Markku Hynynen

Intra-institutional prediction of outcome after cardiac surgery: comparison between a locally derived model and the EuroSCORE

OBJECTIVEnTo construct models for predicting mortality, morbidity and length of intensive care unit (ICU) stay after cardiac surgery and to compare the performance of these models with that of the EuroSCORE in two independent validation databases.nnnMETHODSnClinical data on 4592 cardiac surgery patients operated between 1992 and 1996 were retrospectively collected. In order to derive predictive models and to validate them, the patient population was randomly divided into a derivation database (n=3061) and a validation database (n=1531). Variables that were significant in univariate analyses were entered into a backward stepwise logistic regression model. The outcome was defined as mortality within 30 days after surgery, predefined morbidity, and the length of ICU stay lasting >2 days. In addition to the retrospective database, the models were validated also in a prospectively collected database of cardiac surgical patients operated in 1998-1999 (n=821). The EuroSCORE was tested in two validation databases, i.e. the retrospective and prospective one. Hosmer-Lemeshow goodness-of-fit was used to study the calibration of the predictive models. Area under the receiver operating characteristic (ROC) curve was used to study the discrimination ability of the models.nnnRESULTSnThe overall mortality in the retrospective and the prospective data was 2 and 1%, and morbidity 22 and 18%, respectively. The created predictive models fitted well in the validation databases. Our models and the EuroSCORE were equally good in discriminating patients. Thus, in the prospective validation database, the mean areas under the ROC curve for our models and for the EuroSCORE were similar, i.e. 0.84 and 0.77 for mortality, 0.74 and 0.74 for morbidity, and 0.81 and 0.79 for the length of intensive care unit stay lasting for 2 days or more, respectively.nnnCONCLUSIONSnOur models and the EuroSCORE were equally good in discriminating the patients in respect to outcome. However, our model provided also well calibrated estimation of the probability of prolonged ICU stay for each patient. As was originally suggested, the EuroSCORE may be an appropriate tool in categorizing cardiac surgical patients into various subgroups in interinstitutional comparisons. Our models may have additive value especially in resource allocation and quality assurance purposes for local use.

Propofol sequestration within the extracorporeal circuit

Various drugs administered during cardiac anaesthesia are sequestered in the extracorporeal circuit in vitro, but it is uncertain whether this sequestration phenomenon affects plasma drug concentration in vivo. The present study was undertaken to evaluate (1) in vitro sequestration of propofol in the extracorporeal circuit and (2) whether the change in plasma propofol concentration induced by initiation of cardiopulmonary bypass in vivo can be explained by haemodilution. For the in vitro evaluation, three separate experiments with a closed circuit (membrane oxygenator, reservoir, and tubings) were performed. The pH and PCO2 of the circulating solution (a mixture of Ringer’s acetate and whole blood) were maintained within the normal physiological range, and the temperature of the solution was 28° C. The solution was circulated at a flow of 4 L · min−1 and propofol was added to the solution to achieve a concentration of 2 μg · ml−1. Serial samples were taken from the circulating solution for measurement of propofol concentration by high performance liquid chromatography. In the in vivo part of the study, 14 patients received a continuous infusion of propofol, and samples for the determination of plasma propofol concentration and blood haematocrit were taken before and five and ten minutes after initiation of cardiopulmonary bypass. In vitro, at 5 and 120 min after addition of propofol into the circulating solution, approximately 65% and 25%, respectively, of the predicted propofol level was measurable in the solution. In vivo, five minutes after initiation of the cardiopulmonary bypass plasma propofol concentration decreased (P < 0.001) more (from 2.8 ±0.7 (mean ± SD) to 1.5 ± 0.5 μg · ml−1, a 45 ± 12% decrease) than would have been predicted on the basis of acute haemodilution (a decrease in haematocrit from 0.39 ± 0.04 to 0.28 ± 0.03 is a 29 ± 4% decrease). Ten minutes after initiation of cardiopulmonary bypass, plasma propofol concentration was 1.6 ± 0.5 μg · ml−1 (a 37 ± 27% decrease from the pre-bypass level) and haematocrit was 0.27 ± 0.04 (a 30 ± 6% decrease): the decrease in plasma propofol concentration was not different from the decrease observed in the haematocrit. In conclusion, propofol is markedly sequestered within the extracorporeal circuit in vitro. This sequestration may, to some extent, affect plasma propofol concentration in vivo.RésuméCette étude vise à déterminer I) l’importance de la séquestration in vitro du propofol dans le circuit de circulation extracorporelle (CEC) et 2) si l’hémodilution seule peut expliquer in vivo les changements de concentration plasmatique qui surviennent après l’initiation de la CEC. Pour l’étude in vitro, trois expériences en circuit fermé séparées (oxygénateur à membrane, réservoir et tubulures) sont effectuées. Le pH et la PCO2 de la solution circulée sont maintenus dans les limites de la normale physiologique avec une température de 28° C. La solution circule avec un débit de 4 L · min−1 et du propofol est ajouté à la solution pour obtenir une concentration de 2 μg · ml−1. Des échantillons en série sont prélevés pour la mesure de la concentration du propofol par Chromatographie en phase liquide à haute performance. Pour l’étude in vivo, 14 patients reçoivent du propofol en perfusion continue et des échantillons sont prélevés pour déterminer la concentration plasmatique de propofol et l’hématocrite à cinq et dix minutes après le début de la CEC. In vitro, à 5 et 120 min après l’ajout du propofol dans la solution circulée, environ 65% et 25% respectivement du niveau de propofol prédit sont mesurables dans la solution. In vivo, cinq minutes après l’initiation de la CEC, la concentration plasmatique de propofol diminue (P < 0,001) à un degré plus considérable (de 2,8 ± 0,7 moyenne ± SD à 1,5 ± 0.5 μg · ml−1, une baisse de 45 ± 12%) qu’on pouvait le prédire sur la base de l’hémodilution aiguë (une baisse de l’hématocrite de 0,39 ± 0,04 à 0,28 ± 0,03, soit une baisse de 29 ± 4%). Dix minutes après l’initiation de la CEC, la concentration plasmatique de propofol est de 1,6 ± 0,5 μg · ml−1 (une baisse de 37 ± 27% du niveau pré-CEC) et l’hématocrite se situe à 0,27 ± 0,04 (une baisse de 30 ± 6%); la baisse de la concentration plasmatique de propofol n’est pas différente de la baisse de l’hématocrite. En conclusion, la séquestration in vitro du propofol dans le circuit de CEC est considérable. Cette séquestration peut affecter jusqu’à un certain point la concentration de propofol in vivo.

Remifentanil Infusion Does Not Induce Opioid Tolerance After Cardiac Surgery

OBJECTIVEnRemifentanil is being used increasingly during fast-track cardiac surgery. Postoperative hyperalgesia and opioid tolerance have been reported in volunteer studies and in patients after major abdominal surgery with remifentanil infusion. In the present study, the authors evaluated whether high-dose remifentanil infusion induces opioid tolerance in 90 patients undergoing coronary artery bypass surgery with sternotomy.nnnDESIGNnProspective, randomized, and double-blind study.nnnSETTINGnSingle-institution, tertiary level, university hospital.nnnPARTICIPANTSnNinety patients undergoing coronary artery bypass surgery.nnnINTERVENTIONSnPatients were randomized to receive a 3-hour infusion of remifentanil (0.3 microg/kg/min, n = 45) or placebo (n = 45) intraoperatively as adjunct to a standardized sufentanil/propofol-based general anesthesia.nnnMEASUREMENTS AND MAIN RESULTSnOpioid consumption, pain, and sedation scores, as well as adverse events and patients satisfaction with pain therapy, were recorded for 48 postoperative hours. There were no differences in postoperative opioid consumption between the groups (median oxycodone consumption in the remifentanil group, 98 mg [range, 29-166] and in the placebo group, 99 mg [42-219]). Pain scores were comparable at rest, but during a deep breath pain scores were lower in the remifentanil group (p = 0.020). Sedation scores, satisfaction with analgesia, and adverse events were similar between the 2 groups. The most common adverse event was nausea, with a 33% incidence in the placebo and 40% incidence in the remifentanil group.nnnCONCLUSIONnThree-hour remifentanil infusion did not increase postoperative pain or opioid consumption in cardiac surgery patients. The present results suggest that high-dose remifentanil does not elicit opioid tolerance when given during cardiac surgery.

Plasma atrial natriuretic peptide concentrations during induction of anesthesia and acute volume loading in patients undergoing cardiac surgery

Induction of anesthesia with fentanyl for coronary artery bypass grafting decreased (P less than .05) plasma atrial natriuretic peptide (ANP) concentrations from awake values in twelve patients. During a steady state of anesthesia before surgery, isotonic saline solution (10 mL/kg) was infused simultaneously with the elevation of the lower extremities in six patients, while six subjects served as controls receiving no volume loading and having no leg raising. The ANP levels returned to the awake values in the volume-loaded patients, while plasma ANP remained at anesthetized baseline levels in the control subjects (P less than .01 between the groups). Ten minutes after the end of the loading procedure, plasma ANP had begun to decrease again towards the postinduction level in the loaded group, but a significant (P less than .05) difference was still observed between the groups. These changes in ANP levels paralleled those of cardiac filling pressures. In conclusion, the results suggest that the degree of distention of the atria regulates the secretion of atrial natriuretic peptide into the circulation in patients anesthetized with fentanyl.

Hemodynamic responses to desmopressin acetate after CABG: A double-blind trial

Despite controversial results concerning its effectiveness, cardiac surgical patients commonly receive desmopressin acetate (DDAVP) after cardiopulmonary bypass (CPB) in an effort to prevent or control bleeding diathesis. The side effects associated with DDAVP are usually considered benign. However, numerous authors have observed episodes of severe hypotension after DDAVP. As a part of a larger trial of DDAVP in routine first-time coronary artery bypass grafting (CABG), this randomized double-blind study of the hemodynamic effects of DDAVP was performed. Fifteen patients received DDAVP (0.3 microgram/kg over 15 minutes) and another 15 received saline placebo after skin closure. A statistically significant decrease in mean arterial pressure (MAP) was observed at 5 minutes after the beginning of DDAVP administration and the maximum decrease (mean change, -21 +/- 8 mm Hg, P less than 0.001) was reached as the infusion was completed. MAP did not change significantly in the control group. Hypotension after DDAVP was associated with a corresponding decrease in systemic vascular resistance. Postoperative blood loss was not different between the groups. It is concluded that routine administration of DDAVP to CABG patients is inadvisable because hemodynamic side effects are potentially dangerous and therapeutic benefit is highly unlikely.

Atria1 pressure and hormonal and renal responses to acute cardiac tamponade

The effect of acute cardiac tamponade on atrial pressures, plasma atrial natriuretic factor concentration and renin activity, and renal water and electrolyte excretion was studied in pigs loaded intravenously with hydroxyethyl starch and maintained on a continuous intravenous infusion of isotonic saline solution. Saline solution was infused into the pericardial space in 6 anesthetized pigs until a predetermined decrease of 20% in mean arterial pressure was achieved. Another 6 sham-treated pigs served as controls. Tamponade increased atrial intracavitary pressures but decreased atrial transmural (distending) pressures. These changes in atrial pressures were reversed after release of tamponade. Changes in plasma atrial natriuretic factor concentration correlated positively with changes in atrial transmural pressures. Tamponade increased plasma renin activity and decreased urine flow and renal sodium and potassium excretion, and release of tamponade reversed these changes. Thus, the tamponade-induced reduction in atrial distention is associated with hormonal changes, which may contribute to the reductions in diuresis and natriuresis observed in this connection.

Anaesthesia for Patients Undergoing Prolonged Reconstructive and Microvascular Plastic Surgery

The anaesthesiological problems related to prolonged reconstructive plastic surgery in 22 patients were investigated in retrospect. Surgery consisted mainly of reconstructions, including microvascularization (7 emergency reimplantations, 15 plastic reconstructions), and the duration of the balanced anaesthesias varied between 5 h 10 min and 15 h 35 min. As the patients were relatively young and healthy, no serious cardiovascular complications occurred. Blood loss was intentionally replaced with dextran, in most instances, and in a group of 15 elective patients, mean haematocrit level decreased from 0.41 to 0.31 during surgery. In about half of the material, the central temperature was monitored; it remained within 35.8-38 degrees C. In the longest anaesthesia (15 h 35 min) the temperature stayed within 0.4 degrees C, the patient placed on a heating mattress. In 2 patients, transient paresis of the muscles of the hand, which was exposed and abducted for i.v. infusion and blood pressure recording, was observed. A questionnaire was sent to the patients and 19 of 20 responded. The predominant subjective complaint was nausea, while sensations following catheterization of the bladder were also a common untoward recollection. One patient developed laryngeal oedema after extubation and about a third experienced breathing difficulties on awakening from the anaesthesia. Postoperative pain appeared not to be a significant problem.

Vasodilator properties of atrial natriuretic factor: A comparison with nitroglycerin, nitroprusside, and phentolamine during cardiopulmonary bypass

Thirty-five patients scheduled for coronary artery surgery were studied during hypothermic cardiopulmonary bypass (CPB) to compare the arteriolar and venodilator properties of a bolus dose of atrial natriuretic factor (ANF), 100 micrograms, with those of nitroglycerin, 200 micrograms, sodium nitroprusside, 120 micrograms, phentolamine, 3 mg, and placebo. A decrease observed in mean arterial pressure was used as an indicator of a decrease in systemic vascular resistance (arteriolar dilation), while a decrease in reservoir blood volume of the CPB circuit was considered to indicate an increase in venous capacitance (venodilation). All vasodilators decreased mean arterial pressure, and there was no difference in the maximal decrease of the pressure between the drugs. However, the decrease caused by ANF appeared later than that caused by the other vasodilators and lasted longer than with nitroglycerin and sodium nitroprusside. Nitroglycerin and sodium nitroprusside decreased reservoir blood volume, while ANF and phentolamine had no effect. It is concluded that ANF is an arteriolar dilator with a time profile of its effect differing from those of nitroglycerin, sodium nitroprusside, and phentolamine. ANF seems to have no venodilator activity in patients undergoing hypothermic CPB.

Plasma atrial natriuretic factor during cold-induced diuresis

SummaryThe purpose of this study was to evaluate the possible contribution of atrial natriuretic factor (ANF) to cold-induced diuresis. Seven healthy men, dressed in shorts, were exposed to a cold environment (+12°C) for 90 min, and also to a thermoneutral environment. Exposure to cold increased urine output and sodium excretion significantly but plasma ANF concentration remained unchanged. The increase in urinary potassium excretion during cold exposure was not significant (P=0.0636) and plasma renin activity did not change either. Exposure to cold increased mean arterial pressure significantly but it did not affect heart rate. We concluded that acute exposure to the cold environment induced a diuretic response, which was a solute diuresis in its nature. Our results did not give support to the hypothesis that ANF might be involved in the renal response to cold exposure.

Pharmacokinetics and effects of atrial natriuretic factor during hypothermic cardiopulmonary bypass

SummaryThe pharmacokinetics of a bolus dose of synthetic atrial natriuretic factor (ANF) 50 μg and its effects on urine output, blood pressure and plasma renin activity have been studied in 5 patients undergoing hypothermic cardiopulmonary bypass for cardiac surgery.The half-lives of the fast and slow components were 2.4 min and 14.2 min, respectively. The volume of the central compartment was 16.71 and the volume of distribution at steady-state was 38.91. The total plasma clearance was 3.81-min−1.ANF significantly increased urine output and decreased blood pressure, but it did not affect plasma renin activity.