Manejo y percepciones sobre la anemia y deficiencia de hierro previo a cirugía cardíaca

Preoperative anemia management in the coronavirus disease (COVID-19) era

Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve Replacement

Until now no randomized trial can be considered powered enough to show a reduction on both perioperative myocardial infarction and mortality. We performed an extensive research of the literature to identify drugs or technique that could have an effect on perioperative myocardial infarction in cardiac and non-cardiac surgery. Volatile agents reduce myocardial infarction (NNT=37) and mortality (NNT=83) in cardiac surgery when compared to total intravenous anesthesia. No data regarding the use of volatile agents in non-cardiac surgery exists. Levosimendan reduces myocardial infarction (NNT=21) and mortality (NNT=12) in cardiac surgery when compared to placebo or other inotropic agents. No data regarding its use in non-cardiac surgery exists. Epidural analgesia has promising beneficial effects in both cardiac and on-cardiac surgery. In non cardiac surgery statins, and calcium antagonists have minor beneficial effects while alpha(2) agonists could reduce perioperative mycoardial infarction and are included in the American College of Cardiology / American Heart Association Guidelines. Beta blockers are also included in the international guidelines but benefits and hazards should be careful considered. Volatile agents and levosimendan consistently reduce perioperative myocardial infarction and mortality in cardiac surgery but they have not been properly studied in non-cardiac surgery. Minor (epidural analgesia, statins, calcium antagonists and alpha(2) agonists) or doubtful (beta-blockers) results were found in non-cardiac surgery.

Blood Management

Bone Marrow Iron in CKD: Correlation With Functional Iron Deficiency

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has forced examination of much of routine healthcare provision in the UK, and necessitated changes in practice to protect patients from the virus while continuing to deliver high-quality care for their other health needs. This has been highlighted by the challenges in provision of elective surgical services while SARS-CoV-2 remains prevalent in communities. NHS providers have moved from preoperative assessment pathways routinely involving face-to-face appointments to remote (telephone, digital or combination) assessments.1, 2 Telehealth-based solutions provide an innovative option to provide patient care during pandemic times while helping prevent and contain the spread of infection.3 They are also convenient for the patient and medical staff and are likely to become part of routine care in the future. This reduction in face-to-face contacts means there is a pressing need to rethink how best to prepare patients for elective surgery, ensuring comprehensive assessment is performed within the limitations imposed by pandemic-related changes to working practices. It is also an opportunity to review the evidence for best care to evaluate the benefit of certain aspects of what may have become routine practice in consideration of risk balance to the patient. Surgical PBM has become standard of care over the last decade and involves preoperative, operative and postoperative phases, to manage anaemia, minimise blood loss and ensure appropriate transfusion practices, with benefits for both patient outcomes and the blood supply chain. Appropriate use of blood is critical to mitigate the negative impact of the pandemic on blood collection and resulting blood stocks at a time of great challenge for blood services.4 A systematic review and meta-analysis of 393 randomised controlled trials (n = 54 917) showed that PBM interventions reduced exposure to allogeneic blood components, length of stay and intensive care usage. In a network meta-analysis of the randomised controlled trials most of the effects were explained by the use of tranexamic acid and restrictive transfusion triggers; there was less additive effect of other preoperative interventions.5 Preoperative anaemia is common, affecting 10–15% of patients before elective orthopaedic surgery,8 a third of those undergoing abdominal surgery and half of those undergoing colorectal surgery.9 Several large database analyses have associated preoperative anaemia with worse patient outcomes with regard to postoperative complications, morbidity and mortality.10, 11 The most common cause of anaemia is absolute, or classical iron deficiency due to nutritional deficiency, reduced iron uptake or blood loss.12 Absolute iron deficiency results in reduced ferritin levels, with low circulating iron, raised total iron binding capacity (TIBC) and reduced transferrin saturation (TSAT or iron saturation). It is necessary to distinguish anaemia associated with absolute iron deficiency, that is likely to respond to iron replacement therapy, from anaemia of chronic disease associated with functional iron deficiency (FID). Functional iron deficiency is characterised by low circulating iron levels and TSAT, with normal or reduced TIBC and normal or increased serum ferritin levels. Systemic markers of inflammation C-reactive protein (CRP) may also be elevated. The diagnosis of anaemia necessitates a blood test, and the potential for additional SARS-CoV-2 exposure. Testing in advance of surgery should therefore be limited to those patients in whom it is likely to be of benefit with regard to their surgery. Screening for anaemia should be undertaken in all patients who are themselves high risk or those undergoing major surgery or in whom significant blood loss may be anticipated.13 It should not be undertaken in those who are undergoing minor or intermediate surgical procedures, or in patients who are otherwise well and in whom anaemia would not normally prevent or delay surgery, nor affect the outcome of surgery. Where waiting times for surgery are anticipated to be prolonged, early identification and treatment of anaemia will allow the patient to proceed directly to surgery when a slot becomes available. This may be achieved through close liaison with primary-care teams to enable timely investigations. Patients may have had recent blood tests for other purposes and where these are present, acceptable, and the patient remains clinically stable, repetition may not be necessary. These tests may have been performed by their general practitioner as part of routine care or for instance in the case of cancer surgery in their pathway before operation. Coordination with other health care providers will minimise duplication. Studies in healthy volunteer blood donors suggest haemoglobin results remain steady even after a prolonged inter-test period of up to two years, suggesting that in otherwise healthy patients undergoing elective surgery, it is reasonable to use historic results to assess for anaemia.14 Where blood tests are required, these should be carried out as early in the surgical pathway as possible to allow adequate time for interpretation and effective intervention in those in whom anaemia is identified. Coordination between departments is critical, as such opportunities may be in diverse areas, for example, radiological investigations or appointments for unrelated problems. To avoid multiple visits for blood tests, blood for all diagnostic tests should preferably be taken during one visit. Where laboratory systems allow, automatic reflex testing based on the initial haemoglobin and red-cell indices will provide the relevant diagnostic tests with the minimum of delay, and avoid unnecessary tests. Where this is not possible, samples may still be taken together and additional testing requested manually on the samples held. Alternatively, requesting all diagnostic tests 'up front' will ensure that results are available without delay but may incur additional cost and use of resources. In the preoperative setting, tests must be directed at detection of treatable causes of anaemia, for which effective interventions can be delivered. In the first instance this should include as a minimum full blood count, renal and liver profile. Where there is anaemia associated with a normal or low mean corpuscular volume (MCV) and/or mean corpuscular haemoglobin (MCH), additional diagnostic tests should be directed at diagnosis of iron deficiency and anaemia of chronic disease and include ferritin, iron studies (serum Fe, TIBC, TSAT) and inflammatory markers. Where the MCV is raised, B12 and folate assays should be requested. In most circumstances it is out with the scope of preoperative assessment to investigate and treat anaemia due to other causes and referral for management will be necessary. Further testing can however be undertaken at this stage to prevent the need for further blood tests and infection risk. Consideration should also therefore be given to completion of a full anaemia screen where a simple deficiency is not found. This should include the addition of: thyroid stimulating hormone (TSH), a haemolysis screen (lactate dehydrogenase, reticulocytes, blood film, haptoglobin and direct antiglobulin test) and immunoglobulins. Pathways and individual responsibilities should be agreed for follow-up, particularly for patients for whom the cause of anaemia remains undiagnosed or is found to be unrelated to the reason for surgery. This may require onward referral to a haematologist, gastroenterologist or gynaecologist as indicated, as preoperative assessment clinics will not have the necessary expertise to pursue a diagnosis in such cases. Existing national guidance and local maximum blood ordering schedules (MSBOS) should be followed when determining which patients should have samples taken for group and screen or cross match. Where these are necessary, they should be taken at the same time as other interventions as far as is possible. The recommendation for isolation for 14 days before surgery during the pandemic15 (though in some cases shorter preoperative isolation may be deemed appropriate in accordance with local public health guidance) necessitates that transfusion samples be taken on admission for surgery where this is required. When anaemia is identified, this should be investigated and managed accordingly. Patients should be enrolled and managed within clinical trials where possible; however, trial activity has been significantly curtailed during the pandemic, and the added infection risk incurred due to trial-related hospital attendances must be considered when discussing such options with the patient. Those patients with iron deficiency should be treated, in the preoperative setting as in any other setting. If time allows then a course of oral iron can be effective and does not require hospital attendance. When oral iron is not tolerated, or found to be ineffective, intravenous iron can be used though this will require a hospital attendance and associated exposure risk. The Cochrane review on the use of iron therapy to treat anaemia has recently been updated.16 One hundred and twelve randomised controlled trials (RCTs) totalling 22 169 patients were included. Overall, iron therapy was efficacious in increasing haemoglobin levels and reducing need for blood transfusion. However, patient outcomes were heterogeneously reported. The management of surgical patients in whom the cause of anaemia has not been determined is less clear. The PREVENTT trial17 randomised 487 anaemic patients undergoing major abdominal surgery at multiple UK sites to receive intravenous iron (ferric carboxymaltose, 1 000 mg) or placebo (saline) a median of 15 (12–22) days preoperatively. No diagnostic process was mandated before randomisation. Intravenous iron was efficacious to increase haemoglobin [mean difference, 4·7 g/l; 95% confidence interval (CI), 2·7–6·8] but did not result in a reduced need for blood transfusion (risk ratio, 1·03; 95% CI, 0·78–1·37; P = 0·84). There were no differences between the groups in postoperative complications, hospital stay or days alive and out of the hospital at 30 days. Secondary results from PREVENTT showed significant differences in patients after surgery and on discharge from hospital. The intravenous iron group had significantly higher haemoglobin concentrations at eight weeks following surgery (mean difference, 10·7 g/l; 95% CI, 7·8–13·7), and re-admission to the hospital following surgery was significantly less likely; 31 (13%) vs 51 (22%), risk ratio, 0·61; 95% CI, 0·40–0·91, 38 in the intravenous iron group vs 71 in the placebo group (rate ratio, 0·54; 95% CI, 0·34–0·85). This study indicates that anaemic patients who do not have confirmed iron deficiency should not be treated with empirical intravenous iron. The use of a combination of erythropoietin and intravenous iron to treat preoperative anaemia in patients undergoing non-cardiac surgery has been the subject of a number of trials reviewed recently by Cochrane.18 Conclusions were limited by the quality of evidence, but suggest that administration of recombinant erythropoietin plus iron reduced the risk of red-cell transfusion and when erythropoietin was administered at higher doses, haemoglobin levels were increased. No differences in length of hospital stay or adverse events were identified but further RCTs are required to fully assess this treatment approach. Novel approaches during the inpatient stay that may benefit the patient should be considered. In the setting of cardiac surgery, Spahn randomised 505 patients with anaemia or iron deficiency to a combination of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery.19 The primary end-point demonstrated a reduction in the median number of blood transfusions during the first seven days [odds ratio (OR) of 0·70 (95% CI 0·50–0·98)]. However, there was no difference in patient-reported end-points of postoperative complications or length of hospital stay. Perioperative intravenous (IV) iron in non-anaemic patients undergoing cardiac surgery has been shown to result in reduced postoperative anaemia and has the potential to reduce contact with healthcare settings during the postoperative period, reducing potential exposure events.20 Following treatment, response assessment must be undertaken. Ideally this should not incur an additional potential exposure event, and should be undertaken at the same time as another mandatory intervention whenever possible. A decision should be made at the diagnosis of anaemia how this test will be done and whether it will affect the decision to proceed to surgery. Where the decision is made to proceed to treatment regardless of the effectiveness of the treatment, and there is little or no opportunity for additional treatment, there would be little justification for an additional blood test before the day of surgery. When considering maximising preoperative PBM interventions while minimising patient face-to-face contact, the preoperative elements of the second pillar of PBM, minimising blood loss, gain added importance. Many factors which contribute to a patient's bleeding risk can be readily assessed by history taking which can be undertaken remotely. A review should be performed of the patient's medical notes and electronic records. A management plan to modify features identified in the history which may increase a patient's bleeding risk can then be formulated and communicated to the patient, the operative team and primary care prior to the planned surgery. The patient's past medical history should be reviewed including any personal or family history of inherited bleeding disorders. Conditions which may increase bleeding risk, for example renal or liver impairment, should also be considered. National Institute for Health and Care Excellence (NICE) Guidance recommends blood tests to assess haemostasis should not be performed routinely, but should be considered in patients with chronic liver disease.13 The optimal method for screening for bleeding disorders in the preoperative population is not well defined, though this practice is endorsed by national and international guidelines.21, 22 The International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT) aims to identify people with inherited bleeding disorders (including mild disorders) by using a questionnaire to identify a personal history of non-trivial bleeding.23 While this tool standardises the evaluation of bleeding symptoms, it may be lengthier and more detailed than is required in the preoperative setting but could be employed if initial screening questions raised concerns. Modifiable risk factors for excess bleeding should then be considered, with particular attention paid to medications, namely antiplatelet agents, anticoagulants and other medications which may increase bleeding risk, for example NSAIDs. A comprehensive review of the perioperative management of these medications was published as a BSH guideline in 2016.7 A risk assessment should be undertaken, considering the indication for the drug, the bleeding risk associated with the procedure, and the risks associated with temporary discontinuation of relevant medications in order to formulate a patient- and procedure-specific plan. The need for bridging therapy for patients on therapeutic anticoagulation should be considered, and its requirement (or not) must be documented. It should be noted that bridging therapy is associated with increased postoperative bleeding rates, while placebo was non-inferior to low-molecular-weight heparin bridging therapy for the prevention of arterial thrombotic events in patients with atrial fibrillation anticoagulated with warfarin for stroke prevention.24 Bridging therapy should therefore be reserved for patients at highest risk of thrombotic events during an interruption to anticoagulation.7 The antifibrinolytic drug tranexamic acid has been demonstrated to reduce blood loss and blood transfusions when used to treat patients undergoing orthopaedic surgery25 and cardiac surgery26 with a recent meta-analysis confirming these effects. Data from these studies are reassuring with respect to rates of thrombotic events. NICE guidance recommends its use when total surgical blood loss (which may exceed measured blood loss) is anticipated to be more than 500 ml.27 The planned use of perioperative tranexamic acid should be documented following the remote assessment. For completeness, the perioperative PBM plan should also document whether intraoperative cell salvage is to be used as well as plans for monitoring, and correction of, perioperative body temperature and ionised calcium to help minimise risk of coagulopathy and any particular recommendations regarding patient positioning to reduce blood loss. Transfusion thresholds for red-cell transfusion should also be documented. The body of evidence supporting the safety of restrictive thresholds continues to grow,28, 29 and these thresholds should be adopted unless there is a clear contraindication to their use. The patient should be supplied with information regarding the transfusion process, risks and benefits, alternatives to transfusion which will be considered and ultimately consent for blood transfusion should be obtained during the preoperative assessment.30 The BSH Transfusion task force members at the time of writing this Good Practice Paper were Edwin Massey, Sharon Zahra, Paul Kerr, Richard Soutar, Wendy McSporran, Richard Haggas, Laura Green, Chloe George, Katie Hands, Fiona Regan, Shruthi Narayan, Karen Madgwick and Susan Robinson. The authors would like to thank them, the BSH sounding board, and the BSH guidelines committee for their support in preparing this Good Practice Paper. All the authors were involved in the formulation and writing of the manuscript, as well as approval of its final version. The BSH paid the expenses incurred during the writing of this Good Practice Paper. All the authors have made a declaration of interests to the BSH and Task Force Chairs which may be viewed on request. AK has in the past five years received speaker's fees and expenses related to conference attendance, as well as consultancy fess, from Vifor Pharma and Pharmacosmos (both are pharmaceutical companies that manufacture an IV iron preparation). TR has received speaker's fees and expenses related to conference attendance from Pharmocosmos and Vifor Pharma. TR is a director of The Iron Clinic Ltd. The following members of the writing group have no conflict of interests to declare: KH, CT, SN. Members of the writing group will inform the writing group Chair if any new pertinent evidence becomes available that would alter the strength of the recommendations made in this document or render it obsolete. The document will be archived and removed from the BSH current guidelines website if it becomes obsolete. If new recommendations are made an addendum will be published on the BSH guidelines website (https://b-s-h.org.uk/guidelines/guidelines/). While the advice and information in this guidance is believed to be true and accurate at the time of going to press, neither the authors, the BSH nor the publishers accept any legal responsibility for the content of this guidance.

Optimizing Preoperative Iron Deficiency Anemia in Patients Undergoing Cardiac Surgery

The Impact of Intravenous Iron on Renal Injury and Function Markers in Patients With Chronic Kidney Disease and Iron Deficiency Without Anemia

See article on page 2629–2636, in this issue

Using hemoglobin concentration ([Hb]) to diagnose borderline iron deficiency and monitor the progress of its treatment is difficult because of the confounding effects of plasma volume. Because hemoglobin mass (Hbmass) is not affected by plasma volume, it may be a more sensitive parameter. The aim of this study was to monitor Hbmass, iron storage, and maximal oxygen consumption (V˙O2max) during and after oral iron therapy in subjects with severe and moderate iron deficiency. Three groups of female recreational athletes were monitored for at least 22 wk, as follows: 1) severe iron deficiency group (SID) (n = 8; ferritin, ≤12 ng·mL), 2) moderate iron deficiency group (MID) (n = 14; ferritin, ≤25 ng·mL), and 3) control group (n = 8; ferritin, >25 ng·mL). Hbmass and iron status were determined before, during, and up to 12 wk after at least 10 wk of oral iron supplementation. In total, five V˙O2max tests were performed before, during, and after the supplementation period. Hbmass increased markedly in the SID group (15.6% ± 11.0%, P < 0.001) and slightly in the MID group (2.2% ± 3.7%, P < 0.05) by the end of the supplementation period and remained at this level for the following 12 wk. [Hb] and Hbmass were similarly affected, but Hbmass was more closely related to mean corpuscular volume and mean corpuscular hemoglobin than [Hb]. The SID group incorporated 534 ± 127 mg of iron into ferritin and hemoglobin, whereas the MID group incorporated 282 ± 68 mg of iron. V˙O2max increased only in the SID group by 0.20 ± 0.18 L·min (P < 0.05) and was closely related to Hbmass (P < 0.01). Hbmass is a sensitive tool for monitoring recovery from iron deficiency anemia and assessing the effectiveness of iron supplementation in individuals with severe or moderate iron deficiency.

KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD

BackgroundPostoperative mortality after cardiac surgery remains a significant challenge, with traditional risk scores showing limited predictive accuracy. The hemoglobin-to-red cell distribution width ratio (HRR) has emerged as a novel biomarker with potential prognostic value. This study aims to evaluate the association between preoperative HRR, red cell distribution width (RDW), and 30-day postoperative mortality in cardiac surgery patients. We hypothesized that preoperative HRR and RDW are associated with 30-day postoperative mortality in cardiac surgery patients.MethodsWe conducted a retrospective study of 926 patients who underwent cardiac and aortic surgeries. Data on demographics, comorbidities, and perioperative details were extracted from electronic health records. Multivariable logistic regression was used to assess the HRR-mortality relationship, and Kaplan-Meier analysis with log-rank testing evaluated 30-day survival. Sensitivity analyses were performed to confirm robustness.ResultsThe 30-day mortality rate was 4.2% (38 cases). A lower HRR (≤8.73) was independently associated with increased mortality [odds ratio (OR), 0.1; 95% confidence interval (CI): 0.01–0.97; P=0.047], even after adjustment for covariates. Elevated RDW (>14.8%) also correlated with higher mortality risk, though with less robust confidence intervals. Sensitivity analyses supported the robustness of results. Kaplan-Meier survival analysis demonstrated a significantly elevated cumulative mortality rate in the low-HRR group (9.6%) compared to the high-HRR cohort (2.9%; P=0.001).ConclusionsPreoperative HRR is significantly associated with 30-day mortality in cardiac surgery patients. A low HRR (≤8.73) is an independent risk factor, suggesting its utility in risk stratification and clinical decision-making. Further studies are needed to validate these findings and explore underlying mechanisms.

Major Bleeding, Transfusions, and Anemia: The Deadly Triad of Cardiac Surgery

Invited commentary

Targeting Iron Deficiency in Heart Failure: Existing Evidence and Future Expectations.