Hemodynamic Effect of Different Doses of Fluids for a Fluid Challenge: A Quasi-Randomized Controlled Study.

OBJECTIVE: The objectives of this study are to determine what is the minimal volume required to perform an effective fluid challenge and to investigate how different doses of IV fluids in an fluid challenge affect the changes in cardiac output and the proportion of responders and nonresponders. DESIGN: Quasi-randomized controlled trial. SETTING: Cardiothoracic ICU, tertiary university hospital. PATIENTS: Eighty postcardiac surgery patients. INTERVENTION: IV infusion of 1, 2, 3, or 4 mL/Kg (body weight) of crystalloid over 5 minutes. MEASUREMENTS AND MAIN RESULTS: Mean systemic filling pressure measured using the transient stop-flow arm arterial-venous equilibrium pressure, arterial and central venous pressure, cardiac output (LiDCOplus; LiDCO, Cambridge, United Kingdom), and heart rate. The groups were well matched with respect to demographic and baseline physiologic variables. The proportion of responders increased from 20% in the group of 1 mL/kg to 65% in the group of 4 mL/kg (p = 0.04). The predicted minimal volume required for an fluid challenge was between 321 and 509 mL. Only 4 mL/Kg increases transient stop-flow arm arterial-venous equilibrium pressure beyond the limits of precision and was significantly associated with a positive response (odds ratio, 7.73; 95% CI, 1.78-31.04). CONCLUSION: The doses of fluids used for an fluid challenge modify the proportions of responders in postoperative patients. A dose of 4 mL/Kg increases transient stop-flow arm arterial-venous equilibrium pressure and reliably detects responders and nonresponders.

Pharmacodynamic Analysis of a Fluid Challenge.

OBJECTIVE: This study aims to describe the pharmacodynamics of a fluid challenge over a 10-minute period in postoperative patients. DESIGN: Prospective observational study. SETTING: General and cardiothoracic ICU, tertiary hospital. PATIENTS: Twenty-six postoperative patients. INTERVENTION: Two hundred and fifty-milliliter fluid challenge performed over 5 minutes. Data were recorded over 10 minutes after the end of fluid infusion MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured with a calibrated LiDCOplus (LiDCO, Cambridge, United Kingdom) and Navigator (Applied Physiology, Sydney, Australia) to obtain the Pmsf analogue (Pmsa). Pharmacodynamics outcomes were modeled using a Bayesian inferential approach and Markov chain Monte Carlo estimation methods. Parameter estimates were summarized as the means of their posterior distributions, and their uncertainty was assessed by the 95% credible intervals. Bayesian probabilities for groups' effect were also derived. The predicted maximal effect on cardiac output was observed at 1.2 minutes (95% credible interval, -0.6 to 2.8 min) in responders. The probability that the estimated area under the curve of central venous pressure was smaller in nonresponders was 0.12. (estimated difference, -4.91 mm Hg·min [95% credible interval, -13.45 to 3.3 mm Hg min]). After 10 minutes, there is no evidence of a difference between groups for any hemodynamic variable. CONCLUSIONS: The maximal change in cardiac output should be assessed 1 minute after the end of the fluid infusion. The global effect of the fluid challenge on central venous pressure is greater in nonresponders, but not the change observed 10 minutes after the fluid infusion. The effect of a fluid challenge on hemodynamics is dissipated in 10 minutes similarly in both groups.

Transient stop-flow arm arterial-venous equilibrium pressure measurement: determination of precision of the technique.

Transient stop-flow arm arterial-venous equilibrium pressure (Pmsf-arm) is a validated technique for measuring the mean systemic filling pressure (Pmsf). Pmsf is a functional measure of the effective intravascular volume status. This study aims to assess the precision of the Pmsf-arm measurement. Pmsf-arm was measured by inflating a pneumatic tourniquet around the upper arm 50 mmHg above systolic pressure for 60 s, four times consecutively, with an interval of 5 min. Arterial (Pa) and venous pressure (Pv) were recorded every 10 s. Pa-Pv difference was calculated to determine the stop-flow time. The coefficient error (CE) was determined and used to derive the least significant change (LSC) in Pmsf-arm that this technique could reliably detect. The rANOVA test was used to compare repeated measurements of the four determinations of Pmsf-arm. 80 measurements of Pmsf-arm were studied in 20 patients. Pa and Pv equalised after 60 s of inflation (Pa-Pv difference 0 ± 0.01 mmHg). There were no significant differences of Pmsf-arm values among determinations. For a single measurement, the CE was 5 % (±2 %) and the LSC was 14 % (±5 %). Averaging two, three and four measurements the CE improves to 4 % (±1 %), 3 % (±1 %) and 3 % (±1 %) respectively, and the LSC was reduced to 10 % (±4 %), 8 % (±3 %) and 7 % (±3 %) respectively. One measurement of Pmsf-arm can reliably detect changes on Pmsf-arm of 14 %. The precision of Pmsf-arm technique improves when averaging two or three measurements.

Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial.

INTRODUCTION: There is currently no accurate method of measuring glomerular filtration rate (GFR) during acute kidney injury (AKI). Knowledge of how much GFR varies in stable subjects is necessary before changes in GFR can be attributed to AKI. We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI. The aims of this crossover trial were to establish accuracy and precision of a continuous infusion of low dose Iohexol (CILDI) and variation in GFR in stable volunteers over a range of estimated GFR (23-138 mL/min/1.73 m(2)). METHODS: We randomised 17 volunteers to GFR measurement by plasma clearance (PC) and renal clearance (RC) of either a single bolus of Iohexol (SBI; routine method), or of a continuous infusion of low dose Iohexol (CILDI; experimental method) at 0.5 mL/h for 12 h. GFR was measured by the alternative method after a washout period (4-28 days). Iohexol concentration was measured by high performance liquid chromatography/electrospray tandem mass spectrometry and time to steady state concentration (Css) determined. RESULTS: Mean PC was 76.7 ± 28.5 mL/min/1.73 m(2) (SBI), and 78.9 ± 28.6 mL/min/1.73 m(2) (CILDI), p = 0.82. No crossover effects occurred (p = 0.85). Correlation (r) between the methods was 0.98 (p < 0.0001). Bias was 2.2 mL/min/1.73 m(2) (limits of agreement -8.2 to 12.6 mL/min/1.73 m(2)) for CILDI. PC overestimated RC by 7.1 ± 7.3 mL/min/1.73 m(2). Mean intra-individual variation in GFR (CILDI) was 10.3% (p < 0.003). Mean ± SD Css was 172 ± 185 min. CONCLUSION: We hypothesise that changes in GFR >10.3% depict evolving AKI. If this were applicable to AKI, this is less than the 50% change in serum creatinine currently required to define AKI. CILDI is now ready for testing in patients with AKI. TRIAL REGISTRATION: This trial was registered with the European Union Clinical Trials Register ( https://www.clinicaltrialsregister.eu/ ), registration number: 2010-019933-89 .

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.

Clinical review: Goal-directed therapy-what is the evidence in surgical patients? The effect on different risk groups.

Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery. By augmenting oxygen delivery index (DO2I) with a combination of intravenous fluids and inotropes (goal directed therapy (GDT)), postoperative mortality and morbidity of high-risk patients may be reduced. However, although most studies suggest that GDT may improve outcome in high-risk surgical patients, it is still not widely practiced. We set out to test the hypothesis that GDT results in greatest benefit in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct. We performed a systematic search of Medline, Embase and CENTRAL databases for randomized controlled trials (RCTs) and reviews of GDT in surgical patients. To minimize heterogeneity we excluded studies involving cardiac, trauma, and paediatric surgery. Extremely high risk, high risk and intermediate risks of mortality were defined as >20%, 5 to 20% and <5% mortality rates in the control arms of the trials, respectively. Meta analyses were performed and Forest plots drawn using RevMan software. Data are presented as odd ratios (OR; 95% confidence intervals (CI), and P-values). A total of 32 RCTs including 2,808 patients were reviewed. All studies reported mortality. Five studies (including 300 patients) were excluded from assessment of complication rates as the number of patients with complications was not reported. The mortality benefit of GDT was confined to the extremely high-risk group (OR = 0.20, 95% CI 0.09 to 0.41; P < 0.0001). Complication rates were reduced in all subgroups (OR = 0.45, 95% CI 0.34 to 0.60; P < 0.00001). The morbidity benefit was greatest amongst patients in the extremely high-risk subgroup (OR = 0.27, 95% CI 0.15 to 0.51; P < 0.0001), followed by the intermediate risk subgroup (OR = 0.43, 95% CI 0.27 to 0.67; P = 0.0002), and the high-risk subgroup (OR 0.56, 95% CI 0.36 to 0.89; P = 0.01). Despite heterogeneity in trial quality and design, we found GDT to be beneficial in all high-risk patients undergoing major surgery. The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death. The reduction of complication rates was seen across all subgroups of GDT patients.

Changes in the mean systemic filling pressure during a fluid challenge in postsurgical intensive care patients.

PURPOSE: The difference between mean systemic filling (Pmsf) and central venous pressure (CVP) is the venous return gradient (dVR). The aim of this study is to assess the significance of the Pmsf analogue (Pmsa) and the dVR during a fluid challenge. METHODS: We performed a prospective observational study in postsurgical patients. Patients were monitored with a central venous catheter, a LiDCO™plus and the Navigator™. A 250-ml intravenous fluid challenge was given over 5 min. A positive response to the fluid challenge was defined as either a stroke volume (SV) or cardiac output increase of greater than 10 %. RESULTS: A total of 101 fluid challenges were observed in 39 patients. In 43 events (42.6 %) the SV and CO increased by more than 10 %. Pmsa increased similarly during a fluid challenge in responders and non-responders (3.1 ± 1.9 vs. 3.1 ± 1.8, p = 0.9), whereas the dVR increased in responders (1.16 ± 0.8 vs. 0.2 ± 1, p < 0.001) as among non-responders CVP increased along with Pmsa (2.9 ± 1.7 vs. 3.1 ± 1.8, p = 0.15). Resistance to venous return did not change immediately after a fluid challenge. Heart performance (Eh) decreased significantly among non-responders (0.41 ± 0.15 vs. 0.34 ± 0.13, p < 0.001) whereas among responders it did not change when compared with baseline value (0.35 ± 0.15 vs. 0.34 ± 0.12, p = 0.15). CONCLUSIONS: The changes in Pmsa and dVR measured at the bedside during a fluid challenge are consistent with the cardiovascular model described by Guyton.

Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials.

CONTEXT: Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort. OBJECTIVE: To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients' interaction with nursing care. DESIGN, SETTING, AND PATIENTS: Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251). INTERVENTIONS: Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials. MAIN OUTCOME MEASURES: For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients' ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223). RESULTS: Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients' interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001). CONCLUSIONS: Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients' ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00481312, NCT00479661.

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.

Using midazolam to monitor changes in hepatic drug metabolism in critically ill patients.

OBJECTIVE: Critical illness and associated sequelae can cause severe metabolic disturbances. The effects these have on hepatic drug metabolism are poorly understood. In vivo, enzyme specific drug probes are used to measure changes in hepatic drug metabolism but they require multiple blood sampling and are time consuming. We suggest that a single measurement, 4 h after intravenous administration of midazolam is a reliable indicator of integral plasma midazolam exposure or area under the curve (AUC) in critically ill patients. We also explore the hypothesis that acute kidney injury (AKI) directly impairs hepatic metabolism of drugs in critically ill patients. METHODS: A prospective study in 20 critically ill patients who were not taking specific enzyme inhibitors or inducers or benzodiazepines. Correlation between 4 h midazolam concentration and AUC was calculated. We also assessed the difference in metabolism between the patients with normal renal function and those with AKI. RESULTS: Four hour midazolam concentration correlated with AUC r = 0.956 (p < 0.0001). In addition, the 4 h midazolam concentration was greater in critically ill patients with AKI than those with normal renal function p = 0.023. CONCLUSION: A single-time-point determination of plasma midazolam concentration is a reliable predictor of integral plasma midazolam exposure in critically ill patients. This tool can now be used to assess the effects of critical illness on hepatic drug metabolism. Using this method, we suggest that AKI reduces the hepatic metabolism of midazolam in critically ill patients.

Bench-to-bedside review: the importance of the precision of the reference technique in method comparison studies--with specific reference to the measurement of cardiac output.

Bland-Altman analysis is used for assessing agreement between two measurements of the same clinical variable. In the field of cardiac output monitoring, its results, in terms of bias and limits of agreement, are often difficult to interpret, leading clinicians to use a cutoff of 30% in the percentage error in order to decide whether a new technique may be considered a good alternative. This percentage error of +/- 30% arises from the assumption that the commonly used reference technique, intermittent thermodilution, has a precision of +/- 20% or less. The combination of two precisions of +/- 20% equates to a total error of +/- 28.3%, which is commonly rounded up to +/- 30%. Thus, finding a percentage error of less than +/- 30% should equate to the new tested technique having an error similar to the reference, which therefore should be acceptable. In a worked example in this paper, we discuss the limitations of this approach, in particular in regard to the situation in which the reference technique may be either more or less precise than would normally be expected. This can lead to inappropriate conclusions being drawn from data acquired in validation studies of new monitoring technologies. We conclude that it is not acceptable to present comparison studies quoting percentage error as an acceptability criteria without reporting the precision of the reference technique.

A Prospective Study to Evaluate the Accuracy of Pulse Power Analysis to Monitor Cardiac Output in Critically Ill Patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

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.

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.

Use of recombinant activated factor VII (Novoseven) in trauma and surgery: analysis of outcomes reported to an international registry.

The objective was to evaluate the efficacy and safety of recombinant activated factor VII in patients with massive bleeding. Forty-five patients with severe massive hemorrhage requiring>or= 14 transfusion units of packed red blood cells received recombinant activated factor VII. Postdrug blood loss and transfusion requirements were assessed, and mortality was compared with predicted outcomes. Blood loss was markedly reduced in 40 of 43 (93.0%) patients, and transfusion requirements decreased after recombinant activated factor VII administration. Mortality rate in trauma patients who had massive hemorrhage was significantly reduced compared with predictions using scoring systems. This may be associated with the use of recombinant activated factor VII. This study failed to demonstrate an improvement in surgical patients. The absence of concurrent controls prevents definitive conclusions regarding actual safety or efficacy of recombinant activated factor VII.

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.

Clinical experiences and current evidence for therapeutic recombinant factor VIIa treatment in nontrauma settings.

The hemostatic properties of recombinant activated factor VII (rFVIIa) are established in patients with inherited or acquired hemophilia with inhibitors and in patients with congenital factor VII deficiencies. Emerging clinical evidence suggests that there may be a wider role for rFVIIa in the management of hemorrhage associated with traumatic injury/accident and severe bleeding associated with critical surgery. This article considers recent data from studies in which rFVIIa was used in an attempt to control bleeding in clinical situations as diverse as coagulopathy associated with chronic liver disease, massive perioperative bleeding and bleeding during prostatectomy, organ transplantation and orthopedic surgery, uncontrollable obstetric hemorrhage, and intracerebral hemorrhage. In nontrauma settings involving acute and potentially life threatening bleeding, there may be a place for rFVIIa as adjunctive therapy in the control of hemostasis.

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 beta 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 beta 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 beta blockade.

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.