E. David Bennett

Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram

The value of heart rate variability, ambulatory electrocardiographic (ECG) variables and the signal-averaged ECG in the prediction of arrhythmic events (sudden death or life-threatening ventricular arrhythmias) was assessed before hospital discharge in 416 consecutive survivors of acute myocardial infarction. During the follow-up period (range 1 to 1,112 days), there were 24 arrhythmic events and 47 deaths. The initial relation between several prognostic factors and arrhythmic events was explored with use of the Kaplan-Meier product limit estimates of survival function. Impaired heart rate variability less than 20 ms (p less than 0.0000), late potentials (p less than 0.0000), ventricular ectopic beat frequency (p less than 0.0000), repetitive ventricular forms (p less than 0.0000), left ventricular ejection fraction less than 40% (p less than 0.02) and Killip class (p less than 0.02) were identified as significant univariate predictors of arrhythmic events. When these variables were analyzed by using a stepwise Cox regression model, only impaired heart rate variability, followed by late potentials and repetitive ventricular forms remained independent predictors of arrhythmic events. The combination of impaired heart rate variability and late potentials had a sensitivity of 58%, a positive predictive accuracy of 33% and a relative risk of 18.5 for arrhythmic events and was superior to other combinations including those incorporating left ventricular function, exercise ECG, ventricular ectopic beat frequency and repetitive ventricular forms. These results suggest that a simple method of assessment based on heart rate variability and the signal-averaged ECG can select a small subgroup of survivors of myocardial infarction at high risk of future life-threatening arrhythmias and sudden death.

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.

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.

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

IntroductionRisk 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.MethodsFifty-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 β-haemoglobin gene.ResultsSixteen 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.ConclusionPlasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.

ADVANTAGES OF A NARROW-RANGE, MEDIUM MOLECULAR WEIGHT HYDROXYETHYL STARCH FOR VOLUME MAINTENANCE IN A PORCINE MODEL OF FECAL PERITONITIS

Objective.To compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis. Design.Randomized prospective trial. Setting.Laboratory investigation. Subjects.Adolescent female pigs weighing approximately 30 kg. Interventions.We compared diafiltered 6% pentastarch with 6% high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis. The number average molecular weight of pentastarch is higher than hetastarch, although the weight average molecular weight is lower, i.e., a narrow range of medium weight molecules. The infusion rate of each agent was adjusted to maintain baseline arterial Hct for <7 hr after instrumentation and induction of fecal peritonitis. Main Outcome Measurements.The volume of fluid required to maintain arterial Hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents. Results.Significantly less pentastarch was required to prevent hemoconcentration than hetastarch (109 ± 22.8 vs. 150 ± 10.3 mL/kg; p < .05) while hemodynamics, colloid osmotic pressure, and oxygen transport responses were similar. Capillary patency was greater (21.99 ± 3.68 vs. 10.09 ± 1.17%;p < .05) and mean alveolar capillary barrier thickness was less (2.36 ± 0.13 vs. 3.06 ± 0.17 μm; p < .05) with pentastarch than with hetastarch, as judged by electron microscopy. Conclusions.These data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch. (Crit Care Med 1991; 19:409)

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 (≤1 μg/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.

Inducibility of sustained monomorphic ventricular tachycardia as a prognostic indicator in survivors of recent myocardial infarction: A prospective evaluation in relation to other prognostic variables

The prognostic significance of sustained monomorphic ventricular tachycardia inducible with up to three extrastimuli was assessed in relation to other prognostic markers, including clinical assessment, signal-average electrocardiogram (ECG), Holter monitoring, ejection fraction measurement and exercise testing, in 75 patients after recent myocardial infarction. Among eight patients with inducible sustained monomorphic ventricular tachycardia, six suffered arrhythmic events during a median follow-up period of 16 months. No patient without inducible sustained monomorphic ventricular tachycardia suffered an arrhythmic event. Multivariate analysis showed that of all the variables examined, inducible sustained monomorphic ventricular tachycardia was the only independent predictor of arrhythmic events during the follow-up period. The sensitivity for predicting arrhythmic events by this response was 100%, the specificity 97% and the positive predictive accuracy 75%. Individually, the other prognostic variables were less sensitive and much less accurate predictors of arrhythmic events, but the combination of the occurrence of acute phase complications or frequent ectopic activity with an abnormal signal-averaged ECG approached the sensitivity and accuracy of inducible sustained monomorphic ventricular tachycardia. The prognostic utility of programmed ventricular stimulation in patients with recent myocardial infarction is limited because comparable information can be obtained less invasively. However, the test may have a role in selecting therapy in patients judged to be at risk from arrhythmias on the basis of noninvasive assessment.

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.

Hemodynamic changes during sickle cell crisis

Abstract Marked elevations in cardiac output and reductions in systemic vascular resistance are well-documented features of steady-state sickle cell disease1–4; however, measurements of central hemodynamic changes during acute vaso-occlusive crises have not been reported. Doppler ultrasound measurement of ascending aortic blood flow provides a convenient and reliable means of noninvasive monitoring of changes in cardiac output.5,6 We used Doppler ultrasound to study hemodynamic changes in patients with acute vaso-occlusive crises during their hospital admission. We then compared these with values obtained during the noncrisis steady-state, and also with those of an age-matched group of normal subjects.

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.