Safety and efficacy of Ninjin'yoeito along with iron supplementation therapy for preoperative anemia, fatigue, and anxiety in patients with gynecological disease: an open-label, single-center, randomized phase-II trial
BMC women's health. 2022;22(1):229
BACKGROUND Preoperative anemia affects perioperative outcomes and often causes fatigue and psychological disorders. Therefore, anemia should be treated before a patient undergoes surgery. Ninjin'yoeito (NYT), a Japanese Kampo medicine composed of ginseng and Japanese angelica root with the other 10 herbs, is administered for anemia, fatigue and anxiety; however, there are a few reports that have prospectively examined the effects of NYT before surgery for gynecological diseases. Hence, we tended to investigate its efficacy and safety. METHODS In this open-label randomized trial, women with gynecological diseases accompanied by preoperative anemia (defined as < 11.0 g/dL Hemoglobin [Hb]) were randomly assigned (1:1) into the iron supplementation and NYT groups. Patients of the iron supplementation group and the NYT group received 100 mg/day iron supplementation with and without NYT (7.5 g/day) for at least 10 days before surgery. The primary endpoint was improvement in Hb levels before and after treatment, and Cancer Fatigue Scale (CFS) and Visual Analogue Scale for Anxiety (VAS-A) scores between groups. Statistical analyses were performed with Wilcoxon signed rank test, Wilcoxon rank sum test, and Fisher's exact test as appropriate. RESULTS Forty patients were enrolled of whom 30 patients were finally analyzed after allocating 15 to each group. There was no difference in the characteristics between both groups. Hb significantly increased in both groups (iron supplementation group, 9.9 ± 0.8 g/dL vs. 11.9 ± 1.6 g/dL; NYT group, 9.8 ± 1.0 g/dL vs. 12.0 ± 1.0 g/dL); the difference in the elevations in Hb between both groups was statistically insignificant (P = 0.72). Contrarily, CFS (17.9 ± 10.2 vs. 8.1 ± 5.2) and VAS-A (56 mm (50-70) vs. 23 mm (6-48)) scores were significantly decreased only in the NYT group and these changes were greater in the NYT group (∆CFS, P = 0.015; ∆VAS-A, P = 0.014). Liver dysfunction occurred in one patient of the NYT group. CONCLUSIONS For treating preoperative anemia in women with gynecological conditions, NYT administration along with iron supplementation safely and efficiently improved the preoperative fatigue and anxiety in addition to the recovery from anemia. TRIAL REGISTRATION jRCT1051190012 (28/April/2019, retrospectively registered).
Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for the treatment of preoperative anemia in patients with menorrhagia: An open-label, multicenter, randomized study
The journal of obstetrics and gynaecology research. 2019;45(4):858-864
AIM: To compare ferric carboxymaltose (FCM) with iron sucrose (IS) for the effective and timely treatment of preoperative iron deficiency anemia (IDA) in women with menorrhagia. METHODS This open-label, multicenter, two-arm study randomized patients to receive either a single dose of FCM or multiple doses of IS. The primary endpoint was the proportion of patients who achieved hemoglobin (Hb) levels ≥10 g/dL within 2 weeks after the first administration. Secondary endpoints included mean Hb levels, time to reach Hb ≥10 g/dL and quality of life (QoL). RESULTS In total, 101 patients (FCM n = 52; IS n = 49) were randomized to the study treatments. FCM was as effective as IS in achieving Hb ≥10 g/dL within 2 weeks after the first administration (78.8% vs 72.3%). The time to reach Hb ≥10 g/dL was significantly shorter in the FCM group than in the IS group (7.7 days vs 10.5 days). Mean Hb levels were higher in the FCM-treated patients than in the IS-treated patients with borderline significance. QoL scores did not differ between the two groups. CONCLUSION Ferric carboxymaltose is as effective as IS in correcting preoperative IDA among patients with menorrhagia. The added benefits of FCM over IS included significant rapid correction of IDA, replenishment of iron stores and reduced hospital visits.
IL-6 and IL-8 response to erythropoietin therapy in radical hysterectomy
Acta Anaesthesiologica Scandinavica. 2005;49((1):):47-51.
BACKGROUND The use of recombinant human erythropoietin (rHuEPO) improves autologous blood donation before elective surgery. However, there are other studies indicating that rHuEPO may suppress postoperative endogenous production of erythropoietin and stimulate inflammatory mediator release. Weekly donations generate only a moderate increase in endogenous erythropoietin production. We scheduled patients with cancer to predeposit three units of blood in 2 weeks, with or without rHuEPO therapy. The aim was to determine whether rHuEPO therapy and/or an aggressive donation schedule alter perioperative erythropoietin concentrations and whether rHuEPO therapy leads to the release of the pro-inflammatory cytokines IL-6 and IL-8. METHODS Thirty women scheduled for radical hysterectomy and pelvic lymphadenectomy were randomly assigned to either a control group with no rHuEPO therapy or to receive rHuEPO. Three units of whole blood were collected from each patient before the operation. Concentrations of haemoglobin, erythropoietin (s-EPO) and cytokines (IL-6 and IL-8) were repeatedly analyzed before and after the operation. RESULTS During the preoperative donation period, median s-EPO levels in the control group increased from 7 to 14 IU l(-1). There was a great increase in s-EPO concentrations 1 h postoperatively in the rHuEPO group compared with the control group (P < 0. 001). IL-6 and IL-8 were not significantly changed after intravenous administration of rHuEPO. CONCLUSION The use of rHuEPO therapy to optimise autologous blood donation does not influence IL-6 and IL-8 release. 1 h postoperatively rHuEPO therapy resulted in elevated s-EPO concentrations. There was, however, no difference in s-EPO between the groups from day 1 postoperatively and until the end of the study.
Recombinant human erythropoietin in mildly anemic women before total hysterectomy
Clinical and Experimental Obstetrics & Gynecology. 2003;30((4):):235-8.
UNLABELLED The purpose of this study was to investigate the efficacy of preoperative recombinant human erythropoietin (rHuEPO) treatment in a group of mildly anemic women. METHODS This randomized controlled study included 50 healthy, mildly anemic women who underwent total hysterectomy for leiomyomas. The study group (Group A) included 23 women who received rHuEPO 600 U/kg once weekly for three weeks, plus iron supplementation. The control group (Group B) included 27 women who received only iron supplementation. Blood samples were obtained on days -14, -7, 0, +3, +7 and +14. RESULTS An increase in preoperative mean hemoglobin concentration was noted in both groups; however, the increase was significantly higher in Group A throughout the study period. Mean reticulocyte count was also significantly higher in this group, whereas mean ferritin level was significantly lower. No postoperative transfusion was needed in Group A, whereas five women were transfused in Group B. CONCLUSION Rapid and persistent improvement of hematologic parameters makes the use of rHuEPO for preoperative treatment of mildly anemic women with benign uterine pathology a very interesting approach.
Autologous blood transfusion in radical hysterectomy with and without erythropoietin therapy
Obstetrics & Gynecology. 2002;99((5, Pt 1):):757-62.
OBJECTIVE To investigate whether preoperative treatment with erythropoietin facilitates the collection of a sufficient amount of autologous blood in a short period of time. METHODS Forty-one women scheduled for radical hysterectomy were randomized to preoperative autologous blood donation with or without preoperative recombinant human erythropoietin therapy. All patients were scheduled to deposit three units of blood within 2 weeks before surgery. Hemoglobin, erythrocyte volume fraction, blood cells, iron status, and hemolysis were analyzed before and after surgery. RESULTS Hemoglobin levels decreased continuously in both groups after the first autologous donation until day 1 postoperatively. With erythropoietin therapy, the erythrocyte volume fraction and hemoglobin levels were significantly higher during precollection and day 1 after surgery. Preoperatively, the drop was 12 g/L less in the erythropoietin-treated group. The additional use of erythropoietin therapy reduced the inability of patients to predeposit blood from 17.8% to 3.4%. CONCLUSION Most women can predeposit three units of whole blood in only 2 weeks without obtaining severe anemia. By treating women with erythropoietin, one out of seven can be prevented from a hemoglobin level below the 100 g/L limit for donation.
Preoperative treatment of anemic women with epoetin beta
Acta Obstetricia et Gynecologica Scandinavica. 2001;80((6):):559-62.
AIM: To compare the effects of preoperative treatment with recombinant human erythropoietin (EPO) and iron with iron only on hemoglobin levels (Hb) in anemic women prior to hysterectomy. METHODS The study was an open-labelled randomized parallel study. Fifteen women scheduled for hysterectomy due to uterine myoma were given oral iron and EPO (NeoRecormon) 4 weeks prior to surgery (group I) and 16 women were given oral iron only (group II). RESULTS Group I showed a significantly greater increase in mean Hb during the pre-surgery study period compared with group II (p=0.007). Two weeks postoperatively, however, there was no significant difference in mean Hb between the two groups. CONCLUSION We found that a significantly greater increase in Hb was achieved with iron in combination with EPO, although in most cases iron only seemed to be as efficacious as iron+EPO in correcting anemia in myoma patients pre-operatively.