Akshay Shah

Evidence and triggers for the transfusion of blood and blood products.

Allogeneic red cell transfusion is a commonly used treatment to improve the oxygen carrying capacity of blood during the peri‐operative period. Increasing arterial oxygen content by increasing haemoglobin does not necessarily increase tissue oxygen delivery or uptake. Although the evidence‐base for red cell transfusion practice is incomplete, randomised studies across a range of clinical settings, including surgery, consistently support the restrictive use of red cells, with no evidence of benefit for maintaining patients at higher haemoglobin thresholds (liberal strategy). A recent meta‐analysis of 7593 patients concluded that a restrictive transfusion strategy was associated with a reduced risk of healthcare‐associated infections (pneumonia, mediastinitis, wound infection, sepsis) when compared with a liberal transfusion strategy. The degree to which the optimal haemoglobin concentration or transfusion trigger should be modified for patients with additional specific risk factors (e.g. ischaemic heart disease), remains less clear and requires further research. Although most clinical practice guidelines recommend restrictive use of red cells, and many blood transfusion services have seen marked falls in overall usage of red cells, the use of other blood components such as fresh frozen plasma, platelets, and cryoprecipitate has risen. In clinical practice, administration of fresh frozen plasma is usually guided by laboratory tests of coagulation, mainly prothrombin time, international normalised ratio and activated partial thromboplastin time, but the predictive value of these tests to predict bleeding is poor.

Ultrasound-guided subclavian venous catheterisation – is this the way forward? A narrative review

Central venous catheterisation is a commonly performed procedure in anaesthesia, critical care, acute and emergency medicine. Traditionally, subclavian venous catheterisation has been performed using the landmark technique and because of the complications associated with this technique, it is not commonly performed in the United Kingdom – where the accepted practice is ultrasound‐guided internal jugular vein catheterisation. Subclavian vein catheterisation offers particular advantages over the internal jugular and femoral vein sites such as reduced rates of line‐related sepsis, improved patient comfort and swifter access in trauma situations where the internal jugular vein may not be easily accessible. There is a growing body of evidence to suggest a potential emerging role for ultrasound‐guided subclavian vein catheterisation. Barriers to this approach include many physicians still believing that the clavicle obscures imaging of the vein. In this article, we review the evidence supporting ultrasound‐guided subclavian vein catheterisation and ask the question whether, in view of it potential advantages, it could be the way forward?

Fresh versus old red cell transfusions: what have the recent clinical trials found?

Purpose of reviewRed blood cell transfusion is a common treatment for anaemia worldwide, but concerns continue to be raised about adverse effects of cellular blood components, which are biological products. One hypothesis for the adverse effects associated with blood transfusion is the harmful effects of storage on red cells that have been demonstrated in laboratory and animal studies. Over the past few years, a number of more significant randomized controlled trials comparing ‘fresh’ versus ‘older’ blood have been published in an attempt to address the clinical consequences of storage age, with two further large trials ongoing. Recent findingsThese recent trials enrolled approximately 4000 participants across a variety of populations – cardiac surgical, critically ill, paediatric and acute hospitalized in-patients. All trials achieved statistically significant separation of red cell storage duration between both groups. The results of all these trials have found no clinical benefit to using fresher red cells when compared with older or standard-issue red cells. However, certain subgroups of patients either receiving red cells stored at more extreme ages of storage or those with additional risks for impaired microcirculations (critically ill elderly, severe sepsis and major haemorrhage) were either underrepresented or not included in these trials. SummaryAt present, on the basis of recent trials, there is no indication for blood transfusion services to implement preferential utilization of fresher red cell units.

Use of Plasma for Acquired Coagulation Factor Deficiencies in Critical Care.

Coagulopathy in critically ill patients is common and often multifactorial. Fresh frozen plasma (FFP) is commonly used to correct this either prophylactically or therapeutically. FFP usage is mainly guided by laboratory tests of coagulation, which have been shown to have poor predictive values for bleeding. Viscoelastic tests are an attractive option to guide hemostatic therapy, but require rigorous evaluation. The past few years have seen a gradual reduction in national use of FFP potentially due to an increased awareness of risks such as transfusion-related acute lung injury, patient blood management strategies to reduce transfusion in general, and increased awareness of the lack of high-quality evidence available to support FFP use. Within critical care, FFP is administered before invasive procedures/surgery, to treat major traumatic and nontraumatic hemorrhage, disseminated intravascular coagulation, and for urgent warfarin reversal if first-line agents, such as prothrombin complex concentrate (PCC) are not available. Alternative agents such as fibrinogen concentrate and PCC need further evaluation through large-scale clinical trials.

Serum hepcidin potentially identifies iron deficiency in survivors of critical illness at the time of hospital discharge

Anaemia is common in patients admitted to and discharged from intensive care (ICU) and is associated with poor quality of life in ICU survivors (Walsh et al, 2010; Lasocki et al, 2014). The majority of ICU patients will have an anaemia of inflammation (AI) as a collective result of functional iron deficiency, leading to iron restricted erythropoiesis, increased cytokine production, suppressed bone marrow activity and reduced red blood cell life span (Lasocki et al, 2010). Identifying iron deficiency in this context is challenging because commonly used tests, such as ferritin and transferrin saturation, are significantly confounded by inflammation. Hepcidin is a circulating polypeptide, which, via its inhibitory action on the key iron exporter ferroportin, acts as a key regulator in iron homeostasis (Girelli et al, 2016). Inhibition of ferroportin results in retention of iron within enterocytes, macrophages and hepatocytes with a consequent decrease in serum iron levels, thereby restricting its availability for erythropoiesis. Hepcidin expression is increased by inflammation and iron overload but reduced in iron deficiency, hypoxia and enhanced erythropoietic drive. Elevated hepcidin levels restricting the use of iron, along with suppressed bone marrow function, may partly explain why trials of iron supplementation in the acute phase of critical illness have not shown any benefit (Litton et al, 2016; Shah et al, 2016). Hepcidin may be a better marker of iron deficiency (or requirement for iron) than the routine biochemical assays in current use, allowing more precise identification of anaemic patients likely to respond to iron therapy (Girelli et al, 2016). In order to identify a potential cohort of patients who would probably respond [i.e. increase haemoglobin (Hb) concentration] to iron supplementation, we investigated the utility of serum hepcidin concentrations of ICU survivors at hospital discharge. Patients recruited to the RECOVER (Evaluation of a Rehabilitation Complex Intervention for Patients Following Intensive Care Discharge) trial and who consented to a biomarker sub-study were eligible (Walsh et al, 2015). RECOVER was a randomized controlled trial examining the effect of a complex rehabilitation package on physical outcome in ICU survivors. Laboratory tests recorded included Hb concentration, serum creatinine, albumin and C-reactive protein (CRP). Serum hepcidin was measured by enzyme-linked immunosorbent assay (ELISA) (hepcidin-25 high sensitivity ELISA, DRG Instruments, Marburg, Germany). Other markers of iron status and erythropoiesis, such as ferritin, serum iron, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), erythropoietin, vitamin B12 and folate, were also analysed. Anaemia was defined according to World Health Organization (WHO) guidelines: males Hb <130 g/l and females Hb <120 g/l. A ferritin cut-off of <15 lg/l was used to diagnose iron deficiency anaemia (WHO, 2001). In the presence of inflammation (defined as CRP >8 mg/l), a ferritin cut-off of 150 lg/l was used to differentiate between combined anaemia of iron deficiency and inflammation (IDI) (ferritin <150 lg/l) and AI (ferritin >150 lg/l) as previous reported (Lee et al, 2002). Baseline characteristics are shown in Table 1. Median (interquartile range, IQR) CRP for the entire cohort was 36 (15–72) mg/l, reflecting ongoing inflammation even at hospital discharge. 110/117 (94%) patients were anaemic with a CRP of >8 mg/l prior to hospital discharge. Of these, 89/110 (81%) had AI and 11/110 (10%) had IDI (Table 2). 10 patients developed anaemia that appeared unrelated to iron, B12, and/or folate deficiency or inflammation. Laboratory results are shown in Table 2. Median (IQR) serum hepcidin concentration was significantly lower in the IDI group and there was no statistical difference in CRP concentrations between both groups, indicating the difference in hepcidin values may not reflect a higher level of inflammation in the AI group. Levels of the sTfR-ferritin index, another potential marker of iron deficiency in inflammation, were higher in the IDI group and linear regression of (log) sTfR-ferritin index with (log) hepcidin showed a strong association (co-efficient 0 8, P < 0 001). There were no significant differences in age, illness severity, Hb and renal function between both groups. The maximal Youden index was achieved at a hepcidin cut-off of <19 ng/ml, with a sensitivity of 73% and specificity of 74%. Using current definitions of iron deficiency, 11/110 patients would be considered eligible for oral iron replacement. Applying a hepcidin cut-off <19 ng/ml, a further 24 patients would be included, raising this to 32% of the anaemic cohort. This study has confirmed a high prevalence of anaemia at time of hospital discharge in ICU survivors (Walsh et al, 2010). While inflammatory processes are still active in this patient group, as evidenced by the raised median CRP in the correspondence

Recurrent Acute Severe Pulmonary Oedema as a Presentation of Carcinoid Crisis following Cardiac Surgery

This is a case report of a 75-year-old patient with a pelvic carcinoid tumour who had valve replacements and a patent foramen ovale repair. Her postoperative course was complicated by persistent symptoms related to the carcinoid tumour. Pathophysiology and management are reviewed. Cardiac surgery for carcinoid heart surgery has significantly high morbidity and mortality. Common complications include cardiovascular instability, bronchospasm, complete heart block, gastrointestinal hypermotility and acute kidney injury. Acute pulmonary oedema can be a presenting feature of a carcinoid crisis and should be suspected in the differential diagnoses of pulmonary oedema in carcinoid heart disease patients. Octreotide remains the mainstay of treatment. Doses of up to a maximum of 200 μg/hour can be used. There is emerging evidence that catecholamines can be used safely when used in conjunction with octreotide. Good analgesia is important in suppressing sympathetic stimulation.

Barriers to a career in intensive care medicine

Intensive care medicine (ICM) is an under-resourced area of the medical workforce that has traditionally been viewed as a difficult, demanding career of limited time frame but current legislation requires career intensivists to undergo specialist training. The most recent position paper of the FICM Workforce Advisory Group found that the demand for ICM services, from 2013–2035, is projected to increase from anywhere between 25% and 125%. This will require a proportionate increase in the number of both training and consultant posts.

604: PREVALENCE AND MANAGEMENT OF ANAEMIA IN ICU SURVIVORS: A RETROSPECTIVE STUDY.

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) Learning Objectives: Red blood cell transfusions are commonly used in critically ill children. The benefit of transfusions remains the subject of much controversy. According to current literature, lower transfusion thresholds are well tolerated in critically ill stabilized patients. With this study, we aim to study the impact of a publication (TRIPICU 2007) on transfusion practice in our Institution. Methods: Single center retrospective chart review of patients admitted to a tertiary pediatric intensive care unit (PICU) receiving a blood transfusion over 2 time periods: before TRIPICU (2005-2006, period 1) and after TRIPICU (2008-2009, period 2). Inclusion criteria were those of TRIPICU study (no volume resuscitation nor change in inotropic support in the last 2 hours prior to transfusion).Variables of interest included: body weight, age,diagnosis and evaluation of hemodynamic status at the time of transfusion: systolic blood pressure, inotrope use and/or their escalation and volume resuscitation. We identified the overall mean hemoglobin (Hb) before transfusion, the proportion of patients transfused with Hb>9.5g/dL and the transfusion dose (ml/kg) in those 2 time periods.We also measured PICU mortality during these two periods (28-day mortality in the TRIPICU study was 4.3%). Results: From 545 transfused patients, 243 met inclusion criteria: 146 patients in period 1 and 97 in period 2. Median age was 5.2 years and weight 16.85kg. There was no significant difference between mean Hb before transfusion in period 1 (8.1 ± 2.0 g/dL) and in period 2 (8.0 ± 1.5 g/dL, p= 0.58).In period 1, 22% of patients were transfused with Hb>9.5g/dL and 15.4 % in period 2 (p=0.20). Mean transfusion dose in period 1 was 12 ± 9 ml/kg and 11 ± 8 ml/kg in period 2 (p =0.32). Mortality in period 1 was 11.5% and 15.4% in period 2 (p=0.38). Conclusions: In our institution, the publication of the TRIPICU study did not farther contribute to decrease the transfusion thresholds, as they were already very restrictive. The relationship between these thresholds and the higher mortality in our population compared to the TRIPICU population must be further explored.

Using serum hepcidin to identify iron deficiency in previously critically ill patients at time of hospital discharge

Introduction: Over the last 25 years there has been significant work carried out in producing risk prediction models for patients admitted to critical care units. The most recent of these models is the Intensive Care National Audit and Research Centre (ICNARC) model developed in 2007 (1) which uses data from 231,930 admissions to 163 critical care units to develop and validate a UK based model outperforming other approaches (with an average c index of 0.863). Aims: This research aims to present an artificial neural network based model for critical care admissions that improves over the ICNARC model in terms of the discrimination across the data set used in this study. Results: Figure 1 shows a comparison between the receiver operator characteristics (ROC) curve for our artificial neural network (ANN) model and the ICNARC model presented in (1). This figure shows the ROC curve and point-wise confidence intervals for the true positive values of both our model (in blue) and the ICNARC model (in red). In comparison, our artificial neural network classification model produces an average c value of 0.8983 in 10 fold cross validation of our data compared to a c value of 0.8306 for the ICNARC model using the same data set (consisting of 642 patients admitted to North Middlesex Hospital critical care unit over a 28 month period. Data excludes 432 patients where data was incomplete). Conclusion: Our classification model provides a percentage risk score that outperforms the ICNARC model. This classification model does suffer from some of same issues surrounding the ICNARC model – for instance, the influence of some of the parameters within both models can be unclear to clinicians trying to predict the survival of individual patients. However, further work is ongoing to improve the transparency of this model

Postoperative morbidity after surgical aortic valve replacement or transcatheter valve implantation: a prospective cohort study

Postoperative morbidity after surgical aortic valve replacement or transcatheter valve implantation: a prospective, cohort study. Dr. Akshay Shah, Cardiac Intensive Care Unit, The Heart Hospital, UCLH, London, United Kingdom (Corresponding author) Dr. Helen Brambley, Cardiac Intensive Care Unit, The Heart Hospital, UCLH, London, United Kingdom Mr. Miles Curtis, The Heart Hospital, UCLH, London, United Kingdom Dr. Michael Mullen, The Heart Hospital, UCLH, London, United Kingdom Ms. Nicola Delahunty, The Heart Hospital, UCLH, London, United Kingdom Mr. John Yap, Cardiac Intensive Care Unit, The Heart Hospital, UCLH, London, United Kingdom Dr. Andrew Smith, Cardiac Intensive Care Unit, The Heart Hospital, UCLH, London, United Kingdom Professor Hugh Montgomery, UCL Institute for Human Health and Performance, University College London, London, United Kingdom Dr. Julie Sanders, UCL Institute for Human Health and Performance, University College London, London, United Kingdom