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 $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.

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

To model lung nitric oxide (NO) and carbon monoxide (CO) uptake, a membrane oxygenator circuit was primed with horse blood flowing at 2.5 l/min. Its gas channel was ventilated with 5 parts/million NO, 0.02% CO, and 22% O2 at 5 l/min. NO diffusing capacity (Dno) and CO diffusing capacity (Dco) were calculated from inlet and outlet gas concentrations and flow rates: Dno = 13.45 ml.min(-1).Torr(-1) (SD 5.84) and Dco = 1.22 ml.min(-1).Torr(-1) (SD 0.3). Dno and Dco increased (P = 0.002) with blood volume/surface area. 1/Dno (P < 0.001) and 1/Dco (P < 0.001) increased with 1/Hb. Dno (P = 0.01) and Dco (P = 0.004) fell with increasing gas flow. Dno but not Dco increased with hemolysis (P = 0.001), indicating Dno dependence on red cell diffusive resistance. The posthemolysis value for membrane diffusing capacity = 41 ml.min(-1).Torr(-1) is the true membrane diffusing capacity of the system. No change in Dno or Dco occurred with changing blood flow rate. 1/Dco increased (P = 0.009) with increasing Po2. Dno and Dco appear to be diffusion limited, and Dco reaction limited. In this apparatus, the red cell and plasma offer a significant barrier to NO but not CO diffusion. Applying the Roughton-Forster model yields similar specific transfer conductance of blood per milliliter for NO and CO to previous estimates. This approach allows alteration of membrane area/blood volume, blood flow, gas flow, oxygen tension, red cell integrity, and hematocrit (over a larger range than encountered clinically), while keeping other variables constant. Although structurally very different, it offers a functional model of lung NO and CO transfer.

A Randomized Controlled Trial of High-Flow Nasal Oxygen (Optiflow) as Part of an Enhanced Recovery Program After Lung Resection Surgery.

BACKGROUND: Patients undergoing thoracic surgery are at risk of postoperative pulmonary complications, which are associated with increased morbidity and mortality. High-flow nasal oxygen therapy delivers humidified, warmed positive airway pressure but has not been tested routinely after thoracic surgery. METHODS: We performed a randomized, controlled, blinded study. Patients undergoing elective lung resection were randomly assigned to either high-flow nasal oxygen or standard oxygen therapy. Patients were otherwise treated within an established enhanced recovery program. The primary outcome was the difference between the preoperative and postoperative 6-minute walk test. Secondary outcomes included hospital length of stay, spirometry, and patient-reported outcomes measured using the Postoperative Quality of Recovery Scale. RESULTS: Fifty-nine patients were randomly assigned to either high-flow nasal oxygen (n = 28) or standard oxygen (n = 31) therapy. We found no difference in the 6-minute walk test outcome or spirometry; however, length of hospital stay was significantly lower in the high-flow nasal oxygen group, median 2.5 days (range, 1 to 22), compared with the standard oxygen group, median 4.0 days (range, 2 to 18); geometric mean ratio was 0.68 (95% confidence interval: 0.48 to 0.86, p = 0.03). No significant differences in recovery domains were found, but patients in the high-flow nasal oxygen group reported significantly higher satisfaction (p = 0.046). CONCLUSIONS: Prophylactic high-flow nasal oxygen therapy, when incorporated into an enhanced recovery program, did not improve 6-minute walk test results but was associated with reduced length of hospital stay and improved satisfaction after lung resection, compared with standard oxygen. This finding has implications for reduced costs and better service provision, and a multicenter trial powered for length of stay is required.

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

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.

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 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 Perl's 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.

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

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.

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

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.

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