R Michael Grounds

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

IntroductionGoal-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.MethodsThis 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.ResultsSixty-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).ConclusionPost-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.

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.

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 central venous saturation after major surgery, and association with outcome.

IntroductionDespite 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.MethodsScvO2 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 ScvO2 were identified by receiver operator characteristic analysis.ResultsData 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.ConclusionSignificant 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.

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

BackgroundIntermittent 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.MethodsPulse 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.Results14 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%.ConclusionThe 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.

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= 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.

Propofol or midazolam for short-term alterations in sedation

It is often necessary to adjust a patient’s sedation level while they are in the intensive care unit. The purpose of this study was to compare propofol with midazolam for controlling short-term alterations in sedation. Twenty-three patients undergoing an interactive procedure, physiotherapy, during mechanical ventilation of the lungs were studied. The patients were randomly assigned to receive infusions of propofol or midazolam for sedation. Sedation was assessed using the method of Ramsay, where 3 is drowsy responding only to commands; and 5 is asleep with a slow response to light glabellar tap. Prior to physiotherapy sedation was deepened from 3 to 5 by increasing the sedative infusion rate, and level 5 was maintained during physiotherapy by adjusting the infusion rate whenever necessary. After physiotherapy, the sedative dose was reduced until level 3 was again achieved. During physiotherapy, sedation level 5 was achieved for 53.9% of the time with propofol but for only 25.7% with midazolam (P < 0.01). After physiotherapy, those patients sedated with propofol re-awakened to level 3 faster (8.3 ± 2.3 min, mean ±SE) than those receiving midazolam (92.8 ± 35.0 min, P < 0.05). After physiotherapy, a further 1.8 ± 0.5 dose adjustments were required to the midazolam infusion while only 0.4 ± 0.2 adjustments were required to the propofol infusion (P < 0.05). During physiotherapy 3.0 ± 0.5 dose adjustments to the propofol dose were required compared with 3.6 ± 0.5 adjustments to the midazolam dose (NS). It is concluded that, during a standardized stimulus, physiotherapy, propofol infusion allowed a desired sedation score to be maintained for more of the time than did infusion of midazolam. Subsequently, when the infusion rates were reduced, less time was taken to re-awaken to baseline levels after physiotherapy, with fewer adjustments to the infusion rate, in those patients receiving propofol than midazolam.RésuméAux soins intensifs, il faut fréquemment modifier le niveau de sédation; cette étude compare le propofol au midazolam pour contrôler ces changements de courte durée. Vingt-trois patients sous ventilateur mécanique soumis à des manoeuvres de physiothérapie interactive sont inclus dans l’étude. Ils reçoivent au hasard en sédation une perfusion de profopol ou de midazolam. La sédation est évaluée selon l’échelle de Ramsey; on accorde 3 pour la somnolence avec réponse aux ordres et 5 au sommeil avec réponse lente à la légère percussion de la glabelle. Avant la physiothérapie, la sédation est approfondie du niveau 3 au niveau 5 en augmentant la perfusion au besoin. Après la physiothérapie, on réduit la perfusion jusqu’au retour au niveau 3. Pendant la physiothérapie, le niveau 5 est atteint pendant 53,9% de la durée du traitement avec le propofol contre seulement 25,7% avec le midazolam (P < 0,01). Après la physiothérapie, les patients sous propofol reviennent au niveau 3 plus rapidement (8,3 ± 2,3 min, moyenne ± SD) que ceux qui reçoivent du midazolam (92,8 ± 35,0 min, P < 0,05). Après la physiothérapie, le dosage de midazolam nécessite 1,8 ± 0.5 ajustements comparativement à 0,4 ± 0,2 pour le propofol (P < 0,05). Pendant la physiothérapie, la posologie du propofol doit être ajustée 3,0 ± 0,5 fois comparativement à 3,6 ± 0,5 pour celle du midazolam (NS). En conclusion, pendant une stimulation standardisée, la perfusion de propofol permet de maintenir le niveau de sédation désiré plus souvent que la perfusion de midazolam. Par la suite, lorsqu’on diminue la perfusion, le temps requis pour le retour à la ligne de base nécessite moins d’ajustements pour le propofol que pour le midazolam.

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

BackgroundStudies 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.MethodsPost 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.ResultsGDT was associated with fewer complications, and a reduced duration of hospital stay. Troponin T concentrations above 0.01 μg l-1 were identified in eight patients in the GDT group and six in the control group. Values increased above 0.05 μg 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.ConclusionThe use of post-operative GDT does not result in an increased incidence of myocardial injury.