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Bolus Infusion (bolus + infusion)
Selected Abstracts5-Hydroxytryptamine-induced microvascular pressure transients in lungs of anaesthetized rabbitsACTA PHYSIOLOGICA, Issue 2 2001N. Sen We determined lung microvascular pressure transients induced by 5-hydroxytryptamine (5HT), by the micropuncture technique. We mechanically ventilated anaesthetized (halothane 0.8%), open-chested rabbits, in which we recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and cardiac output. For 4-min periods of stopped ventilation, we constantly inflated the lung with airway pressure of 7 cmH2O, then micropunctured the lung to determine pressures in arterioles and venules of 20,25 ,m diameter. An intravenous bolus infusion of 5HT (100 ,g), increased total pulmonary vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular and venous segments comprised 30, 50 and 19% of the total pulmonary vascular pressure drop, respectively. However 14 s after 5HT infusion, the PA-arteriole pressure difference (arterial pressure drop) increased 46%, while the venule-LA pressure difference (venous pressure drop) increased >100%. The arteriole,venule pressure difference (microvascular pressure drop) was abolished. The increase in the arterial pressure drop was maintained for 4.8 min, whereas the increased venous pressure drop reverted to baseline in <1 min. We conclude that in the rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a strong but transient venous constriction. [source] Recombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: a review of the literatureHAEMOPHILIA, Issue 2 2008A. OBERGFELL Summary., Arthropathy is prevalent in patients with haemophilia and inhibitors and is a major source of pain and disability, significantly reducing quality of life. Recombinant activated factor VII (rFVIIa; NovoSeven®) is one of the treatments available for acute life-threatening bleeding episodes in haemophilia patients with inhibitors. It has also been used successfully in a range of orthopaedic surgical procedures in these patients. This is a review of published data on elective orthopaedic procedures in haemophilia patients with inhibitors under cover of rFVIIa from January 2002 to November 2006. Articles were retrieved from MEDLINE using specified search parameters. Twelve articles covering a total of 80 orthopaedic procedures were identified. In the vast majority of cases, rFVIIa provided safe and effective haemostatic cover during orthopaedic surgery with no bleeding complications. There was variation in the administered dose, although the majority of patients were treated with 90 ,g kg,1 bolus followed by either continuous infusion or bolus infusion. Of those cases reporting bleeding complications, most were considered to be related to an inadequate amount of rFVIIa. The cumulative experience presented here suggests that rFVIIa is safe and effective for providing adequate haemostatic cover for haemophilia patients with inhibitors undergoing orthopaedic surgery. The optimal dosing regimen and mode of administration has yet to be identified. Further controlled trials are needed to confirm these experiences. [source] In vivo pharmacology and antidiarrheal efficacy of a thiazolidinone CFTR inhibitor in rodentsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2005N.D. Sonawane Abstract A small-molecule inhibitor of the cystic fibrosis transmembrane conductance regulator (CFTR), 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh -172), reduces enterotoxin-induced intestinal fluid secretion in rodents. Here, we study CFTRinh -172 pharmacology and antidiarrheal efficacy in rodents using 14C-labeled CFTRinh -172, liquid chromatography/mass spectrometry, and a closed intestinal loop model of fluid secretion. CFTRinh -172 was cleared primarily by renal glomerular filtration without chemical modification. CFTRinh -172 accumulated in liver within 5 min after intravenous infusion in mice, and was concentrated fivefold in bile over blood. At 30,240 min, CFTRinh -172 was found mainly in liver, intestine, and kidney, with little detectable in the brain, heart, skeletal muscle, or lung. Pharmacokinetic analysis in rats following intravenous bolus infusion showed a distribution volume of 770 mL with redistribution and elimination half-times of 0.14 h and 10.3 h, respectively. CFTRinh -172 was stable in hepatic microsomes. Closed-loop studies in mice indicated that a single intraperitoneal injection of 20 ,g CFTRinh -172 inhibited fluid accumulation at 6 h after cholera toxin by >90% in duodenum and jejunum, ,60% in ileum and <10% in colon. No toxicity was seen after high-dose CFTRinh -172 administration (3 mg/kg/day in two daily doses) in mice over the first 6 weeks of life. The metabolic stability, enterohepatic recirculation, slow renal elimination, and intestinal accumulation of CFTRinh -172 account for its efficacy as an antidiarrheal. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:134,143, 2005 [source] Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humansTHE JOURNAL OF PHYSIOLOGY, Issue 2 2001Thad E. Wilson 1Prior findings suggest that baroreflexes are capable of modulating skin blood flow, but the effects of baroreceptor loading/unloading on sweating are less clear. Therefore, this project tested the hypothesis that pharmacologically induced alterations in arterial blood pressure in heated humans would lead to baroreflex-mediated changes in both skin sympathetic nerve activity (SSNA) and sweat rate. 2In seven subjects mean arterial blood pressure was lowered (,8 mmHg) and then raised (,13 mmHg) by bolus injections of sodium nitroprusside and phenylephrine, respectively. Moreover, in a separate protocol, arterial blood pressure was reduced via steady-state administration of sodium nitroprusside. In both normothermia and heat-stress conditions the following responses were monitored: sublingual and mean skin temperatures, heart rate, beat-by-beat blood pressure, skin blood flow (laser-Doppler flowmetry), local sweat rate and SSNA (microneurography from peroneal nerve). 3Whole-body heating increased skin and sublingual temperatures, heart rate, cutaneous blood flow, sweat rate and SSNA, but did not change arterial blood pressure. Heart rate was significantly elevated (from 74 ± 3 to 92 ± 4 beats min,1; P < 0.001) during bolus sodium nitroprusside-induced reductions in blood pressure, and significantly reduced (from 92 ± 4 to 68 ± 4 beats min,1; P < 0.001) during bolus phenylephrine-induced elevations in blood pressure, thereby demonstrating normal baroreflex function in these subjects. 4Neither SSNA nor sweat rate was altered by rapid (bolus infusion) or sustained (steady-state infusion) changes in blood pressure regardless of the thermal condition. 5These data suggest that SSNA and sweat rate are not modulated by arterial baroreflexes in normothermic or moderately heated individuals. [source] Use of additional oxytocin to reduce blood loss at elective caesarean section: A randomised control trialAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2010Kemal GÜNGÖRDÜK Objective:, The purpose of this prospective, randomised, double-blind, placebo-controlled study was to assess the effects of a 5-IU oxytocin bolus and placebo infusion versus a 5-IU oxytocin bolus and 30 IU infusion on the control of blood loss at elective lower segment caesarean section (C/S). Methods:, Participants with indication for elective C/S were randomly allocated to two groups. Group A, 360 women, received oxytocin 5 IU bolus and placebo; group B, 360 women received oxytocin 5 IU bolus and 30 IU infusion. Blood loss was estimated based on the haematocrit values before and 48 h after delivery. The primary outcome was the incidence of excessive bleeding (estimated blood loss of >1000 mL), while secondary outcomes included use of additional uterotonics, estimated blood loss, need for blood transfusion, duration of hospital stay and the incidence of adverse effects. Results:, No demographic difference was observed between groups. Mean estimated blood loss (P < 0.001) and the proportion of women with blood loss estimated to be greater than 1000 mL were significantly less for group B than for group A (relative risk (RR) 0.35, 95% confidence interval (CI) 0.20,0.63). In addition, more women in the group A required additional uterotonic agents (RR 0.35, 95% CI 0.22,0.56) and blood transfusion (RR 0.12, 95% CI 0.01,0.98). Conclusion:, An additional oxytocin infusion after 5 IU oxytocin bolus infusion at elective C/S may reduce blood loss and required blood transfusion. [source] Phase 1 trial of temozolomide plus irinotecan plus O6 -benzylguanine in adults with recurrent malignant gliomaCANCER, Issue 13 2009Jennifer A. Quinn MD Abstract BACKGROUND: The current study was a phase 1 clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG). The trial was designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan (CPT-11) when administered with temozolomide (TMZ) and O6 -benzylguanine (O6 -BG). METHODS: All 3 drugs, CPT-11, TMZ, and O6 -BG, were administered on Day 1 of a 21-day treatment. First, patients were treated with a 1-hour bolus infusion of O6 -BG at a dose of 120 mg/m2 followed immediately by a 48-hour continuous infusion of O6 -BG at a dose of 30 mg/m2/d. Second, within 60 minutes of the end of the 1-hour bolus infusion of O6 -BG, TMZ was administered orally at a dose of 355 mg/m2. Third, 1 hour after administration of TMZ, CPT-11 was infused over 90 minutes. Patients were accrued to 1 of 2 strata based on CYP3A1- and CYP3A4-inducing antiepileptic drug (EIAED) use; dose escalation was conducted independently within these strata. RESULTS: Fifty-five patients were enrolled. In both strata, the dose-limiting toxicities were hematologic and included grade 4 neutropenia, febrile neutropenia, leukopenia, and/or thrombocytopenia. For Stratum 1 (EIAEDs), when TMZ was administered at a dose of 355 mg/m2, the MTD of CPT-11 was determined to be 120 mg/m2. In contrast, for Stratum 2 (no EIAEDs), when TMZ was administered at a dose of 200 mg/m2, the MTD of CPT-11 was determined to be 80 mg/m2. CONCLUSIONS: The authors believe that the results of the current study provide the foundation for a phase 2 trial of O6 -BG in combination with CPT-11 and TMZ in patients with MG. Cancer 2009. © 2009 American Cancer Society. [source] Augmentation of the Cooling Capacity of Refrigerated Fluid by Minimizing Heat Gain of the Fluid Using a Simple Method of Cold InsulationACADEMIC EMERGENCY MEDICINE, Issue 6 2010Byung Kook Lee MD Abstract Objectives:, This study was undertaken to determine how rapidly refrigerated fluids gain heat during bolus infusion and to determine whether the refrigerated fluids could be kept cold by a simple cold-insulation method. Methods:, One liter of refrigerated fluid was run through either a 16-gauge catheter (16G(,) and 16G(+) groups) or an 18-gauge catheter (18G(,) and 18G(+) groups) while monitoring the temperature in the fluid bag and the outflow site. In the 16G(+) and the 18G(+) groups, the fluid bag was placed with an ice pack inside an insulating sleeve during the fluid run. Results:, In the 16G(,) and the 18G(,) groups, the outflow temperature increased to 10,12°C during the fluid run. Meanwhile, outflow temperatures in the 16G(+) and the 18G(+) groups remained below 4.6 and 6.8°C, respectively. The temperatures differed significantly between the 16G(,) and the 16G(+) groups (p < 0.001) and between the 18G(,) and the 18G(+) groups (p < 0.001), respectively. Conclusions:, Substantial heat gain occurred in the refrigerated fluid even during the relatively short duration of bolus infusion. The heat gain could, however, be easily minimized by cold insulation of the fluid bag. ACADEMIC EMERGENCY MEDICINE 2010; 17:673,675 © 2010 by the Society for Academic Emergency Medicine [source] Overdose of methyldopa, indapamide and theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an elderly patient,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2009Thomas Y. K. Chan MBChB Abstract An 89-year-old man with a history of hypertension, chronic obstructive pulmonary disease, personality disorder and previous attempts of self-poisoning attempted suicide by swallowing two mouthfuls of tablets (methyldopa 250,mg, theophylline SR 200,mg, indapamide 2.5,mg and paracetamol 500,mg). He had prolonged, severe hypotension, necessitating the use of 3000,ml of Gelofusine® and almost 2 days of intravenous norepinephrine infusion. He had marked diuresis for 4.5 days, requiring continuous and bolus infusions of intravenous fluids. He had marked renal potassium loss, requiring vigorous potassium replacement therapy. Multiple-dose activated charcoal was used to enhance theophylline elimination. The plasma paracetamol level was below the treatment line. Methyldopa via its metabolite stimulates postsynaptic , -adrenergic receptors in cardiovascular control centres in the brain, causing a reduction in peripheral sympathetic tone and a fall in arterial blood pressure and heart rate. In overdose, it causes hypotension, bradycardia and drowsiness. The natriuretic, kaliuretic and vasodilatory effects of indapamide are exaggerated in overdose, resulting in diuresis, hypokalaemia and hypotension. Theophylline markedly increases the level of circulating catecholamines, which stimulate the vascular ,2 -adrenergic receptors with decreased peripheral vascular resistance. Peripheral vasodilation and hypotension occur in significant theophylline poisoning. Intracellular shift of potassium results in hypokalaemia. The prescribing physicians should recognise elderly patients at a high risk of self-poisoning and avoid using drugs with a high toxicity in overdose (e.g. theophylline and methyldopa). Restricting access to hazardous drugs (in overdose) would be of paramount importance to reduce the number of severe acute poisoning cases and case-fatalities. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||