Stability and compatibility of doxofylline with phentolamine mesilate in 0.9% sodium chloride or 5% dextrose injection for intravenous infusion

What is know and objective: The use of extemporaneously prepared admixtures of drugs must be supported by documentation of their chemical stability. The objective was to assess the physical compatibility and the chemical stability of doxofylline with phentolamine mesilate in 0·9% sodium chloride or 5% dextrose injection for intravenous infusion. Methods: Total volumes of 20 and 1 mL of doxofylline solution and phentolamine mesilate solution, respectively, were added to 250 mL polyolefin bags containing 5% dextrose injection or 0·9% sodium chloride injection. Bags were stored for 24 h at 20–25 °C. Chemical compatibility was measures with high‐performance liquid chromatography, and physical compatibility was determined visually. Results: The samples were clear and colourless when viewed in normal fluorescent room light. The pH value and particulate content of the admixtures exhibited little change. The retentions of the initial concentration of doxofylline and phentolamine mesilate in the admixtures were within 97–105%. Doxofylline and phentolamine mesilate were stable in 5% dextrose injection or in 0·9% sodium chloride for up to 24 h at 20–25 °C. What is new and conclusion: Doxofylline and phentolamine mesilate mixed in both 5% dextrose injection and 0·9% sodium chloride injection in 250 mL multilayer polyolefin bags at concentrations of 0·74 mg/mL and 36·9 μg/mL, respectively, were stable for up to 24 h at 20–25 °C.     

Stability of cyclosporine in dextrose 5%, NaCl 0.9%, dextrose/amino acid solution, and lipid emulsion.

OBJECTIVE: Because of limited intravenous access in patients who have undergone bone marrow transplant (BMT), we undertook a study to determine the safety of mixing cyclosporine in intravenous preparations commonly administered to BMT patients. DESIGN: In a pilot study, we investigated the stability of intravenous cyclosporine (Sandimmune) in four types of intravenous fluids: dextrose 5%, NaCl 0.9%, dextrose/amino acid solutions, and lipid emulsion. Because the pilot study showed highly variable cyclosporine concentrations that suggested inadequate mixing, we undertook another study to determine the effect of the mixing method on cyclosporine concentrations. OUTCOME MEASURE: Cyclosporine was considered stable in the study solutions if concentrations remained above 90 percent of the initial concentrations. RESULTS: Substantial variation in cyclosporine concentrations was observed in lipid emulsion and dextrose/amino acid solutions and gentle swirling of the solutions was insufficient to adequately disperse the drug. The variation was eliminated by vigorous shaking either before each sampling or once after the initial addition of cyclosporine. We used vigorous shaking methods to establish that cyclosporine is stable for up to 72 hours at room temperature in dextrose 5%, 10% amino acid solution with dextrose 50%, and Liposyn 10%, and up to 8 hours in NaCl 0.9%. CONCLUSIONS: These data may be used to simplify cyclosporine administration in patients who have limited intravenous access.     

Influence of NaCl 0.9% Infusion during Plasmapheresis on IgG Content in Plasma

Zusammenfassung

Hintergrund

Das Ziel dieser Untersuchung war, den Einfluss einer Infusion von NaCl 0,9% 500 ml während der präparativen Plasmapherese oder Apherese auf den Immunglobulin-G(IgG)-Gehalt im getrennten Plasma zu bestimmen.

Methoden

Das Plasma von 32 Spendern wurde in einem Crossover-Design nach schriftlicher Einverständniserklärung an einem Tag ohne NaCl-Infusion während der Apherese und an einem anderen Tag mit einer Infusion von 500 ml NaCl 0,9% während der Apherese untersucht. Die Infusion von NaCl 0,9% 500 ml wurde allmählich in geteilten Dosen nach jedem Zyklus über das Einmalschlauchsystem (Harness Set) des Haemonetics® Plasma Collecting System 2 (PCS2) verabreicht. Die IgG-Konzentrationen im Serum und im Plasma wurden mit einem immunturbidimetrischen Test gemessen. Der prozentuale Anteil der IgG-Konzentrationen im hergestellten Plasma wurde durch Division durch die mittleren Werte (Mittelwerte) der IgG-Serumkonzent-rationen berechnet (× 100).

Ergebnisse

Ohne Infusion von NaCl 0,9% 500 ml betrug der prozentuale Anteil von IgG im Plasma 85,5 ± 2,3% der mittleren IgG-Serumkon-zentrationen; mit NaCl 0,9% 500 ml war der Anteil 80,5 ± 3,4%. Der Unterschied zwischen den beiden Stichproben war statistisch hoch signifikant (p < 0,001).

Schlussfolgerung

Wir schlussfolgern, dass die allmähliche Infusion von NaCl 0,9% 500 ml während einer Apherese zu einer statistisch hoch signifikanten Verminderung des IgG-Gehalts im Produktplasma führt.     

Stability of foscarnet sodium in 5% dextrose and 0.9% sodium chloride injections

The stability of foscarnet sodium injection in 5% dextrose and 0-9% sodium chloride injections was determined using a stability-indicating assay reported in the literature. The solutions were stable for at least 35 days when stored at 25 or 5C. They remained clear throughout the study and pH values did not change. The solutions were stored in plastic bags as used by patients at home.     

Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study

ABSTRACT: INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups. CLINICALTRIALS.GOV: NCT00464204.     

Plasma volume expansion after infusion of 5%, 20% and 25% albumin solutions in patients.

Fifty grams of albumin were infused into patients in the immediate post-operative period as either 5, 20 or 25% solutions. With all three solutions the increase in plasma volume was 500 ml or 11 ml/g of retained albumin, which is less than the normal water-binding capacity of albumin found in studies in vitro and in some clinical studies. This might be explained by a blocking of the water-binding capacity of the albumin or by the action of other unknown mechanisms, when albumin is given in an amount exceeding the losses. The expansion of the plasma volume did not depend on the concentration of the solutions given but only on the amount of albumin given and the deficit in plasma volume. Since albumin is a good plasma expander and a drug with a few secondary effects it is recommended in the treatment of shock. We prefer the 5% solution, which contains an electrolyte solution and is more easily infused, because of its low viscosity.     

Persistent hypercalcemia after parathyroidectomy in an adolescent and effect of treatment with cinacalcet HCl

BACKGROUND: Hyperparathyroidism is uncommon in adolescence and is more likely to persist after parathyroidectomy than in adults. Cinacalcet HCl is a new calcimimetic that has been used successfully for the treatment of primary and secondary hyperparathyroidism in adults, but its use in adolescents has not been reported. Case: A 16 year-old male presented with hypercalcemia that had persisted for 1.5 years after parathyroidectomy for primary hyperparathyroidism. Parathyroid hormone (PTH) concentrations were nonsupressed despite a mean (SD) serum calcium concentration of 2.82 (0.06) mmol/L. Treatment with cinacalcet HCl was initiated and a pharmacodynamic profile was obtained for serum calcium, phosphorus, and PTH. Cinacalcet HCl normalized serum calcium. The changes in PTH were assay dependent. Issues: We use this case conference to review the evaluation of hypercalcemia in adolescents, examine the changes in relevant laboratory results during treatment with cinacalcet HCl, and discuss differences among assays for PTH. CONCLUSIONS: Interpretation of PTH results in patients treated with cinacalcet HCl requires consideration of the pharmacodynamic effects of the drug and the nature of the PTH assay.     

Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients

Objective To determine the pharmacokinetics of long-term infusion of sufentanil in ICU patients.Design and setting Open-label study in a surgical intensive care unit.Patients Ten consecutive patients without renal or hepatic failure requiring mechanical ventilation for at least 6 days.Interventions Patients received sufentanil (initial bolus 0.5 µg/kg and continuous infusion rate of 0.5 µg/kg per hour) and midazolam (initial bolus 0.08 mg/kg and continuous infusion 0.05 mg/kg per hour). Sedation was adjusted according to the Ramsay scale (score >3). Blood samples were taken during and up to 72 h after the infusion, and plasma concentrations were measured using a sensitive radioimmunoassay method.Measurements and results Plasma concentration-time profiles of sufentanil and pharmacokinetic parameters such as initial postinfusion half-life (t_1/2), elimination half-life (t_1/2), total clearance (Cl), volume of distribution (Vd), and time required to obtain a 50% decrease in plasma concentration (tcp_0/2). The mean duration of sedation was 12±7 days. The initial half-life t_1/2 was 1.33±1.15 h. The observed prolonged elimination half-life (t_1/2=25.5±9.4 h) was related to the large volume of distribution (Vd=22.6±9.4 l/kg). The mean total clearance was 13.4±7.0 ml/kg per minute. The mean time required to obtain a 50% decrease in plasma concentration was short (tcp_0/2=4.7±3.7 h).Conclusions The pharmacokinetic analysis of sufentanil for ICU sedation revealed increased volume of distribution and elimination half-life. Nevertheless the rapid distribution and elimination processes suggest that the rapid reversibility of sedation with sufentanil is maintained after long duration of infusion. Further studies should be carried out to evaluate the clinical relevance of these results.     

Comparison of the effects of bolus vs. slow infusion of 7.5% NaCl/6% dextran-70 in a model of near-lethal uncontrolled hemorrhage

Bolus infusion of of 7.5% NaCl/6% dextran-70 (HSD-B) improves outcome from controlled hemorrhage. In contrast, HSD-B during uncontrolled hemorrhage increases bleeding and short-term mortality. The purpose of this study was to compare the effects of bolus vs. slow infusion of HSD in a near-fatal vascular injury hemorrhage model. Sixteen (15-20 kg) swine with 4-mm aortic tears were hemorrhaged to a pulse pressure of 5 mmHg. An ultrasonic flow probe was placed proximal to the aortic tear for continuous blood flow (AF) measurements. Group I (slow infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 0.4 mL/kg/min. Group II (bolus infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 1.33 mL/kg/min. In both groups, HSD infusion was followed by administration of 30 mL/kg of shed blood at 3 mL/kg/min. Hemorrhage volume and 90-min mortality were greater in group II (79+/-11 mL/kg; 75%) compared with group I (43+/-9 mL/kg; 12.5%) (P(Hem) < 0.001; P(Mort) = 0.04). Mean arterial pressure (MAP) and AF were greater in group II compared with group I during the first 15 min of resuscitation. In group I, MAP, AF, cardiac indices, and O2 delivery gradually returned to baseline levels and were significantly greater than group II at 30 min and throughout the remainder of the protocol. In this model of near-lethal uncontrolled hemorrhage, slow infusion of HSD restored cardiodynamics while minimizing hemorrhage volume and mortality. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation.     

0.75%速卡腰硬联合麻醉在老年患者全髋置换术中的应用

Objective To evaluate the efficacy and safety of 0.75% levobupivacaine for combined spi-nal and epidural anesthesia (CSEA) in old patients undergoing total hip replacement surgery. Methods Sixty ASA Ⅰ～Ⅱ patients, scheduled for selective total hip replacement surgery, were randomly divided into two groups. The patients in group L, received 0.75% levobupivaeaine 15 nag(2 ml)for spinal anesthesia, and those in group B, received same amount of 0.75 % bupivacane. 2% lidocaine was supplemented via epidural catheter when spinal analgesia was inadequate. During operation, BP, HR and SpO2 were monitored continually. Sensory and motor blockade, side effects were recorded. Results The plane of block, onset time, duration of blockade, motor block were comparable between two groups. There was no neural side effects in both groups. Conclusion 0.75% levobupivacaine for CSEA is effective and safe for total hip replacement surgery.     

Vacuolar hepatocyte degeneration induced by infusion of 20% glucose solution with insulin after hepatopancreatectomy in rats

To investigate the causes of hepatic dysfunction after extensive resection of the liver together with pancreatectomy, rats were subjected to sham operation, to 68% hepatectomy alone, to 90% pancreatectomy alone, or to 68% hepatectomy combined with 90% pancreatectomy (hepatopancreatectomy). Solutions of 5% or 20% glucose were infused post-operatively for 48 h at a constant rate (250 ml/kg body weight/day) under fasting conditions. To improve the survival rates of pancreatectomized and hepatopancreatectomized rats given 20% glucose, it was necessary to use insulin. In hepatopancreatectomized rats, infusion of 20% glucose with insulin (1 U/5 g glucose) induced prominent hepatocyte vacuolar degeneration and mitochondrial swelling, associated with reduced hepatic protein content. The severity of histological changes was proportional to the insulin dose and the activity of hepatic glucokinase, a key glycolytic enzyme. were observed in These histological changes pancreatectomized rats albeit in a milder form, but not in sham-operated or hepatectomized rats given 20% glucose nor in any rats given 5% glucose. Our results suggest that hepatopancreatectomy followed post-operatively by a high glucose load and exogenously administered insulin enhances the development of hepatocyte swelling.     

0.75%速卡腰硬联合麻醉在老年患者全髋置换术中的应用

Objective To evaluate the efficacy and safety of 0.75% levobupivacaine for combined spi-nal and epidural anesthesia (CSEA) in old patients undergoing total hip replacement surgery. Methods Sixty ASA Ⅰ～Ⅱ patients, scheduled for selective total hip replacement surgery, were randomly divided into two groups. The patients in group L, received 0.75% levobupivaeaine 15 nag(2 ml)for spinal anesthesia, and those in group B, received same amount of 0.75 % bupivacane. 2% lidocaine was supplemented via epidural catheter when spinal analgesia was inadequate. During operation, BP, HR and SpO2 were monitored continually. Sensory and motor blockade, side effects were recorded. Results The plane of block, onset time, duration of blockade, motor block were comparable between two groups. There was no neural side effects in both groups. Conclusion 0.75% levobupivacaine for CSEA is effective and safe for total hip replacement surgery.     

0．75％速卡腰硬联合麻醉在老年患者全髋置换术中的应用

目的探讨0．75％速卡（左旋布比卡因）腰硬联合麻醉在老年患者全髋置换术中的I临床麻醉效果和可行性。方法60例老年全髋置换术患者随机分为两组,每组30例。B组使用0．75％布比卡因,L组使用0．75％左旋布比卡因,两组均行腰硬联合麻醉（CSEA）,鞘内各注人15mg。术中必要时经硬膜外导管注入1．5％利多卡因。术中监测BP、HR、SpO：、R的变化并观察感觉阻滞起效时间、最高感觉阻滞平面、达最高感觉阻滞平面时间、运动阻滞评分以及围术期不良反应的发生。结果两组感觉阻滞起效时间差异无显著性（P〉0．05）;最高感觉阻滞平面L组略低于B组,但差异无显著性;达最高感觉阻滞平面时间L组略短于B组,但无显著性差异;两组患者运动阻滞评分差异无显著性;两组均无神经系统的不良反应。结论0．75％速卡（左旋布比卡因）腰硬联合麻醉用于老年患者全髋置换术中对血流动力学影响小,其临床麻醉效果是安全可行的。     

2种枸橼酸抗凝方法在甲状旁腺切除术后患者血液透析治疗中的应用效果

目的比较2种枸橼酸抗凝方法在甲状旁腺切除术后患者血液透析治疗中的应用效果。方法回顾性分析58例甲状旁腺切除术后血液透析患者的临床资料,患者均采用4%枸橼酸抗凝治疗(共98例次)。将采用滤器前泵入4%枸橼酸300 mL/h血液透析治疗的34例(50例次)患者纳入对照组,将采用滤器前泵入4%枸橼酸250 mL/h,同时静脉壶端泵入4%枸橼酸50 mL/h的"两段法"血液透析治疗的24例(48例次)患者纳入观察组。比较2组血液透析治疗前后钙离子(Ca~(2+))、碳酸氢根离子(HCO_3~-)、钠离子(Na~+)、pH值水平,并比较2组透析器和透析管路凝血级别。结果透析前,2组Na~+、Ca~(2+)、HCO_3~-、pH值水平比较,差异均无统计学意义(P0.05);透析后,2组Na~+、HCO_3~-、pH值水平均高于透析前,差异有统计学意义(P0.05), 2组Ca~(2+)水平与透析前比较,差异均无统计学意义(P0.05);透析后,观察组Na~+水平高于对照组,差异有统计学意义(P0.05), 2组间Ca~(2+)、HCO_3~-、pH值水平比较,差异均无统计学意义(P0.05)。2组透析器凝血及透析管路凝血情况比较,差异均有统计学意义(P0.05)。结论与传统枸橼酸抗凝方式比较,枸橼酸"两段法"抗凝方式安全有效,可显著降低静脉壶凝血发生率,保证4 h透析时间,改善透析效果。     

0.75%速卡腰硬联合麻醉在老年患者全髋置换术中的应用

Objective To evaluate the efficacy and safety of 0.75% levobupivacaine for combined spi-nal and epidural anesthesia (CSEA) in old patients undergoing total hip replacement surgery. Methods Sixty ASA Ⅰ～Ⅱ patients, scheduled for selective total hip replacement surgery, were randomly divided into two groups. The patients in group L, received 0.75% levobupivaeaine 15 nag(2 ml)for spinal anesthesia, and those in group B, received same amount of 0.75 % bupivacane. 2% lidocaine was supplemented via epidural catheter when spinal analgesia was inadequate. During operation, BP, HR and SpO2 were monitored continually. Sensory and motor blockade, side effects were recorded. Results The plane of block, onset time, duration of blockade, motor block were comparable between two groups. There was no neural side effects in both groups. Conclusion 0.75% levobupivacaine for CSEA is effective and safe for total hip replacement surgery.