Parenteral iron therapy and phosphorus homeostasis: A review.

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

Ferric Carboxymaltose as Treatment in Women with Iron-Deficiency Anemia.

Objective. To evaluate safety and efficacy of intravenous ferric carboxymaltose (FCM) versus standard medical care (SMC) for iron-deficiency anemia (IDA) in postpartum women and women with heavy menstrual bleeding. Study Design. This open-label, multicenter study randomized women with IDA (hemoglobin ≤ 11.0 g/dL) to single doses of FCM (15 mg/kg [maximum 1000 mg]) or SMC (this treatment was determined by the investigator and there may have been no treatment). Safety data (primary outcome) were collected for 30 days. Results. Of 2045 subjects enrolled (FCM: n = 1023; SMC: n = 1022), 996 received FCM and 1022 received SMC. At least 1 serious adverse event (AE) was reported by 0.6% and 2.2% of subjects in the FCM and SMC groups, respectively; none were considered treatment related. The difference in serious AEs was primarily due to higher rates of uterine leiomyoma, uterine hemorrhage, and menorrhagia in SMC subjects with heavy menstrual bleeding. Common AEs were generally predictable, with higher rates of infusion site reactions in FCM subjects and gastrointestinal AEs in SMC subjects. Mean hemoglobin increases were greater in the FCM group than the SMC group. Conclusion. FCM was well tolerated and effectively increased mean hemoglobin levels in postpartum women or women with heavy menstrual bleeding and IDA. This trial is registered with ClinicalTrials.gov, NCT00548860.

Iron deficiency anemia in women: a practical guide to detection, diagnosis, and treatment.

INTRODUCTION: Iron deficiency anemia (IDA) remains a widely underdiagnosed and unappreciated women's health issue, affecting women of all ages. Despite the fact that IDA is easily diagnosed and treated, it continues to be a major public health issue. The World Health Organization estimates that 30% of nonpregnant and more than 42% of pregnant women have anemia. METHODS: A multidisciplinary Group for the Research and Education on Anemia Therapy in Women (GREAT Women II) was formed, sponsored by the Society for the Advancement of Blood Management. The goal was to focus attention on the impact of IDA on women at various stages of life and evaluate and use published literature to provide a simple, evidence-based approach to diagnose and treat IDA. RESULTS: The group developed specific recommendations for evaluating and treating IDA in women. Initial diagnosis is defined as hemoglobin less than 12 g/dL in nonpregnant women. A trial of iron therapy (4 weeks) can be considered a first-line diagnostic tool. Alternatively, a low or normal mean corpuscular volume (<100 fL), low serum ferritin (<30 µg/L), and/or low transferrin saturation (transferrin saturation <20%) is sufficient to confirm IDA. If the patient does not fit the diagnosis of IDA or fails to respond to a trial of oral iron, or mean corpuscular volume is elevated, further diagnostic evaluation is needed, including iron studies, B12, folate levels, and renal function tests. If results are not definitive, and IDA persists, a hematology referral is recommended. CONCLUSION: Clinicians should routinely identify and treat IDA, thereby decreasing its negative impact on health and quality of life of women.

Neostigmine decreases bupivacaine use by patient-controlled epidural analgesia during labor: a randomized controlled study.

BACKGROUND: Intrathecal neostigmine not only produces analgesia but also severe nausea. In contrast, epidural neostigmine enhances opioid and local anesthetic analgesia without causing nausea. Previous studies examined only single epidural neostigmine bolus administration and did not assess the efficacy of continuous epidural infusion or several aspects of maternal and fetal safety. We therefore tested the hypothesis that epidural neostigmine in combination with bupivacaine by continuous infusion during labor would reduce the amount of bupivacaine required. METHODS: Twelve healthy women scheduled for elective cesarean delivery were assigned to receive epidural neostigmine, 40 microg (first six subjects) or 80 microg (second six subjects) as a single bolus, with fetal heart rate (FHR) and uterine contractions monitored for 20 min. In a subsequent experiment, 40 healthy laboring women were randomized to receive bupivacaine 1.25 mg/mL alone or with neostigmine 4 microg/mL by patient-controlled epidural analgesia. The primary outcome measure was hourly bupivacaine use. RESULTS: Epidural neostigmine bolus did not alter baseline FHR, induce contractions, or produce nausea. Epidural neostigmine infusion reduced bupivacaine requirement by 19% in all patients and 25% in those with >4 h of treatment (P < 0.05 for both) but might have contributed to the incidence of mild sedation. Mode of delivery, incidence of maternal nausea, and FHR abnormality were similar between groups. CONCLUSIONS: These data show that adding epidural neostigmine 4 microg/mL reduces the hourly bupivacaine requirement by 19%-25% with patient-controlled epidural analgesia during labor. Administered as a bolus and by continuous infusion at the studied doses, epidural neostigmine does not cause nausea and does not induce uterine contractions or FHR abnormalities, but mild sedation can occur.

Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial.

OBJECTIVE: The objective of the study was to evaluate the efficacy, safety, and tolerability of intravenous ferric carboxymaltose, compared with oral ferrous sulfate in women with postpartum anemia. STUDY DESIGN: In a multicenter, randomized, controlled study, 291 women less than 10 days after delivery with hemoglobin 10 g/dL or less were randomized to receive ferric carboxymaltose (n = 143) 1000 mg or less intravenously over 15 minutes or less, repeated weekly to a calculated replacement dose (maximum 2500 mg) or ferrous sulfate (n = 148) 325 mg orally thrice daily for 6 weeks. RESULTS: Ferric carboxymaltose-treated subjects were significantly more likely to: (1) achieve a hemoglobin greater than 12 g/dL in a shorter time period with a sustained hemoglobin greater than 12 g/dL at day 42, (2) achieve hemoglobin rise 3 g/dL or greater more quickly, and (3) attain higher serum transferrin saturation and ferritin levels. Drug-related adverse events occurred less frequently with ferric carboxymaltose. CONCLUSION: Intravenous ferric carboxymaltose was safe and well tolerated with an efficacy superior to oral ferrous sulfate in the treatment of postpartum iron deficiency anemia.

Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial.

OBJECTIVE: To estimate efficacy of rapid, large-dose intravenous (IV) administration of ferric carboxymaltose compared with oral iron therapy in anemic postpartum women. METHODS: In a randomized, controlled trial, we assigned anemic women (hemoglobin [Hb] less than or equal to 10 g/dL) within 10 days postpartum to receive either IV ferric carboxymaltose (less than or equal to 1,000 mg over 15 minutes, repeated weekly to achieve a total calculated replacement dose) or ferrous sulfate (FeSO(4)) 325 mg orally thrice daily for 6 weeks. RESULTS: One hundred seventy-four patients received 350 IV doses of ferric carboxymaltose (mean total dose 1,403.1 mg) in 3, 2, or 1 injection (10.9%, 79.3%, or 9.8% of patients, respectively); 178 received FeSO(4). Patients assigned to IV ferric carboxymaltose compared with those assigned to oral iron achieved a Hb rise greater than or equal to 2.0 g/dL earlier (7.0 compared with 14.0 days, P<.001), were more likely to achieve a Hb rise greater than or equal to 3.0 g/dL at any time (86.3% compared with 60.4%, P<.001), and were more likely to achieve a Hb greater than 12.0 g/dL (90.5% compared with 68.6%, P<.001). A similar proportion of patients achieved a Hb rise greater than or equal to 2.0 g/dL (96.4% compared with 94.1%, IV compared with oral, P=.443). There were no serious adverse drug reactions. CONCLUSION: Large-dose IV ferric carboxymaltose administration is a new iron agent that is effective for the treatment of postpartum anemia. When compared with oral ferrous sulfate, IV ferric carboxymaltose is better tolerated, prompts a more rapid Hb response, and corrects anemia more reliably. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00396292 LEVEL OF EVIDENCE: I.

Multifactorial preoperative predictors for postcesarean section pain and analgesic requirement.

BACKGROUND: The study aimed to determine predictive factors for postcesarean pain and analgesia using an assessment of pain threshold and suprathreshold thermal stimuli as well as degree of somatization and anxiety. METHODS: Thirty-four healthy parturients scheduled for cesarean delivery under subarachnoid anesthesia were enrolled. Preoperative thermal pain threshold, intensity, and unpleasantness to heat stimuli applied to arm and lower back, State Trait Anxiety Inventory, and patient expectation for postoperative pain and need for analgesia were assessed. After surgery, overall, resting, and movement pain and analgesic consumption were recorded. Prediction of pain and analgesic use outcomes was made by principal component factor analysis, followed by stepwise linear regression. RESULTS: Resting pain was predicted by two factors, thermal pain and unpleasantness and patient expectation (r2 = 0.26, P < 0.01), evoked pain by thermal pain threshold in the back (r2= 0.20, P < 0.009), composite pain by thermal pain and unpleasantness and preoperative blood pressure (r2 = 0.28, P < 0.008), intraoperative analgesic need by preexisting pain (r2 = 0.22, P < 0.006), recovery room analgesia by thermal pain threshold and State Trait Anxiety Inventory (r2 = 0.27, P < 0.01), and total analgesic need by State Trait Anxiety Inventory (r2 = 0.22, P < 0.01). These models predicted the upper twentieth percentile of composite pain scores and analgesic requirement with sensitivity of 0.71 to 0.80 and specificity of 0.76 to 0.80. CONCLUSIONS: The authors' results suggest a meaningful combination of preoperative patient responses from physical and psychological tests yields a valid multifactorial predictive model for postoperative pain and analgesic requirement with significant improvements over individual predictive variables.