Allogeneic Blood Transfusion and Risk of Postoperative Complications in Patients with Mild and Moderate Anemia of Any Cause? A Retrospective Cohort Study in Total Revision Hip Surgery.

Introduction: Patients undergoing revision total hip surgery (RTHS) have a high prevalence of mild and moderate preoperative anemia, associated with adverse outcomes. The aim of this study was to investigate the association of perioperative allogeneic blood transfusions (ABT) and postoperative complications in preoperatively mild compared to moderate anemic patients undergoing RTHS who did not receive a diagnostic anemia workup and treatment before surgery. Methods: We included 1,765 patients between 2007 and 2019 at a university hospital. Patients were categorized according to their severity of anemia using the WHO criteria of mild, moderate, and severe anemia in the first Hb level of the case. Patients were grouped as having received no ABT, 1-2 units of ABT, or more than 2 units of ABT. Need for intraoperative ABT was assessed in accordance with institutional standards. Primary endpoint was the compound incidence of postoperative complications. Secondary outcomes included major/minor complications and length of hospital and ICU stay. Results: Of the 1,765 patients, 31.0% were anemic of any cause before surgery. Transfusion rates were 81% in anemic patients and 41.2% in nonanemic patients. The adjusted risks for compound postoperative complication were significantly higher in patients with moderate anemia (OR 4.88, 95% CI: 1.54-13.15, p = 0.003) but not for patients with mild anemia (OR 1.93, 95% CI: 0.85-3.94, p < 0.090). Perioperative ABT was associated with significantly higher risks for complications in nonanemic patients and showed an increased risk for complications in all anemic patients. In RTHS, perioperative ABT as a treatment for moderate preoperative anemia of any cause was associated with a negative compound effect on postoperative complications, compared to anemia or ABT alone. Discussion: ABT is associated with adverse outcomes of patients with moderate preoperative anemia before RTHS. For this reason, medical treatment of moderate preoperative anemia may be considered.

The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

[The costs of preoperative anemia in hip joint revision surgery]. / Die Kosten der präoperativen Anämie bei Hüftgelenkrevisionsoperationen.

BACKGROUND: Anemia is highly prevalent in patients before hip joint revision surgery (HJRS) and is associated with an increased complication rate. This paper is the first to investigate costs, real diagnosis-related group (DRG) revenues and case coverage of preoperative anemia in elective HJRS. METHODS: Medical data, transfusions, costs, and revenues of all patients undergoing HJRS at two campuses of the Charité -Universitätsmedizin Berlin between 2010 and 2017 were used for subgroup analyses and linear regressions. RESULTS: Of 1187 patients included 354 (29.8%) showed preoperative anemia. A total of 565 (47.6%) patients were transfused with a clear predominance of anemic patients (72.6% vs. 37.0%, p < 0.001). Costs (12,318€ [9027;20,044€] vs. 8948€ [7501;11,339€], p < 0.001) and revenues (11,788€ [8992;16,298€] vs. 9611€ [8332;10,719€], p < 0.001) were higher for preoperatively anemic patients and the coverage was deficient (-1170€ [-4467;1238€] vs. 591€ [-1441;2103€], p < 0.001). In anemic patients, case contribution margins decreased with increasing transfusion rates (p ≤ 0.001). Comorbidities had no significant economic impact. CONCLUSION: Preoperative anemia and perioperative transfusions in HJRS are associated with increased treatment costs and a financial undercoverage for healthcare providers and health insurance companies. Concepts for the treatment of preoperative anemia (e.g. patient blood management) could reduce treatment costs in the medium term.

Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non-cardiac surgery.

BACKGROUND: Approximately 30% of adults undergoing non-cardiac surgery suffer from preoperative anaemia. Preoperative anaemia is a risk factor for mortality and adverse outcomes in different surgical specialties and is frequently the reason for blood transfusion. The most common causes are renal, chronic diseases, and iron deficiency. International guidelines recommend that the cause of anaemia guide preoperative anaemia treatment. Recombinant human erythropoietin (rHuEPO) with iron supplementation has frequently been used to increase preoperative haemoglobin concentrations in patients in order to avoid the need for perioperative allogeneic red blood cell (RBC) transfusion. OBJECTIVES: To evaluate the efficacy of preoperative rHuEPO therapy (subcutaneous or parenteral) with iron (enteral or parenteral) in reducing the need for allogeneic RBC transfusions in preoperatively anaemic adults undergoing non-cardiac surgery. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE(R), Ovid Embase, ISI Web of Science: SCI-EXPANDED and CPCI-S, and clinical trial registries WHO ICTRP and ClinicalTrials.gov on 29 August 2019. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared preoperative rHuEPO + iron therapy to control treatment (placebo, no treatment, or standard of care with or without iron) for preoperatively anaemic adults undergoing non-cardiac surgery. We used the World Health Organization (WHO) definition of anaemia: haemoglobin concentration (g/dL) less than 13 g/dL for males, and 12 g/dL for non-pregnant females (decision of inclusion based on mean haemoglobin concentration). We defined two subgroups of rHuEPO dosage: 'low' for 150 to 300 international units (IU)/kg body weight, and 'high' for 500 to 600 IU/kg body weight. DATA COLLECTION AND ANALYSIS: Two review authors collected data from the included studies. Our primary outcome was the need for RBC transfusion (no autologous transfusion, fresh frozen plasma or platelets), measured in transfused participants during surgery (intraoperative) and up to five days after surgery. Secondary outcomes of interest were: haemoglobin concentration (directly before surgery), number of RBC units (where one unit contains 250 to 450 mL) transfused per participant (intraoperative and up to five days after surgery), mortality (within 30 days after surgery), length of hospital stay, and adverse events (e.g. renal dysfunction, thromboembolism, hypertension, allergic reaction, headache, fever, constipation). MAIN RESULTS: Most of the included trials were in orthopaedic, gastrointestinal, and gynaecological surgery and included participants with mild and moderate preoperative anaemia (haemoglobin from 10 to 12 g/dL). The duration of preoperative rHuEPO treatment varied across the trials, ranging from once a week to daily or a 5-to-10-day period, and in one trial preoperative rHuEPO was given on the morning of surgery and for five days postoperatively. We included 12 trials (participants = 1880) in the quantitative analysis of the need for RBC transfusion following preoperative treatment with rHuEPO + iron to correct preoperative anaemia in non-cardiac surgery; two studies were multiarmed trials with two different dose regimens. Preoperative rHuEPO + iron given to anaemic adults reduced the need RBC transfusion (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.38 to 0.80; participants = 1880; studies = 12; I2 = 84%; moderate-quality evidence due to inconsistency). This analysis suggests that on average, the combined administration of rHuEPO + iron will mean 231 fewer individuals will need transfusion for every 1000 individuals compared to the control group. Preoperative high-dose rHuEPO + iron given to anaemic adults increased the haemoglobin concentration (mean difference (MD) 1.87 g/dL, 95% CI 1.26 to 2.49; participants = 852; studies = 3; I2 = 89%; low-quality evidence due to inconsistency and risk of bias) but not low-dose rHuEPO + iron (MD 0.11 g/dL, 95% CI -0.46 to 0.69; participants = 334; studies = 4; I2 = 69%; low-quality evidence due to inconsistency and risk of bias). There was probably little or no difference in the number of RBC units when rHuEPO + iron was given preoperatively (MD -0.09, 95% CI -0.23 to 0.05; participants = 1420; studies = 6; I2 = 2%; moderate-quality evidence due to imprecision).  There was probably little or no difference in the risk of mortality within 30 days of surgery (RR 1.19, 95% CI 0.39 to 3.63; participants = 230; studies = 2; I2 = 0%; moderate-quality evidence due to imprecision) or of adverse events including local rash, fever, constipation, or transient hypertension (RR 0.93, 95% CI 0.68 to 1.28; participants = 1722; studies = 10; I2 = 0%; moderate-quality evidence due to imprecision). The administration of rHuEPO + iron before non-cardiac surgery did not clearly reduce the length of hospital stay of preoperative anaemic adults (MD -1.07, 95% CI -4.12 to 1.98; participants = 293; studies = 3; I2 = 87%; low-quality evidence due to inconsistency and imprecision). AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests that preoperative rHuEPO + iron therapy for anaemic adults prior to non-cardiac surgery reduces the need for RBC transfusion and, when given at higher doses, increases the haemoglobin concentration preoperatively. The administration of rHuEPO + iron treatment did not decrease the mean number of units of RBC transfused per patient. There were no important differences in the risk of adverse events or mortality within 30 days, nor in length of hospital stay. Further, well-designed, adequately powered RCTs are required to estimate the impact of this combined treatment more precisely.

The impact of antenatal factor XIII levels on postpartum haemorrhage: a prospective observational study.

PURPOSE: Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and morbidity. Our aim was to investigate the relationships between antenatal factor XIII (FXIII), fibrinogen levels, and blood loss at childbirth. METHODS: This prospective observational study evaluated an unselected cohort of pregnant women admitted for intended vaginal deliveries of singletons at term. To determine clotting factor levels, we obtained blood samples at a maximum of three days prior to vaginal delivery. A calibrated collecting drape was used to quantify blood loss in the third stage of labour. Moderate and severe PPH were diagnosed as blood losses ≥ 500 mL and ≥ 1000 mL, respectively. In a multiple logistic regression analysis, we determined whether coagulation factors and their interactions could independently predict (severe) PPH. RESULTS: We analysed 548 vaginal deliveries that occurred during the study period. Of those, 78 (14.2%) lost ≥ 500 mL and 18 (3.3%) lost ≥ 1000 mL of blood. The mean pre-delivery FXIII activity in women with PPH (79.33% ± 15.5) was significantly (p < 0.001) lower than in women without PPH (86.45% ± 14.6). A receiver operating characteristic curve analysis detected antenatal FXIII cutoff levels of 83.5% and 75.5% for PPH and severe PPH, respectively. The multiple logistic regression analysis showed that FXIII alone (p < 0.001) and its interaction with fibrinogen (p = 0.03) significantly predicted PPH. FXIII was not significantly correlated with blood loss among patients with severe PPH. CONCLUSION: Our results suggested that antenatal FXIII levels may have a significant influence on PPH. The interaction between FXIII and fibrinogen might also provide slight advantages in forecasting PPH.

Perioperative Management of Elderly Patients with Gastrointestinal Malignancies: The Contribution of Anesthesia.

INTRODUCTION: Elderly patients suffering from gastrointestinal malignancies are particularly prone to perioperative complications. Elderly patients often present with reduced physiological reserves, and comorbidities can limit treatment options and promote complications. Surgeons and anesthesiologists must be aware of strategies required to deal with this vulnerable subgroup. METHODS: We provide a brief review of current and emerging perioperative strategies for the treatment of elderly patients with gastrointestinal malignancies and frequent comorbidities. RESULTS: Especially in combination with advanced age, the effects of malignancies can be devastating, bringing new health challenges, exacerbating preexisting conditions, and exerting severe psychological strain. An interdisciplinary assessment and process planning provide an ideal setting to identify and prevent potential complications, especially in regards to frailty and cardiovascular risk. In addition, important perioperative considerations are presented, such as malnutrition, fasting, intraoperative neuromonitoring, and hemodynamic control, as well as postoperative early mobilization, pain, and delirium management. CONCLUSION: The decisions and interventions made in the perioperative stage can positively influence many intra- and postoperative factors, significantly improving the chances of successful treatment of elderly cancer patients. Appropriate management can help prevent or mitigate complications, secure a quick recovery, and improve short- and long-term outcomes.

Does the severity of preoperative anemia or blood transfusion have a stronger impact on long-term survival after cardiac surgery?

BACKGROUND: Preoperative anemia and transfusion are associated with increased morbidity and mortality in cardiac surgery patients. It is unclear which of these factors plays the leading role in poor outcomes after cardiac surgery. The goal of this study was to analyze the influence of anemias of varying severity and intraoperative transfusion on long-term survival, and to characterize their interaction in cardiac surgery patients. METHODS: This was an observational cohort study conducted at a German university hospital. All patients undergoing cardiac surgery between 2006 and 2011 were screened for eligibility; duration of follow-up was 3 years. A total of 4494 patients were suitable for analysis; data on long-term survival were available for 3131 of these patients. The main outcome measure was survival at the 3-year follow-up. Length of stay and in-hospital mortality were assessed as secondary outcomes. RESULTS: Multivariate Cox regression analyses indicated that both the severity of preoperative anemia (mild anemia: hazard ratio [HR], 1.441; 95% confidence interval [CI], 1.201-1.728; severe anemia: HR, 1.805; 95% CI, 1.336-2.440) and intraoperative transfusion (HR, 1.340; 95% CI, 1.109-1.620) were associated with decreased long-term survival. Long-term survival was worse in anemic patients who received an intraoperative transfusion compared with those who did not receive an intraoperative transfusion. CONCLUSIONS: Both preoperative anemia and transfusion are by themselves and in combination associated with decreased long-term survival. When anemic patients require transfusion, our results provide evidence that the risk of death after cardiac surgery may depend to a considerable extent on the severity of preoperative anemia.

Predelivery maternal fibrinogen as a predictor of blood loss after vaginal delivery.

PURPOSE: The present study investigated whether fibrinogen level during the first stage of labor is associated with bleeding severity in the third stage of labor. METHODS: We prospectively enrolled 1019 pregnant women with planned vaginal delivery. Upon admission to delivery, maternal fibrinogen levels, hemoglobin content, and coagulation parameters were evaluated. Blood loss in the third stage of labor was systematically measured using a calibrated collecting drape. Univariate and multivariate analyses were performed to identify predictors of PPH (blood loss ≥500 mL) and S-PPH (blood loss ≥1000 mL). RESULTS: Among 809 vaginal deliveries, mean maternal predelivery fibrinogen was 4.65 ± 0.77 g/L, PPH incidence was 12 %, S-PPH incidence was 3.5 %, and median blood loss was 250 mL. Fibrinogen levels were significantly lower in women with S-PPH (4.22 ± 0.82 g/L) than without S-PPH (4.67 ± 0.75 g/L; p = 0.004), but did not significantly differ between women with PPH (4.67 ± 0.84 g/L) and those without PPH (4.67 ± 0.75 g/L; p = 0.985). Instrumental delivery and predelivery fibrinogen levels were independent predictors of S-PPH. Primiparous status, birth weight >4000 g, genital tract laceration, episiotomy and instrumental delivery were independent predictors of PPH. CONCLUSION: For each 1 g/L increase of predelivery fibrinogen level, the risk of S-PPH after vaginal delivery decreases by a factor of 0.405 (95 % CI 0.219-0.750; p = 0.004).

Surgery at primary versus relapsed epithelial ovarian cancer: a study on aspects of anaesthesiological management.

BACKGROUND: Primary cytoreductive surgery (CS) for epithelial ovarian cancer (EOC) is well-established. CS at relapse remains controversial, with an unclear morbidity profile. PATIENTS AND METHODS: We analyzed 121 patients with EOC who underwent CS. Two groups were identified by timing of surgery due to primary disease and due to recurrent disease. RESULTS: CS for primary versus recurrent EOC led to no differences in haemodynamic management, such as transfusion rates, application of vasopressors, ICU and hospital length of stay, or mortality. The risk for postoperative ileus was higher in patients with relapsed versus primary EOC. This might be attributed to patients being operated due to preoperative ileus and a higher small bowel resection rate at CS for relapse. CONCLUSION: CS for EOC relapse does not seem to be more challenging in terms of perioperative management compared to that at initial diagnosis. The major surgical morbidity profile was comparable apart from a higher risk for postoperative ileus at relapse.

[Perioperative management and therapy of bleeding complications]. / Perioperatives Management und Therapie von Blutungskomplikationen.

The new oral anticoagulants directly inhibit either thrombin (Dabigatran, Pradaxa®,) or activated Factor X (rivaroxaban, Xarelto®, and apixaban, Eliquis®) and have been approved for thromboprophylaxis after hip and knee replacement surgery and stroke prevention in non-valvular atrial fibrillation. Moreover, rivaroxaban has been approved for the treatment of deep venous thrombosis, prevention of pulmonary embolism and anticoagulation after acute myocardial infarction. The direct FXa-inhibitor edoxaban (Lixiana®) expects approval for the prevention of stroke in atrial fibrillation in Germany in 2014. The half lives of all direct anticoagulants range between 8 and 17 hours. Dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) are mainly excreted by the kidneys, apixaban (Eliquis®) by the liver (75%) and edoxaban (Lixiana®) by the kidneys (40%) and the faeces in 60%. Prior to surgery a shorter cessation is expected compared to the vitamin k antagonists phenprocoumon (Marcumar®, Falithrom®) and warfarin (Coumadin®). For acute bleedings caused by the direct thrombin inhibitor dabigatran (Pradaxa®) hemodialysis is recommended to eliminate the drug from the plasma. Due to the high protein binding the direkt FXa-inhibitors rivaroxaban (Xarelto®) and apixaban (Eliquis®) can not be hemodialysed. For edoxaban (Lixiana®) no data on elimination by renal replacement therapy are available. In case of life-threatening bleeding the replacement of a prothrombin complex preparation (PCC) containing the factors II, VII, IX and X and, second line, activated factor concentrates as recombinant factor VIIa or activated prothrombin complex preparations are recommended.

Impact of ascites on the perioperative course of patients with advanced ovarian cancer undergoing extensive cytoreduction: results of a study on 119 patients.

OBJECTIVE: Cytoreductive surgery for epithelial ovarian cancer (EOC) is the cornerstone of multimodal therapy and considered as a high-risk surgery because of extensive multivisceral procedures. In most patients, ascites is present, but its impact on the surgical and clinical outcomes is unclear. METHODS: One hundred nineteen patients undergoing surgical cytoreduction because of EOC between 2005 and 2008 were included. All surgical data and the individual tumor pattern were collected systematically based on a validated documentation tool (intraoperative mapping of ovarian cancer) during primary surgery. The amount of ascites was determined at the time of surgery, and 3 groups were classified (no ascites [NOA, n = 56], low amount of ascites [< 500 mL, n = 42], and high amount of ascites [HAS > 500 mL, n = 21]). RESULTS: Group NOA compared with HAS showed less transfusions of packed red blood cells (median [quartiles], 0 [0-2] vs 0 [0-2] vs 3 [1-4] U; P < 0.001) and fresh frozen plasma (median [quartiles], 0 [0-2] vs 0 [0-4] vs 2 [2-6] U; P < 0.001). In addition, in patients with ascites, noradrenaline was administered more frequently and in higher doses. The postoperative length of stay in the intensive care unit was significantly shorter in the NOA versus the group with low amount of ascites and HAS (median [quartiles], 1 [0-1] vs 1 [0-2] vs 2 [1-5] days; P < 0.001). The hospital length of stay is extended in HAS compared with that in NOA (median [quartiles], 16 [13-20] vs 17 [14-22] vs 21 [17-41] days; P = 0.004). Postoperative complications were increased in patients with ascites at the time of surgery (P = 0.007). CONCLUSIONS: The presence of a high amount of ascites at cytoreductive surgery because of EOC is associated with higher amounts of blood transfusions, whereas the length of hospital stay and the postoperative intensive care unit treatment are significantly prolonged compared with those of patients without ascites.

[Anesthesiological management of the drug-abusing parturient: relevance of maternal substance abuse for obstetric anesthesia]. / Kreißende mit Substanzkonsum - Bedeutung in der geburtshilflichen Anästhesie.

Most of the female consumers of legal and illegal substances are of childbearing age. Occasional use, use disorder and addiction commonly devolve into each other. A lot of young women quit consuming when planning a family or at the latest with the knowledge of pregnancy. The ongoing substance abuse during pregnancy requires a coordinated interdisciplinary collaboration for a sufficient care of these highly complex and individual cases.

One-pot synthesis of pegylated ultrasmall iron-oxide nanoparticles and their in vivo evaluation as magnetic resonance imaging contrast agents.

A well-defined copolymer poly(oligo(ethylene glycol) methacrylate-co-methacrylic acid) P(OEGMA-co-MAA) was studied as a novel water-soluble biocompatible coating for superparamagnetic iron oxide nanoparticles. This copolymer was prepared via a two-step procedure: a well-defined precursor poly(oligo(ethylene glycol) methacrylate-co-tert-butyl methacrylate), P(OEGMA-co-tBMA) (M(n) = 17300 g mol(-1); M(w)/M(n) = 1.22), was first synthesized by atom-transfer radical polymerization in the presence of the catalyst system copper(I) chloride/2,2'-bipyridyl and subsequently selectively hydrolyzed in acidic conditions. The resulting P(OEGMA-co-MAA) was directly utilized as a polymeric stabilizer in the nanoparticle synthesis. Four batches of ultrasmall PEGylated magnetite nanoparticles (i.e., with an average diameter below 30 nm) were prepared via aqueous coprecipitation of iron salts in the presence of variable amounts of P(OEGMA-co-MAA). The diameter of the nanoparticles could be easily tuned in the range 10-25 nm by varying the initial copolymer concentration. Moreover, the formed PEGylated ferrofluids exhibited a long-term colloidal stability in physiological buffer and could therefore be studied in vivo by magnetic resonance (MR) imaging. Intravenous injection into rats showed no detectable signal in the liver within the first 2 h. Maximum liver accumulation was found after 6 h, suggesting a prolongated circulation of the nanoparticles in the bloodstream as compared to conventional MR imaging contrast agents.

Maghemite nanoparticles protectively coated with poly(ethylene imine) and poly(ethylene oxide)-block-poly(glutamic acid).

Superparamagnetic iron oxide particles (SPIO) of maghemite were prepared in aqueous solution and subsequently stabilized with polymers in two layer-by-layer deposition steps. The first layer around the maghemite core is formed by poly(ethylene imine) (PEI), and the second one is formed by poly(ethylene oxide)-block-poly(glutamic acid) (PEO-PGA). The hydrodynamic diameter of the particles increases stepwise from D(h) = 25 nm (parent) via 35 nm (PEI) to 46 nm (PEI plus PEO-PGA) due to stabilization. This is accompanied by a switching of their zeta-potentials from moderately positive (+28 mV) to highly positive (+50 mV) and finally slightly negative (-3 mV). By contrast, the polydispersity indexes of the particles remain constant (ca. 0.15). Mössbauer spectroscopy revealed that the iron oxide, which forms the core of the particles, is only present as Fe(III) in the form of superparamagnetic maghemite nanocrystals. The magnetic domains and the maghemite crystallites were found to be identical with a size of 12.0 +/- 0.5 nm. The coated maghemite nanoparticles were tested to be stable in water and in physiological salt solution for longer than 6 months. In contrast to novel methods for magnetic nanoparticle production, where organic solvents are necessary, the procedure proposed here can dispense with organic solvents. Magnetic resonance imaging (MRI) experiments on living rats indicate that the nanoparticles are useful as an MRI contrast agent.