Clinical review: How to optimize management of high-risk surgical patients

For many patients optimal perioperative care may require little or no additional medical management beyond that given by the anaesthetist and surgeon. However, the continued existence of a group of surgical patients at high risk for morbidity and mortality indicates an ongoing need to identify such patients and deliver optimal care throughout the perioperative period. A group of patients exists in whom the risk for death and serious complications after major surgery is in excess of 20%. The risk is related mainly to the patient's preoperative physiological condition and, in particular, the cardiovascular and respiratory reserves. Cardiovascular management of the high-risk surgical patient is of particular importance. Once the medical management of underlying disease has been optimized, two principal areas remain: the use of haemodynamic goals to guide fluid and inotropic therapy, and perioperative β blockade. A number of studies have shown that the use of goal-directed haemodynamic therapy during the perioperative period can result in large reductions in morbidity and mortality. Some patients may also benefit from perioperative β blockade, which in selected patients has also been shown to result in significant mortality reductions. In this review a pragmatic approach to perioperative management is described, giving guidance on the identification of the high-risk patient and on the use of goal-directed haemodynamic therapy and β blockade

Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445]

INTRODUCTION: Goal-directed therapy (GDT) has been shown to improve outcome when commenced before surgery. This requires pre-operative admission to the intensive care unit (ICU). In cardiac surgery, GDT has proved effective when commenced after surgery. The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery. METHODS: This was a randomised controlled trial with concealed allocation. High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min(-1 )m(-2 )or to conventional management. Cardiac output was measured by lithium indicator dilution and pulse power analysis. Patients were followed up for 60 days. RESULTS: Sixty-two patients were randomised to GDT and 60 patients to control treatment. The GDT group received more intravenous colloid (1,907 SD ± 878 ml versus 1,204 SD ± 898 ml; p < 0.0001) and dopexamine (55 patients (89%) versus 1 patient (2%); p < 0.0001). Fewer GDT patients developed complications (27 patients (44%) versus 41 patients (68%); p = 0.003, relative risk 0.63; 95% confidence intervals 0.46 to 0.87). The number of complications per patient was also reduced (0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient; p = 0.002). The median duration of hospital stay in the GDT group was significantly reduced (11 days (IQR 7 to 15) versus 14 days (IQR 11 to 27); p = 0.001). There was no significant difference in mortality (seven patients (11.3%) versus nine patients (15%); p = 0.59). CONCLUSION: Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay. The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission

Changes in central venous saturation after major surgery, and association with outcome

INTRODUCTION: Despite recent interest in measurement of central venous oxygen saturation (ScvO(2)), there are no published data describing the pattern of ScvO(2 )changes after major general surgery or any relationship with outcome. METHODS: ScvO(2 )and other biochemical, physiological and demographic data were prospectively measured for 8 hours after major surgery. Complications and deaths occurring within 28 days of enrolment were included in the data analysis. Independent predictors of complications were identified with the use of logistic regression analysis. Optimum cutoffs for ScvO(2 )were identified by receiver operator characteristic analysis. RESULTS: Data from 118 patients was analysed; 123 morbidity episodes occurred in 64 these patients. There were 12 deaths (10.2%). The mean ± SD age was 66.8 ± 11.4 years. Twenty patients (17%) underwent emergency surgery and 77 patients (66%) were male. The mean ± SD P-POSSUM (Portsmouth Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity) score was 38.6 ± 7.7, with a predicted mortality of 16.7 ± 17.6%. After multivariate analysis, the lowest cardiac index value (odds ratio (OR) 0.58 (95% confidence intervals 0.37 to 0.9); p = 0.018), lowest ScvO(2 )value (OR 0.94 (0.89 to 0.98); p = 0.007) and P-POSSUM score (OR 1.09 (1.02 to 1.15); p = 0.008) were independently associated with post-operative complications. The optimal ScvO(2 )cutoff value for morbidity prediction was 64.4%. In the first hour after surgery, significant reductions in ScvO(2 )were observed, but there were no significant changes in CI or oxygen delivery index during the same period. CONCLUSION: Significant fluctuations in ScvO(2 )occur in the immediate post-operative period. These fluctuations are not always associated with changes in oxygen delivery, suggesting that oxygen consumption is also an important determinant of ScvO(2). Reductions in ScvO(2 )are independently associated with post-operative complications

Identification and characterisation of the high-risk surgical population in the United Kingdom

INTRODUCTION: Little is known about mortality rates following general surgical procedures in the United Kingdom. Deaths are most common in the 'high-risk' surgical population consisting mainly of older patients, with coexisting medical disease, who undergo major surgery. Only limited data are presently available to describe this population. The aim of the present study was to estimate the size of the high-risk general surgical population and to describe the outcome and intensive care unit (ICU) resource use. METHODS: Data on inpatient general surgical procedures and ICU admissions in 94 National Health Service hospitals between January 1999 and October 2004 were extracted from the Intensive Care National Audit & Research Centre database and the CHKS database. High-risk surgical procedures were defined prospectively as those for which the mortality rate was 5% or greater. RESULTS: There were 4,117,727 surgical procedures; 2,893,432 were elective (12,704 deaths; 0.44%) and 1,224,295 were emergencies (65,674 deaths; 5.4%). A high-risk population of 513,924 patients was identified (63,340 deaths; 12.3%), which accounted for 83.8% of deaths but for only 12.5% of procedures. This population had a prolonged hospital stay (median, 16 days; interquartile range, 9–29 days). There were 59,424 ICU admissions (11,398 deaths; 19%). Among admissions directly to the ICU following surgery, there were 31,633 elective admissions with 3,199 deaths (10.1%) and 24,764 emergency admissions with 7,084 deaths (28.6%). The ICU stays were short (median, 1.6 days; interquartile range, 0.8–3.7 days) but hospital admissions for those admitted to the ICU were prolonged (median, 16 days; interquartile range, 10–30 days). Among the ICU population, 40.8% of deaths occurred after the initial discharge from the ICU. The highest mortality rate (39%) occurred in the population admitted to the ICU following initial postoperative care on a standard ward. CONCLUSION: A large high-risk surgical population accounts for 12.5% of surgical procedures but for more than 80% of deaths. Despite high mortality rates, fewer than 15% of these patients are admitted to the ICU

Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP): an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients

Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill

The incidence of myocardial injury following post-operative Goal Directed Therapy.

BACKGROUND: Studies suggest that Goal Directed Therapy (GDT) results in improved outcome following major surgery. However, there is concern that pre-emptive use of inotropic therapy may lead to an increased incidence of myocardial ischaemia and infarction. METHODS: Post hoc analysis of data collected prospectively during a randomised controlled trial of the effects of post-operative GDT in high-risk general surgical patients. Serum troponin T concentrations were measured at baseline and on day 1 and day 2 following surgery. Continuous ECG monitoring was performed during the eight hour intervention period. Patients were followed up for predefined cardiac complications. A univariate analysis was performed to identify any associations between potential risk factors for myocardial injury and elevated troponin T concentrations. RESULTS: GDT was associated with fewer complications, and a reduced duration of hospital stay. Troponin T concentrations above 0.01 microg l-1 were identified in eight patients in the GDT group and six in the control group. Values increased above 0.05 microg l-1 in four patients in the GDT group and two patients in the control group. There were no overall differences in the incidence of elevated troponin T concentrations. The incidence of cardiovascular complications was also similar. None of the patients, in whom troponin T concentrations were elevated, developed ECG changes indicating myocardial ischaemia during the intervention period. The only factor to be associated with elevated troponin T concentrations following surgery was end-stage renal failure. CONCLUSION: The use of post-operative GDT does not result in an increased incidence of myocardial injury

Fluid Optimisation in Emergency Laparotomy (FLO-ELA) Trial: study protocol for a multi-centre randomised trial of cardiac output-guided fluid therapy compared to usual care in patients undergoing major emergency gastrointestinal surgery

INTRODUCTION: Postoperative morbidity and mortality in patients undergoing major emergency gastrointestinal surgery are a major burden on healthcare systems. Optimal management of perioperative intravenous fluids may reduce mortality rates and improve outcomes from surgery. Previous small trials of cardiac-output guided haemodynamic therapy algorithms in patients undergoing gastrointestinal surgery have suggested this intervention results in reduced complications and a modest reduction in mortality. However, this existing evidence is based mainly on elective (planned) surgery, with little evaluation in the emergency setting. There are fundamental clinical and pathophysiological differences between the planned and emergency surgical setting which may influence the effects of this intervention. A large definitive trial in emergency surgery is needed to confirm or refute the potential benefits observed in elective surgery and to inform widespread clinical practice. METHODS: The FLO-ELA trial is a multi-centre, parallel-group, open, randomised controlled trial. 3138 patients aged 50 and over undergoing major emergency gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid, or usual care without cardiac output monitoring. The trial intervention will be carried out during surgery and for up to 6 h postoperatively. The trial is funded through an efficient design call by the National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) programme and uses existing routinely collected datasets for the majority of data collection. The primary outcome is the number of days alive and out of hospital within 90 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation. Participant recruitment started in September 2017 with a 1-year internal pilot phase and is ongoing at the time of publication. DISCUSSION: This will be the largest contemporary randomised trial examining the effectiveness of perioperative cardiac output-guided haemodynamic therapy in patients undergoing major emergency gastrointestinal surgery. The multi-centre design and broad inclusion criteria support the external validity of the trial. Although the clinical teams delivering the trial interventions will not be blinded, significant trial outcome measures are objective and not subject to detection bias. TRIAL REGISTRATION: ISRCTN 14729158. Registered on 02 May 2017

Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study

INTRODUCTION Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications. METHODS Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria. RESULTS One hundred and nineteen patients were recruited. Fifteen (13%) patients required blood transfusion within 24 hours of surgery, 44 (37%) patients developed infections and 3 (2%) patients died prior to discharge. Patients receiving a blood transfusion were more likely to develop postoperative infections (P =0.02) and to have lower tumour necrosis factor alpha (TNFα), interleukin (IL)-12, IL-23 and RAR-related orphan receptor gamma T (RORγt) gene expression in the postoperative period (P <0.05). The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving a blood transfusion over this period. Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult. CONCLUSIONS An association between an immunosuppressive pattern of gene expression and blood transfusion following major elective gastrointestinal surgery is described. This gene expression profile includes a reduction in the activity of innate immunity and T helper cell type 1 (Th1) and T helper cell type 17 (Th17) pathways in those patients receiving a blood transfusion. Blood transfusion was also associated with an excess of infectious complications in this cohort. A mechanistic link is suggested but not proven

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis

Background: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. Methods: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). Conclusions: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels.This study was supported in part by an unrestricted grant from the local hospital fund, Medical Center Leeuwarden, Leeuwarden, The Netherland

Ergocalciferol and Microcirculatory Function in Chronic Kidney Disease and Concomitant Vitamin D Deficiency: An Exploratory, Double Blind, Randomised Controlled Trial

Vitamin D deficiency and endothelial dysfunction are non-traditional risk factors for cardiovascular events in chronic kidney disease. Previous studies in chronic kidney disease have failed to demonstrate a beneficial effect of vitamin D on arterial stiffness, left ventricular mass and inflammation but none have assessed the effect of vitamin D on microcirculatory endothelial function.We conducted a randomised controlled trial of 38 patients with non diabetic chronic kidney disease stage 3-4 and concomitant vitamin D deficiency (<16 ng/dl) who received oral ergocalciferol (50,000 IU weekly for one month followed by 50,000 IU monthly) or placebo over 6 months. The primary outcome was change in microcirculatory function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Secondary endpoints were tissue advanced glycation end products, sublingual functional capillary density and flow index as well as macrovascular parameters. Parallel in vitro experiments were conducted to determine the effect of ergocalciferol on cultured human endothelial cells.Twenty patients received ergocalciferol and 18 patients received placebo. After 6 months, there was a significant improvement in the ergocalciferol group in both endothelium dependent microcirculatory vasodilatation after iontophoresis of acetylcholine (p = 0.03) and a reduction in tissue advanced glycation end products (p = 0.03). There were no changes in sublingual microcirculatory parameters. Pulse pressure (p = 0.01) but not aortic pulse wave velocity was reduced. There were no significant changes in bone mineral parameters, blood pressure or left ventricular mass index suggesting that ergocalciferol improved endothelial function independently of these parameters. In parallel experiments, expression of endothelial nitric oxide synthase and activity were increased in human endothelial cells in a dose dependent manner.Ergocalciferol improved microcirculatory endothelial function in patients with chronic kidney disease and concomitant vitamin D deficiency. This process may be mediated through enhanced expression and activity of endothelial nitric oxide synthase.Clinical trials.gov NCT00882401