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PubMed1996

Modification of the blood-brain barrier permeability by vinorelbine: effect of intracarotid infusion compared with intravenous infusion.

Brain levels of the antineoplastic compound, vinorelbine, and its effects on the permeability of the blood-brain barrier (BBB) were studied. Preliminary experiments were carried out to define the dose of 10 mg/kg and the delay of 3 h after infusion required to induce BBB disruption. Vinorelbine was infused by i.c. or i.v. infusion to anesthetized male Sprague-Dawley rats. BBB disruption was evaluated qualitatively by the presence in the infused hemisphere of i.v. administered Evans blue dye (2%) and vinorelbine intratissular levels were measured by HPLC. After an i.c. infusion, there is an important variability in the degree of extravasation of Evans blue albumin complex, which is correlated with vinorelbine levels (p < 0.01). The percent of dose in brain tissue is less than 1%. After an i.v. infusion, the parenchyma is globally affected as shown by the uniform faint bluish staining of the two hemispheres. Vinorelbine levels are homogenous and similar to levels of brains graded + 1 after an i.c. infusion. These results seem to indicate that an i.c. infusion induces localized BBB disruptions while the effect of an i.v. infusion is global and that the gain in tissue level after an i.c. infusion is low compared with i.v. infusion.

Animals↗
PubMed1987

Pharmacodynamics and pharmacokinetics of urapidil in hypertensive patients: a crossover study comparing infusion with an infusion-capsule combination.

The pharmacokinetics and haemodynamic effects of infused urapidil and an infusion-capsule combination were followed to study the correlation between the serum urapidil level and the blood pressure. Prior to urapidil administration, basal blood pressure and heart rate were measured for 16 h in 12 male hypertensive patients. Six patients received infusions lasting for 4 h of urapidil 10, 2.5 and 5 mg/h. Six patients were infused with urapidil 10 mg/h for 4 h and 2 h after the end of the infusion each took a 60-mg capsule. After a 5 day washout period the procedures were crossed over. A maximum serum urapidil level of 625 +/- 232 ng/ml was achieved at the end of the 10 mg/h infusion, when the fall in blood pressure was 37/21 mmHg. During the 2.5 and 5 mg/h infusions the serum urapidil level was 330 and 420 ng/ml, respectively, and the corresponding decreases in blood pressure were 28/16 mmHg and 31/8 mmHg. Although the urapidil concentration 1 hour after beginning the infusion was only 184 +/- 89 ng/ml a near maximal blood pressure decrease had already occurred 33 +/- 9/20 +/- 8 mmHg, whereas, 1 h after the end of the infusion the reduction in blood pressure was only 10 +/- 12/3 +/- 8 mm, with a urapidil concentration of 358 +/- 120 ng/ml. During the plateau phases of both the infusion and infusion-capsule treatments the falls in blood pressure followed the serum urapidil levels. Only in the initial rising and final falling phases of the treatments were the pharmacodynamics and pharmacokinetics of urapidil not correlated.

Blood Pressure↗
PubMed2000

Effect of intravenous dopamine infusion on plasma concentrations of dopamine and dopamine sulfate in men, during and up to 18 h after infusion.

OBJECTIVE: We investigated whether sulfoconjugation contributes to the inactivation of intravenously infused dopamine (DA) in low concentrations with a predominant action on the kidney. METHODS: Plasma DA and dopamine sulfate (DA-S) concentrations were determined during 4 h of intravenous infusion of DA (2 microg/kg/min) and up to 18 h after cessation of infusion. Twenty-seven healthy young subjects participated in the placebo controlled, randomised and double-blind study. RESULTS: Intravenously administered DA was sulfoconjugated rapidly and to a great extent. After starting the infusion, DA levels rose within minutes and reached a steady state after 30-60 min. The steady-state levels averaged 151.3 +/- 8.2 nmol/l. DA-S levels also increased markedly with infusion from 16.7 +/- 9.9 nmol/l at the start of infusion up to 261.2 +/- 24.2 nmol/l at 30 min after cessation of infusion. Plasma DA concentrations after cessation of the infusion decreased rapidly with an initial half-life of elimination of 4.8 min. Concentrations of plasma DA-S declined with a half-life of 4.5 h. Persistent elevations of free and conjugated DA compared with pre-treatment levels were observed even 18 h after cessation. Heart rate and blood pressure remained unchanged both during DA and saline infusion. CONCLUSION: Findings indicate that the sulfoconjugation pathway contributes markedly to the inactivation of intravenously infused DA and seems not to be saturable by DA infusion in low doses.

Adult↗
PubMed2001

Cost-effectiveness of ceftazidime by continuous infusion versus intermittent infusion for nosocomial pneumonia.

STUDY OBJECTIVE: To determine if continuous-infusion ceftazidime is more cost-effective and efficacious than intermittent infusion in patients with nosocomial pneumonia. DESIGN: Prospective, open-label, randomized trial. SETTING: Large, community teaching hospital. PATIENTS: Intensive care unit (ICU) patients with nosocomial pneumonia. INTERVENTIONS: Ceftazidime 3 g/day was administered as a continuous infusion or as 2 g 3 times/day by intermittent infusion to treat nosocomial pneumonia in the ICU. Patients also received tobramycin 7 mg/kg once/day. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were evaluable; 17 received continuous infusion and 18 intermittent infusion. Clinical efficacy (94% and 83% successful outcomes with continuous and intermittent infusion, respectively), adverse events, and length of stay did not vary significantly between groups. Costs associated with continuous infusion, $627 +/- 388, were significantly lower (p < or = 0.001) than with intermittent infusion, $1007 +/- 430. CONCLUSIONS: Continuous infusion of ceftazidime is a cost-effective alternative to intermittent infusion for nosocomial pneumonia in the ICU.

Adult↗
PubMedDate not supplied

Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate.

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting.

Absorption↗
PubMed1996

Pharmacokinetics following a loading plus a continuous infusion of pralidoxime compared with the traditional short infusion regimen in human volunteers.

BACKGROUND: Many authors currently recommend infusing the adult dose (1 g) of pralidoxime over a 15-30 minute period. When administered in this manner, computer simulations predict that plasma pralidoxime concentrations will fall below 4 mg/L as early as one and one half hours after administration. The objective of this study was to assess whether a loading dose followed by a continuous infusion would maintain therapeutic levels longer than the traditional short infusion regimen of pralidoxime if the same total dose was administered. METHODS: Utilizing a randomized, crossover design, healthy volunteers were administered either 16 mg/kg of pralidoxime intravenous over 30 minutes or 4 mg/kg of pralidoxime intravenous over 15 minutes followed by 3.2 mg/kg/h for 3.75 h (for a total dose of 16 mg/kg). Pralidoxime levels were obtained at 0, 10, 20, 30, 60, 120, 180, 240, 300, and 390 minutes and patients were observed for vital sign changes and adverse effects. RESULTS: Seven subjects completed both arms of the study. One subject's data were excluded from pharmacokinetic analysis due to aberrant plasma pralidoxime analysis. The loading dose followed by the continuous infusion maintained therapeutic levels for 257.3 +/- 50.5 minutes whereas the short infusion maintained therapeutic levels for 118.1 +/- 52.1 (p < 0.001). Adverse effects were encountered during the short infusion regimen which did not occur during the continuous infusion. Dizziness or blurred vision occurred in all subjects during the short infusion regimen. Additionally, statistically significant increases in diastolic blood pressure occurred during the short infusion regimen. CONCLUSIONS: The results of this study indicate that a loading dose followed by a continuous infusion of pralidoxime maintains therapeutic concentrations for a longer period of time than the currently recommended short infusion regimen in healthy volunteers.

Adult↗
PubMed1988

[Preventive long-term intravenous immunoglobulin infusion in children with acute lymphatic leukemia. I. Anticomplementary activity of gamma globulin preparations is a function of the preparation and IgG concentration prior to infusions].

The influence of intravenous gammaglobulin infusions (ivGG) on hemolytic complement function and the concentration of serum C3 and its split product C3dg was studied in 20 children with acute lymphocytic leukemia (ALL) undergoing ivGG prophylaxis. IvGG was infused once monthly over a period of 20 months using two different preparations commercially available. Serum and EDTA-plasma were collected before initiation of ivGG therapy (time 1), after 10 and 20 months (time 2 and 3), before and immediately after the infusions. IvGG was infused in connection with chemotherapy (according to the CoAll 82 protocol). 16 of 60 sera collected prior to infusions contained less than 700 mg/dl IgG. Mean IgG concentrations could be raised to 198 mg/dl (time 1), 219 mg/dl (time 2), and 213 mg/dl (time 3), respectively. -CH 50 prior to infusions was below normal in 15 of 59 sera, afterwards in 25 of 59 sera. AP 50 before (after) infusions was decreased in 29 of 59 (36 of 60) sera, C3 in 18 of 60 (24 of 60) sera. C3dg was slightly elevated in one EDTA-plasma prior to ivGG infusions and in 5 of the plasmas following infusions. IvGG infusions resulted in a significant loss of hemolytic activity of serum complement (p less than 0.01, F-test). The effect was more profound if IgG concentrations before infusions were less than 700 mg/dl, but this was true for only one of the two used ivGG preparations. The long term follow up over two years showed no significant changes of complement functions (F-test), indicating complete recovery of complement function from short term anticomplementary effects.

Child↗
PubMed1990

A rodent model of infusion brain edema: methodology and pathophysiological effects of saline and protein infusions.

To evaluate the potency of putative secondary mediators of brain edema and their possible contribution to edema related brain dysfunction an infusion model of brain edema was developed in rats. 100 ul of fluid (saline, 20% nonautologous protein) was infused over one hour into the left forebrain white matter through a stereotaxically placed (+1.2 mm ant to bregma, 3 mm lateral and 2.9 mm depth) 25 G needle. Brain tissue hydraulic resistance (Rt), regional cerebral blood flow (rCBF), cortical somatosensory evoked potentials (SEPs) and intracranial pressure (ICP) (intraventricular needle) were monitored during the infusion and rCBF CO2 reactivity (hydrogen clearance), local brain water content (microgravimetry), BBB integrity (Evans Blue 2%) and brain histology (H & E. Solochrome-cyanin) were evaluated after the infusion. Saline infusates caused no physiological dysfunction despite ipsilateral expansion and vacuolation of the subcortical white matter, separation of axonal bundles and a significant decrease (p = 3.8 x 10(-5] in local subcortical tissue specific gravity. Cortical histology and specific gravity adjacent to the infusion locus were normal. Rt significantly decreased (p = 6.5 x 10(-4] during the infusion but there were only minor increases in ICP. Findings with 20% protein infusates were similar despite a focal 65% decrement in the rCBF CO2 reactivity adjacent to the infusion site. This study has shown that a simple and inexpensive model of infusion brain edema can be created in the rat and that it provides a useful model for assessing the physiological effects of mediator compounds in the infusate. Potential applications and methodological improvements for this model are discussed.

Animals↗
PubMed1983

The effect of changes in the amount of energy infused as volatile fatty acids on the nitrogen retention and creatinine excretion of lambs wholly nourished by intragastric infusion.

The nitrogen balance and creatinine excretion of wether lambs of 30-48 kg, wholly nourished by the intragastric infusion of nutrients, were measured in two experiments. Four lambs were used in each experiment. In Expt 1 a constant amount of casein was infused into the abomasum (640 mg N/kg body-weight (W)0.75 per d) and the amount of volatile fatty acids (VFA) infused into the rumen ranged from 0 to 670 kJ/kg W0.75 per d as six increments. Expt 2 was of similar design but two levels of casein were infused (530 and 1060 mg N/kg W0.75 per d) and, with each level of casein, VFA infused ranged from 0 to 700 kJ/kg W0.75 per d as seven increments. Daily creatinine excretion was not constant, but varied between 2-d means with standard deviations of between 7.1 and 16.5% (average 13.1%) of the over-all means. There was an apparent correlation between creatinine excretion and the amount of energy infused in six out of eight lambs. There was no effect of the amount of casein infused. In both experiments N balance was negative only when the amount of energy infused was substantially below published values for energy maintenance. In Expt 1, N equilibrium was calculated to be achieved at a gross (VFA plus protein) energy infusion level of 162 (SE 29) kJ/kg W0.75 per d. In Expt 2 it was observed that, at a given level of energy infusion, N retention was greater when the amount of energy had been increased from the previous level, than when it had been decreased. It is concluded that the animal appears to allocate available amino acids to protein synthesis, rather than to oxidation, even when in negative energy balance. It is also concluded that enhanced N retention observed when the amount of energy infused had been increased represented compensation after a period of energy restriction.

Animals↗
PubMed1991

Controlled ruminal infusion of sodium bicarbonate. 2. Effects of dietary and infused buffer on ruminal milieu.

Four ruminally cannulated, lactating Holstein cows were assigned to a 4 X 4 Latin square to monitor the effects of NaHCO3 infusion on ruminal environment of cows receiving dietary sodium bicarbonate. Sodium bicarbonate (110 g) was mixed with 3.8 L of water and infused at a constant rate into the rumen from 0 to 2, 2 to 4, or 4 to 6 h postfeeding twice daily. All cows were fed sorghum silage and concentrate in a 35:65 DM ratio for 45 min twice daily. Ruminal fluid was collected at feeding and every 30 min postfeeding for 8 h on the last day of each 1-wk experimental period. Dry matter intake was not affected by NaHCO3 infusion. Yields of milk and its components were reduced with 4- to 6-h NaHCO3 infusion. At certain isolated times, especially during infusion, NaHCO3 infusion increased ruminal fluid buffer. Concentrations of ruminal fluid total VFA were not affected by NaHCO3 infusions, whereas acetate to propionate ratio tended to be reduced. Ruminal liquid volume tended to be increased by 0- to 2-h NaHCO3 infusion, and ruminal outflow rate tended to be reduced by the 2- to 4-h infusion. Intraruminal infusion of NaHCO3 into cows receiving supplemental dietary NaHCO3 altered ruminal acid-base status as typically reported for those receiving dietary NaHCO3; however, these alterations were not accompanied by shifts in ruminal VFA patterns or in milk composition that normally result from such feeding regimens. The effects of NaHCO3 infused directly into the rumen may be different from those of dietary NaHCO3 and are possibly related to the different time of entry into the rumen relative to feeding.

Acid-Base Equilibrium↗
PubMedDate not supplied

Acceptance of external infusion pumps in patients with advanced breast cancer receiving continuous infusion fluorouracil.

BACKGROUND: We investigated the physical and psychological adaptation to a protracted continuous infusion system in a series of patients receiving protracted continuous infusion of 5-fluorouracil for advanced breast cancer. PATIENTS AND METHODS: The protracted continuous infusion of 5-fluorouracil was administered by means of a portable elastomeric pump (Baxter Seven-Day Infusor, 0.5 mL/hr) via an indwelling Groshong catheter. Patients were asked to complete a questionnaire exploring the impact of the continuous infusion system upon various aspects of daily life, the overall level of disturbance, the general judgement on its quality, and their willingness to resume the same kind of treatment in the future. All items were graded on a 4-point scale from 0 = not at all, to 4 = very much. RESULTS: Seventy-one patients were evaluated. All patients received 5-fluorouracil at the dose of 250 mg/m2/day as a protracted continuous infusion alone (n = 14) or in combination with vinorelbine (n = 45) or Taxol (n = 12). The median duration of the protracted continuous infusion before evaluation was 9 months (3-31). The mean level of disturbance to daily activities was 0.86 points. The activities most frequently disturbed by treatment included daily personal care (mean, 1.76 points) and sexual activity (mean, 1.20 points). Twenty-one patients required medical intervention because of problems related to the protracted continuous infusion system. The overall level of disturbance was rated at a mean level of 0.72 points, whereas the overall merits of the protracted continuous infusion system and the willingness of the patient to resume protracted continuous infusion in the future were rated at a mean level of 2.90 and 2.55 points, respectively. CONCLUSIONS: The system for the protracted continuous infusion of 5-fluorouracil was well tolerated by the patients, who were able in most cases to perform their daily activities with little or no disturbance, needing only occasional help, and were willing to resume the same treatment modality if necessary.

Activities of Daily Living↗
PubMedDate not supplied

The infusion rate of most disposable, non-electric infusion pumps decreases under hypobaric conditions.

PURPOSE: To examine the delivery rates of four disposable, non-electric infusion pumps during hypobaric conditions. METHODS: Four models categorized by three different driving forces, one vacuum unit (Coopdech Syringector), one spring unit (Linear-fuser), and two elastomeric balloon-powered units (Multirate Infuser LV and Large DIB), were tested. Each infusion pump was placed in an airtight container, and the pressure in the container was decreased to 1,000, 900, and 800 hPa. The catheter tip of each pump was exposed either to atmospheric pressure (1,000 hPa) or to similar hypobaric conditions (800-1,000 hPa). RESULTS: Under normal atmospheric pressure, each pump showed an accurate delivery rate in the range of -2% to +8% of the set infusion rate (4.0-5.0 mL x hr(-1)). With the catheter tip exposed to atmospheric pressure, the infusion rate of each pump was reduced from 35% in the case of the Large DIB to 64% in the case of the Coopdech Syringector, depending on the magnitude of change in hypobaric pressure. When the pressure acting on the catheter tip was reduced to a level similar to that exerted on the pump body, infusion rate was reduced (by 19%-27%) in all three types of pump, and the Large DIB showed no significant difference in performance compared to normal atmospheric pressure. CONCLUSION: The infusion rates of disposable infusion pumps are reduced under hypobaric conditions. Even though we still do not know how the epidural pressure changes under hypobaric conditions, clinicians should be aware that the infusion rate of disposable infusion pumps is decreased under hypobaric conditions.

Analgesia, Epidural↗
PubMed2002

Effect of distance and infusion rate on operation of Medfusion 2010 infusion pump during magnetic resonance imaging.

STUDY OBJECTIVES: To determine the accuracy and reliability of intravenous infusion, as well as magnetic resonance image effect of the Medfusion 2010 infusion pump (Medex Medical Supplies, Inc., Duluth, GA) at distances of 2, 4, 8, 12, and 16 feet from a 1.5 Tesla MRI magnet over a four-week time interval, using infusion rates that would correspond to those of propofol administration. DESIGN: Prospective, open-label study. SETTING: Radiology department MRI in an American academic medical center. INTERVENTIONS: Five infusion pumps, including one outside the MRI suite as control, were tested. Pumps were evaluated at distances of 2, 4, 8, 12, and 16 feet from a 1.5 Tesla magnet. One pump at distances of 2 and 16 feet was tested during 30 and 90 hours of operation, respectively. Three pumps at distances of 4, 8, and 12 feet were tested during 120 hours of operation. Pump batteries were recharged for 18 hours outside the MRI suite between the 6-hour test periods. Distilled, deionized water was infused from a 30-mL or 60-mL syringe via a 36-inch Medex small-bore extension set into a graduated collection cylinder at rates of 5, 10.5, 21, or 42 mL/hr. Each rate was increased to the next infusion rate level at 30-hour weekly intervals. The collection cylinder with infused water was weighed on an electronic scale accurate to within +/-0.001 g. Analysis of variance and regression analysis were used to analyze data. A p < 0.05 value was considered statistically significant. MEASUREMENTS AND MAIN RESULTS: There was no significant difference comparing the grams weight of volume measured and the mL volume visualized within and between groups at varying distances from the magnet. Increasing infusion rates resulted in corresponding increases in volume delivered irrespective of the distance from the magnet. CONCLUSIONS: The Medfusion 2010 infusion pumps were found to be reliable and accurate, without causing failure or any significant degradation of MRI images compared to control at infusion rate of 42 mL/hr at a distance of 2 feet for 30 hours; and a rate of 5.0, 10.5, 21, and 42 mL/hr at 16 feet for 90 hours; and at 4, 8, and 12 feet for 120 hours of operation.

Anesthesiology↗
PubMed1995

Phase I study of paclitaxel by three-hour infusion: hypotension just after infusion is one of the major dose-limiting toxicities.

The primary objectives of this study were to determine the maximum tolerated dose (MTD) of paclitaxel administered by 3-h infusion to patients with solid tumors, and to characterize the pharmacokinetics of a 3-h infusion in comparison with those of a 24-h infusion. Twenty-seven patients each received one of six levels of paclitaxel, 105, 135, 180, 210, 240 and 270 mg/m2, with premedication. Two patients given 240 mg/m2 and one patient given 270 mg/m2 unexpectedly had grade 3/4 hypotension just after finishing the paclitaxel infusion. Peripheral neuropathy was also dose-limiting at 270 mg/m2. Although granulocytopenia was significantly less severe than with a 24-h infusion, more than half of the patients experienced grade 4 toxicity at doses of 240 or 270 mg/m2. Severe hypersensitivity reactions (HSRs) were not observed. Pharmacokinetic studies using high performance liquid chromatography demonstrated proportionally greater increases in the peak plasma concentration and area under the curve, and decreases in clearance and volume of distribution with increasing dose, suggesting non-linear pharmacokinetics of paclitaxel when given by 3-h infusion. The MTD of paclitaxel given as a 3-h infusion was determined to be 240 mg/m2 with dose-limiting toxicities of granulocytopenia, peripheral neuropathy and hypotension. Hypotension just after infusion, induced by 3-h infusion of paclitaxel, is a new observation which has not been reported previously. The recommended dose for phase II study is 210 mg/m2. Although hypotension was observed as an unexpected toxic effect, paclitaxel could be administered safely over 3 h with premedication and proper monitoring, resulting in reduced myelotoxicity and with no increase in the incidence of HSRs as compared with a 24-h infusion.

Adult↗
PubMed1992

pH-feedback controlled infusions of ranitidine are no more effective than fixed-dose infusions in reducing gastric acidity and variability in antisecretory responses.

1. The antisecretory responses to pH-feedback controlled (maximum dose 800 mg 24 h-1) and fixed-dose (0.25 mg kg-1 h-1) continuous infusions of ranitidine were compared in a randomised, placebo-controlled, cross-over study in 10 healthy male volunteers. 2. To assess tolerance during repeated dosing with ranitidine, the same infusion regimens were given before and after 6 days oral dosing with ranitidine 300 mg four times daily. 3. With the pH-feedback controlled infusion of ranitidine the median % time (interquartile range) with pH greater than 4 in the 24 h period was 57% (45-76) before and 23% (17-34) after 6 days oral dosing (P less than 0.001). The respective values with fixed-dose infusion were 51% (38-63) and 26% (15-32) (P less than 0.002). 4. The median 24 h doses (interquartile range) of ranitidine given by feedback-controlled infusion before and after 6 days oral dosing were 675 mg (542-728) and 749 mg (709-760), respectively (P less than 0.01). The dose of ranitidine given by fixed-rate infusion was 423 mg (393-502) on both study days (P less than 0.001 vs feedback infusion). 5. Plasma gastrin concentrations remained slightly elevated after 6 days of oral ranitidine dosing, whereas pancreatic polypeptide plasma levels remained unchanged. 6. The antisecretory efficacy of infusions of ranitidine is significantly decreased by circadian stimuli and tolerance. Individually-adapted infusions of high doses of ranitidine were not superior to fixed-dose infusion of 0.25 mg kg-1 h-1 in overcoming this variability.

Adult↗
PubMed1992

Assessment of glucose turnover rates in euglycaemic clamp studies using primed-constant [3-3H]-glucose infusion and labelled or unlabelled glucose infusates.

Underestimation of glucose turnover rates has been a problem in clamp studies using primed-constant [3-3H]-glucose infusion technique. Due to slow mixing in interstitial compartments concealed specific activity gradients may arise between plasma and interstitial compartments during intravenous unlabelled glucose infusion. Such specific activity gradients, however, can be prevented if plasma specific activity is maintained constant. Two euglycaemic clamp studies (insulin infusion 40 mU m-2 min-1) were performed in six lean normal subjects. Using conventional unlabelled glucose infusates plasma specific activity declined by 74%, tracer determined glucose appearance was smaller than actual glucose infusion rates (317 +/- 11 vs 366 +/- 15 mg m-2 min-1, p < 0.001), and erroneous negative values were calculated for glucose production (- 49 +/- 7 mg m-2 min-1). Average underestimation during the first 2 h correlated with glucose infusion rates (r = 0.88, p < 0.02). In contrast, when plasma specific activity was maintained constant, using appropriately labelled glucose infusates, tracer determined glucose appearance and glucose infusion rates were similar (385 +/- 16 vs 385 +/- 17 mg m-2 min-1), and negative errors for glucose production were avoided. In conclusion, using unlabelled glucose infusates, as in previous studies, suppression of glucose production is overestimated and stimulation of glucose utilization is underestimated. As errors were greater with larger glucose infusions, the mistakes may have been greatest in insulin sensitive control subjects, and smaller in insulin resistant subjects. Therefore, re-evaluation of hepatic insulin sensitivity seems appropriate in diabetes, obesity, and other insulin resistant states.

Adult↗
PubMed1996

No effect of 96-hour paclitaxel infusion in patients with relapsed non-Hodgkin's lymphoma refractory to a 3-hour infusion schedule.

PURPOSE: Preclinical data suggest that the efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is schedule-dependent. Schedule dependency is currently under investigation in ongoing randomized trials. PATIENTS AND METHODS: Twelve patients with relapsed non-Hodgkin's lymphoma (NHL) refractory to a 3-hour infusion of 200 mg/m2 Taxol were crossed over to receive a 96-hour infusion of 140 mg/m2 Taxol every 3 weeks in an outpatient setting. Premedication with corticosteroids and antihistamines was not used. Patients who did not achieve at least a partial remission (PR) after two courses or whose disease progressed after one course were removed from the study. RESULTS: All 12 patients were assessable for response. Eleven patients received at least two courses and one patient received one course of 96-hour Taxol infusion. None of the 12 patients crossed over to receive 96-hour Taxol infusion achieved a PR or complete response (CR). Eight patients (67%) developed progressive lymphoma, three (25%) had stable disease, and only one (8%) had a minor response. No major hypersensitivity reactions or life-threatening toxicities were observed. CONCLUSION: Ninety-six-hour Taxol infusion does not produce significant responses in patients with NHL refractory to 3-hour Taxol infusion. Until the results of an ongoing multicenter trial comparing a 3- with a 96-hour infusion are published, the use of 96-hour Taxol infusion in NHL patients should be restricted to investigational programs. Because 48- to 72-hour infusions can produce higher plasma concentrations of Taxol than a 96-hour infusion, these schedules should be investigated to determine if they can induce better clinical responses.

Adult↗
PubMed1992

[A comparison of a tramadol/metamizole infusion with the combination tramadol infusion plus ibuprofen suppositories for postoperative pain management following hysterectomy].

Postoperative pain management is still a grossly neglected field. In most cases, antipyretic analgesics alone are insufficient during the early postoperative period. Powerful narcotics are often avoided or underdosed because they are associated with the risk of respiratory depression. Some authors recommend combined infusion of tramadol and metamizole, which is assumed to provide sufficient pain relief without the risk of respiratory depression. However, this regimen has not yet been investigated in a study that meets currently accepted scientific standards. METHODS. Sixty patients who underwent vaginal hysterectomy were included in a randomised, prospective double-blind study. Thirty women received two placebo suppositories immediately after induction of anaesthesia and a postoperative infusion of tramadol and metamizole (400 mg tramadol plus 5 g [= 10 ml] metamizole in 500 ml electrolyte solution). The 30 women of the control group received two ibuprofen suppositories (585.2 mg) preoperatively and a post-operative tramadol infusion (400 mg tramadol plus 10 ml placebo [NaCl 0.9%] in 500 mg electrolyte solution). The patients of both groups received 125 ml of the appropriate infusion solution as a loading dose over 10 min (corresponding to 1.25 mg metamizole and 100 mg tramadol in the metamizole/tramadol group or 100 mg tramadol in the ibuprofen/tramadol group) 10 min after awakening. The remaining solution was administered at an infusion rate of 12.5-25 ml/h (corresponding to 125-250 mg metamizole and 10-20 mg tramadol/h or 10-20 mg tramadol/h). On request or when complaining of stronger pain, the patients received an additional bolus infusion of 125 ml over 10 min. In case of insufficient pain reduction despite repeated infusion of 125-ml boli or consumption of the entire infusion solution, the patients discontinued the study and received demand-adapted intravenous titration of piritramide. Postoperative pain was evaluated on the visual analogue scale (VAS) and the 101-point numerical rating scale immediately before the start of the infusion. Pain evaluation was repeated 20, 30, 40, 60, 100, 120, and 240 min after awakening accompanied by registration of heart rate, respiratory rate, systolic and diastolic blood pressure, and side effects. RESULTS. About 60% of the entire infusion solution was administered within 60 min in both groups. Significant postoperative pain reduction in both groups and on both the 101-point scale and the VAS was observed only at 100, 120, and 240 min after awakening. In the tramadol/metamizole group, nausea occurred in 7 cases and vomiting in 1. Nine patients in this group additionally required intravenous piritramide because of insufficient pain relief. In the tramadol/ibuprofen group, 8 patients complained about nausea and 4 patients vomited. Six patients additionally received intravenous piritramide because of insufficient pain reduction. CONCLUSIONS. Satisfactory pain reduction occurred rather late despite high doses of both the tramadol/metamizole and the tramadol/ibuprofen. Both analgesic combination must be regarded as insufficient after inhalational anaesthesia because of the very slow onset of action and the high failure rate.

Adult↗