The use of neurone specific enolase to prognosticate neurological recovery and long term neurological outcomes in OOHCA patients.

Introduction: Hypoxic-ischaemic brain injury (HIBI), is a common sequalae following out-of-hospital cardiac arrest (OOHCA), it is reported as the cause of death in 68% of patients who survive to ICU admission, while other patients can be left with permanent neurological disability. Prediction of neurological outcome follows a multimodal approach, including use of the biomarker, neurone specific enolase (NSE). There is however no definitive cut-off value for poor neurological outcome, and little research has analysed NSE and long-term outcomes in survivors. We investigated an NSE threshold for poor short-term neurological outcome and the relationship between NSE and poor neurological outcome in survivors. Methods: A retrospective study was conducted of all adult OOHCA patients admitted to the Royal County Sussex Hospital ICU between April 2017 and November 2018. NSE levels, Targeted Temperature Management (TTM), cross-sectional imaging, mortality and GCS on ICU discharge were recorded. Assessment of neurological function after a median of 19 months (range 14-32 months) post ICU discharge was undertaken following ICU discharge and related to NSE. Results: NSE levels were measured in 59 patients; of these 36 (61%) had a poor neurological outcome due to hypoxic ischaemic brain injury. Youden's index and ROC analysis established an NSE cut-off value of 64.5 µg/L, with AUC of 0.901, sensitivity of 77.8% and specificity of 100%. Follow-up of 26 survivors after 19 months did not show a significant relationship between NSE after OOHCA and long-term neurological outcome. Conclusion: Our results show that NSE >64.5 µg/L has a poor short-term neurological outcome with 100% specificity. Whilst limited by a low sample size, NSE in survivors showed no relationship with neurological outcome post OOHCA in the long term.

Mortality and readmission rates of patients discharged in-hours and out-of-hours from a British ICU over a 3-year period.

Excess in-hospital mortality following out-of-hours ICU discharge has been reported worldwide. From preliminary data, we observed that magnitude of difference may be reduced when patients discharged for end-of-life care or organ donation are excluded. We speculated that these patients may be disproportionately discharged out-of-hours, biasing results. We now compare in-hospital mortality and ICU readmission rates following discharge in-hours and out-of-hours over 3 years, excluding discharges for organ donation or end-of-life care. This single-centre retrospective study includes patients discharged alive following ICU admission between 01/07/2015-31/07/2018, excluding readmissions and discharges for end-of-life care/organ donation. A multiple logistic regression model was fitted to estimate adjusted odds ratio of death following out-of-hours versus in-hours discharge. Characteristics and outcomes for both groups were compared. 4678 patients were included. Patients discharged out-of-hours were older (62 vs 59 years, p < 0.001), with greater APACHE II scores (15.7 vs 14.4, p < 0.001), length of ICU stay (3.25 vs 3.00 days, p = 0.01) and delays to ICU discharge (736 vs 489 min, p < 0.001). No difference was observed in mortality (4.6% vs 3.7%, p = 0.25) or readmission rate (4.1% vs 4.2%, p = 0.85). In the multiple logistic regression model out-of-hours discharge was not associated with in-hospital mortality (OR = 1.017, 95% CI 0.682-1.518, p = 0.93). Our findings present a possible explanation for reported excess mortality following out-of-hours ICU discharge, related to inclusion of organ donation and end-of-life care patients in data sets rather than standards of care delivered out-of-hours. We are not aware of any other studies investigating the influence of this group on reported post-ICU mortality rates.

A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis.

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uraemic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins. Small and large monoliths were synthesised using an optimised ratio of lignin binder to porous resin of 1 in 4. Small monoliths showing combined significant IS, p-CS and IL-6 adsorption were used to measure haemocompatibility in an ex vivo healthy donor blood perfusion model, assessing coagulation, platelet, granulocyte, T cells and complement activation, haemolysis, adsorption of electrolytes and plasma proteins. The small monoliths were tested in a naive rat model and showed stable blood gas values, blood pressure, blood biochemistry and the absence of coagulopathies. These monoliths were scaled up to a clinically relevant size and were able to maintain adsorption of protein bound uraemic toxins IS, PCS and high molecular weight cytokines TNF-α and IL-6 over 240 min using a flow rate of 300 ml min-1 without platelet activation. The nanoporous monoliths where haemocompatible and retained adsorptive efficacy on scale up with negligible pressure drop across the system indicating potential for use as an in-line device to improve haemodialysis efficacy by adsorption of otherwise poorly removed uraemic toxins.

A snapshot summary of consultant cover and current working practices in Intensive Care Medicine across the United Kingdom.

A challenge lies ahead in ensuring that consultant workforce planning within Intensive Care Medicine meets changing and expanding health care needs at a time of financial constraint. During the development of an enlarging consultant intensivist workforce, it is important to explore existing practices to ensure subsequent contracts provide optimal work intensity and on-call frequency as well as appropriate SPA time for clinical governance and professional development. We conducted a survey across 14 deaneries, 43 ICUs and 398 consultant job plans to compare current working practices and set these against new guidelines and standards. It demonstrated that 93% of consultants work 10 PAs or more, with an average of 5.14 Direct Clinical Care PAs in Intensive Care and an average of 2.14 SPAs. Seven of 43 ICUs had consultant-to-patient ratios greater than 1:8 and 33 ICUs had insufficient resident cover overnight, highlighting challenges with trainee staffing and anticipated service reconfiguration.

An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis.

Adsorbents designed with porosity which allows the removal of protein bound and high molecular weight uraemic toxins may improve the effectiveness of haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated carbon monolith prototype designed for direct blood contact was first assessed for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p-cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked healthy donor studies. Haemodialysis patient blood samples were then used to measure the presence of these markers in pre- and post-dialysis blood and their removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20-100 nm) were necessary for marker uraemic toxin removal during in vitro studies. Limited removal of IS and p-CS occurred during haemodialysis, whereas almost complete removal occurred following perfusion through the carbon monoliths suggesting a key role for such adsorbent therapies in CKD patient care.

Our study 20 years on: a randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.

INTRODUCTION: Goal-directed perioperative therapy (GDT) is now part of a number of international perioperative protocols and, to some extent, seems to have come of age, but no research takes place in isolation and it is valuable to retrospectively look at influential papers to understand the context and influences of the time the research was undertaken. METHODS: One of the earliest publication of a randomised trial of GDT was a study we published 20 years ago in 1993, with co-author Professor E. David Bennett. In this article we describe the work leading up to our research, and look at the historical context of our study and choices we made in designing a protocol. CONCLUSION: With 20 years of hindsight we consider the issues that have arisen following our study and place this into the whole of the debate around the use of GDT.

Serum proteins modulate lipopolysaccharide and lipoteichoic acid-induced activation and contribute to the clinical outcome of sepsis.

Bacterial cell wall components, such LPS and LTA, are potent initiators of an inflammatory response that can lead to septic shock. The advances in the past were centered around membrane-bound receptors and intracellular events, but our understanding of the initial interactions of these bacterial components with serum proteins as they enter the bloodstream remain unclear. In this study we identified several serum proteins, which are involved in the innate recognition of bacterial products. Using affinity chromatography and mass spectrometry we performed proteomic analysis of LPS- and LTA-binding serum proteins. We isolated proteins from normal serum that can interact with LPS and LTA. Fluorescent binding experiments and cytokine assays revealed that serum proteins, such as apolipoprotein, LDL, transferrin and holotransferrin could neutralize LPS/LTA binding as well as the subsequent inflammatory response, suggesting that serum proteins modulate LPS/LTA-induced responses. When compared with the proteomic profile of serum from septic patients it was shown that these proteins were in lower abundance. Investigation of serum proteins in 25 critically ill patients with a mortality rate of 40% showed statistically higher levels of these proteins in survivors. Patients surviving sepsis had statistically significant higher levels of apolipoprotein, albumin, LDL, transferrin and holotransferrin than individuals that succumbed, suggesting that these proteins have an inhibitory effect on LPS/LTA-induced inflammatory responses and in their absence there might be an augmented inflammatory response in sepsis.

Haemodynamic optimisation: are we dynamic enough?

Perioperative haemodynamic optimisation of high-risk surgical patients has long been documented to improve both short-term and long-term outcomes, as well as to reduce the rate of postoperative complications. Based on the evidence, cardiac output monitoring and fluid resuscitation, combined with the use of inotropes, would seem to be the gold standard of care for these difficult surgical cases. However, clinicians do not universally apply these techniques and principles in their everyday practice. By exploring the reasons why this is so, perhaps we could move forward in the standardisation of care and the application of evidence-based practice.

Goal-directed therapy in high-risk surgical patients: a 15-year follow-up study.

PURPOSE: Goal-directed therapy in the perioperative setting has been shown to be associated with short-term improvements in outcome. This study assesses the longer-term survival of patients from a previous randomized controlled trial of goal-directed therapy in high-risk surgical patients. METHODS: All patients from a previous randomized controlled study were followed up for 15 years following randomization to ascertain their length of survival following surgery. Factors that may be associated with increased survival were evaluated to determine what influenced long-term outcomes. RESULTS: Data from 106 of the original 107 patients (99%) were available for analysis. At 15 years, 11 (20.7%) of the goal-directed therapy patients versus 4 (7.5%) of the control group were alive (p = 0.09). Median survival for the goal-directed group was increased by 1,107 days (1,781 vs. 674 days, p = 0.005). Long-term survival was associated with three independent factors: age [hazard ratio (HR) 1.04 (1.02-1.07), p < 0.0001], randomization to the goal-directed group of the study [HR 0.61 (0.4-0.92), p = 0.02], and avoidance of a significant postoperative cardiac complication [HR 3.78 (2.16-6.6), p = 0.007]. CONCLUSIONS: Long-term survival after major surgery is related to a number of factors, including patient age and avoidance of perioperative complications. Short-term goal-directed therapy in the perioperative period may improve long-term outcomes, in part due to its ability to reduce the number of perioperative complications.

Quality of life and persisting symptoms in intensive care unit survivors: implications for care after discharge.

BACKGROUND: We assessed the quality of life of ICU survivors using SF-36 at 4 months after ICU discharge and investigated any correlation of PCS and MCS with age, illness severity and hospital or ICU length of stay. We examined the relationship between these variables, persisting physical and psychological symptoms and the perceived benefit of individual patients of follow-up. FINDINGS: For one year, adult patients admitted for multiple organ or advanced respiratory support for greater than 48 hours to a 16-bedded teaching hospital general intensive care unit were identified. Those surviving to discharge were sent a questionnaire at 4 months following ICU discharge assessing quality of life and persisting symptoms. Demographic, length of stay and illness severity data were recorded. Higher or lower scores were divided at the median value. A two-tailed Students t-test assuming equal variances was used for normally-distributed data and Mann-Whitney tests for non-parametric data.87 of 175 questionnaires were returned (50%), but only 65 had sufficient data giving a final response rate of 37%. Elderly patients had increased MCS as compared with younger patients. The PCS was inversely related to hospital LOS. There was a significant correlation between the presence of psychological and physical symptoms and desire for follow-up. CONCLUSION: Younger age and prolonged hospital stay are associated with lower mental or physical quality of life and may be targets for rehabilitation. Patients with persisting symptoms at 4 months view follow-up as beneficial and a simple screening questionnaire may identify those likely to attend outpatient services.

Computer says 2.5 litres--how best to incorporate intelligent software into clinical decision making in the intensive care unit?

What will be the role of the intensivist when computer-assisted decision support reaches maturity? Celi's group reports that Bayesian theory can predict a patient's fluid requirement on day 2 in 78% of cases, based on data collected on day 1 and the known associations between those data, based on observations in previous patients in their unit. There are both advantages and limitations to the Bayesian approach, and this test study identifies areas for improvement in future models. Although such models have the potential to improve diagnostic and therapeutic accuracy, they must be introduced judiciously and locally to maximize their effect on patient outcome. Efficacy is thus far undetermined, and these novel approaches to patient management raise new challenges, not least medicolegal ones.

Sedation practice: is it time to wake up and embrace change?

Recommendations for sedation regimes in the intensive care unit (ICU) have evolved over the last decade based on findings that relate the clinical approach to improved patient outcomes. Martin and co-workers conducted two surveys into German sedation practice covering the time period during which these changes occurred and as such provide an insight into how these recommendations are being incorporated into everyday clinical practice.

Perioperative goal directed haemodynamic therapy--do it, bin it, or finally investigate it properly?

The literature concerning the use of goal directed haemodynamic therapy (GDHT) in high risk surgical patients has been importantly increased by the study of Lopes and colleagues. Using a minimally invasive assessment of fluid status and pulse pressure variation monitoring during mechanical ventilation, improvements were seen in post-operative complications, duration of mechanical ventilation, and length of hospital and intensive care unit (ICU) stay. Many small studies have shown improved outcome using various GDHT techniques but widespread implementation has not occurred. Those caring for perioperative patients need to accept the published evidence base or undertake a larger, multi-centre study.

How is risk defined in high-risk surgical patient management?

The definition of risk in surgical patients is a complex and controversial area. Generally risk is poorly understood and depends on past individual and professional perception, and societal norms. In medical use the situation is further complicated by practical considerations of the ease with which risk can be measured; and this seems to have driven much risk assessment work, with a focus on objective measurements of cardiac function. The usefulness of risk assessment and the definition of risk is however in doubt because there are very few studies that have materially altered patient outcome based on information gained by risk assessment. This paper discusses these issues, highlights areas where more research could usefully be performed, and by defining limits for high surgical risk, suggests a practical approach to the assessment of risk using risk assessment tools.