Effect of dopexamine infusion on mortality following major surgery: individual patient data meta-regression analysis of published clinical trials.

OBJECTIVES: To establish whether perioperative low-dose dopexamine infusion (< or = 1 microg/kg/min) is associated with a reduction in mortality and duration of hospital stay following major surgery. DATA SOURCE: Medline, EMBASE, CINAHL, Cochrane Library, Google Scholar, and reference lists. STUDY SELECTION: Two reviewers independently screened studies for inclusion, assessed trial quality, and extracted data. Eligible trials were randomized controlled trials comparing dopexamine infusion to control treatment. Data are reported as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals. DATA EXTRACTION: Systematic review and meta-regression analysis of individual patient data. DATA SYNTHESIS: Five studies fulfilled the inclusion criteria. Analysis of pooled data from high- and low-dose dopexamine groups identified a reduction in duration of hospital stay (median 14 vs. 15 days; HR 0.85 [0.73-0.91]; p = .03) but no improvement in mortality (9.1% vs. 12.3%; OR 0.78 [0.31-1.99]; p = .61). However, low-dose dopexamine was associated with a 50% reduction in 28-day mortality (6.3% vs. 12.3%; OR 0.50 [0.28-0.88]; p = .016) as well as a reduced duration of stay (median 13 vs. 15 days; HR 0.75 [0.64-0.88]; p = .0005). When high-dose dopexamine groups were compared with controls, there was no difference in either mortality (OR 1.06 [0.60-1.87]; p = .85) or duration of stay (HR 1.04 [0.94-1.16]; p = .36). CONCLUSIONS: For pooled data describing perioperative dopexamine infusion at all doses, there was an improvement in duration of hospital stay but no survival benefit. However, at low doses, dopexamine was associated with improved survival and reduced duration of stay. Further clinical trials are warranted to confirm this observation.

Year in review 2005: critical care--cardiology.

This review summarizes key research papers published in the fields of cardiology and intensive care during 2005 in Critical Care. The papers have been grouped into categories: haemodynamic monitoring; goal-directed therapy; cardiac enzymes and critical care; metabolic considerations in cardiovascular performance; thrombosis prevention; physiology; and procedures and techniques.

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.

Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients.

INTRODUCTION: Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis. METHODS: Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human beta-haemoglobin gene. RESULTS: Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65-362) ng/ml versus 74 (46-156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185-430) ng/ml versus 71 (46-113) ng/ml, P < 0.001) or in hospital (260 (151-380) ng/ml versus 68 (47-103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0-1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU. CONCLUSION: Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.

Advances in protocolising management of high risk surgical patients.

Despite studies clearly demonstrating significant benefit from increasing oxygen delivery in the peri-operative period in high risk surgical patients, the technique has not been widely accepted. This is due to a variety of reasons, including non-availability of beds, particularly in the pre-operative period, and the requirement of inserting a pulmonary artery catheter. There are now data that suggest that increasing oxygen delivery post-operatively using a nurse-led protocol based on pulse contour analysis leads to a major improvement in outcome with reduction in infection rate and length of hospital stay.

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 (ScvO2), there are no published data describing the pattern of ScvO2 changes after major general surgery or any relationship with outcome. METHODS: ScvO2 and other biochemical, physiological and demographic data were prospectively measured for 8 hours after major surgery. Complications and deaths occurring within 28 days of enrollment were included in the data analysis. Independent predictors of complications were identified with the use of logistic regression analysis. Optimum cutoffs for ScvO2 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 ScvO2 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 ScvO2 cutoff value for morbidity prediction was 64.4%. In the first hour after surgery, significant reductions in ScvO2 were observed, but there were no significant changes in CI or oxygen delivery index during the same period. CONCLUSION: Significant fluctuations in ScvO2 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 ScvO2. Reductions in ScvO2 are independently associated with post-operative complications.

Early goal-directed therapy: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for early goal-directed therapy that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: During the first 6 hrs of resuscitation of sepsis-induced hypoperfusion, specific levels of central venous pressure, mean arterial pressure, urine output, central venous (or mixed venous) oxygen saturation should be targeted. When central venous oxygen saturation remains low, despite achieving central venous pressure and mean arterial pressure targets, packed red blood cells or dobutamine should be considered. Increasing cardiac index to achieve an arbitrarily predefined elevated level is not recommended.

A randomised, controlled trial of the pulmonary artery catheter in critically ill patients.

OBJECTIVE: To compare the survival and clinical outcomes of critically ill patients treated with the use of a pulmonary artery catheter (PAC) to those treated without the use of a PAC. DESIGN: Prospective, randomised, controlled, clinical trial from October 1997 to February 1999. SETTING: Adult intensive care unit at a large teaching hospital. PATIENTS: Two hundred one critically ill patients were randomised either to a PAC group ( n=95) or the control group ( n=106). One patient in the control group was withdrawn from the study and five patients in the PAC group did not receive a PAC. All participants were available for follow-up. INTERVENTIONS: Participants were assigned to be managed either with the use of a PAC (PAC group) or without the use of a PAC (control group). MAIN OUTCOME MEASURES: Survival to 28 days, intensive care and hospital length of stay and organ dysfunction were compared on an intention-to-treat basis and also on a subgroup basis for those participants who successfully received a PAC. RESULTS There was no significant difference in mortality between the PAC group [46/95 (47.9%)] and the control group [50/106 (47.6)] (95% confidence intervals for the difference -13 to 14%, p>0.99). The mortality for participants who had management decisions based on information derived from a PAC was 41/91 (45%, 95% confidence intervals -11 to 16%, p=0.77). The PAC group had significantly more fluids in the first 24 h (4953 (3140, 7000) versus 4292 (2535, 6049) ml) and an increased incidence of renal failure (35 versus 20% of patients at day 3 post randomisation p<0.05) and thrombocytopenia ( p<0.03). CONCLUSIONS: These results suggest that the PAC is not associated with an increased mortality.