Hot topics in liver intensive care.

Liver dysfunction is an independent predictor of mortality among intensive care patients. Avoidance or early restoration of normal liver function should therefore be targeted in all critically ill patients. The present work seeks to provide an overview of the "hottest topics" among liver-related problems in intensive care. The management of increased intracranial pressure in severe hepatic encephalopathy is still not sufficiently documented. The promising results with regard to intracranial pressure control by the molecular adsorbent recycling system (MARS) in animal studies are only partially reproducible in patients. Intracranial pressure monitoring is inconsistently applied in various centers, mainly because of the lack of information about the risk benefit ratio. Further, we still do not know which coagulation management protocol reduces the risk of intracranial bleeding. Type I hepatorenal syndrome is a complication of liver failure that is strongly associated with bad outcomes. Only about the half of the patients will recover from dialysis-dependent hepatorenal syndrome after liver transplantation. The usefulness of combined liver and kidney transplantation has not been sufficiently clarified. Terlipressin together with fluid and albumin substitution appear to be the most promising therapeutic interventions. Extracorporeal liver support systems, such as single-pass albumin dialysis, MARS, and the dialysis- and plasmapheresis-based Prometheus, are still under investigation with regard to effectiveness of toxin elimination, appropriate indications, and number duration of treatments.

Molecular weight of hydroxyethyl starch molecules influences coagulation profile measured by thrombelastography.

BACKGROUND: The consensus about the ideal intravenous fluid in trauma patients remains open. However, hypertonic saline and hydroxyethyl starch (HES) seems to have advantages in terms of immuno-modulatory and haemodynamic effects. Nevertheless clotting abnormalities are frequently reported in association with the use of HES. We investigated the influence of light, medium and heavy molecular weight (MW) hydroxyethyl starch (HES) on coagulation in 29 healthy subjects. METHODS: Ringer's lactate (RL) served as a control solution. Thrombelastography using Haemoscope's Thrombelastograph (TEG) hemostasis system was used to assess the effect of HES polymers and RL. TEG analysis was performed using recalcified native whole blood both with and without the addition of platelet activating factor IV (PAF IV) before and immediately after infusion of one of the solutions. RESULTS: Infusion of RL or one of the three HES solutions exerts an anticoagulant effect as demonstrated by a increase in clot formation time (R) and a decrease in maximum amplitude (MA), and the angle. The addition of PAF IV reversed these changes. CONCLUSIONS: This data indicate clear evidence of platelet activity per se or platelet interaction with the plasmatic coagulation system.

Effects of acute increases in left ventricular preload on indices of myocardial function in conscious, unrestrained and intact, tranquilized baboons.

The effects of acute volume loading were examined on indices of left ventricular (LV) function in conscious, unrestrained and intact, tranquilized baboons. Experiments were conducted 1-3 mo after implantation of ultrasonic transducers to measure LV internal diameter and wall thickness, and miniature LV pressure gauges and aortic and left atrial catheters. In 10 intact, tranquilized baboons, rapid volume loading with saline increased LV end-diastolic pressure by 23.7+/-2.6 mm Hg, LV end-diastolic diameter by 7.8+/-1.5%, LV stroke work by 37.5+/-7.8%, while mean arterial pressure and peak LV wall stress did not change significantly. Despite the increase in preload and activation of the Frank-Starling mechanism, LV dP/dt(max) and the maximum velocity of myocardial fiber shortening (LV dD/dt(max)) did not change. Volume loading after beta-adrenergic or combined beta-adrenergic and cholinergic blockades or volume loading with blood instead of saline also failed to augment LV dP/dt(max) and LV dD/dt(max) despite the increase in preload. In order to volume load the baboons in the conscious state, a radiofrequency (RF) interrogator system was devised, which upon receipt of a radio command, activated a battery operated pump to infuse 1,000 ml of saline i.v. to the baboons. In these experiments, preload rose, i.e., LV end-diastolic diameter increased by 13.9+/-2.1% and the Frank-Starling mechanism could be demonstrated, i.e., stroke work rose by 42.8+/-7.4%, but LV dP/dt(max) and LV dD/dt(max) did not change. After preload was depressed by hemorrhage, the rapid infusion of either blood or saline increased LV dP/dt(max) by 92.7+/-18.5% and LV dD/dt(max) by 64.3+/-10.1%. Thus, acute volume loading in the conscious baboons increased LV end-diastolic size and even stroke work substantially. However, preload dependency of LV dP/dt(max) and the maximum velocity of myocardial fiber shortening was only encountered at low levels of LV preload.

Base deficit and lactate: early predictors of morbidity and mortality in patients with burns.

Severe burn results in severe and unique physiological changes called burn shock. Historically, resuscitation has been guided by a combination of basic laboratory values, invasive monitoring and clinical findings, but the optimal guide to the endpoint of resuscitation still remains controversial. Two hundred and eighty patients, who were admitted to our Burn Unit, were enrolled in this prospective study. Resuscitation of these patients was undertaken according to the current standard of care. Parkland formula was used as a first approximation of acquired fluid administration rates; final fluid administration was adapted in order to meet clinical needs. The aim of this study was to evaluate if plasma lactate (PL) and base deficit (BD) are useful early parameters to estimate the severity of a burn. One of the main objectives was to evaluate if BD and its changes due to fluid resuscitation adds additional information in comparison to the evaluation of PL alone. The results of this study indicate that initial PL and BD level (Day 0) are useful parameters to separate survivors from non-survivors. Moreover, an outcome predictor of shock and effective resuscitation could be defined by evaluating the changes of BD on Day 1. Normalization of the BD within 24 h is associated with a better chance of survival. One explanation for this phenomenon might be the fact that many burn patients are still sub-optimally resuscitated; in summary, measuring PL and BD may help to identify critically injured patients either for enhancement of treatment, or selection of therapeutic options.

Antithrombin deficiency and its relationship to severe burns.

Antithrombin (AT) is an important endogenous anticoagulant and exhibits marked anti-inflammatory properties. To evaluate the incidence of AT deficiency in severe burn and its correlation to the variables of the abbreviated burn severity index (ABSI), length of hospital stay (LOS) and mortality we collected data on the substitution of human plasma-derived AT concentrate in 201 consecutive patients suffering from severe burn. One hundred and eight patients (54%) developed AT deficiency during their hospitalisation and, according to our institutional practice, received substitution therapy by continuous infusion to maintain physiological plasma activity (70-120%). The mean administered dose served as a measure of AT deficiency. The percentage of patients in an AT deficient state was highest within the first 5 days after injury. It was 26% on day 1 and between 38% and 41% on days 2-5 and thereafter decreased constantly over time. A multiple regression analysis between the dependent variable mean administered dose of AT concentrate and the independent variables age, total body surface area burned (TBSA), gender, inhalation injury (INHAL), full thickness burn (FTB), LOS and mortality was performed. Age, gender and FTB showed no significant influence on the development of AT deficiency. Increasing TBSA and INHAL clearly increase the risk of developing AT deficiency (p-values 0.0001 and 0.037). The analysis also identified AT deficiency as an independent predictor of LOS and mortality (p-values 0.036 and 0.003). Development of AT deficiency is a frequent event after burn with significant correlation to TBSA and INHAL, increased mortality rates and longer hospital stays.

[The use of oxygen as drug and its relevance for wound healing]. / Sauerstoff als Medikament und seine Bedeutung für die Wundheilung.

Plastic surgeons often have to deal with problematic wounds. In reconstructive surgery, as well as in chronic wounds, tissue oxygen supply is often critically low. Similarly in the treatment of severely burned patients, perfusion and oxygen supply to the areas beneath burn wounds are often critical. This paper explains the mechanisms and impact of oxygen for wound healing. It is important to mention that it has been shown that oxygen even used at ambient pressure can improve wound healing. Whereas treatment with oxygen under hyperbaric conditions is not everywhere available, at least normobaric oxygen is cheap and ubiquitously available and should therefore be used routinely. Oxygen treatment under hyperbaric conditions, especially in critically ill patients, needs a special infrastructure and is quite more expensive. Therefore, it has to be evaluated whether the potential benefit for the patient meets the risk and costs of treatment. In 2006, at the Hyperbaric Centre of the Medical University of Vienna almost 2200 hyperbaric treatments including 330 in critically ill patients have been performed. Beside 2 patients suffering from Fournier's gangrene, 2 suffering from gas gangrene and 4 patients with severe carbon monoxide intoxications, all other intensive-care patients were treated for severe burns. Indications for less severely ill patients mainly included problem wounds mostly of diabetic patients, osteomyelitis of the mandible and less severe carbon monoxide poisoning. Our experience with the use of oxygen under hyperbaric conditions so far has been good enough to consider this kind of therapy at least in our centre as an option in the adjunctive treatment for the so far used indications. However, it has to be mentioned that there is still lack of prospective randomised controlled studies to introduce this kind of therapy as a level 1 indication in clinical routine.

Effect of aminophylline on coronary reactive hyperaemia following brief and long occlusion periods.

The effects of an intracoronary aminophylline infusion, adjusted to give a constant concentration of 25 microgram.cm-3 coronary blood, on the reactive hyperaemic responses following coronary occlusion for 4, 10, and 25 heart beats were investigated in anaesthetised, open-chest dogs. The vasodilator effect of intracoronarily-administered adenosine and the hyperaemic response after coronary occlusion for 10 and 25 heart beats were both significantly diminished under the influence of aminophylline. However, the decrease in the coronary dilator effect of adenosine amounted to 80%, whereas the hyperaemic response was diminished by only 20%. The hyperaemic response following a coronary occlusion for only 4 heart beats remained unchanged. The present results obtained with aminophylline suggest at least a partial involvement of adenosine in mediating reactive hyperaemia after sufficiently long periods of coronary artery occlusion.

Influence of positive end-expiratory pressure on right and left ventricular performance assessed by Doppler two-dimensional echocardiography.

The advent of modern Doppler two-dimensional ultrasound technology has overcome the need of invasive measurements of several important cardiac parameters. It allows estimation of preload, contractility, and afterload. Positive end-expiratory pressure (PEEP) is associated with a reduction in cardiac output. The responsible mechanisms are controversial. To evaluate the cardiovascular responses to PEEP, we employed different Doppler hemodynamic indices for the first time, combined with conventional two-dimensional echocardiography. Twenty-one healthy, young, and unsedated volunteers were admitted to the study. Under spontaneous respiration, PEEP level was increased stepwise (0, 5, 7.5, 10, 12.5 cm H2O). At each PEEP level, the following right and left ventricular parameters were assessed with Doppler two-dimensional echocardiography: two-dimensional variables: end-diastolic volume indices (EDVI), ejection fraction (EF), and left ventricular afterload-LaPlace relation (combined with cuff systolic pressure); Doppler variables: cardiac index (CI) (combined with two-dimensional measure of valve area), maximum velocity (Vmax), time velocity integral (TVI), acceleration time (AT), deceleration time (DT), deceleration rate (DR), ratio of early to atrial peak (E/A), ratio of isovolumic contraction time to ejection time (IVCT/ET), and maximum blood acceleration (dv/dt) in aorta and main pulmonary artery. Increasing PEEP resulted in a proportional decrease in biventricular EDVI. Moreover, PEEP application is also causing a drop of CI, which is determined from a decrease in Vmax and TVI, while EF, IVCT/ET, dv/dt, Doppler trans-atrioventricular parameters, and afterload stay in normal ranges. Employing Doppler hemodynamic indices for the first time in this study setting clearly supports data that the drop in EDVI and CI during PEEP is caused by reduction in ventricular filling due to decreased venous return. Using the Doppler parameters IVCT/ET and dv/dt, changes in myocardial contractility, as well as changes in afterload (LaPlace relation) can be ruled out.

First experience with fiberoptically directed wire-guided endobronchial blockade in severe pulmonary bleeding in an emergency setting.

We report the first use of a new wire-guided endobronchial blocker in a critical respiratory situation caused by localized pulmonary bleeding. During emergency management, it became increasingly difficult to ventilate a multiple-trauma patient with a conventional single-lumen tube because of massive bleeding through the bronchus of the left lower lobe. Using the Arndt endobronchial blocker set (William Cook Europe A/S; Bjaeverskor, Denmark), we were able to prevent the spread of hemorrhaging and achieved effective ventilation and marked improvement in gas exchange. This new device allows the effective blockade of an isolated lobe under direct bronchoscopy to buy time for further intervention.

Addition of nitric oxide to oxygen improves cardiopulmonary function in patients with severe COPD.

STUDY OBJECTIVE: To assess the effect of nitric oxide inhalation on pulmonary hemodynamics and oxygenation in patients with COPD receiving long-term oxygen therapy (LTOT). DESIGN: Prospective study. SETTING: ICU of a university medical center. PATIENTS: A total of 18 (6 female, 12 male) patients with COPD, spontaneously breathing with LTOT. INTERVENTIONS: Oxygenation and hemodynamic variables were measured and calculated at an inspired oxygen fraction (FIO2) adjusted to mimic LTOT conditions (control), and then 1 h after each sequential addition of 5, 10, and 20 ppm nitric oxide to the gas mixture. A newly developed device (Pulmonox) provided both the delivery and continuous analysis of nitric oxide and oxidative nitric oxide products. MEASUREMENTS AND RESULTS: There was a significant improvement in oxygenation at 5 ppm nitric oxide (PaO2/FIO2 ratio improved from 244+/-37 to 303+/-59, p<0.05), but no further improvement at higher doses (ceiling effect). There was a dose-dependent improvement in hemodynamic variables that was maximal at 20 ppm nitric oxide (mean pulmonary artery pressure decreased from 29+/-7 to 24+/-5 mm Hg, pulmonary vascular resistance index decreased from 565+/-321 to 392+/-215 dyne x s x cm(-5) x m(-2), and right ventricular ejection fraction improved from 34+/-6 to 39+/-7%, all p<0.05). CONCLUSION: Prior studies have demonstrated that inhaled nitric oxide may improve or worsen oxygenation in patients with COPD. Our data show an unequivocal improvement in oxygenation (albeit with a ceiling effect at 5 ppm) and pulmonary hemodynamics (dose dependent) in COPD patients receiving LTOT. Further studies are warranted to examine the usefulness of inhaled nitric oxide during acute exacerbations of COPD, or even the possibility of long-term application in patients receiving LTOT.

Platelet disorders in uraemia before and after haemodialysis under the influence of low dose aspirin.

Thrombocyte dysfunction and increased bleeding time (BT) are well documented in uraemic patients. However, these patients are frequently medicated with low dose aspirin (ASA) in order to maintain shunt patency and prevent cardiovascular events. Recently, life- threatening gastrointestinal haemorrhage in an uraemic subject taking low dose aspirin has been reported. In this work ASA related bleeding risk in uraemic patients and the effect of haemodialysis on their bleeding tendency was studied by measuring in vitro bleeding time (BT) using the Thrombostat 4000 in 34 uraemic patients on chronic haemodialysis compared to 50 healthy subjects. Our results indicate that low dose aspirin does not influence uraemic thrombopathia 8 to 10h after ingestion but seems to increase bleeding risk shortly after ingestion. Moreover, haemodialysis alters uraemic in vitro BT with regard to the time after ingestion of ASA.

Blood flow in intact and constricted coronary arteries under the influence of ouabain.

The effects of ouabain on intact and experimentally constricted coronary arteries were investigated in anaesthetized, thoracotomized dogs. Ouabain decreased the blood flow in the intact artery without changing the flow per beat values and increased flow in the constricted artery. Since ouabain decreased left ventricular enddiastolic pressure, it is proposed that the drug-induced augmentation of flow in the constricted artery is related to an elevation of driving pressure to the endocardial layers of the myocardium which are supplied by the constricted artery.

Haemodynamic and coronary actions of ouabain during coronary infusion.

The investigations were carried out on 24 mongrel dogs which were anaesthetized with chloralose or sodium pentobarbital. Ouabain was added to the coronary blood (50, 100 and 200 ng/ml coronary blood or 0.7, 1.4 and 2.8 X 10(-7) M) over periods of 30 or 60 min by intracoronary infusion of the glycoside. Under chloralose anaesthesia, ouabain at concentrations of 100 and 200 ng/ml coronary blood augmented left ventricular dp/dt significantly. No significant changes were observed in coronary resting flow and flow per beat at the same time. Likewise, the maximum reactive hyperaemic blood flow remained constant, indicating the absence of any changes in the tone of the large extramural arteries. Under sodium pentobarbital anaesthesia small decreases in heart rate and increases in left ventricular dp/dt were seen only at the highest ouabain concentration (200 ng/ml). All flow parameters remained unchanged. These experiments provide evidence that concentrations of ouabain which 100- and 200-fold exceed therapeutic maintenance levels and 10- and 20-fold exceed the concentrations that produce constriction of helically cut pig and rabbit coronary arteries in vitro, do not diminish the coronary blood supply of the anaesthetized dog in vivo.

Inhibition of the carotid chemoreceptor reflex by enflurane in chronically instrumented dogs.

The effect of the volatile inhalational anaesthetic enflurane (2 vol% and 4 vol%) on the cardiovascular response to carotid chemoreceptor stimulation (CCRS) was studied in 8 chronically instrumented dogs. Intracarotid injections of nicotine were used to evoke CCRS. Ventilation was held constant during the unanaesthetized state as well as the anaesthetized state. In the unanaesthetized state CCRS evoked an increase in iliac vascular resistance, and an increase in cardiac cycle length. Enflurane 2 vol% significantly attenuated the increases both in iliac vascular resistance as well as in cardiac cycle length. Enflurane 4 vol% abolished the response to CCRS.

Superimposed high-frequency jet ventilation for laryngeal and tracheal surgery.

OBJECTIVE: To describe our experience with superimposed high-frequency jet ventilation (SHFJV), which does not require any endotracheal tubes or catheters, for performing laryngeal and tracheal surgery. DESIGN: A case series of 500 patients. SETTING: A university medical center. PATIENTS: Four hundred sixty adult patients and 40 children in a consecutive sample who required laryngeal or tracheal surgery under SHFJV. INTERVENTIONS: The SHFJV uses 2 jet streams with different frequencies simultaneously and is applied using a jet laryngoscope. Ventilation was performed with an air-oxygen mixture, and intravenous agents were used for anesthesia. Arterial blood gas values were analyzed. MAIN OUTCOME MEASURES: Reported values of oxygenation and ventilation during the application of SHFJV and laryngotracheal surgery. RESULTS: In 497 patients, adequate oxygenation with a mean +/- SD PaO2 of 91.8 +/- 22.9 mm Hg and ventilation with a PaCO2 of 29.7 +/- 5.5 mm Hg were achieved using SHFJV. The average duration of the application of ventilation was 27 minutes, and the longest duration was 118 minutes. No complications due to the ventilation technique were observed. Laser surgery was performed in 150 patients. CONCLUSIONS: The use of SHFJV in combination with the jet laryngoscope provides patients with sufficient ventilation during laryngotracheal surgery. Even in patients at high risk because of pulmonary or cardiac disease, this technique can be applied safely. In patients with stenosis, the ventilation is applied from above the stenosis, reducing the risk of barotrauma. The SHFJV can be used for tracheobronchial stent insertion, and laser can be used without any additional protective measures.

Oxygen kinetics during liver transplantation: the relationship between delivery and consumption.

In anesthetized humans, oxygen consumption is independent of oxygen delivery above a critical threshold. Below this critical level, lactic acid is a marker of anaerobic metabolism and tissue oxygen debt, and heralds a supply dependency of oxygen consumption. The goal of this study was to determine whether a threshold value for oxygen delivery below which oxygen consumption becomes supply dependent can be identified in patients with normal, impaired, or absent liver function. Measurements were made in 34 surviving patients (group 1) and in 16 nonsurvivors with sepsis and postoperative liver graft failure (group 2). Hemodynamic measurements and blood samples were taken 10 minutes after introduction of anesthesia, 10 minutes after cross-clamping, and 10 minutes after reperfusion of the new liver. At these time points, we measured blood lactate, cardiac output, and arterial and mixed venous oxygen contents in order to calculate oxygen consumption and oxygen delivery. In both groups, cardiac output, oxygen delivery, and oxygen consumption decreased during the anhepatic phase and increased after unclamping of the inferior vena cava. Lactate increased in both groups during surgery, but was significantly higher in nonsurvivors (6.6 +/- 0.4 mmol/L) than in survivors (4.6 +/- 0.1 mmol/L) (P < .05). With similar changes for oxygen delivery and oxygen consumption during increased lactate levels we could not identify a clear supply dependency of oxygen consumption in survivors and nonsurvivors during liver transplantation. We conclude that the interpretation of blood lactate levels during circulatory shock can be biased due to a reduced lactate clearance in patients with impaired liver function, unrelated to the status of the relationship between oxygen delivery and consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen uptake-oxygen delivery alterations in the isolated liver after hydrogen peroxide challenge.

Acute, diffuse lung injury is frequently complicated by systemic organ injury and alterations in the relationship between oxygen uptake (VO2) and oxygen delivery (QO2). In this regard, systemic organ neutrophil accumulation and morphologic alterations consistent with systemic organ injury often occur in nonpulmonary organs in these settings. However, whether VO2-QO2 matching is also altered in these injured systemic organs remains unproven. Thus, the present study was designed to test the hypothesis that hydrogen peroxide (H2O2), a product of neutrophil oxidative metabolism, will cause systemic organ structural abnormalities and alter VO2-QO2 matching. To test this hypothesis, VO2-QO2 relationships, morphologic changes, and organ water content were evaluated in both uninjured, isolated perfused rabbit livers and in isolated perfused rabbit livers after injury with 5 mmol/L H2O2. Following H2O2 injury, peak VO2 fell from 1.36 +/- 0.35 mL/min/100 g to 0.79 +/- 0.16 mL/min/100 g (P < .05) and peak O2 extraction fell from 0.83 +/- 0.09 to 0.66 +/- 0.04 (P < .05). In addition, VO2 was lower for any given level of QO2 in the H2O2-injured livers compared with the control livers (P < .01). Finally, liver extravascular water content was increased in H2O2-injured livers compared with the control livers (0.79 +/- 0.02 v 0.71 +/- 0.05; P < .05). These observations indicate that H2O2, a product of neutrophil oxidative metabolism, is capable of producing both morphologic changes as well as gas exchange alterations in the isolated, perfused liver.

Impact of early high caloric duodenal feeding on the oxygen balance of the splanchnic region after severe burn injury.

Early enteral nutrition is recommended in burned patients. Depending on the amount administered, enteral feeding causes an increase of intestinal oxygen-demand. Although early moderate enteral nutrition has been shown to be beneficial, early high calorie enteral nutrition might lead to an imbalance of the O(2)-balance of the gut since intestinal perfusion is decreased after major burns. In 20 severely burned patients during the first 48 h of early high caloric duodenal feeding an assessment of the CO(2)-gap between the arterial and the gastric CO(2), as parameter for the intestinal O(2)-balance, was performed. Time points were prior to starting the enteral nutrition (BASE) subsequently every 30 min after increasing the amount of nutrition administered and from the 11th to the 48th h after beginning of nutrition in intervals of 6 h. In none of the patients was the CO(2)-gap increased during the rapid increase of enteral nutrition. On the contrary the CO(2)-gap decreased significantly. We conclude that high caloric duodenal feeding in the early hypodynamic postburn phase does not have adverse effects on the oxygen balance of the intestine.

The axillary vein central venous catheter in severely burned patients.

In severely burned patients the approach to the central vein is often difficult due to concomitant edema, but also due to the fact that the skin area, where commonly used approaches are performed, is burned as well, whereas the axillary region is often not involved. In order to perform an axillary approach to the central vein as an alternative to the commonly used approaches in patients, an anatomical dissection in fresh human cadavers was carried out. Considering the anatomical landmarks which were found during dissection of the axillary region, the axillary approach to the central vein was used in 35 patients in our intensive burn care unit with unaffected axillary skin. In three cases the only complication observed was an occasional puncture of the axillary artery without major hematoma. The infection rate of the catheters was similar to the commonly used puncture sites. This approach to the central venous line in severely burned patients can be recommended.

[Cardiac and peripheral vascular effects of the volatile inhalational anaesthetic enflurane in chronically instrumented dogs (author's transl)]. / Kardiale und peripher vaskuläre Effekte des volatilen Inhalationsanästhetikums Enfluran bei chronisch instrumentierten Hunden.

While enflurane is generally held to induce arterial hypotension, its overall effects on left ventricular (LV) performance are less clear. Accordingly, mongrel dogs were chronically instrumented with miniature LV pressure transducers, with aortic and left atrial catheters and with electromagnetic flow probes and hydraulic cuff occluders on a common iliac artery. A pair of ultrasonic transducers was implanted on opposing endocardial surfaces to measure LV internal minor axis diameter. Experiments were performed 2 to 9 weeks after surgery when the animals were resting quietly without premedication. Enflurane (2 and 4 vol.-%) decreased mean arterial pressure by 27% and 36% and led to a progressive, dose-dependent decrease in myocardial contractility and induced striking peripheral vasodilatation, i.e. LV-dP/dtmax was reduced by 32% and 54% and iliac conductance rose by 101% and 163%. However, the decrease in contractility was not associated with an increase in LV preload, i.e. LV-end-diastolic diameter was decreased by 2 vol.-%, while it was not significantly different from control values with 4 vol.-%. Thus, in intact chronically instrumented dogs the direct negative inotropic effect of enflurane is modified by a synchronous decrease in myocardial loading conditions.