不同静脉铁剂用量对维持性血液透析患者的疗效观察及生存分析

目的 观察不同静脉铁剂用量对维持性血液透析（maintenance hemodialysis,MHD患者的疗效,并分析患者生存情况。方法 选取80例MHD患者（秦皇岛市第一医院于2017年5月至2019年5月收治）,采用随机数字表法分为低剂量组（40例）和高剂量组（40例）。其中低剂量组给予100 mg/2周,200 mg/月;高剂量组给予100 mg/周,400 mg/月。比较2组患者氧化应激水平[超氧化物歧化酶（superoxide dismutase,SOD）、谷胱甘肽过氧化物酶（glutathione peroxidases,GSHpx）],炎症因子水平[肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、超敏C反应蛋白（hypersensitive c-reactive protein,hs-CRP）],重组人红细胞生成素（recombinant human erythropoietin,rHuEPO）用量、铁蛋白、血红蛋白水平及不良反应发生情况;绘制生存曲线分析MHD患者使用不同剂量静脉铁剂给药...     

鞘内注射吗啡用于胸腔镜肺叶切除术患者术后镇痛的半数有效剂量

目的 探讨鞘内注射吗啡（ITM）用于胸腔镜肺叶切除术患者术后镇痛的半数有效剂量（ED50）。
方法 选择拟行全麻下胸腔镜肺叶切除术患者22例,年龄35～64岁,BMI 18～30 kg/m²,ASA Ⅰ或Ⅱ级。所有患者于术前在L_2-3间隙行蛛网膜下腔穿刺。患者鞘内吗啡的初始给药剂量为5 μg/kg,相邻药物剂量比值为1∶1.1,剂量梯度依次为5.00、4.55、4.14、3.76、3.42、3.11 μg/kg。根据上一例患者术后镇痛效果,下一例患者上升或下降一个剂量梯度。术后镇痛有效标准：若术后6、12、24、48 h活动时VAS疼痛评分均≤3分,则认为术后镇痛有效;若任一时刻活动时VAS疼痛评分＞3分,则认为镇痛无效。采用Probit法计算ED50、ED95及其95%可信区间（CI）。记录呼吸抑制、恶心呕吐、皮肤瘙痒、尿潴留等不良反应的发生情况。
结果 ITM用于胸腔镜肺叶切除术的ED50为3.468 μg/kg（95%CI 2.926～3.782 μg/kg）,ED95为4.037 μg/kg（95%CI 3.746～7.127 μg/kg）。有2例（9%）出现皮肤轻微瘙痒,3例（14%）出现恶心呕吐,未观察到其他不良反应发生。
结论 鞘内注射吗啡用于胸腔镜肺叶切除术的ED50为3.468 μg/kg（95%CI 2.926～3.782 μg/kg）。     

复合不同剂量艾司氯胺酮时舒芬太尼引起呼吸抑制半数有效剂量的比较

目的 比较复合不同剂量艾司氯胺酮时舒芬太尼引起全麻患者呼吸抑制的半数有效剂量（ED₅₀）。
方法 选择2022年2—10月择期行气管插管全麻手术的患者150例，男86例，女64例，年龄20～50岁，BMI 18～24 kg/m²，ASA Ⅰ或Ⅱ级。将患者随机分为三组：A组、B组和C组，每组50例。A组静注咪达唑仑0.03 mg/kg；B组静注咪达唑仑0.03 mg/kg和亚麻醉剂量艾司氯胺酮0.25 mg/kg；C组静注咪达唑仑0.03 mg/kg和麻醉剂量艾司氯胺酮0.5 mg/kg；5 min后三组单次静注舒芬太尼。舒芬太尼单次注射剂量按Dixon序贯法确定，初始剂量0.05 μg/kg，相邻剂量梯度为0.025 μg/kg。若出现呼吸抑制，则下一例患者舒芬太尼降低一个剂量梯度；若未出现呼吸抑制，则下一例升高一个剂量梯度。呼吸抑制标准为SpO₂≤92％或RR<10次/分。计算复合不同剂量艾司氯胺酮时舒芬太尼引起呼吸抑制的ED₅₀及95％可信区间（CI）。
结果 A组出现呛咳3例，C组出现HR＞100次/分2例，经相应处理后未影响研究进行。A组、B组和C组达到呼吸抑制时舒芬太尼的ED₅₀及95%CI分别为0.152 μg/kg（95%CI 0.142～0.164 μg/kg）、0.199 μg/kg（95%CI 0.186～0.212 μg/kg）和0.109 μg/kg（95%CI 0.100～0.118 μg/kg）。
结论 咪达唑仑0.03 mg/kg辅助镇静时，单用舒芬太尼静脉注射致呼吸抑制的ED₅₀为0.152 μg/kg；复合艾司氯胺酮0.25 mg/kg可以提高舒芬太尼静脉注射致呼吸抑制的ED₅₀；复合艾司氯胺酮0.5 mg/kg可以降低舒芬太尼静脉注射致呼吸抑制的ED₅₀。     

不同剂量舒芬太尼术后镇痛方案对面肌痉挛微血管减压术后恶心呕吐的影响

目的:观察面肌痉挛微血管减压术后应用不同剂量舒芬太尼镇痛方案对术后恶心呕吐不良反应的影响。方法:回顾性纳入行微血管减压术的面肌痉挛女性患者183例,在相同麻醉方法的基础上根据术后是否使用舒芬太尼镇痛泵及其不同剂量将患者分为舒芬太尼2 μg/kg组（A组,60例）、舒芬太尼1 μg/kg组（B组,60例）和未使用镇痛泵组...     

氨甲环酸对类风湿关节炎患者全髋关节置换围手术期失血的影响

目的：探索氨甲环酸对类风湿关节炎患者全髋关节置换围手术期失血的影响。方法回顾性分析2012年6月至2014年6月行初次全髋关节置换术患者资料,仅纳入因类风湿关节炎（Steinbrocker 3、4级）行初次单侧全髋关节置换术患者数据,最终纳入197例。其中68例术前20 min静脉滴注氨甲环酸15 mg/kg（单次给药组）,74例术前20 min静脉滴注氨甲环酸15 mg/kg+术后3 h再次静脉滴注氨甲环酸10 mg/kg（重复给药组）,55例未使用氨甲环酸（对照组）。单次给药组女52例、男16例,平均年龄58岁;重复给药组女54例、男20例,平均年龄59岁;对照组女40例、男15例,平均年龄55岁。比较三组患者总失血量、输血率、深静脉血栓及肺栓塞发生率、术后引流量、术后血红蛋白下降值及并发症情况。结果单次给药组、重复给药组和对照组围手术期总失血量分别为（816.80±245.09）ml、（975.15±216.33）ml和（1295.68±263.85）ml,术后引流量为（221.60±70.05）ml、（337.20±113.10）ml和（479.74±120.66）ml,输血率为5.41%、10.29%和25.45%,术后血红蛋白降低值为（2.71±0.74）g/dl、（3.18±0.62）g/dl和（3.83±0.70）g/dl;各指标给药组均较对照组低,重复给药组较单次给药组围手术期总失血量、输血率、术后引流量更低。术后三组患者均未发生深静脉血栓及肺栓塞;单次给药组8例、重复给药组6例、对照组8例出现切口并发症,发生率分别为11.8%（8/68）、8.1%（6/74）、14.5%（8/55）,三者比较差异无统计学意义（χ2=1.355,P=0.508）。结论静脉使用氨甲环酸可有效降低类风湿关节炎患者全髋关节置换围手术期总失血量与输血率,且不增加血栓事件的风险,相对于术前单次使用氨甲环酸,更推荐术前及术后3h重复给药。     

舒芬太尼不同自控剂量对儿科术后镇痛有效性和安全性的比较

目的:比较1~7岁患儿术后使用舒芬太尼行患者自控静脉镇痛（patients control intravenous analgesia,PCIA）时不同自控给药剂量的有效性和安全性。方法:全身麻醉下行择期手术的患儿术后使用舒芬太尼行PCIA,舒芬太尼总量为2 μg/kg,使用0.9%氯化钠稀释至100 ml,背景剂量为...     

经皮穴位电刺激对咪达唑仑致老年患者意识消失半数有效量的影响

目的：探讨经皮穴位电刺激对咪达唑仑致老年患者意识消失半数有效量（ED50）的影响。方法：选择在我院择期椎管内麻醉行骨科下肢手术老年患者 52 例,随机将患者分为 2 组：经皮穴位电刺激组和对照组。实施椎管内麻醉,刺激组选择双侧合谷穴、内关穴给予经皮穴位电刺激 20 min 后静脉注射咪达唑仑。对照组患者在相应穴位贴电极片,并连接刺激器,不予电刺激。以 OAA/S 评分≤ 2 分判定为意识消失。采用序贯法确定咪达唑仑剂量,初始剂量为 40 μg/kg,相邻剂量比为 1∶1.1。当出现 7 次阴阳交叉时终止试验。采用序贯法公式法计算咪达唑仑致患者意识消失 ED50 及其 95% 置信区间。结果：刺激组咪达唑仑致患者意识消失 ED50 及其 95% 置信区间为 40.5 μg/kg（95% CI 为 28.1~58.2 μg/kg）,对照组为 47.7 μg/kg（95% CI 为 33.1~68.9 μg/kg）,两组比较差异有统计学意义（P<0.05）。结论：经皮穴位电刺激可降低咪达唑仑致老年患者意识消失的 ED50。     

咪达唑仑和丙泊酚镇静用于结肠镜检查的比较(前瞻性随机对照研究)

目的借助脑电双频指数（bispectral index,BIS）监测,随机前瞻性比较咪达唑仑和丙泊酚用于结肠镜检查的镇静深度、镇静效果和安全性。方法接受无痛结肠镜检查患者60例,用随机数字表分为3组,每组20例：Ⅰ组,咪达唑仑首次剂量0．06mg／kg;Ⅱ组,丙泊酚首次剂量1．0mg／kg;Ⅲ组,丙泊酚首次剂量1．5mg／kg。于丙泊酚给药后1min、眯达唑仑给药后2min进镜。病人出现不良反应且影响操作时追加丙泊酚20～30mg。监测血压、心率、血氧饱和度值（SpO,）、BIS值,以BIS值反映镇静深度。结果进镜时镇静深度由浅到深依次为Ⅰ、Ⅱ、Ⅲ组（F=25．40,P=0．000）,检查中的BIS最低值无统计学差异。进镜时三组患者均无不良反应,丙泊酚追加剂量Ⅰ组明显少于Ⅱ、Ⅲ组,清醒时间Ⅰ组明显长于Ⅱ、Ⅲ组。Ⅰ组有1例心率〈60次／min,Ⅲ组有1例血压〈90／60inmHg,均为一过性,三组SpO2均大于90％。结论咪达唑仑0．06mg／kg和丙泊酚1．0mg／kg作为首次剂量用于结肠镜检查,检查中适时追加丙泊酚镇静深度,镇静效果满意且安全。     

影响干扰素治疗慢性乙型肝炎的相关因素分析

重组干扰素－α（ＩＦＮ－α）是治疗慢性乙型肝炎疗效稳定，安全可靠的药物，由于治疗过程中需长期应用，对机体具有一定的毒副作用，往往影响患者接受治疗的耐受性，甚至导致治疗的失败。本文对３４２例采用ＩＦＮ－α治疗的慢性乙肝患者进行定向性观察。分析影响ＩＦＮ－α治疗的相关因素有：（１）ＩＦＮ－α的不良反应；（２）患者个体间的差异；（３）给药的剂量，次数与时间。针对上述因素，采取相应的护理措施；（１）做好用     

舒芬太尼复合布托啡诺对依托咪酯全麻诱导肌震颤的影响

目的观察舒芬太尼复合布托啡诺对依托咪酯全麻诱导肌震颤的影响以及合适剂量。 方法选择2018年11月至2019年6月河北省保定市第一中心医院择期行全麻手术患者120例,ASA Ⅰ~Ⅱ级,随机分为S组、BS1组和BS2组。S组静注舒芬太尼0.4 μg/kg;BS1组预注布托啡诺10 μg/kg,3 min后静注舒芬太尼0.3 μg/kg;BS2组预注布托啡诺20 μg/kg,3 min后静注舒芬太尼0.2 μg/kg,三组患者均于1 min后静注依托咪酯0.3 mg/kg（推注时间10~15 s）。连续观察2 min,静注顺苯磺酸阿曲库铵0.25 mg/kg,2 min后行气管插管。记录呛咳反应发生率,肌震颤发生情况,给药前、插管前即刻及插管后即刻的心率（HR)、平均动脉压（MAP）,术后6 h内恶心呕吐的发生率。 结果三组患者肌震颤的发生率无明显差异,S组呛咳反应的发生率高（χ²=10.350,P=0.006）;S组给药前至插管前即刻MAP、HR降低较BS1、BS2组明显（F=25.910、22.057,均P<0.001）,BS1、BS2组间差异无统计学意义;插管前后BS1组HR、MAP升高最小,其次为S组,BS2升高最大（F=8.849、16.101,均P<0.001）。三组患者术中情况均稳定,术后均无严重的麻醉相关并发症。 结论舒芬太尼复合布托啡诺与等效镇痛剂量的单纯舒芬太尼对于依托咪酯所致肌震颤的抑制作用相同,布托啡诺对舒芬太尼所致的呛咳反应具有抑制作用。布托啡诺10 μg/kg复合舒芬太尼0.3 μg/kg更能维持全麻患者气管插管血流动力学的稳定,为比较合适的麻醉诱导复合剂量。     

Pharmacokinetics of darbepoetin alfa in pediatric patients with chronic kidney disease

Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 micro g/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.     

Correction of anaemia with darbepoetin alfa in patients with chronic kidney disease receiving dialysis.

BACKGROUND: Darbepoetin alfa is a new recombinant erythropoietic protein with a 3-fold longer half-life than recombinant human erythropoietin (rHuEpo). The optimal starting dose and frequency of administration of darbepoetin alfa were investigated for treating renal anaemia in dialysis patients. METHODS: Two multicentre, sequential dose-escalation studies examined the i.v. route of administration of darbepoetin alfa in haemodialysis patients (n=75) and the s.c. route in peritoneal dialysis patients (n=47). Patients were randomized to receive darbepoetin alfa at doses ranging from 0.075 to 0.75 microg/kg/week administered as either a once weekly or a three-times weekly injection. Patients achieving the primary endpoint of a > or = 1 g/dl increase in haemoglobin after 4 weeks continued darbepoetin alfa for up to 52 weeks. Safety was assessed by adverse event reports, changes in laboratory values and vital signs, and antibody screening. RESULTS: Darbepoetin alfa produced dose-related increases in haemoglobin over the first 4 weeks of treatment in both studies. Two dose levels (0.45 and 0.75 microg/kg/week) increased the haemoglobin by > or = 1 g/dl in 60-80% of patients, and no difference between once weekly and three-times weekly dosing was apparent. For patients who continued treatment up to 52 weeks, haemoglobin was maintained between 10 and 13 g/dl from mean baseline values of 8.4 and 8.7 g/dl. The adverse event profile was similar to that associated with rHuEpo therapy, and no antibodies to darbepoetin alfa were detected. CONCLUSIONS: Darbepoetin alfa is safe and effective for the treatment of anaemia in dialysis patients. The optimal weekly starting dose is 0.45-0.75 microg/kg and once weekly dosing is possible for both the s.c. and i.v. routes of administration.     

Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients: a combined analysis of eight multicenter trials

AIM: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa in a large cohort of dialysis patients. METHODS: Data were combined from eight similarly designed 24-week phase 3b European studies, in which patients receiving EPO alfa or beta once-weekly were converted to Q2W darbepoetin alfa. Darbepoetin alfa dosage was titrated to maintain hemoglobin (Hb) between 10 and 13 g/dl and efficacy was evaluated during a 4-week evaluation period. RESULTS: In the 1,101 patients assigned to Q2W darbepoetin alfa (i.v., n = 196, s.c., n = 905), mean (SD) Hb levels were 11.53 (0.77) g/dl at baseline and 11.35 (1.04) g/dl at evaluation (mean change in Hb -0.27 g/dl, 95% confidence interval 0.34, -0.20). Hb levels were maintained between 10 and 13 g/dl during evaluation in 85% of patients. Darbepoetin alfa doses were similar at baseline and evaluation, and the i.v. and s.c. routes were associated with similar efficacy and dose requirements. Darbepoetin alfa was well-tolerated. CONCLUSIONS: Q2W darbepoetin alfa is effective in maintaining Hb levels in dialysis patients switched from weekly rHuEPO, regardless of the route of administration and with no notable increase in the weekly equivalent dose.     

Darbepoetin alfa effectively treats anemia in patients with chronic kidney disease with de novo every-other-week administration

AIM: This multicenter, open-label study determined safety and efficacy of once-every-other-week administration of darbepoetin alfa for anemia of chronic kidney disease in erythropoietin-naive patients not on dialysis. METHODS: Participants with hemoglobin levels <11.0 g/dl at baseline were administered darbepoetin alfa at an initial dosage of 0.75 microg/kg once every other week. The dose was titrated to achieve and maintain a hemoglobin response, defined as a hemoglobin range of between 11.0 and 13.0 g/dl for up to 24 weeks. The primary end point was the dose of darbepoetin alfa at initial hemoglobin response. RESULTS: Six hundred and eight patients were enrolled, and 463 completed the study; 95% (95% confidence interval: 0.93, 0.97) of the patients who completed treatment achieved a hemoglobin response. The mean darbepoetin alfa dose at the time of response was 63.5 +/- (SD) 16.9 microg, and the mean time to hemoglobin response was 5.7 +/- (SD) 4.5 weeks. Oral iron therapy was administered to 60% and intravenous iron to 16% of the participants. Darbepoetin alfa was well tolerated, and adverse events were consistent with those expected in patients with chronic kidney disease. CONCLUSION: Darbepoetin alfa administered once every other week is effective and safe for achieving and maintaining target hemoglobin levels in anemic patients with chronic kidney disease.     

Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo).

BACKGROUND: Darbepoetin alfa is an erythropoietic agent with a 3-fold longer elimination half-life than recombinant human erythropoietin (rHuEpo), which allows less frequent dosing. This study investigated the safety and efficacy of darbepoetin alfa for treating anaemia in dialysis patients, using a dosing regimen that was independent of the patient's body weight (unit dosing). METHODS: Dialysis patients (n=341) maintained on rHuEpo treatment (alfa or beta) were switched to darbepoetin alfa at a reduced dosing frequency, but by the same route of administration [intravenous (i.v.) or subcutaneous (s.c.)]. Patients receiving rHuEpo two or three times weekly changed to once-weekly darbepoetin alfa, and those receiving rHuEpo once weekly changed to once every other week darbepoetin alfa. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations within -1.0 and +1.5 g/dl of the individual mean baseline haemoglobin and between 10 and 13 g/dl for 24 weeks. RESULTS: Mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was 0.13 g/dl (95% CI, 0.01, 0.25), which was not clinically relevant. An analysis by route of administration revealed that mean haemoglobin concentrations had increased by 0.58 g/dl (95% CI, 0.33, 0.82) in patients receiving i.v. darbepoetin alfa, and previously treated with i.v. rHuEpo, while remaining unchanged in s.c. patients (0.00 g/dl; 95% CI, -0.13, 0.13) previously treated by s.c. rHuEpo. In addition, there was a statistically significant decrease in mean weekly i.v. darbepoetin alfa dose requirements from 25.2 microg/week at baseline to 21.5 microg/week (P=0.004) during the evaluation period (-17.3%). Subcutaneous weekly dosage requirements increased slightly during the study period (20.8 to 22.7 microg/week; P=0.014). An i.v./s.c. dose ratio of 0.95 (95% CI, 0.78, 1.14) at evaluation confirms previous findings that dose requirements by the i.v. and s.c. routes were not different in patients treated with darbepoetin alfa. Haemoglobin concentrations were also effectively maintained in patients who received darbepoetin alfa once weekly and once every other week. Darbepoetin alfa was well tolerated. CONCLUSIONS: The treatment of renal anaemia in dialysis patients with unit doses of darbepoetin alfa effectively and safely maintains target haemoglobin concentrations with less frequent dosing. Dose requirements for darbepoetin alfa following i.v. and s.c. administration were not different. The results of this study demonstrate that darbepoetin alfa administered i.v. once weekly, or once every other week is an effective treatment regimen for haemodialysis patients with renal anaemia.     

Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.

BACKGROUND: Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEpo), darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo. This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia. METHODS: In this multicentre, prospective, open-label study, 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [intravenous (i.v.), n = 900 or subcutaneous (s.c.), n = 602]. Subjects receiving rHuEpo two (n = 408, 27%) or three times (n = 884, 59%) a week were switched to darbepoetin alfa once a week, and those receiving rHuEpo once a week (n = 210, 14%) were switched to darbepoetin alfa once every 2 weeks. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations of 10-13 g/dl for 24 weeks. RESULTS: Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks. The overall mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was +0.10 g/dl [95% confidence interval (CI) 0.04+/- 0.17]. The mean haemoglobin concentration increased by 0.19 g/dl (95% CI 0.11+/-0.27) in subjects receiving i.v. darbepoetin alfa, and was unchanged (-0.02 g/dl; 95% CI -0.12 to 0.07) in patients treated with s.c. darbepoetin alfa. Subjects with baseline haemoglobin < 11 g/dl experienced a clinically relevant increase in mean haemoglobin concentration of 0.67 g/dl (95% CI 0.56+/-0.77) from baseline to the evaluation period. The mean weekly i.v. and s.c. darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week (95% CI 19.02+/-20.87) and 21.6 microg/week (95% CI 20.36+/- 22.94), respectively. Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects. CONCLUSIONS: Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated. Moreover, administration of darbepoetin alfa by both the i.v. and s.c. route is associated with stable haemoglobin concentrations.     

What is the practical conversion dose when changing from epoetin alfa to darbepoetin outside of clinical trials?

BACKGROUND: The recommended conversion dose for changing from epoetin alfa to darbepoetin alfa is 200 units to 1 microg. However, this may result in the over treatment of uraemic anaemia. METHODS: All in-centre haemodialysis patients (n = 60) were converted from an existing subcutaneous epoetin alfa regimen to weekly intravenous darbepoetin alfa. The protocol for anaemia management included a target haemoglobin (Hb) concentration of 120-130 g/L and a ferritin of 300-600 microg/L. Patient treatments were converted from subcutaneous epoetin alfa to weekly, intravenous darbepoetin alfa at month 0, at a conversion dose of 200 units epoetin alfa to 1 microg darbepoetin. RESULTS: Both Hb and ferritin concentrations remained within the target range, but darbepoetin dosages fell from 50.8 to 42.3 microg/week by month 3 (P = 0.02). The initial conversion factor of 210 units/microg rose to 275 units/microg (P = 0.01) at month 4. No difference in conversion dosage could be determined between patients who were epoetin sensitive (<200 units/kg per week) or resistant (>200 units/kg per week, P = NS). Patients were then switched to fortnightly darbepoetin alfa dosing treatments; the existing weekly dose being doubled and Hb levels fell from 125 to 110 g/L (P < 0.0001), despite an increase in the mean dose from 44.9 to 47.5 microg/week (P = 0.02). CONCLUSION: The original dosage reduction after the switch from epoetin alfa to weekly intravenous darbepoetin alfa may offset the increased relative cost of the latter. When administered weekly and intravenously, darbepoetin alfa maintains Hb at a more favourable conversion rate than is currently recommended.     

Darbepoetin alfa administered once monthly maintains hemoglobin concentrations in patients with chronic kidney disease

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed. RESULTS: Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% Cl = 78% - 93%) of patients who completed the study period. The mean +/- standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 +/- 49.9 microg) and the evaluation period (86.6 +/- 78.8 microg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration. CONCLUSION: Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.     

A trial of subcutaneous administration of darbepoetin alfa once every other week for the treatment of anemia in peritoneal dialysis patients

BACKGROUND: Darbepoetin alfa (Aranesp, Amgen) is an erythropoietic stimulating protein with a three fold longer terminal half life than recombinant human erythropoietin (rHuEPO). The purpose of this single center, single arm study was to determine whether darbepoetin alfa is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis when administered at a reduced dosing frequency of once every other week irrespective of the initial rHuEPO dose frequency. METHODS: A total of 17 patients on peritoneal dialysis receiving stable rHuEPO therapy were changed to darbepoetin alfa every other week, using the recommended 200:1 conversion factor . The doses of darbepoetin alfa were titrated to maintain hemoglobin within -1.0 to +1.5 g/dL of the patients' baseline value and also within a range of 10.0 to 13.0 g/dL for up to 24 weeks (20 weeks dose titration period followed by 4 week evaluation period). The primary end point was change in hemoglobin levels between baseline and evaluation period. RESULTS: Mean change in hemoglobin levels from baseline to evaluation period was 0.03 g/dL (95% CI -0.62 to +0.69). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. There were no serious or major adverse effects observed with darbepoetin alfa during the study. CONCLUSION: These results show that darbepoetin alfa maintains hemoglobin concentrations effectively and safely in patients on peritoneal dialysis, but with a reduced dose frequency as compared to rHuEPO.     

Treatment of anemia with darbepoetin alfa administered de novo once every other week in chronic kidney disease

BACKGROUND/AIMS: Darbepoetin alfa is an erythropoiesis-stimulating protein that works via the same mechanism and has a threefold longer serum half-life than recombinant human erythropoietin (rHuEPO). The objective of this study was to evaluate extending the dosing interval of darbepoetin alfa to once every other week administration for the treatment of anemia in patients with chronic kidney disease (CKD) not requiring dialysis who were naive to rHuEPO therapy. METHODS: This was a multi-center, open-label study. Seventy-six rHuEPO-naive patients were enrolled to receive darbepoetin alfa (0.75 microg/kg) once every other week for up to 24 weeks. Doses were titrated to achieve and maintain a hemoglobin target of 11.0 to 13.0 g/dl. RESULTS: Ninety-seven percent (95% CI: 0.92, 1.00) of patients completing 24 weeks of treatment achieved a hemoglobin response. The median time to response was 5 weeks (range 1-25 weeks). The median darbepoetin alfa dose at the time of response was 60 microg(range 30-130 microg). Darbepoetin alfa was safe and well tolerated, and no antibodies to darbepoetin alfa were detected. CONCLUSION: These results demonstrate the utility of darbepoetin alfa administered once every other week in rHuEPO-naive CKD patients. This new treatment paradigm may allow for more widespread management of anemia in patients with CKD.