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

A prospective study to evaluate the accuracy of pulse power analysis to monitor cardiac output in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Intermittent measurement of cardiac output may be performed using a lithium dilution technique (LiDCO). This can then be used to calibrate a pulse power algorithm of the arterial waveform which provides a continuous estimate of this variable. The purpose of this study was to examine the duration of accuracy of the pulse power algorithm in critically ill patients with respect to time when compared to measurements of cardiac output by an independent technique.</p> <p>Methods</p> <p>Pulse power analysis was performed on critically ill patients using a proprietary commercial monitor (PulseCO). All measurements were made using an in-dwelling radial artery line and according to manufacturers instructions. Intermittent measurements of cardiac output were made with LiDCO in order to validate the pulse power measurements. These were made at baseline and then following 1, 2, 4 and 8 hours. The LiDCO measurement was considered the reference for comparison in this study. The two methods of measuring cardiac output were then compared by linear regression and a Bland Altman analysis. An error rate for the limits of agreement (LOA) between the two techniques of less than 30% was defined as being acceptable for this study.</p> <p>Results</p> <p>14 critically ill medical and surgical patients were enrolled over a three month period. At baseline patients showed a wide range of cardiac output (median 7.5 L/min, IQR 5.1 -9.0 L/min). The bias and limits of agreement between the two techniques was deemed acceptable for the first four hours of the study with percentage errors being 29%, 22%, and 285 respectively. The percentage error at eight hours following calibration increased to 36%. The ability of the PulseCo to detect changes in cardiac output was assessed with a similar analysis. The PulseCO tracked the changes in cardiac output with adequate accuracy for the first four hours with percentage errors being 20%, 24% and 25%. However at eight hours the error had increased to 43%.</p> <p>Conclusion</p> <p>The agreement between lithium dilution cardiac output and the pulse power algorithm in the PulseCO monitor remains acceptable for up to four hours in critically ill patients.</p

Idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis: a case report

BACKGROUND: Pulmonary vein thrombosis represents a potentially fatal disease. This syndrome may clinically mimic pulmonary embolism but has a different investigation strategy and prognosis. Pulmonary vein thrombosis is difficult to diagnose clinically and usually requires a combination of conventionally used diagnostic modalities. CASE PRESENTATION: The authors report a case of a 78-year-old previously healthy female presenting with collapse and shortness of breath. Serum biochemistry revealed acute kidney injury, positive D-dimmer's and increased C reactive protein. Chest radiography demonstrated volume loss in the right lung. The patient was started on antibiotics and also therapeutic doses of low molecular weight heparin. The working diagnosis included community acquired pneumonia & pulmonary embolism. A computed tomography pulmonary angiogram was performed to confirm the clinical suspicions of pulmonary embolism. This demonstrated a thrombus in the pulmonary vein, with associated fibrosis and volume loss of the right lower lobe. A subsequent thrombophilia screen revealed a positive lupus anticoagulant antibody and rheumatoid factor and also decreased anti thrombin III and protein C levels. The urine protein/creatinine ratio was found to be 553 mg/mmol. CONCLUSION: The diagnosis of this patient was therefore of idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis. Whether or not the pulmonary vein thrombosis was a primary cause of the fibrosis or a consequence of it was unclear. There are few data on the management of pulmonary vein thrombosis, but anticoagulation, antibiotics, and, in cases of large pulmonary vein thrombosis, thrombectomy or pulmonary resection have been used

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke