Caroline Gerrard

The Papworth Bleeding Risk Score: a stratification scheme for identifying cardiac surgery patients at risk of excessive early postoperative bleeding

OBJECTIVE We have developed a risk stratification score to identify cardiac surgical patients at higher risk of severe postoperative bleeding to aid a decision of whether to use a specific intervention preoperatively. METHODS We prospectively created a database of 11592 consecutive patients, who underwent cardiac surgery with cardiopulmonary bypass. An adverse outcome was formally defined as a mean blood loss exceeding 2 ml kg(-1)h(-1) measured between arrival in the intensive care unit (ICU) and the earliest of the elapse of 3h; the start of transfusion of any one of fresh-frozen plasma, platelets or cryoprecipitate; return to theatre or death. Univariate and multivariate associations of severe postoperative bleeding with patient characteristics, clinical features and procedure details were analysed on a development set. The final risk stratification scheme was then evaluated on a test set. RESULTS Severe postoperative bleeding was associated with urgent or emergency surgery, surgery that was not coronary artery bypass grafting or single valve surgery, presence of aortic valve disease, low body mass index and older age. A risk stratification score was constructed from the above variables to define preoperative categories that demonstrated high, medium and low risk of severe postoperative bleeding. Patients deemed to be at high, medium and low risk by our preoperative scoring had a 21% (95% confidence interval: 18-24%), 8% (7-10%) and 3% (2-4%) rate of severe postoperative bleeding, respectively, within the test set. CONCLUSION We have developed a simple risk stratification score that can separate, preoperatively, patients into risk groups with markedly different rates of severe postoperative bleeding.

An Exploratory Cohort Study Comparing Prothrombin Complex Concentrate and Fresh Frozen Plasma for the Treatment of Coagulopathy After Complex Cardiac Surgery

BACKGROUND:Administration of coagulation factor concentrates to treat bleeding after cardiac surgery with cardiopulmonary bypass might be a strategy for reducing allogeneic blood transfusions, particularly for patients treated with warfarin preoperatively. We performed an exploratory analysis on whether the use of prothrombin complex concentrate (PCC) is safe and effective compared with fresh frozen plasma (FFP) to treat coagulopathy after pulmonary endarterectomy surgery with deep hypothermic circulatory arrest. METHODS:Consecutive adult patients who underwent pulmonary endarterectomy surgery between January 2010 and September 2012 and received PCC or FFP to treat coagulopathy were studied. Blood loss during the first 12 hours of admission to the intensive care unit and patient outcomes were compared with propensity score adjustment. RESULTS:Three hundred fifty-one patients underwent pulmonary endarterectomy surgery, all of whom had warfarin discontinued for up to 5 days before surgery; bleeding complications requiring transfusion of blood products were observed in 108 (31%) patients. Of those, 55 received only FFP and 45 received only PCC, whereas 8 received both. Blood loss was significantly greater in the FFP group compared with the PCC group after 12 hours (median [interquartile range], 650 mL [325–1075] vs 277 mL [175–608], P = 0.008). However, there was no difference in the frequency of patients receiving a red blood cell transfusion (number [percent], 44 [80%] vs 34 [76%], P = 0.594) or in the number of units of red blood cells transfused (median [interquartile range], 2 [1–4] vs 3 [1–5] units, P = 0.181). The final propensity score included preoperative international normalized ratio, postoperative activated partial thromboplastin time, and postoperative platelet count. After inclusion of the propensity score in the regression analyses, there were no differences between patients receiving only PCC and patients receiving only FFP in the need for renal replacement therapy (odds ratio [OR] 2.39, 95% confidence interval [CI] 0.51–11.20, P = 0.27), 30-day-mortality (OR 0.32, 95% CI 0.03–3.36, P = 0.35), intracranial hemorrhage (OR 0.73, 95% CI 0.14–3.89, P = 0.71), hospital length of stay (hazard ratio 0.77, 95% CI 0.50–1.19, P = 0.24), or duration of intensive care stay (hazard ratio 0.91, 95% CI 0.59–1.40, P = 0.66). CONCLUSIONS:This retrospective analysis suggests that PCC may be an alternative to FFP in patients previously treated with warfarin who are coagulopathic after major cardiac surgery. Randomized controlled studies powered to evaluate efficacy and important postoperative outcomes for patients receiving PCC versus FFP for coagulopathic bleeding after cardiopulmonary bypass are warranted.

Survival and length of stay following blood transfusion in octogenarians following cardiac surgery.

Our aim was to assess if peri‐operative blood transfusion is an independent risk factor for mortality and morbidity in the elderly. We report the results of a cohort study of all patients aged 80 or more on the day of their emergency or elective cardiac surgery (n = 874), using routinely collected data from January 2003 to November 2007. The primary outcome was all‐cause mortality in hospital. The secondary outcomes were duration of stay in the intensive care unit (ICU) and overall hospital stay. Confounding variables were used to build up a risk model using a multivariable logistic regression analysis, and blood transfusion was added to assess whether it had additional predictive value for hospital mortality. Patients were divided into three groups: (i) transfusion of 0–2 units of red blood cells; (ii) transfusion of > 2 units of red blood cells and (iii) transfusion of red blood cells plus other clotting products. The strongest independent predictors of hospital death were logistic EuroSCORE and body mass index. After inclusion of these two variables, the odds ratio for transfusion remained significant. Relative to 0–2 units, the odds ratio for > 2 units was 6.80 (95% CI 2.46–18.8), and for other additional blood products was 14.4 (95% CI 5.34–37.3), with a p value of < 0.001. Duration of stay in the ICU was significantly associated with the amount of blood products administered (median (IQR [range]) ICU stay 1 (1‐2 [0‐15]) day if transfused 0–2 units of red blood cells, 2 (1‐6 [0‐128]) days if transfused > 2 units of red blood cells and 3 (1‐76 [0‐114]) days if other clotting products were used; p value < 0.001). Hospital stay was also associated with the amount of red cells used (p < 0.001).

Postoperative fibrinogen level is associated with postoperative bleeding following cardiothoracic surgery and the effect of fibrinogen replacement therapy remains uncertain

Background: Traditionally, a fibrinogen level > 1 g L−1 has been viewed as the critical plasma concentration required for hemostasis. No definitive trial has investigated the plasma fibrinogen hemostatic threshold and fibrinogen replacement in complex surgical patients with acquired bleeding. Objectives: To explore the plasma fibrinogen level required for hemostasis in cardiothoracic surgery patients and assess the association of fibrinogen replacement therapy (using cryoprecipitate or fibrinogen concentrate) with reducing postoperative bleeding rate. Patients/Methods: Data from a prospectively collated database were used to examine the relationship between postoperative plasma fibrinogen level and the postoperative rate of bleeding within the hour of plasma fibrinogen measurement (n = 430) and to explore the effect of cryoprecipitate infusion (n = 76) or fibrinogen concentrate administration (n = 8) on postoperative bleeding rate. Results: A low plasma fibrinogen level was significantly associated with bleeding, with an odds ratio of 3.06 for every 1 g L−1 decrease in fibrinogen (95% confidence interval 1.05–8.90) with adjustment for confounders. A fibrinogen threshold associated with excess bleeding was not identified, but this relationship was a continuum. There was no reduction in bleeding following administration of cryoprecipitate or fibrinogen concentrate to raise the post‐infusion fibrinogen level to a median of 2.00 and 1.70 g L−1, respectively. Conclusions: There is a continuum of bleeding severity with reducing fibrinogen concentration. Fibrinogen concentrate or cryoprecipitate infusion did not significantly reduce bleeding rate; however, confirmation by a randomized controlled trial is required. It remains uncertain whether low postoperative fibrinogen levels are causally associated with postoperative bleeding.

Prolonged Stay in Intensive Care Unit Is a Powerful Predictor of Adverse Outcomes After Cardiac Operations

BACKGROUND The aim of this study was to examine the impact of prolonged intensive care unit (ICU) stay on in-hospital mortality and long-term survival. METHODS Prospectively collected data from 6,101 consecutive patients who underwent surgery between 2003 and 2007 were analyzed. Prolonged ICU stay was defined as a total duration of ICU stay of 3 days or more postoperatively, including readmissions; patients with an ICU stay less than 3 days were identified as controls. Univariate and multiple variable analyses were performed to identify risk factors associated with prolonged ICU stay. RESULTS Of 6,101 patients, 1,139 (18.7%) patients had a prolonged ICU stay. These patients had a higher ICU mortality (10%) compared with controls (0.6%; p < 0.001). On discharge from the ICU, their hospital mortality was still 6-fold higher (1.2%) compared with controls (0.2%; p < 0.001). Finally, the patients who had prolonged ICU stays had lower survival after discharge from the ICU-89.2% and 81.2% at 1 year and 3 years, respectively, compared with 97.8% and 93.6%, respectively, for controls (p < 0.001). Multiple variable analysis revealed prolonged ICU stay to be an independent predictor of prolonged hospital stay, higher hospital mortality, and poorer long-term survival (all p < 0.001). CONCLUSIONS Prolonged ICU stay is an important predictor of adverse immediate, short-term, and long-term outcomes after cardiac operations.

Safety and Efficacy of Aprotinin and Tranexamic Acid in Pulmonary Endarterectomy Surgery With Hypothermia: Review of 200 Patients

BACKGROUND The effectiveness and safety of aprotinin in cardiac surgery has been questioned. The study aim was to compare both the blood-sparing effect and side effects of aprotinin and tranexamic acid in patients undergoing pulmonary endarterectomy. METHODS Data were analyzed retrospectively for 200 consecutive patients who underwent pulmonary endarterectomy between October 2006 and September 2009. Pulmonary endarterectomy was performed with deep hypothermia (20°C) in all patients. Antifibrinolytic therapy changed from aprotinin to tranexamic acid in June 2008 after the withdrawal of aprotinin in the United Kingdom. RESULTS Mean age was 55.9 years, and 58% of subjects were male. One hundred patients were studied in each group. Postoperatively, a higher incidence of seizures in the first 48 hours was seen with tranexamic acid compared with aprotinin (11% versus 4%, p = 0.06). This difference became statistically significant when excluding patients with structural brain lesions from both groups (7 versus 0, p = 0.02). Tranexamic acid patients had significantly higher median blood loss (700 mL versus 525 mL, p = 0.01). There was no significant difference between the groups in reexploration for bleeding, renal failure requiring hemofiltration, intensive care unit stay, median total stay in hospital, or in-hospital mortality. CONCLUSIONS In our experience of patients undergoing pulmonary endarterectomy, the tranexamic acid group had a higher median blood loss and more seizures. The trend to increased seizure frequency in the tranexamic acid group may be a direct consequence of this treatment, consistent with other recently published reports.

Reducing blood transfusion. BMJ 's cover and headline exaggerated importance of study's findings.

Editor—The randomised controlled trial on mechanical methods of reducing blood transfusion in cardiac surgery by McGill et al is laudable, but we challenge the BMJ for highlighting this paper on the front cover with the headline: “Cell salvage reduces the need for a transfusion.”1 We believe that the journal has a responsibility not to exaggerate the perceived importance of findings, either in press releases or by other means.2 The authors themselves highlighted the main limitations of the study in their discussion, and we believe that such declarations are important safeguards against widespread use of the described methods without further scientific evaluation. The authors comment on the high cost of transfusion, but they did not include a cost analysis in their study. We understand the risks associated with transfusion and agree that these in themselves may justify any added cost. However, introducing strict transfusion guidelines and monitoring their use is certainly a step that should precede the introduction of new equipment. We have been reinforcing transfusion guidelines for the past two years in our institution and are continuously monitoring blood transfusion in our hospital. Interestingly, when looking at a similar patient population to that of McGill et al, but lacking the research methods and statistics, we have achieved a similar decrease in use of all blood products, mainly by insuring that blood is transfused only when required and blood products given when need is documented (table). Despite our programme, blood products are still administered too often outside the hospital guidelines, and we think that we could decrease their use even further before introducing new expensive equipment to our routine practice. The BMJ s cover may only reinforce incorrect practices by encouraging widespread use of techniques without common sense. We agree that the combination of acute normovolaemic haemodilution and cell salvage did not confer any benefit in this study, but McGill et al have not explored acute normovolaemic haemodilution as such and therefore no conclusion can be made with certainty about the absence of benefit of acute normovolaemic haemodilution itself. In the authors own words, this study adds to many others that are inconclusive because of the quality of the evidence. We believe that the BMJ s cover, while attractive, may have mislead readers, and we therefore question the rationale behind such a decision.

The impact of administration of tranexamic acid in reducing the use of red blood cells and other blood products in cardiac surgery

BackgroundTo study the effect of administration of tranexamic acid on the use of blood and blood products, return to theatre for post-operative bleeding and the length of intensive care stay after primary cardiac surgery, data for 4191 patients, of all priorities, who underwent primary cardiac operation during the period between 30/10/00 and 21/09/04 were analysed.MethodsRetrospective analysis of data collected prospectively during the study period. The main outcome measures were whether or not patients were transfused with red blood cells, fresh frozen plasma or any blood product, the proportion of patients returned to theatre for investigation for post-operative bleeding and length of stay in the intensive care unit. We performed univariate analysis to identify the factors influencing the outcome measures and multivariate analysis to identify the effect of administration of tranexamic acid on the outcome measures.ResultsAdministration of tranexamic acid was an independent factor affecting the transfusion of red blood cells, fresh frozen plasma or any blood product. It was also an independent factor influencing the rate of return to theatre for exploration of bleeding. The odds of receiving a transfusion or returning to theatre for bleeding were significantly lower in patients receiving tranexamic acid. The administration of tranexamic acid also significantly decreased blood loss. We did not find any association between the administration of tranexamic acid and the length of intensive care stay.ConclusionBased on the analysis of 4191 patients who underwent a primary cardiac operation, administration of tranexamic acid decreased the number of patients exposed to a transfusion or returned to theatre for bleeding in our institute.

The association between borderline pre-operative anaemia in women and outcomes after cardiac surgery: a cohort study

Anaemia is common before cardiac surgery and is associated with increased morbidity and mortality. The World Health Organization (WHO) definition of anaemia is lower for women than for men by 10 g.l−1, potentially putting women at a disadvantage compared with men with regard to pre‐operative optimisation. Our hypothesis was that women with borderline anaemia (defined by us as haemoglobin concentration 120–129 g.l−1) would have a higher rate of red cell transfusion, morbidity and mortality than non‐anaemic women (haemoglobin ≥ 130 g.l−1). This retrospective observational study included all adult patients admitted for elective cardiac surgery from January 2013 to April 2016. During the study period, 1388 women underwent cardiac surgery. Pre‐operatively, 333 (24%) had a haemoglobin level < 120 g.l−1; 408 (29%) 120–129 g.l−1; and 647 (47%) ≥ 130 g.l−1. Compared with non‐anaemic women, women with borderline anaemia were more likely to be transfused (68.6% vs. 44.5%; RR 1.5, 95%CI 1.4–1.7; p < 0.0001) and were transfused with more units of red cells, mean (SD) 1.8 (2.8) vs. 1.3 (3.0); p < 0.0001. Hospital length of stay was significantly longer in the borderline anaemia group compared with non‐anaemic women, median (IQR [range]) 8 (6–12 [3–45]) vs. 7 (6–11 [4–60]); p = 0.0159. Short‐ and long‐term postoperative survival was comparable in both groups. Borderline anaemia is associated with increased red cell transfusion and prolonged hospital stay. Future research should address whether correction of borderline anaemia results in improved outcomes.

Agreement between ACT and aPTT during extracorporeal membrane oxygenation shows intra- and inter-individual variation

Aim: We explored the relationship between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) when used to monitor anticoagulation in patients undergoing extracorporeal membrane oxygenation (ECMO) support. Methods: Data obtained in patients undergoing ECMO support between October 2012 and August 2013 in a single centre were reviewed. Clinical data were extracted from our Clinical Information System and ECMO database. ACT and aPTT values were paired when taken from the same patient, with the ACT preceding the aPTT and the heparin infusion rate was kept constant between samples. The aPTT and ACT were normalized by dividing by the mean of their respective reference ranges and are referred to as APR and N-ACT, respectively. Bivariate analysis and Bland-Altman plots were used to assess correlation and agreement. Mixed effects regression was used to model the effects of variables, including platelet count, creatinine and urea levels, plasma free haemoglobin, white cell count and ECMO flow rate on concordance between APR and N-ACT measurements. Results: The Pearson product-moment correlation coefficient in 15 patients was calculated as r=0.55. The Bland-Altman plot shows a mean difference between the APR and the N-ACT of −0.08. The 95% limits of agreement were −0.67 to 0.51. Results from mixed effects regression analysis on data from the 15 patients identified platelet count (and thrombocytopenia) and urea as significant independent predictors of concordance between APR and N-ACT. Conclusion: We report a moderate degree of positive correlation between APR and N-ACT. We conclude that there is poor agreement between the ACT and aPTT for the heparin concentrations in patients supported with ECMO. Our results indicate that platelet count and urea are significant independent variables affecting concordance between ACT and aPTT measurements.