23) months for the HAO and HAI group, respectively. CONCLUSION: Regional intraarterial infusion with 5-Fu gives significantly better survival than hepatic artery occlusion followed by portal infusion. A limited amount of extrahepatic cancer does not influence survival time. A trial comparing hepatic artery 5-FU infusion and Leucovorin versus the most effective systemic therapy is warranted.

Adult↗
PubMed2006

[Comparison of a propofol-based anesthesia regimen using optimated-target-controlled-infusion (OTCI) and manually-controlled infusion (MCI) technique].

BACKGROUND: Propofol anesthesia based on target-controlled-infusion (TCI) has been shown to be superior to a manually-controlled-infusion (MCI) technique. A new optimal-target-controlled-infusion (OTCI) technique enables an individual plasma-targeted adjustment by including the concentration in the effect-compartment. This study compared practicability and costs of the new system with a conventional MCI-based propofol anesthesia regimen. METHODS: In a prospective study, 50 patients scheduled for elective surgery of nose or nasal sinuses were randomly enrolled to receive BIS-controlled anaesthesia (level: 40-55) using either OTCI (n = 25) or MCI (n = 25). Hemodynamics, extubation times and time of awaking, rate and quality of propofol adjustment, total drug requirements, costs, postanaesthetic care unit (PACU) stay, Aldrete and pain scores, and adverse effects (postoperative nausea and vomiting (PONV), shivering) were recorded. RESULTS: Demographics, hemodynamics, and perioperative data including extubation times were comparable for both study groups. Propofol consumption was similar within the first 60 min for both groups, thereafter, significantly less propofol in the OTCI group (5.03 mg/kg/h) than the MCI group (5.79 mg/kg/h) was used. Costs for propofol was significantly reduced with OTCI (0.2 vs. 0.23 Cent/anaesthesia minute/kg), the administration of other anaesthetics (fentanyl, remifentanil, cis-atracurium) did not differ between the groups. The number of infusion adjustments to BIS values were not significantly different. CONCLUSION: The new OTCI-system is a safe and easily controllable technique. The obvious advantage of this infusion system appears to be a reduction in propofol consumption and direct drug costs for anaesthesia lasting longer than 60 min.

Adolescent↗
PubMed1991

A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome.

BACKGROUND: Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. METHODS: We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). RESULTS: The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient. CONCLUSIONS: In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.

Acute Disease↗
PubMed2006

Phase I trial of continuous infusion 9-aminocamptothecin in patients with advanced solid tumors: 21-day infusion is an active well-tolerated regimen.

This study's objectives were to determine the maximum tolerated dose (MTD) of 9-aminocamptothecin (9-AC), given as a prolonged continuous infusion (CI) for 7-21 days, when formulated in dimethylacetamide/polyethylene glycol 400 (DMA) and then later as a colloidal dispersion (CD), and to determine the steady-state pharmacokinetics of 9-AC. Patients with solid tumors refractory to standard therapy were enrolled on this study. Total dose/cycle of 9-AC/DMA was initially escalated by duration (7-21 days), while keeping the dose rate constant at 6.2 microg/m/h (1.04-3.12 mg/m/4-week cycle). Then, the dose rate was escalated from 6.2 to 21.1 microg/m/h (3.12-10.6 mg/m/4-week cycle) while keeping the infusion duration constant at 21 days. CD formulation was escalated from 14.1 to 25 microg/m/h (7.11-12.60 mg/m/4-week cycle) while keeping the infusion duration constant at 21 days and then escalated from 28.1 to 37.5 microg/m/h (9.44-12.60 mg/m/3-week cycle) while keeping the infusion duration constant at 14 days. Sixty-two patients were evaluable for toxicity; 61 received prior chemotherapy (median 3 regimens/patient). No consistent dose-limiting toxicity (DLT) was encountered with the DMA formulation until dose level 10.60 mg/m/cycle, when two patients experienced DLTs. With the 21-day CD formulation, the MTD was 12.60 mg/m/cycle with three DLTs out of five patients. When 9-AC was given on the 14-day schedule, DLT was seen at 9.44, 11.20 and 12.60 mg/m/cycle, with consistent DLT at the two highest dose levels. All DLTs for both formulations were grade 4 hematologic toxicities (neutropenia and/or thrombocytopenia), while non-hematologic toxicities were relatively mild (including gastrointestinal toxicities and fatigue). One patient with ovarian cancer had a complete response and three had partial responses (PRs). One patient each with non-Hodgkin's lymphoma and cancer of unknown primary had a PR. Pharmacokinetic studies of both formulations of 9-AC revealed a linear relationship between increasing plasma 9-AC lactone concentration and dose. The median plasma 9-AC lactone concentration for 9-AC/CD was approximately twice that achieved by 9-AC/DMA for the same dose level. Both 9-AC formulations, given as a 21-day CI, were well tolerated with dose-limiting myelosupression at the MTD. This dose intensity exceeds that of other 9-AC phase I/II schedules. The recommended phase II dose (RPTD) is 9.42 mg/m/4-week cycle, given as a 21-day infusion. The 14-day schedule of 9-AC/CD was equally myelosuppressive with the RPTD of 9.44 mg/m/3-week cycle, although two heavily pre-treated patients (one with pelvic radiotherapy) could not tolerate this dose. Objective responses were observed in six out of 57 heavily pre-treated patients, most of which had ovarian cancer.

Adult↗
PubMed1992

Relationship between infusion rates, plasma concentrations, and cardiovascular and metabolic effects during the infusion of norepinephrine in healthy volunteers.

OBJECTIVE: To determine the relationship between iv infusion rate, plasma concentrations, and hemodynamic and metabolic actions of norepinephrine. DESIGN: Norepinephrine was administered by using five iv infusion rates (0.01 to 0.2 micrograms/kg/min) for 30 mins each to eight volunteers, for the purpose of constructing cumulative plasma concentration-response curves. SETTING: Laboratory of the Department of Anesthesiology at a university hospital. MEASUREMENTS AND MAIN RESULTS: Systolic and diastolic BP, heart rate, and the plasma concentrations of norepinephrine, glucose, nonesterified fatty acids, and insulin were measured at the end of each infusion rate. During the highest infusion rate, plasma norepinephrine concentrations increased from 199 +/- 75 to 7475 +/- 1071 pg/mL (1.18 +/- 0.44 to 44.18 +/- 6.33 nmol/L). Typical hemodynamic responses, such as increases in BP and decreases in heart rate, were seen, while the plasma concentrations of glucose and nonesterified fatty acids increased from 92 +/- 10 to 132 +/- 17 mg/dL (5.1 +/- 0.6 to 7.3 +/- 0.9 mmol/L) and 11 +/- 4 to 34 +/- 6 mg/dL (0.11 +/- 0.04 to 0.34 +/- 0.06 g/L), respectively, during the 0.2 micrograms/kg/min infusion rate (p less than .05). Despite the increase in glucose concentration, insulin remained at baseline values. Metabolic and hemodynamic effects occurred at similar plasma concentrations throughout the study. CONCLUSIONS: Administration of norepinephrine showed no selective hemodynamic actions. The metabolic responses observed in this investigation were similar to those responses seen during increased endogenous sympathetic nervous system activity, such as stress, exercise, or trauma.

Adult↗
PubMedDate not supplied

Hepatic CT contrast enhancement: effect of dose, duration of infusion, and time elapsed following infusion.

Contrast enhancement of the liver of anesthetized, paralyzed, and artificially ventilated rabbits was measured during suspended respiration prior to, during, and after the intravenous infusion of meglumine diatrizoate at doses of 208, 416, and 624 mg I/kg. Infusion time was 30 seconds, and, at the highest dose, infusion times of 1, 2, and 4 minutes were also used. Highest contrast enhancement values were obtained at the conclusion of each infusion, with contrast enhancement increasing proportionately with increase in dose. Highest enhancement was obtained at all times studied from the most rapid infusion. Unlike cranial CT, optimum hepatic contrast enhancement in body CT requires rapid contrast medium injection with immediate CT scanning with a very fast scanner.

Animals↗
PubMed1980

The intraarterial infusion of chemotherapeutic agents as "basal" treatment of cancer: evidence of increased drug activity in regionally infused tissues.

There is evidence from a number of centres that some forms of locally advanced and aggressive cancers which are difficult to eradicate by standard means can be reduced by the use of "basal" chemotherapy and/or surgery. Clinicians have been divided as to whether there is an advantage in giving the chemotherapeutic agents directly into a regional artery of supply where this is feasible, as opposed to their systemic administration. This paper documents supportive evidence that some and possibly many chemotherapeutic agents are more effective if given regionally into an artery of supply. There is a higher incidence of local side-effects in the region infused, including loss of hair, inflammatory changes, and ulceration of the skin or mucosa of the region infused. After intraarterial infusion of tagged bleomycin (indium-III bleomycin) into a limb, the radioactive isotope remained more concentrated in the limb infused than in the opposite limb for at least 24 hours. Systemic side-effects, including bone-marrow depression, are less frequent and less severe in patients given chemotherapeutic agents by intra-arterial infusion than if the same doses of agents are given intravenously. There is now sufficient evidence of the value of basal chemotherapy used in this way to make it mandatory that medical oncologists and surgeons, working together, should plan controlled studies to determine the most appropriate applications of this technique of management.

Antineoplastic Agents↗