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Effects of intravenous infusion of amino acids and glucose on the yield and concentration of milk protein in dairy cows.

To test the hypothesis that the availability of glucose or its precursors can influence the response of milk protein concentration to the intravenous infusion of amino acids, five cows were used in a 5 x 5 Latin square design with period lengths of 7 d. The five treatments were the basal diet of grass silage ad lib. plus 5 kg/d of a cereal-based supplement containing feather meal (Basal); Basal plus 4 g/d histidine, 8 g/d methionine and 26 g/d lysine (4H); Basal plus 8 g/d histidine, 8 g/d methionine and 26 g/d lysine (SH); and these two amino acid mixtures together with 600 g/d of gluctose (4HG and 8HG respectively). Earlier experiments with this basal diet had shown that histidine was first-limiting for secretion of milk protein, followed by methionine and lysine. The yield of milk protein was increased progressively with the amount of histidine infused. The efficiency of transfer of histidine into milk protein was 0.42 for the 4H and 4HG and 0.35 for the 8H and 8HG treatments, and the concentration of milk protein was increased over Basal by all infusion treatments. However, milk protein concentrations were higher, and lactose concentrations in the milk were lower, in the absence of added glucose. Concentrations of insulin in blood plasma were not affected by treatment. It is concluded that, with the treatments without added glucose, a shortage of glucose prevented an increase in lactose secretion, and hence limited the increase in milk yield, leading to an increased concentration of protein in the milk.

Amino Acids↗

Pharmacokinetics of Pamidronate Disodium in Cancer Patients after a Single Intravenous Infusion of 30-, 60- or 90-mg Dose over 4 or 24 Hours.

The objective of this study was to determine the pharmacokinetics of pamidronate disodium in plasma and urine after a single intravenous infusion of the drug to cancer patients at risk for developing bone metastases. Thirty-six patients were randomized into six treatment groups to receive 30-, 60- or 90-mg doses of the drug by 4- or 24-h intravenous infusions. Plasma and urine samples were collected at intervals for up to 144 h after drug administration and were assayed for pamidronate disodium using validated reversed-phase HPLC methods. The percentage of the administered dose excreted in urine following a 4- or 24-h infusion of 30-, 60- or 90-mg pamidronate disodium ranged from 30% to 60% except for one individual who excreted 96% by this route of elimination. There was a linear relationship between amount of drug excreted in urine and dose. Curve fitting of ARE (amount of drug to be excreted in urine) data indicated that the disposition kinetics of the drug was consistent with a biexponential process with overall mean plus minus S.D. half-life values of 2.1 plus minus 1.8 and 26.9 plus minus 8.7 h for the alpha and beta phases, respectively. The results of this study showed that the drug exhibited dose proportionality in its pharmacokinetic behavior over the 30--90-mg range regardless of whether it was infused over a 4- or 24-h interval.

Journal Article↗

Intravenous infusion anesthesia for upper extremity surgery.

Regional anesthesia by intravenous infusion was successfully performed in 126 cases with only three complications. The technic is particularly useful for outpatient surgery and for cases where general anesthesia is unsuitable. This type of anesthesia is not for routine use. Proper equipment and personnel must be available. We do not recommend its usage in very obese patients or where absolute hemostasis is essential. Caution is urged in cases where edema has developed as the absorbtion of local anesthetic is not predictable.

Anesthesia, Conduction↗

Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest--a feasibility study.

OBJECTIVE: Mild therapeutic hypothermia has shown to improve neurological outcome after cardiac arrest. Our study investigated the efficacy and safety of cold simple intravenous infusions for induction of hypothermia after cardiac arrest preceding further cooling and maintenance of hypothermia by specialised endovascular cooling. METHODS: All patients admitted after cardiac arrest of presumed cardiac aetiology were screened. Patients enrolled received 2000 ml of ice-cold (4 degrees C) fluids via peripheral venous catheters. As soon as possible endovascular cooling was applied even if the cold infusions were not completed. The target temperature was defined as 33 +/- 1 degrees C. All temperatures recorded were measured via bladder-temperature probes. The primary endpoint was the time from return of spontaneous circulation to reaching the target temperature. Secondary endpoints were changes in haemodynamic variables, oxygenation, haemoglobin, clotting variables and neurological outcome. RESULTS: Out of 167 screened patients 26 (15%) were included. With a total amount of 24 +/- 7 ml/kg cold fluid at 4 degrees C the temperature could be lowered from 35.6 +/- 1.3 degrees C on admission to 33.8 +/- 1.1 degrees C. The target temperature was reached 185 +/- 119 min after return of spontaneous circulation, 135 +/- 112 min after start of infusion, and 83 +/- 85 min after start of endovascular cooling. Except for two patients showing radiographic signs of mild pulmonary edema no complications attributable to the infusions could be observed. Thirteen patients (50%) survived with favourable neurological outcome. CONCLUSION: Our results indicate that induction of mild hypothermia with infusion of cold fluids preceding endovascular cooling is safe and effective.

Advanced Cardiac Life Support↗

Pulmonary extraction and pharmacokinetics of prostaglandin E1 during continuous intravenous infusion in patients with adult respiratory distress syndrome.

Prostaglandin E1 (PGE1) is currently being evaluated in clinical trials to determine its usefulness in the treatment of adult respiratory distress syndrome (ARDS). The drug is administered to ARDS patients by continuous intravenous infusion at dosage rates of up to 30 ng/kg/min for 7 days. The present study was conducted to determine the pulmonary extraction efficiency and pharmacokinetics of PGE1 under these conditions. Plasma levels of PGE1 were determined by high performance liquid chromatography in 14 patients who either had ARDS or were considered to be at risk of developing ARDS following trauma or sepsis. Predose plasma levels of PGE1 were below the detection limit of the assay (50 pg/ml). At a dosage rate of 30 ng/kg/min, pulmonary arterial and systemic arterial plasma levels ranged from 265 to 1,009 pg/ml and 50 to 796 pg/ml, respectively. The pulmonary extraction ratio (Ep) of PGE1 varied from 0.11 to 0.90 and was independent of dose but dependent on cardiac output. The data were adequately described by first-order pharmacokinetic equations which assumed that the lung was the only site of PGE1 clearance. Nine of 10 patients with AaPO2/FlO2 below 510 mm Hg had Ep greater than 0.7 and high pulmonary intrinsic clearance for PGE1 (ca. 250 L/min), but all 4 patients with AaPO2/FlO2 above 510 mm Hg had Ep less than 0.6 and low intrinsic clearance (ca. 37 L/min or less). The intrinsic clearance of the lung for PGE1 in ARDS patients therefore appears to decrease abruptly once a threshold of severe respiratory failure is achieved.

Adult↗

Ocular changes induced in the beagle dog by intravenous infusion of a novel dopaminergic compound, FPL 65447.

FPL 65447, a selective D1 receptor agonist with a potential for the acute treatment of renal and cardiac failure and of sepsis and septic shock, was administered to beagle dogs by continuous intravenous infusion for a maximum of 14 days. Ophthalmoscopical examination revealed dose-related changes in the eye and associated structures, consisting of foci of retinal discolouration, corneal changes including oedema, keratitis, opacities and neovascularisation, and inflammation of the iris, periorbital tissues, and adnexa. Microscopical examination confirmed the presence of inflammatory lesions in the eye. These were predominantly histiocytic and were mainly focal circumscribed lesions. More diffuse inflammation with a granulocytic and lymphocytic component was also encountered in the limbus and uveal tract. A predominantly interstitial histiocytic adenitis involving various glandular structures associated with the eye and adnexa was also identified. Possible mechanisms to account for the histiocytic changes are discussed.

Animals↗

A comparison of benflurone effects after intravenous infusion or oral administration. A study on laboratory rats.

The effects of oral administration and intravenous infusion of benflurone were compared using the single dose of 100 mg/kg b.w. Oral administration of benflurone induced more moderate changes in both white and red blood picture than the equal dose of orally administered cyclophosphamide. In contrast to oral benflurone administration, intravenous benflurone induced deep anaemia, deep reticulocytopenia, transient neutrophilia and slight decrease in small lymphocyte counts. The recovery from intravenous benfluorone effects was rapid.

Administration, Oral↗

Reduction of reperfusion injury with preoperative rapid intravenous infusion of taurine during myocardial revascularization.

To assess a possible free-radical scavenging action of taurine during coronary artery bypass grafting, 12 patients were randomly divided into two equal groups. One to 3 hours before surgery, they received a rapid intravenous infusion of either placebo (group 1) or taurine (5 gm) (group 2). During surgery, biopsy samples were taken before ischemia (preischemic samples) and after 10 minutes of reperfusion (reperfusion samples). Lipoperoxidation was determined by hydroperoxide-initiated chemiluminescence of heart homogenates, and myocardial cell damage was assessed by electron microscopy. The values for chemiluminescence in preischemic and reperfusion samples from group 1 were 7500 +/- 1600 and 18,600 +/- 4600 cpm/mg of protein, respectively (p less than 0.03). This difference was not observed in group 2 where the values were 10,050 +/- 2700 and 11,800 +/- 4200 cpm/mg of protein, for preischemic and reperfusion samples, respectively. The number of severely damaged mitochondria (grades 3 and 4) in reperfusion samples from group 1 increased significantly compared to preischemic samples (25 +/- 8% vs 12 +/- 3%, p less than 0.01). Conversely no differences were observed between the number of severely damaged mitochondria in reperfusion and preischemic samples from group 2 (8 +/- 3% vs 8 +/- 2%). The number of damaged and necrotic myocytes increased in group 1 after reperfusion from 22 +/- 9% to 34 +/- 10% (p less than 0.03) and from 10 +/- 7% to 26 +/- 20% (p = NS), respectively. No changes were observed between reperfusion and preischemic samples in group 2. Treatment with taurine seems to reduce lipoperoxidation and decrease cell damage at the time of reperfusion.

Biopsy↗

Fatal myocardial toxicity during continuous infusion intravenous isoproterenol therapy of asthma.

We recently utilized continuous infusion intravenous isoproterenol in the treatment of respiratory failure in an 18-yr-old steroid-dependent asthmatic female. Aminophylline, hydrocortisone, aerosolized isoetharine, and oxygen were also administrered. The patient responded to this therapy, with PaCO2 falling from 70 torr to 33 torr in 18 hr. The maximum isoproterenol dosage administered was 0.32 microgram/kg/min. Thirty-six hours following the institution of therapy, while the isoproterenol was being tapered, the patient experienced an increase in respiratory distress followed by cardiac arrest. Postmortem examination revealed multiple small areas of myocardial necrosis. These findings, unusual in asthma, probably were related to the effects of isoproterenol or the combination of isoproterenol and aminophylline on the stressed myocardium. The vulnerability of the hypoxic myocardium to the effects of isoproterenol suggests that careful cardiac monitoring is essential in the management of patients receiving this medication for treatment of respiratory failure secondary to severe asthma.

Adolescent↗

Does prophylactic intravenous infusion of indomethacin improve the management of postoperative pain in children?

The efficacy of prophylactic intravenous infusion of indomethacin as a postoperative analgesic was studied in 100 children aged one to 16 years. At the end of surgery a bolus dose of indomethacin 0.35 mg.kg-1 followed by an infusion 0.07 mg.kg-1.hr-1 for 24 hr or placebo was given in double-blind manner. The efficacy of the treatment was measured by the need of additional morphine given 0.1 mg.kg-1 intravenously in the Recovery Room and 0.15 mg.kg-1 intramuscularly on the ward according to clinical needs. The other measure of the efficacy was assessment of pain intensity in the Recovery Room and pain relief on the ward. In the Recovery Room the pain scores differed between the groups in advantage of indomethacin only at 30 minutes (p less than 0.05) but the need of morphine was significantly less (p less than 0.01) in the indomethacin group. On the ward the mean doses of morphine given and the nurses' pain relief scores were not different between the study groups. However, in the indomethacin group the total dose of morphine given during 24 hr was lower (p = 0.02) and the children assessed the pain relief to be significantly better (p less than 0.02). Twenty per cent of the children in both groups had transient nausea and vomiting. No skin reactions or other allergic manifestations were observed. Prophylactic indomethacin infusion diminished the need of morphine and resulted in better postoperative analgesia than morphine p.r.n. alone.

Anesthesia↗

Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous infusion.

Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2',2'-difluorodeoxycytidine 5'-triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady-state, and terminal elimination half-life (t(1/2)) for gemcitabine were 0.421 L/h.kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t(1/2) of 14.9 h.

Animals↗

Effects of intravenous infusions of angiotensin II on muscle sympathetic nerve activity in humans.

The effect of angiotensin II (ANG II) on the sympathetic outflow was examined in normal humans. The mean arterial pressure and muscle sympathetic nerve activity (MSNA) were measured before and during intravenous infusions of phenylephrine (0.5 and 1.0 micrograms.kg-1.min-1) or ANG II (5, 10, and 20 ng.kg-1.min-1) for 15 min at 30-min intervals. The baroreflex slope for the relationship between the increases in mean arterial pressure and the reductions in MSNA was significantly less acute during the infusions of ANG II than during the infusions of phenylephrine. When nitroprusside was infused simultaneously to maintain central venous pressure at the basal level, MSNA significantly increased during the infusions of ANG II (5 ng.kg-1.min-1 for 15 min) but not during the infusions of phenylephrine (1.0 micrograms.kg-1.min-1 for 15 min), with accompanying attenuation of the elevation in arterial pressure induced by these pressor agents. These findings suggest that ANG II stimulates the sympathetic outflow without mediating baroreceptor reflexes in humans.

Adult↗

Acute physical dependence induced by continuous intravenous infusion of morphine or meperidine in the rat.

An intravenous infusion method is described for rapidly producing physical dependence in rats. Rats were infused with morphine or meperidine for 24 or 48 h at constant rates and the development of physical dependence was assessed by body weight loss after naloxone challenge. Naloxone challenge induced body losses that were dependent upon magnitude, rate and duration of infusion. The steady-state concentrations of morphine (4 mg/kg/h) in serum and meperidine (6 mg/kg/h) in plasma were 4 and 2.5 microgram/ml, respectively. Morphine concentration in the brain in the steady-state (40 mg/kg/h) was 0.7 micrograms 1 g and in the serum was proportional to the infusion rate. Maximum body weight loss was significantly correlated with total amount of infused morphine, but not with the steady-state concentration of the drug in the serum. These results suggest that total doses of infused morphine, not steady-state concentrations, are critical in producing body weight loss.

Animals↗

The induction of labour by the intravenous infusion of prostaglandin F2alpha.

Labour was induced by the intravenous infusion of prostaglandin F2alpha in 106 patients at 36-44 weeks of pregnancy. The induction was successful in 80% of the women. The total dose needed ranged from 0.1 to 14.2 mg of PGF2alpha. The uterine activity and fetal heart rate were recorded by cardiotocography. The contraction pattern and induction-delivery time were the same as reported for induction with oxytocin. In one case uterine hyperactivity occurred after rupture of the membranes. No serious adverse effects were seen, but in a few cases local irritation was noted at the site of infusion. The condition of the infants was generally good. It might be concluded that PGF2alpha seems valuable for the induction of labour, but due to the risk for over-stimulation careful supervision is needed.

Adult↗

Serum and tissue tinidazole concentrations after intravenous infusion.

Before appendectomy 36 adult patients were given an intravenous infusion of 500 mg of tinidazole. In the operation tissue samples were taken (blood, base of appendix vermiformis, muscle, fat) either 10, 20, 30, 60, or 120 min after cessation of infusion. The tinidazole concentrations were determined by liquid chromatography. The weight-standardized tinidazole concentrations in the serum, muscle tissue and appendix in all specimens were higher than the minimal inhibitory concentration (2 micrograms/g) of Bacteroides fragilis. The tinidazole concentrations of adipose tissue exceeded the limit of 1 microgram/g in all samples. The concentrations were high already in the 10-min patient group. The authors consider a tinidazole infusion started half an hour before the operation at a dose of 10 mg/kg of the patient's body weight to be a reliable procedure if the objective is to acquire a sufficient tissue concentration of tinidazole (2 micrograms/g) to prevent infection complications caused by anaerobic bacteria.

Adipose Tissue↗

[Treatment of atrial fibrillation using intravenous infusion of quinidine].

Quinidine gluconate was administered slowly by intravenous infusion to 20 patients with atrial fibrillation. Nineteen of them had rheumatic heart disease and the other one had Ebstein's disease. The first ten patients received 0.027 mg/kg/min during 6 hs or less if they returned to normal sinus rhythm (SR). The other ten received 0.041 mg/kg/min with the same protocol. Plasma quinidine concentrations were determined in all patients. Atrial functional refractory period was measured in five of the patients returning to normal sinus rhythm. Six patients in the first group were returned to SR. The required time of infusion was 4.2 hs. The maximal quinidine plasma level was 1.91 ug/ml. In the Second group; five patients returned to normal sinus rhythm, four of them in a mean time of 4.75 hs ofinfusion and the other one spontaneously 11 hs after the infusion was finished. The maximal quinidine plasma level in this group was 4.7 ug/ml. Side effects were observed in five patients. Diarrhea in one, vomiting in one, hypotension in two atrial flutter with 1: 1 A-V conduction in one.

Adolescent↗

[Prolonged intravenous infusion chemotherapy. General review of theoretical bases and results].

Continuous intravenous infusion of chemotherapy is now widely used to enhance the therapeutic index of cancer drugs. Cellular kinetics and pharmacological basis for protracted intravenous chemotherapy are reviewed for the main available drugs. From the increasingly published data it is now possible to separate routine and research utilization of protracted infusion chemotherapy.

Antineoplastic Agents↗

A randomized study of inpatient versus outpatient continuous intravenous infusion chemotherapy: psychosocial aspects.

This study was designed to test whether previously untreated patients with head and neck cancer could effectively manage home continuous infusion chemotherapy, and to compare their acceptance and adjustment to home versus inpatient treatment. Twenty-two patients received 3-4 cycles of induction chemotherapy and a 5-day continuous intravenous infusion (CVI). Patients were randomized to receive the CVI portion of cycle 1 either in the hospital via a standard chemotherapy delivery device or at home via the Travenol Infusor, a portable and disposable drug delivery system. For their second cycle of chemotherapy, patients crossed over to the alternate drug delivery method. Patients who did not want to receive their treatment at home received their chemotherapy as inpatients via the Infusor. Therefore, all patients received treatment with both drug delivery methods. Nineteen patients were evaluable for this study. Eleven patients received at least one cycle of home CVI chemotherapy, and adjusted well to this method of drug delivery. Levels of psychological distress decreased for this group of patients when receiving outpatient chemotherapy compared to their inpatient cycles. The eight patients who received all chemotherapy cycles as inpatients (refused home treatment) were found to be less educated and reported greater physical impairment prior to study entry than future home CVI acceptors. Levels of psychological distress in this group increased with each inpatient chemotherapy cycle. We conclude that home CVI chemotherapy may be an alternative to inpatient treatment for patients who have had at least one cycle of inpatient chemotherapy. The best candidates for home treatment are patients with unimpaired daily functioning and a minimum high school education.

Drug Therapy↗