Department of Radiology and Nuclear Medicine, Division of Endocrine Diagnostics and Radionuclide Therapy, University Hospital Basel, 4031, Basel, Switzerland.
Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1675-82. doi: 10.1007/s00259-011-1826-9. Epub 2011 May 7.
Administration of positively charged amino acids has been introduced to reduce the nephrotoxicity of targeted radiopeptide therapy (TRT). However, the amino acid solution may have side effects, including hyperkalaemia. The aim of this study was to evaluate the frequency and the magnitude of hyperkalaemia in neuroendocrine tumour (NET) patients undergoing TRT.
Enrolled in the study were 31 patients with NET eligible for TRT with [(90)Y-DOTA(0),Tyr(3)]octreotide ((90)Y-DOTATOC). Their mean age was 54 ± 14 years. Of these 31 patients, 21 (67%) were referred for the first treatment cycle, while 10 (33%) were referred for a subsequent therapy cycle. Patients were treated with therapeutic doses of (90)Y-DOTATOC ranging from 7,030 to 35,520 MBq. To inhibit tubular reabsorption of (90)Y-DOTATOC, 1 l of physiological saline solution containing 25 g of arginine hydrochloride and 25 g of lysine hydrochloride was given over 4 h starting 1 h before (90)Y-DOTATOC injection. All patients underwent a standard biochemical blood analysis at baseline, and 4 h and 24 h after the beginning of the amino acid infusion.
ANOVA repeated measures showed a significant overall effect on K(+) levels over time (F = 118.2, df = 2, P < 0.0001). Mean serum levels of K(+) were 4.00 ± 0.33 mmol/l at baseline, 5.47 ± 0.57 mmol/l at 4 h, and 4.38 ± 0.63 mmol/l at 24 h after the beginning of the infusion. Post-hoc analysis showed that K(+) levels at 4 h were significantly (P < 0.05) higher than at baseline. K(+) levels at 24 h were significantly (P < 0.05) lower than at 4 h but they were still significantly (P < 0.05) higher than K(+) levels at baseline. On a subject-by-subject basis, none of the 31 patients had increased K(+) levels at baseline. At 4 h, 24 of the 31 patients (77%) had K(+) levels above the normal range, and 6 patients (19%) experienced severe hyperkalaemia (K(+) ≥ 6 mmol/l). All patients with increased K(+) levels were clinically asymptomatic. At 24 h, only 4 patients (13%) had increased K(+) serum levels. The magnitude of the increase in K(+) levels between baseline and 4 h was relatively homogeneous over the whole group (1.41 ± 0.50 mmol/l) and it was not related (linear regression, P>0.05) to baseline K(+) levels. Intravenous administration of 40 mg furosemide 1 h after the beginning of the amino acid infusion did not have a significant effect on K(+) levels (P>0.05). No clinical characteristic was predictive for the increase in K(+) levels (chi-squared test, P > 0.05).
Hyperkalaemia is a frequent, potentially life-threatening side effect of basic amino acid infusion during TRT. K(+) levels 4 h after the beginning of the infusion should be monitored in patients at risk of complications, such as those with heart disease and those with risk factors for nephrotoxicity.
为了降低靶向放射性肽治疗(TRT)的肾毒性,已引入了正电荷氨基酸的给药。然而,氨基酸溶液可能有副作用,包括高钾血症。本研究的目的是评估接受 TRT 的神经内分泌肿瘤(NET)患者发生高钾血症的频率和程度。
本研究纳入了 31 名适合接受 [(90)Y-DOTA(0),Tyr(3)]octreotide ((90)Y-DOTATOC)TRT 的 NET 患者。他们的平均年龄为 54±14 岁。其中 21 例(67%)为首次治疗周期就诊,10 例(33%)为后续治疗周期就诊。患者接受了 7,030 至 35,520MBq 的治疗剂量 [(90)Y-DOTATOC]。为了抑制 [(90)Y-DOTATOC]的肾小管重吸收,在 [(90)Y-DOTATOC]注射前 1 小时开始输注 1 升含有 25 克盐酸精氨酸和 25 克盐酸赖氨酸的生理盐水。所有患者在基线、氨基酸输注开始后 4 小时和 24 小时进行了标准生化血液分析。
重复测量方差分析显示,K(+)水平随时间的变化有显著的总体影响(F=118.2,df=2,P<0.0001)。K(+)的平均血清水平在基线时为 4.00±0.33mmol/l,4 小时时为 5.47±0.57mmol/l,24 小时时为 4.38±0.63mmol/l。事后分析显示,4 小时时的 K(+)水平明显高于基线时(P<0.05)。24 小时时的 K(+)水平明显低于 4 小时时(P<0.05),但仍明显高于基线时(P<0.05)。在个体基础上,31 例患者中没有任何一个在基线时有 K(+)水平升高。在 4 小时时,31 例患者中有 24 例(77%)K(+)水平超过正常范围,有 6 例(19%)发生严重高钾血症(K(+)≥6mmol/l)。所有 K(+)水平升高的患者均无临床症状。在 24 小时时,只有 4 例(13%)患者的 K(+)血清水平升高。K(+)水平从基线到 4 小时的升高幅度在整个组中相对均匀(1.41±0.50mmol/l),与基线 K(+)水平无关(线性回归,P>0.05)。氨基酸输注开始后 1 小时静脉注射 40mg 呋塞米对 K(+)水平没有显著影响(P>0.05)。没有任何临床特征可以预测 K(+)水平的升高(卡方检验,P>0.05)。
高钾血症是 TRT 期间基础氨基酸输注的常见、潜在危及生命的副作用。应在有并发症风险的患者(如心脏病患者和有肾毒性风险因素的患者)中监测输注开始后 4 小时的 K(+)水平。