The added value of cardiac index and pulse pressure variation monitoring to mean arterial pressure-guided volume therapy in moderate-risk abdominal surgery (COGUIDE): a pragmatic multicentre randomised controlled trial.

There is disagreement regarding the benefits of goal-directed therapy in moderate-risk abdominal surgery. Therefore, we tested the hypothesis that the addition of non-invasive cardiac index and pulse pressure variation monitoring to mean arterial pressure-based goal-directed therapy would reduce the incidence of postoperative complications in patients having moderate-risk abdominal surgery. In this pragmatic multicentre randomised controlled trial, we randomly allocated 244 patients by envelope drawing in a 1:1 fashion, stratified per centre. All patients had mean arterial pressure, cardiac index and pulse pressure variation measured continuously. In one group, healthcare professionals were blinded to cardiac index and pulse pressure variation values and were asked to guide haemodynamic therapy only based on mean arterial pressure (control group). In the second group, cardiac index and pulse pressure variation values were displayed and kept within target ranges following a pre-defined algorithm (CI-PPV group). The primary endpoint was the incidence of postoperative complications within 30 days. One hundred and seventy-five patients were eligible for final analysis. Overall complication rates were similar (42/94 (44.7%) vs. 38/81 (46.9%) in the control and CI-PPV groups, respectively; p = 0.95). The CI-PPV group had lower mean (SD) pulse pressure variation values (9.5 (2.0)% vs. 11.9 (4.6)%; p = 0.003) and higher mean (SD) cardiac indices (2.76 (0.62) l min-1 .m-2 vs. 2.53 (0.66) l min-1 .m-2 ; p = 0.004) than the control group. In moderate-risk abdominal surgery, we observed no additional value of cardiac index and pulse pressure variation-guided haemodynamic therapy to mean arterial pressure-guided volume therapy with regard to postoperative complications.

Influence of pH management on hemodynamics and metabolism in moderate hypothermia.

In moderate hypothermia, three different concepts of pH management have been described to date: pH-stat, alpha-stat, and alkalinity. In our study these pH strategies were compared in adult sheep, with animals serving as their own controls for direct comparability. Hemodynamic parameters, such as mean aortic pressure (from 109 +/- 12 to 72 +/- 23 mm Hg), cardiac output (from 5.55 +/- 1.25 to 4.5 +/- 0.82 L/min), and systemic oxygen consumption (from 3.73 +/- 0.8 to 1.81 +/- 0.4 ml/kg/min), decreased significantly with alpha-stat at 28 degrees C from values for normothermia. No marked or even significant differences were found among the three pH strategies in any value, with the exception of body oxygen consumption. The difference of 2% between pH-stat and alpha-stat, at 0.06 ml oxygen/kg/min, was significant (p < or = 0.05), however of no practical relevance because hypothermia itself caused a decrease of nearly 52%. With regard to myocardial parameters, pH-stat impaired myocardial function compared with both alpha-stat and alkalinity. At nearly identical mean aortic pressures and cardiac outputs, myocardial oxygen consumption reached the highest level in pH-stat (7.65 ml oxygen/100 gm/min; alpha-stat, 6.76 ml oxygen/100 gm/min; p < or = 0.05). Myocardial efficiency thus decreased from 21% (alpha-stat) to 17% (pH-stat). No evident changes in hemodynamic and metabolic values were found for alkalinity vs alpha-stat. The best response to continuously infused epinephrine, however, was found with alkalinity. According to our data there was an impairment of myocardial function without any evident further reduction in body metabolism with pH-stat vs alpha-stat. There were, however, no marked metabolic or hemodynamic differences between alkalinity and alpha-stat, with the exception of a better preservation of sensitivity to adrenergic stimuli with alkalinity.

Calculation of body transport function.

A new model for simulation of recirculation has been developed which describes the measured concentration-time course of a drug in the aorta. It is based on repetitive convolution of the injected input dilution curve with a body transport function plus the input dilution curve. If the basic shape of a body transport function, i.e. such as log-normal distribution, is known, it is possible to calculate the parameters of this function with a non-linear least-squares procedure from measured tracer dilution data. In the present investigation this algorithm is used to estimate the body transport function for experimental data, obtained in two experiments with sheep. Once the body transport function is known, the formula can be used to describe the dispersion of a drug. Intravascular concentration time curves at different places in the body can also be predicted or the blood volume can be estimated.

Application of a CCD linear array camera in the quantification of tissue staining: NBT detection in ischaemic myocardium.

A method was developed to quantify the intensity of tissue staining using a CCD (charge-coupled device) camera. Reflection spectra of NBT-stained (nitro-blue tetrazolium-stained) and unstained myocardium were recorded via fibre optics coupled to a CCD camera, connected to a microcomputer. The calculation of the intensity of staining was based on evaluation of the NBT-related changes of the reflectance spectrum. In each of six anaesthetized sheep, global ischaemia was induced by cross-clamping of the aorta. The hearts were removed and incubated at 35 degrees C. At predetermined times two sections of ventricular myocardium were taken, one of which was then stained with NBT, the other being left unstained. Evaluation of the reflectance spectra from stained sections during the first phase of ischaemia showed a slight loss of NBT colour intensity followed by a more rapid loss of staining until the values of the unstained sections were reached. In contrast to the conventional visual evaluation, the method provides quantitative data on the intensity of staining, and allows use of the NBT technique for statistical evaluation of what happens over time, and the regional distribution of ischaemic injury of tissue. This method may also be applied to other staining techniques.

Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

[Concomitant hemodynamic effects of intracoronary injections of a new transpulmonary contrast medium]. / Hämodynamische Begleiterscheinungen intrakoronarer Injektionen eines neuen lungengängigen Ultraschallkontrastmittels.

AIM: A new transpulmonary echo contrast agent (SH U 508) was injected intracoronally to six anaesthetised sheep to examine its possible direct cardiac effects. METHOD: SH U 508 was injected in randomised order in three different volumes (2, 4 and 8 ml; n = 12, 10, 9) with the same drug concentration of 200 mg/ml. RESULTS: The 2 ml and 4 ml injections had no relevant effect on the arterial, pulmonary-arterial and ventricular pressures, on the left ventricular contraction velocity and on the myocardial blood flow (less than +/- 10% of the control value). The left ventricular relaxation velocity decreased by 20%. The disturbance of the left ventricular relaxation at a volume of 8 ml was pronounced (about 40% decrease). Slight left ventricular dysfunction further manifested itself in a decreased systolic pressure (-15%) and increased left ventricular enddiastolic pressure (20%). CONCLUSION: In summary the overall effect of the intracoronary injections of SH U 508 exhibited only minor cardiac side effects. If the current results are extrapolated to peripheral-venous application, the clinically required central-venous 8 ml injection of a 400 mg/ml suspension is not expected to produce any coronary haemodynamic side effects, due to drug dilution in the pulmonary circulation and resulting low intra-coronary concentrations.

Peripheral and cardiac effects of a new phosphodiesterase inhibitor in comparison with enoximone.

The effect of the new phosphodiesterse inhibitor R80122 (E)-N-cyclohexyl-N-methyl-2-[[[phenyl(1,2,3,5-tetrahydro-2-oxoimidazo [2,1-b]-quinazolin-7-yl)methylene] amino]oxy]acetamide, (CAS 133718-29-3) on haemodynamic parameters and myocardial oxygen consumption were intraindividually compared with those of enoximone, a clinically established phosphodiesterase inhibitor. In 12 anaesthetised sheep the drugs were given in randomized order as i. v. infusions for 6 min at each setting (10, 20 and 30 micrograms.kg-1.min-1 (R80122) and 32, 64 and 96 micrograms.kg-1.min-1 (enoximone)). R 80122 as well as enoximone caused a significant increase in cardiac inotropism with a simultaneous increase of myocardial oxygen consumption. The peripheral resistance was significantly decreased by both drugs. The haemodynamic effects elicited by the application of equieffective doses of R80122 and enoximone did not show any differences.

Left-ventricular unloading by transvalvular axial flow pumping in experimental cardiogenic shock and during regional myocardial ischemia.

The efficacy of the transfemoral left-ventricular assist device Hemopump (HP; 21 Fr outer diameter) was examined in experiments with adult sheep in two different models of cardiogenic shock (tachycardia shock; ischemia shock), and during ventricular fibrillation. During tachycardia (high frequency pacing-induced; n = 14), HP assist led to a significant increase in cardiac output (from 2.2 to 2.8 liters/min), mean aortic pressure (from 47.6 to 65.6 mmHg), and myocardial perfusion pressure (from 25.5 to 59.0 mmHg). Simultaneously, a normalization of body oxygen-uptake (from 1.4 to 2.5 ml/min.kg), a decrease in myocardial oxygen consumption (from 6.1 to 4.8 ml/min.100 g), and a normalization of myocardial lactate metabolism were observed during HP assist. During regional myocardial ischemia (PTCA balloon occlusion of the proximal LAD (3.5 min; n = 12), HP assist led to significant decrease in LV end-diastolic pressure (from 21.1 to 12.1 mmHg), and increase in diastolic aortic pressure (from 58 to 67 mmHg) resulting in significant increase in coronary perfusion pressure. In the early reperfusion period, myocardial release of both lactate and potassium was significantly lowered with HP assist. During ventricular fibrillation (induced by electrical stimulation; n = 9), HP flow rates decreased from 2.5 (after 10 min) to 2.1 liters/min (after 30 min). Mean aortic pressures simultaneously decreased from 64.0 to 54.6 mmHg. Perfusion conditions were sufficient for maintenance of aerobic myocardial metabolism, but were borderline for peripheral circulation. Our hemodynamic and metabolic data demonstrate beneficial effects of cardiac assist with the Hemopump 21 Fr in both tachycardia-induced severe cardiogenic shock and during acute regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial extraction of bupivacaine in anaesthetized sheep and by hearts of sheep and rats in vitro.

We observed the in vivo kinetics of bupivacaine in the cardiopulmonary system, particularly in the pulmonary artery, the upper part of the descending aorta and the coronary sinus of anaesthetized sheep, each of which received a high dose infusion into the central vein. In some experiments dilution curves were monitored for the non-extracted dye, indocyanine green. Concentrations of bupivacaine were approximately 20% lower in the aorta than in the pulmonary artery. This gradient of bupivacaine was present across the lung for 5-10 min. Concentrations of bupivacaine in the coronary venous plasma were also markedly lower than at the arterial site. Initially more than 50% of the amount of bupivacaine at the arterial site was removed by the heart. Later, the myocardial extraction ratio decreased and plateaued at a value of 0.30-0.40. At this time, concentrations of bupivacaine in the pulmonary artery were approximately 12 micrograms ml-1. Therefore, approximately 0.3-0.6 mg of bupivacaine were extracted per minute by the sheep heart in vivo. On the other hand, isolated perfused rat hearts did not substantially remove bupivacaine (2 micrograms ml-1) from the medium. Approximately one-third of 14C-bupivacaine was retained in slices of rat and sheep myocardial tissue. However, there was no evidence that metabolism played a substantial role in the cardiac kinetics of bupivacaine.

Dopamine-dependent diastolic dysfunction in moderate hypothermia.

We designed an experimental animal study to study the effects of dopamine (DA) on diastolic function in hypothermia. DA was applied at five incremental infusion rates in 6 sheep during normothermia and moderate hypothermia (29 degrees C). Left ventricular end-diastolic pressure (LVEDP) was increased during hypothermia as compared with normothermia at all doses of DA. Contraction and relaxation velocity were changed only slightly during hypothermia; during normothermia, both velocities were markedly increased. The pronounced hemodynamic effect observed during hypothermia was further intensified by occurrence of aftercontractions, which disappeared at very high DA doses. These paradoxic results were considered the result of hypothermia-induced reduction in active transport mechanisms responsible for regulation of the cytoplasmic CA2+ concentration. The generally reduced inotropic effect of DA, the risk of paradoxic reactions, and the occurrence of aftercontractions must be taken into account when emergency drugs are administered clinically during hypothermia.

Myocardial support and protection during regional myocardial ischemia using the Hemopump assist device.

A study was designed to quantify the influence of the Hemopump on myocardial metabolism in regional myocardial ischemias induced by repetitive balloon-occlusions (3.5 minutes) of the LAD in 12 sheep (b.w. 49-61 kg). In order to make immediate comparisons and obtain paired-couples, ischemias were carried out with and without the Hemopump in operation. An energetic unloading of the left ventricle was achieved by the Hemopump already under preocclusion conditions, reducing myocardial O2-consumption from 7.52 to 5.98 ml/min/100 g LV (= 20%) as well as lowering the LVEDP from 13.3 to 9.8 mmHg (p less than or equal to 0.01). During ischemia a clear increase of LVEDP (13.3 to 21.0 mmHg) occurs, which was prevented in the group with Hemopump-assist (9.8 to 12.1 mmHg). Combined with a sustained higher diastolic aortic pressure, a better myocardial perfusion pressure resulted. Energetic unloading and improvement of perfusion conditions might be the cause of the significantly lowered release of lactate and potassium. Due to theses fibrillation (n = 3) only occurred during occlusions without Hemopump-support. In summary, a significant reduction of the ischemic burden on the myocardium was found. Thus the Hemopump could be of benefit to patients who fail to be weaned from CPB or who are suffering from instable cardiovascular performance.

Efficiency of the left ventricle assist device Hemopump in cardiac fibrillation.

We have examined in sheep the efficiency of the Hemopump during ventricular fibrillation. Circulatory arrest was induced by electrical stimulation and maintained for 30 min. Haemodynamic measurements were recorded continuously and blood samples were taken before, during and after fibrillation to determine total body and myocardial metabolic activity. All hearts were defibrillated successfully after 30 min of fibrillation. During fibrillation, the Hemopump sustained a mean arterial pressure of about 60 mm Hg with a blood flow rate of about 2.3 litre min-1. These perfusion conditions were sufficient for maintenance of aerobic myocardial metabolism, but with a borderline circulatory supply to the total organism.

[The percutaneous implantable heart-lung machine in the coronary angioplasty of high-risk and emergency patients]. / Perkutane Herz-Lungen-Maschine bei Koronarangioplastie von Risiko- und Notfallpatienten.

Using a recently developed, percutaneously introduced cardiopulmonary support system (PCPS) seven high-risk patients (four men, three women; mean age 61 [41-77] years) underwent percutaneous transluminal coronary angioplasty. In one patient, with unstable angina and in incipient cardiogenic shock, perfusion with PCPS was begun immediately before coronary angioplasty. In six patients it was undertaken with the PCPS on stand-by, but eventually not needed. Coronary angioplasty was successful in six patients, partially successful in one. Angina was considerably improved long-term in all patients, but one of them died 2.5 months afterwards at home. In two other patients (men, aged 41 and 71 years) with acute myocardial infarction, the PCPS was employed under circumstances of emergency resuscitation. In both cases recanalization of the occluded coronary artery was achieved mechanically during perfusion with PCPS; one patient survived. Availability of PCPS, also in an emergency, makes it possible to extend the indications for coronary angioplasty to include even high-risk patients.

Need for active left-ventricular decompression during percutaneous cardiopulmonary support in cardiac arrest.

During ventricular fibrillation, myocardial hemodynamic and metabolic effects of percutaneous cardiopulmonary support (PCPS) were analyzed in 11 adult sheep (body weight 77-112 kg). During supported fibrillation, an abrupt increase in left-ventricular pressures with alignment to aortic pressures was observed in 2 animals, which was probably due to spontaneous aortic regurgitation, and resulted in deterioration of coronary perfusion. In 9 animals, left-ventricular pressures rose from 22.9 +/- 4.9 to 31.2 +/- 7.9 mm Hg elevating left ventricular wall stress from 16,750 +/- 8,745 to 28,835 +/- 8,892 dyn/cm2 after 10 min of PCPS-supported fibrillation (mean flow rate 4.5 +/- 0.7 liters/min). Simultaneously, myocardial perfusion pressures decreased from an average of 32.4 +/- 11.7 to 22.3 +/- 9.4 mm Hg and myocardial lactate release was observed. Additional transapical LV venting using a 9-Fr catheter led to a decrease in both LV pressure (to 25.7 +/- 5.3 mm Hg) and wall stress (to 20,612 +/- 7,499 dyn/cm2). Left-ventricular decompression decreased myocardial oxygen consumption (from 5.3 +/- 1.4 to 4.8 +/- 0.9 ml/min.100 g), and reduced myocardial lactate release, which indicates myocardial protection. Protective effects were most pronounced using 12-Fr-, and 21-Fr-venting cannulas (with 21 Fr: decrease in myocardial oxygen consumption to 2.7 +/- 0.6 ml/min.100 g, and reversal of myocardial lactate release to lactate uptake during fibrillation). Conclusions. Hemodynamic and metabolic data clearly demonstrate the deleterious effects of PCPS to the unvented left ventricle during cardiac arrest. The results emphasize the need for active left-ventricular decompression during PCPS in ventricular fibrillation.

Pulmonary and left ventricular decompression by artificial pulmonary valve incompetence during percutaneous cardiopulmonary bypass support in cardiac arrest.

BACKGROUND: In cardiac arrest, use of percutaneous cardiopulmonary bypass support (PCPS) may lead to left ventricular loading, with deleterious effects on the myocardium, and is often accompanied by an increase in pulmonary artery pressure. The present study was designed to assess the potential of artificially induced pulmonary valve incompetency to retrogradely decompress the left ventricle during PCPS in ventricular fibrillation. METHODS AND RESULTS: Studies were performed using a standardized experimental animal model in sheep (n = 12; body weight, 77 to 112 kg). When PCPS was used during fibrillation, an increase in left ventricular pressure (from 21.4 +/- 5.0 mm Hg after 1 minute to 28.4 +/- 9.5 mm Hg after 10 minutes of fibrillation) was observed in all animals, with a simultaneous increase in pulmonary artery pressure in 6 animals, from 15.5 +/- 3.8 to 24.3 +/- 5.4 mm Hg (group A). In these animals, artificial pulmonary valve incompetency, which was induced by a special "pulmonary valve spreading catheter," led to effective decompression of both the pulmonary circulation (decrease in pulmonary artery pressure from 24.3 to 11.3 mm Hg) and the left ventricle (decrease in left ventricular pressure from 30.5 to 17.7 mm Hg). We simultaneously measured a decrease in the myocardial release of lactate (increase in arterial coronaryvenous difference in lactate content from -0.01 to 0.14 mmol/L), demonstrating the myocardial protective effect of the procedure. In contrast, in 6 animals without an increase in pulmonary artery pressure during PCPS (group B), artificial pulmonary valve incompetency did not reduce left ventricular loading, which was probably because of competent mitral valves in these animals. CONCLUSIONS: In case of increasing pulmonary artery pressure during PCPS in cardiac arrest, artificial pulmonary valve incompetency might be a useful tool for effective pulmonary and retrograde left ventricular decompression.

Transfemoral placement of the left ventricular assist device "Hemopump" during mechanical resuscitation.

The Hemopump is a new left-ventricular assist device (21 F diameter), which provides up to 3.5 L/min output after placement in the left ventricle via the femoral artery. We describe the first case in which the device was inserted during resuscitation. The patient developed untreatable sustained ventricular tachycardias/fibrillation 40 hours after coronary artery bypass grafting. After prolonged mechanical resuscitation (about 3 hours) as a last resort the Hemopump was inserted and rhythm and hemodynamics stabilized. In the following hours a decrease in aortic pressure pulsatility indicated, effective left ventricular support when the Hemopump was running. For short periods the patient had nonpulsatile aortic pressure wave forms, implying complete pump dependence. In this situation cardiac output was about 3.0 L/min, mean aortic pressure reached nearly 50 mmHg using high dosage of catecholamines. The patient remained pump-dependent and died due to untreatable ventricular fibrillation. There was no significant hemolysis during the 20 hours the Hemopump was running. Autopsy revealed no signs of thrombembolism, but intimal lesions of the A. iliaca and of the abdominal aorta with subsequent thrombus formation were demonstrated. In view of the experimentally proven benefit in cardiogenic shock and problems and risks caused by the insertion, future indications for clinical use of this new device are discussed.