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Effect of maternal intravenous infusions on fetal extracellular fluid composition in pregnant ewes.

Infusion of intravenous solutions to women in labor is common clinical practice. Since these infusions may change the volume and electrolyte balance between the mother and fetus, we investigated the influence of acute maternal volume expansion upon fetal and maternal fluid and electrolyte equilibrium in the chronically catheterized fetal lamb. Paired measurements of maternal and fetal plasma sodium and potassium concentrations, osmolality, and colloid osmotic pressure (COP), plus measurements in the fetal-placental plasma volume were obtained following rapid maternal infusions with saline, dextrose, and dextran solutions. Maternal infusions resulted in changes in fetal electrolyte concentrations as well as alterations in transplacental COP differences. Despite these changes, however, no changes in fetal plasma volume were noted.

Animals↗

Boron biodistribution in beagles after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose complex.

Boron biodistribution after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose (BPA-F) complex was investigated in six dogs. Blood samples were evaluated during and following doses of 205 and 250 mg/kgbw BPA in a 30 min infusion, and 500 mg/kgbw in a 1h infusion. Samples from whole blood, urine, brain and other organs were analysed for boron content after varying times following the onset of infusion. The whole blood boron concentrations declined from 27 to 8.4 ppm over the period of 39-165 min after the onset of infusion and the levels increased from 1.9 to 12 ppm in the grey matter of the brain over the same period. The boron concentrations in whole blood decreased steadily, whereas the boron values in brain tissue rose steadily with time. It was concluded that whole blood boron concentrations do not seem to reflect accurately the boron concentration in brain tissue at respective time points.

Animals↗

Effect of four intravenous infusion methods on tobramycin pharmacokinetics.

The influence of four intermittent intravenous infusion methods on the determination of tobramycin pharmacokinetic values and predicted doses was evaluated in 11 healthy adult volunteers. Each subject received tobramycin (as the sulfate salt) 1.5 mg/kg by each of four i.v. infusion methods: (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric pump (MP), (3) metered chamber via volumetric pump (MC), and (4) syringe pump (SP). Infusion rates were initially set to administer each dose over a 30-minute period. Sixteen blood samples were obtained over an eight-hour period before and at various time intervals after each dose and were analyzed for tobramycin content by fluorescence polarization immunoassay. Area under the serum concentration-time curve from time zero to infinity (AUC0-infinity) was calculated by the trapezoidal rule. Serum tobramycin concentration data for each subject were fitted to a biexponential decay model with zero-order input. beta and V beta were calculated from fitted data. One-compartment pharmacokinetic values, elimination rate constant (kappa), apparent volume of distribution (V), and predicted doses to achieve steady-state peak concentrations of 6 micrograms/mL were calculated by the method of Sawchuk and Zaske. There were no significant differences in either beta or kappa among the infusion methods. V beta values (mean +/- S.D.) for the methods were 0.240 +/- 0.025 (MG), 0.257 +/- 0.025 (MP), 0.221 +/- 0.027 (MC), and 0.231 +/- 0.032 (SP) L/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Pharmacokinetics and metabolism of an oligodeoxynucleotide phosphorothioate (GEM91) in cynomolgus monkeys following intravenous infusion.

The pharmacokinetics and metabolism of an antisense oligonucleotide phosphorothioate (GEM91) were studied in cynomolgus monkeys following intravenous infusion. [35S]-Labeled GEM91 was administered to 12 monkeys by means of a 2-hour intravenous infusion at a dose of 4 mg/kg. Plasma pharmacokinetic analysis revealed that the maximum plasma concentration was 41.7 microg equivalents/ml, which was achieved in 2.13 hours. The plasma elimination half-life was 55.8 hours based on radioactivity levels. Urinary excretion represented the major pathway of elimination, with 70% of the administered dose excreted in urine over 240 hours. The oligonucleotide was widely distributed to tissues. The highest concentrations were observed in the liver and kidney. Analysis of the extracted oligonucleotide following post-labeling with [32p] on polyacrylamide gel electrophoresis showed the presence of both intact and degraded oligonucleotide in plasma, kidney, liver, spleen, and lymph nodes. Based on the methods used for post-labeling (either 3'-end or 5'-end), different patterns of bands were observed on polyacrylamide gel electrophoresis, suggesting metabolic modification of the administered oligonucleotide.

Animals↗

An attempt to reduce the side effects of mannitol bowel preparation by intravenous infusion.

The authors compared two groups of patients receiving oral 5% mannitol for bowel preparation to see whether the volume of rectal effluent and quantity of bowel preparation could be maintained by a smaller oral mannitol intake supplemented by an intravenous infusion. Nineteen patients drank 2--3 1 5% mannitol, supplemented by an intravenous infusion of N/saline (intravenous Group) and 19 patients drank 4--5 1 5% mannitol (oral group). The volume of rectal effluent and the quality of bowel preparation was the same in both groups. The loss of sodium in the oral group was corrected by the intravenous infusion, but the infusion resulted in greater water retention. There was no reduction in the incidence of vomiting between the two groups.

Administration, Oral↗

[The treatment of Paget's disease of bone with second-generation bisphosphonates via intravenous infusion].

We compared the biochemical effects and safety of pamidronate (30 mg a day for 3 consecutive days) versus clodronate (300 mg a day for 3 consecutive days) via intravenous infusion in 14 patients with Paget's disease of bone (PDB). Both drugs induced a decrease in serum alkaline phosphatase levels as well as the elimination of hydroxyproline from urine, an effect most marked in the group treated with pamidronate. The response was maintained for 6 months after the infusion in the majority of the patients. No relevant side effects were found, except post-infusion febricula and in one patient, self-limiting thrombopenia 6 months after the infusion. We conclude that the intravenous infusion of either of the two drugs may constitute a safe and effective alternative for treatment of PDB with marked biochemical activity or resistant to conventional therapy.

Aged↗

Evaluation of appropriate blood level in continuous intravenous infusion from trough concentrations after oral administration based on area under trough level in tacrolimus and cyclosporine therapy.

The target blood concentrations of tacrolimus (TAC) and cyclosporine (CYA) during continuous intravenous infusion (C(ss)) have been determined based on clinical experience. However, it is desirable that C(ss) should be set so that the AUC after intravenous infusion is equal to the AUC after oral administration (AUC(po)). Accordingly, we performed 12-hour monitoring of blood concentrations to calculate C(ss) from the blood trough levels (C(TL)) on 15 kidney recipients administered TAC and 12 recipients administered CYA (Neoral). We used an area under the trough level (AUTL) as a new pharmacokinetic parameter. The C(ss) was evaluated from C(TL), AUC(po), and AUTL was calculated to be C(ss) = C(TL) x (AUC(po)/AUTL). In addition, AUTL/AUC(po) ratio and blood peak/trough level ratio (C(max)/C(min)) were examined to compare pharmacokinetics of TAC and CYA. The formula for TAC was C(ss) = C(TL) x 1.40 and that for CYA, C(ss) = C(TL) x 2.55. The calculated target C(ss) of TAC was 1.40 times that of C(TL), which was similar to the present clinical C(TL). In contrast, the calculated target C(ss) of CYA was 2.55 times the C(TL), and therefore an extremely high C(ss) was necessary to obtain a sufficient AUC that will be available after oral administration. Consequently, intravenous administration of CYA twice a day was considered to be more appropriate to obtain sufficient CYA pharmacokinetics, rather than a continuous intravenous administration. We conclude that the formula, C(ss) = C(TL) x (AUC(po)/AUTL) was useful to calculate the target blood concentration of calcineurin inhibitors when changing from continuous intravenous infusion to oral administration of these drugs.

Administration, Oral↗

[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion].

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adult↗

Effects of intravenous infusion of amino acids, fat, or glucose on unstimulated pancreatic secretion in healthy humans.

The effects of intravenous infusion of amino acids, fat, or glucose on unstimulated pancreatic secretion were studied in 31 healthy male volunteers. Each subject was studied twice on two separate days. On both days pancreatic outputs were measured during a 4-hr basal period that was followed by a 4-hr test period. During the test period either one of the digestive end products (100 ml/hr 10% amino acids in 13 subjects; 100 ml/hr 10% fat in 8 subjects; 150 ml/hr 10% glucose in 10 subjects) or saline was intravenously infused. The infusion of the digestive end products or saline on the two separate days was done in a randomized order. Six of the 10 subjects that had already been studied for glucose received a higher glucose dose (100 ml 20% glucose as a bolus followed by 300 ml/hr 10% glucose) in a third additional experiment. Intravenous infusion of amino acids significantly stimulated pancreatic outputs of trypsin and chymotrypsin, but left the outputs of amylase, lipase, bicarbonate, and volume unaffected. The low-glucose dose, as well as the fat infusion did not alter any of the pancreatic outputs. To analyze the relationships between different enzymes during the infusion of digestive end products, regression lines were calculated from the scatter of all individual pairs of enzyme measurements. Significantly different regression functions found for each condition (NaCl control, amino acids, fat, glucose) when trypsin and chymotrypsin were plotted versus lipase and amylase: amino acids shifted the function to a trypsin- and chymotrypsin-dominant pattern of secretion, glucose to an amylase-dominant pattern, and fat to a lipase-dominant pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Diabetic ketoacidosis and hyperosmolar diabetic coma in childhood. Low-dose continuous intravenous infusion of insulin (author's transl)].

Continuous intravenous infusion of low doses of insulin has been successfully used since 1972 in the treatment of "diabetic coma". The achieved levels of plasma insulin satisfy the transport of glucose and the inhibition of lipolysis. We are to report upon 8 children (mean age: 8.5 years), 6 with diabetic ketoacidosis and 2 with hyperosmolar diabetic coma. Blood sugar levels of 300 mg/dl or less were reached after averagely 8 hours of therapy and an average consumption of 0.8 U insulin/kg. Sodium and potassium levels, osmolality and acid base parameters for the first 24 hours are described. Low-dose continuous intravenous insulin infusion was effective, simple and safe in all cases. The presently recommended dosage of 0.1 insulin/kg x hour is to be used flexibly (range: 0.05--0.2 U/kg x hour). The administration of bicarbonate should be cautiously used for patients with severe acidosis. Infusion of hypotonic solutions as part of the treatment of the hyperosmolar diabetic coma can be dangerous. A new therapeutic regime based on our results is proposed.

Adolescent↗

The effects of intravenous infusion of solutions with different colloid osmotic pressures on rat mesenteric lymph pressure.

The effects of intravenous infusion of solutions of varied colloid osmotic pressure on mesenteric lymph pressure were measured by a glass micropipette. The lymph pressure was 4.0 +/- 1.6 cm H2O between the second and third valve of rat mesenteric lymphatic vessels with diameter of 101 +/- 25 micron (mean +/- SD). Intravenous infusion of 1 ml/100g body weight (B.W.) of isotonic saline, 5% glucose solution, and 20% glucose solution increased the lymph pressure by 1.6 +/- 0.5 cm H2O, 1.5 +/- 0.3 cm H2O and 2.0 +/- 1.0 cm H2O, respectively. Infusion of 2 ml/100g B.W. of the same solutions increased the lymph pressure by 3.3 +/- 1.3 cm H2O, 3.3 +/- 1.6 cm H2O and 3.7 +/- 0.8 cm H2O, respectively. Infusion of hydroxyethyl starch solution, with colloid osmotic pressure of 25 mmHg, minimally altered the lymph pressure. One ml/100g B.W. infusion of low molecular weight dextran solution, with colloid osmotic pressure of 162 mmHg, decreased the lymph pressure by 1.3 +/- 0.9 cm H2O, and 2 ml/100g B.W. infusion of this solution decreased the lymph pressure by 2.0 +/- 1.0 cm H2O. The different effects on lymph pressure derive from the differences in colloid osmotic pressure of these solutions in conformity with the Starling hypothesis.

Animals↗

Diazepam by continuous intravenous infusion for status epilepticus in anticonvulsant hypersensitivity syndrome.

OBJECTIVE: To report a case of status epilepticus in a patient with anticonvulsant hypersensitivity syndrome (AHS) that was controlled successfully using continuous intravenous infusion diazepam. AHS and alternatives for treatment of status epilepticus are also reviewed. DESIGN: Single case report. SETTING: 217-bed children's university hospital. PATIENT: Four-year-old, 20-kg girl, diagnosed with idiopathic tonic-clonic epilepsy, who developed AHS to phenobarbital and phenytoin and status epilepticus unresponsive to lorazepam. RESULTS: Diazepam intravenous infusion at dosages titrated to 8 mg/h was used successfully to control seizures for eight days until signs and symptoms of AHS had resolved and maintenance therapy with valproic acid was started. CONCLUSIONS: Continuous intravenous infusion diazepam is a reasonable therapeutic choice for the management of status epilepticus in a patient with AHS when traditional therapy such as phenytoin and phenobarbital cannot be used.

Anticonvulsants↗

Effect of intravenous infusion of amitriptyline on total blood serotonin content.

18 female patients with primary depression received a slow intravenous infusion of amitriptyline and a good therapeutic response was observed in 15 patients as early as after 6 days. A highly significant correlation was found between improvement scores following the first and last infusions, which suggests that intravenous infusion of amitriptyline may serve as a prognostic test for prediction of drug efficacy. Total blood serotonin content prior to treatment was significantly lower than in normal controls. Amitriptyline infusion caused variable changes in blood serotonin and the changes were inversely correlated with pretreatment levels. A series of six infusions caused a gradual increase in baseline levels, together with a rapid decrease in the magnitude of the amitriptyline-induced changes in serotonin content.

Adult↗

Regional intravenous infusion of calcium gluconate for hydrofluoric acid burns of the upper extremity.

STUDY OBJECTIVE: To describe regional intravenous infusion of calcium gluconate as a therapy for hydrofluoric acid (HF) burns of the forearm, hand, or digits. METHODS: This study describes seven patients with HF burns. Calcium gluconate, 10 mL of 10% solution with 30 to 40 mL normal saline solution, was injected intravenously into the affected limb using a Bier block technique. Ischemia was maintained for 20 to 25 minutes. Therapy was considered successful if significant reduction of pain and tenderness was noted after tourniquet release. RESULTS: Seven patients were treated. HF concentration varied from 5% to 49%. Exposure sites included the forearm (two cases), thenar eminence and digits (two cases), or digits only (three cases). Complete pain resolution occurred on tourniquet release in four patients (two with burns to the forearm, two with burns to digits only). One patient had partial relief (thenar but not digital exposure site), and two had no relief of symptoms. Intraarterial calcium gluconate perfusion was subsequently administered to the three patients with persistent subungual and pulp, or thenar pain. Recovery was complete in all cases. No adverse effects were noted. CONCLUSION: Regional intravenous infusion of calcium gluconate should be considered a therapeutic option in HF burns of the forearm, hand, or digits when topical therapy fails.

Adult↗

Influence of intravenous infusion duration on the tissue drug concentration profile.

The influence of intravenous infusion duration of a single dose of drug on the time course of drug concentration in the peripheral compartment of the classical two-compartment pharmacokinetic model was studied by computer simulation. The aim was to illustrate the general relationships among infusion duration T, dose, minimum effective concentration MEC at the effector (tissue) site, maximum tissue drug concentration C2,max, and the duration of effective tissue concentrations tD,tiss for those drugs where there is an equilibration delay between concentration at the effector site and plasma. Simulations of C2,max vs. T for meperidine, sulfamethoxazole, ampicillin, and metronidazole showed that, although maximum plasma concentration may decrease markedly with increasing T, C2,max decreased only slightly with increasing T. Simulations of the influence of T on the duration of effective plasma concentrations tD and tD,tiss of metronidazole showed that for a given T, tD,tiss may be greater than or less than tD, depending on the dose, and that it is possible to obtain effective concentrations in the tissue compartment even though the infusion duration is too long to achieve effective concentrations in plasma. It was found that, depending on the dose, it was possible to cause an increase in tD,tiss compared with bolus administration by increasing the infusion duration of the dose. It was also found that increasing T could cause opposite changes in tD and tD,tiss (compared with bolus administration, respectively), e.g., an increase in tD and a decrease in tD,tiss or vice versa, depending on the dose. It should thus be possible to make precise predictions of the influence of T on drug concentration at the effector site for individual drugs by incorporating effect compartment modeling into the analysis.

Computer Simulation↗

Insulin response to amino acid and glucose intravenous infusions in dairy cows: synergistic effect.

The effect of 30 minute intravenous infusions of amino acids (90 or 180 g) or glucose (114 g or 228 g) was studied in five non-pregnant lactating dairy cows. At each dose the same amounts of energy were delivered by glucose or amino acids. The nutrients were infused separately or in combination. In response to each nutrient, plasma insulin increased proportionally to the dose infused. The increase induced by amino acids was lower than that induced by glucose, and plasma insulin returned to its baseline value more rapidly after amino acid than after glucose infusion. The hypoglycemia that developed after amino acid infusions partly explains the short-lived amino acid induced in insulin response. The plasma insulin increase which resulted from the glucose-amino acid mix significantly exceeded that obtained by separate but isocaloric infusions of amino acids or glucose. Therefore, amino acids and glucose acted synergistically to increase plasma insulin release. The mechanism leading to the synergistic effect would be partially due to a permissive effect of hyperglycemia. Other possible potentiating mechanisms are discussed.

Amino Acids↗

Acute haemodynamic effects of intravenous infusion of adenosine in conscious man.

The acute haemodynamic effects of intravenous infusion of adenosine, a dilator of most vascular beds, were studied in 16 patients (seven with coronary artery disease, nine with normal coronary arteries) undergoing cardiac catheterization for investigation of chest pain. At the lowest dose used (4.3 mg min-1) adenosine increased minute ventilation by 44% (P less than 0.01, n = 11) and reduced pulmonary vascular resistance by 20% (P less than 0.05) without causing other significant haemodynamic changes. Symptoms, including chest discomfort in 14 patients and dyspnoea in 11, limited the maximum dose to 8.5 +/- 2.3 mg min-1 (mean +/- SD, 108 +/- 24 micrograms kg-1 min-1). At this dose, adenosine reduced pulmonary and systemic vascular resistance (by 38% and 34%, respectively) and increased heart rate (by 34%), stroke index (by 12%) and cardiac index (by 52%). Systemic blood pressure and right atrial pressure did not change. Unexpectedly, adenosine increased left ventricular end-diastolic pressure (LVEDP) (from 5 +/- 6 to 14 +/- 10 mmHg, n = 8), pulmonary capillary wedge pressure (from 3 +/- 2 to 10 +/- 5 mmHg, n = 16) and consequently mean pulmonary artery pressure (from 10 +/- 2 to 16 +/- 5 mmHg). Minute ventilation increased by 84% (n = 11), resulting in hypocapnia (PCO2: 31 +/- 3 mmHg, n = 8) and alkalosis (pH: 7.46 +/- 0.02, n = 8). Oxygen consumption was unchanged during the infusion, but increased by 21% 5 min post infusion. All effects were similar in patients with and without coronary artery disease. Adenosine therefore causes pulmonary and systemic vasodilation and respiratory stimulation. Symptoms and an increase in LVEDP of uncertain cause, which occur with high doses, may limit the use of adenosine as a systemic vasodilator in conscious subjects. However at lower doses adenosine causes selective pulmonary vasodilation which merits further study.

Adenosine↗