The association between iron deficiency and outcomes: a secondary analysis of the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial.

In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre-operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 µg.l-1 ; functional iron deficiency as ferritin 30-100 µg.l-1 or transferrin saturation < 20%; and the remainder as non-iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co-primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri-operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one-third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre-operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l-1 , 95%CI 5.3-12.5; moderate in functional iron deficiency, mean difference 2.8 g.l-1 , 95%CI -0.1 to 5.7; and with little change seen in those patients who were non-iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay.

Validation of viscoelastic coagulation tests during cardiopulmonary bypass.

BACKGROUND: Viscoelastic point-of-care tests such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are increasingly used to guide hemostatic therapy after cardiac surgery. The aim of this study was to assess their clinical utility during cardiopulmonary bypass to predict postbypass coagulation status and to guide therapy. METHODS: In this prospective study, TEG and ROTEM tests were performed in 52 adult patients undergoing elective cardiac surgery at two time points: near the end of cardiopulmonary bypass and after heparin reversal with protamine. The 95% confidence intervals of the mean difference were compared with a prespecified clinically relevant limit of ± 20% of the value after protamine. RESULTS: Both viscoelastic fibrinogen assays were well within the prespecified clinically relevant limit (≥ 79% of patients). The laboratory Clauss fibrinogen was much lower during cardiopulmonary bypass than after protamine (mean difference 1.2 g L(-1) , 95% CI 1.03-1.4, which was outside a clinically acceptable difference. For intrinsically activated tests, clotting times (CT) were different and outside the prespecified limit on TEG (mean difference -1.2 min, 95% CI -1.8 to -0.6) but not on ROTEM (mean difference 2.3 sec, 95% CI -8.6 to 13.2), while clot strength was well within the clinical limit on both devices (≥ 94% of patients). For extrinsically activated tests, clot strength on both TEG and ROTEM was within the pre-specified limit in 98% of patients. CONCLUSIONS: Results from TEG and ROTEM tests performed toward the end of cardiopulmonary bypass are similar to results after reversal of heparin. Amplitudes indicating clot strength were the most stable parameters across all tests, whereas CT showed more variability. In contrast, laboratory testing of fibrinogen using the Clauss assay was essentially invalid during cardiopulmonary bypass.

Haemoconcentration of residual cardiopulmonary bypass blood using Hemosep ®: a randomised controlled trial.

Cardiac surgery and cardiopulmonary bypass are associated with haemodilution, activation of haemostasis and blood transfusion. We undertook a randomised controlled trial that included 53 patients in order to compare autotransfusion of residual cardiopulmonary bypass blood with residual blood concentrated using the novel Hemosep(®) device. There was no difference in patients' mean (SD) haemoglobin concentration after autotransfusion of unprocessed blood compared with Hemosep; 103.5 (10.2) g.l(-1) vs 106.2 (12.4) g.l(-1), respectively, p = 0.40. The mean (SD) change in haemoglobin concentration after autotransfusion was 5.9 (5.3) g.l(-1) in the control group compared with 4.9 (6.3) g.l(-1) in the Hemosep group, p = 0.545. Adjusted for baseline haemoglobin concentrations, the estimated mean (95% CI) difference in change in haemoglobin concentration (control vs Hemosep) was 0.57 (-2.65 to 3.79) g.l(-1), p = 0.72. This was despite Hemosep's reducing the weight of the blood from a mean (SD) of 778.7 (243.0) g to 607.3 (248.2) g, p < 0.001. The haemoglobin concentration in the processed blood increased from a mean (SD) of 87.0 (15.1) g.l(-1) to 103.7 (17.4) g.l(-1), p < 0.001. We conclude that Hemosep is capable of haemoconcentration when employed to process residual cardiopulmonary bypass blood, but that this is insufficient to increase patient haemoglobin.

Haemostatic management of cardiac surgical haemorrhage.

Almost 30,000 cardiopulmonary bypass operations are performed in the UK every year, consuming a considerable portion of the UK blood supply. Each year, in cardiac surgery, 90% of blood products are used by only 10% of patients, and over the past 25 years, much innovation and research has gone into improving peri-operative diagnosis and therapy for these patients. Visco-elastic tests performed at the bedside, with modifications to allow direct quantification of fibrinogen levels, are probably the biggest advancement. There is no clear advantage of thromboelastometry over thromboelastography, and the published literature remains scarce. Visco-elastic testing has recently been coupled with the systematic replacement of clotting factors by means of factor concentrates, with objective improvement in terms of blood loss, red blood cell usage and surgical re-exploration. The National Institute for Health and Care Excellence has reviewed the available evidence and recommended visco-elastic tests as cost effective in cardiac surgery. Factor concentrates, however, carry significant risks, particularly unnecessary donor exposures, potential selective over-correction of partial deficiencies and the possibility that the postoperative risk of venous thromboembolism is increased; as yet there are no data on risk-benefit analysis. There are a number of promising drugs used in topical haemostasis, but the requirement to apply these before major bleeding is manifest limits their use considerably. Hyperfibrinolysis is less important than in the past due to the wide spread adoption of antifibrinolytic agents and close intra-operative monitoring of heparin effect.

Antifibrinolytic agents in current anaesthetic practice.

Antifibrinolytic drugs have become almost ubiquitous in their use during major surgery when bleeding is expected or commonplace. Inhibition of the fibrinolytic pathway after tissue injury has been consistently shown to reduce postoperative or traumatic bleeding. There is also some evidence for a reduction of perioperative blood transfusion. However, evidence of complications associated with exaggerated thrombosis also exists, although this appears to be influenced by the choice of the individual agent and the dose administered. There is controversy over the use of the serine protease inhibitor aprotinin, whose license was recently withdrawn but may shortly become available on the market again. In the UK, tranexamic acid, a tissue plasminogen and plasmin inhibitor, is most commonly used, with evidence for benefit in cardiac, orthopaedic, urological, gynaecological, and obstetric surgery. In the USA, ε-aminocaproic acid, which also inhibits plasmin, is commonly used. We have reviewed the current literature for this increasingly popular class of drugs to support clinical judgement in daily anaesthetic practice.

THE PAPWORTH PLUG - successful use of high dose fibrinogen concentrate and platelet concentrate in potential life-threatening complication after cardiopulmonary bypass surgery in a patient with Type 2M Vicenza von Willebrand Disease.

Anecdotally, fibrinogen concentrate (FC) has been used as a "universal" haemostatic agent in complex post-cardiopulmonary bypass (CPB) coagulopathy. We present a case where FC and two pools of platelets prevented life-threatening bleeding in a patient with moderate von Willebrand Disease (vWD) immediately post CPB.

Coagulopathy associated with massive cell salvage transfusion following aortic surgery.

Cell saver blood is used within the peri-operative setting of cardiothoracic surgery to reduce the need for transfusion of allogenic blood products. Several meta-analyses have proven a significant decrease in allogenic transfusion with the use of cell salvage techniques. Washing of red cells by the cell saver and subsequent transfusion of suspended red cells can occasionally cause coagulopathy, particularly when using high concentration heparin saline to wash the spilled blood. We present the case of a 74-year-old female who underwent complicated aortic surgery and was transfused large volumes of cell-saved blood due to post-operative bleeding, which subsequently led to coagulopathy.

Near-patient platelet function testing in patients undergoing coronary artery surgery: a pilot study.

Platelet dysfunction after cardiopulmonary bypass contributes to microvascular bleeding and is associated with blood transfusion and resternotomy. Platelet count can be readily performed, but currently there are no standardised, reproducible, rapidly available platelet function tests. We studied platelet function as measured by multiple electrode platelet aggregometery (multiplate) and light transmission aggregometry in 44 patients undergoing routine coronary artery surgery. Platelet aggregation as measured by multiplate was reduced during and after cardiopulmonary bypass compared with baseline with evidence of partial recovery by the time of transfer to ITU. In patients transfused blood, platelet aggregation measured by multiplate was reduced during chest closure with adenosine diphosphate (18 U vs 29 U, p = 0.01) and thrombin receptor agonist peptide-6 agonist (65 U vs 88 U, p = 0.01) compared with patients not transfused. This suggests that multiplate, a new point of care analyser, can detect platelet dysfunction in this setting.

A case of Mollitias and Fragilitas Ossium - unusual presentation of hairy cell leukaemia followed by the diagnosis of nonsecretory myeloma.

Hairy cell leukaemia (HCL) is a B-cell malignancy with a late developmental arrest. This report describes a patient that presented with leucocytosis and splenomegaly. The abnormal leucocytes showed typical morphology and expressed CD103, CD11c, CD19 and CD20 but not CD25 by immunophenotyping. The patient failed to respond to splenectomy and then developed lytic bone lesions and pathological fractures, which progressed despite a single course of cladribine chemotherapy. Review of the pathology of the bone reamings showed nonsecretory myeloma of the same kappa-light chain isotype. He went on to receive induction chemotherapy in preparation for an autologous stem-cell transplant but failed to mobilize sufficient numbers of stem cells. He has had two localized relapses with bony lesions, one within 6 weeks of stopping chemotherapy for which he received localized radiotherapy and thalidomide consolidation. Sequential myeloma has been described in HCL. There is controversy whether this represents clonal evolution or a secondary malignancy. An increased rate of secondary malignancies has been reported by some, but not other, authors in long-term survivors of HCL. This case illustrates the value of a repeat pathological review in case of unexpected complications.

Entonox as a sedative for bone marrow aspiration and biopsy.

Bone marrow aspiration and biopsy can be a painful procedure. Sedation techniques may make this investigation more acceptable to patients, but have the potential to cause life-threatening complications, as well as requiring additional staff and equipment for safe administration. We assessed the use of Entonox, a 50 : 50 mix of nitrous oxide and oxygen, as a sedation and analgesic agent, and compared it to previous experience with the intravenous (i.v.) benzodiazepine midazolam. Patients' perception of pain, and both the operator and patient's views on the ease of the procedure and safety factors were recorded. Twenty-two patients who had previously required i.v. midazolam sedation (16), or who requested sedation (6) were studied. Fifteen of 16 (94%) found Entonox better or equal to midazolam, and only one patient (6%) found it worse. There were no serious adverse events due to Entonox. We have shown, in this small group of patients, that Entonox is an effective, safe alternative to intravenous midazolam for sedation during bone marrow biopsy, and is considered acceptable by both patients and staff. It has the major advantage that no additional staff or facilities are required for safe administration or monitoring the patient during or after the procedure.