Fiona Bottrill

Significant blood resistance to nitric oxide transfer in the lung

Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNO<infinity. We now show in a membrane oxygenator model perfused with whole blood that addition of a cell-free bovine hemoglobin (Hb) glutamer-200 solution increased diffusing capacity of the circuit (D) for NO (DNO) by 39%, D for carbon monoxide (DCO) by 24%, and the ratio of DNO to DCO by 12% (all P<0.001). In three anesthetized dogs, DLNO and DLCO were measured by a rebreathing technique before and after three successive equal volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total exchange 30 ml/kg). At baseline, DLNO/DLCO=4.5. After exchange transfusion, DLNO rose 57+/-16% (mean+/-SD, P=0.02) and DLNO/DLCO=7.1, whereas DLCO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite thetaNO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DLNO is sensitive to dynamic hematological factors and is not a pure index of conductance of the alveolar tissue membrane. With successive exchange transfusion, the estimated in vivo thetaNO [5.1 ml NO.(ml blood.min.Torr)(-1)] approached 4.5 ml NO.(ml blood.min.Torr)(-1), which was derived from in vitro measurements by Carlsen and Comroe (J Gen Physiol 42: 83-107, 1958). Therefore, we suggest use of thetaNO=4.5 ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary blood volume from DLNO and DLCO.

A randomized controlled trial of cell salvage in routine cardiac surgery.

BACKGROUND: Previous trials have indicated that cell salvage may reduce allogeneic blood transfusion during cardiac surgery, but these studies have limitations, including inconsistent use of other blood transfusion-sparing strategies. We designed a randomized controlled trial to determine whether routine cell salvage for elective uncomplicated cardiac surgery reduces blood transfusion and is cost effective in the setting of a rigorous transfusion protocol and routine administration of antifibrinolytics. METHODS: Two-hundred-thirteen patients presenting for first-time coronary artery bypass grafting and/or cardiac valve surgery were prospectively randomized to control or cell salvage groups. The latter group had blood aspirate during surgery and mediastinal drainage the first 6 h after surgery processed in a cell saver device and autotransfused. All patients received tranexamic acid and were subjected to an algorithm for red blood cell and hemostatic blood factor transfusion. RESULTS: There was no difference between the two groups in the proportion of patients exposed to allogeneic blood (32% in both groups, relative risk 1.0 P = 0.89). At current blood products and cell saver prices, the use of cell salvage increased the costs per patient by a minimum of

A prospective observational cohort study to identify the causes of anaemia and association with outcome in cardiac surgical patients

103. When patients who had mediastinal re-exploration for bleeding were excluded (as planned in the protocol), significantly fewer units of allogeneic red blood cells were transfused in the cell salvage compared with the control group (65 vs 100 U, relative risk 0.71 P = 0.04). CONCLUSION: In patients undergoing routine first-time cardiac surgery in an institution with a rigorous blood conservation program, the routine use of cell salvage does not further reduce the proportion of patients exposed to allogeneic blood transfusion. However, patients who do not have excessive bleeding after surgery receive significantly fewer units of blood with cell salvage. Although the use of cell savage may reduce the demand for blood products during cardiac surgery, this comes at an increased cost to the institution.

The significant blood resistance to lung nitric oxide transfer lies within the red cell

Objectives Preoperative anaemia is associated with increased morbidity and mortality. We sought to determine the relative frequencies of the different causes of anaemia including absolute and functional iron deficiency, and the association of different haematological parameters, including plasma hepcidin, a key protein responsible for iron regulation, with outcomes after cardiac surgery. Methods Prospective observational study between January 2012 and 2013; 200 anaemic cardiac surgical patients were recruited and 165 were studied. Detailed blood and bone marrow analysis was performed. Primary outcome was days alive and out of hospital. Results Mean (SD) haemoglobin (Hb) was 102 (8) g/L for women and 112 (11) g/L for men. Regarding outcomes, 137 (83%) patients were transfused at least one unit of red blood cells; 30-day mortality was 1.8% (three patients). Functional iron deficiency was diagnosed in 78 patients (47%). Plasma hepcidin concentration was the only haematological variable associated with outcome, with mean days alive and out of hospital 2.7 (95% CI 0.4 to 5.1) days less if hepcidin ≥20 ng/mL compared with <20 ng/mL (p=0.024). Multivariable analysis showed that the association between hepcidin and outcome was independent of risk (European System for Cardiac Operative Risk Evaluation), transfusion and Hb. Conclusions Functional iron deficiency was the most common cause of anaemia but was not associated with outcome. The only haematological parameter that was associated with outcome was hepcidin concentration, which is a novel finding and introduces further complexity into our understanding of the role of iron and its regulation by hepcidin. We propose that future research should target patients with elevated hepcidin.

A lipopolysaccharide adsorber in adult cardiopulmonary bypass: a single centre randomised controlled pilot trial

The lung nitric oxide (NO) diffusing capacity (DlNO) mainly reflects alveolar-capillary membrane conductance (Dm). However, blood resistance has been shown in vitro and in vivo. To explore whether this resistance lies in the plasma, the red blood cell (RBC) membrane, or in the RBC interior, we measured the NO diffusing capacity (Dno) in a membrane oxygenator circuit containing ∼1 liter of horse or human blood exposed to 14 parts per million NO under physiological conditions on 7 separate days. We compared results across a 1,000-fold change in extracellular diffusivity using dextrans, plasma, and physiological salt solution. We halved RBC surface area by comparing horse and human RBCs. We altered the diffusive resistance of the RBC interior by adding sodium nitrite converting oxyhemoglobin to methemoglobin. Neither increased viscosity nor reduced RBC size reduced Dno. Adding sodium nitrite increased methemoglobin and was associated with a steady fall in Dno (P < 0.001). Similar results were obtained at NO concentrations found in vivo. The RBC interior appears to be the site of the blood resistance.

Clinical use of low haemoglobin density, transferrin saturation, bone marrow morphology, Perl's stain and other plasma markers in the identification of treatable anaemia presenting for cardiac surgery in a prospective cohort study

OBJECTIVES The aim of this study was to describe the biochemical effects and safety of selective removal of endotoxin from whole blood using a lipopolysaccharide adsorber during complex cardiac surgery. METHODS We carried out a single centre prospective randomised controlled pilot trial in patients undergoing elective cardiac surgery using cardiopulmonary bypass (CPB) at a large UK cardiothoracic institution. Seventeen patients were randomly allocated to one of two groups: with or without an adsorber included in the CPB circuit. Fourteen patients were included in a complete case analysis. Blood samples were taken at the time of consent, immediately following anaesthesia, at 60, 180 and 360 min after the institution of CPB, and the morning following surgery. Primary outcomes were plasma levels of endotoxin, IL-6, IL-8 and TNF-alpha. Secondary outcomes were measures of patient safety including blood chemistry and coagulation parameters, length of stay, and adverse events. RESULTS No differences were seen in endotoxin or cytokine levels between adsorber and control groups at any of the measured time-points. No difference between groups was detected in measures of patient safety following the intervention. Haemoglobin and haematocrit were significantly lower in the intervention group pre-bypass, P=0.02 in both instances. CONCLUSION There was no effect of the adsorber on endotoxin levels or inflammatory response in this study, we have demonstrated the device to be safe in a complex cardiac surgery setting.

Can a membrane oxygenator be a model for lung NO and CO transfer

Objectives The differential diagnosis between iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) with or without associated iron deficiency can be challenging. We assessed the use of different parameters, both classical like ferritin, transferrin saturation and stainable bone marrow iron stores, and novel markers such as low haemoglobin density (LHD) and hepcidin to help discriminate between the three entities. This would allow the detection of patients with ACD with associated iron deficiency, which could benefit from iron supplementation that would have otherwise remained undetected. Materials and methods Prospective and observational cohort study from 2012 to 2013 where 200 anaemic cardiac surgical patients were recruited and 165 were studied. Detailed blood and bone marrow analyses were performed to establish the aetiology of anaemia. Results Seventy-four patients (44.8%) had ACD and 29 (39%) of these had an elevated LHD indicating concomitant iron deficiency. Hepcidin was inappropriately normal or increased in the IDA and ACD group. Mean hepcidin was however lower in the group with IDA (4.8 ng/mL) than in the ACD group (15.0 ng/mL; p=0.002). Median hepcidin was lower in patients with ACD and iron restriction as indicated by LHD >4% (17.5 ng/mL) than on those with no iron restriction (25.9 ng/mL; p=0.045). In patients with ACD there was no concordance between Perls stain and LHD. Conclusions LHD was superior to hepcidin and bone marrow iron stores in identifying patients with ACD and associated iron deficiency, which would potentially benefit from parenteral iron therapy.