Cardiac outcome after sevoflurane versus propofol sedation following coronary bypass surgery: a pilot study.

BACKGROUND: Studies of volatile anesthetic administration during coronary artery bypass grafting (CABG) report reduced serum levels of post-operative cardiac troponin-T (cTnT). Our primary objective was to evaluate whether short-term sedation with sevoflurane in the intensive care unit (ICU)--after CABG--could affect the release of cTnT, compared with propofol sedation. METHODS: Following isolated CABG with cardiopulmonary bypass, 100 patients were randomized to either sevoflurane via the Anesthetic Conserving Device (AnaConDa(®)) or propofol for ICU sedation. Study drugs were administered for 2 h during mechanical ventilation and thereafter until extubation criteria were met. The primary endpoint was cTnT 12 h post-operatively. Crude cTnT data were not normally distributed and therefore compared with the Mann-Whitney U-test. Because of the skewed pre-operative and post-operative cTnT data, we performed a post hoc analysis of the change in cTnT between pre-operative values and 12 h post-operatively. RESULTS: There was no statistically significant difference between groups in the primary endpoint cTnT values at 12 h post-operatively, cardiac events or the need for hemodynamic support. In the post hoc analysis, the cTnT increase from pre-operative values to 12 h post-operatively was less pronounced in the sevoflurane group (P=0.008). CONCLUSION: Post-operative short-term sevoflurane sedation following CABG, in comparison with propofol, did not affect the cTnT values at 12 h post-operatively and clinical outcome was equal between groups. The result from the post hoc analysis, with less cTnT change over time, is nevertheless hypothesis-generating and warrants a larger study.

Release of neuropeptide Y and noradrenaline from the human heart after aortic occlusion during coronary artery surgery.

STUDY OBJECTIVE: The aim was to study the influence of complete myocardial ischaemia during aortic occlusion on release of neuropeptide Y and noradrenaline from the human myocardium. DESIGN: Coronary sinus neuropeptide Y and noradrenaline were measured after 46(SEM 7) min of aortic occlusion with cold cardioplegia in patients undergoing coronary artery surgery. Patients - Seven patients (all male), aged 64(SEM 3) years, were studied. All were undergoing coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS: Reperfusion was associated with an increase in coronary sinus blood flow as determined by thermodilution. Simultaneously there was cardiac release of both neuropeptide Y and noradrenaline during the first two sampling periods: 3(0.6) and 7(0.6) min after the start of reperfusion. The outflow of neuropeptide Y and noradrenaline returned to preischaemic values by 14(1) min after reperfusion. Coronary sinus blood lactate and pyruvate concentrations were also increased at the start of reperfusion, while the lactate/pyruvate ratio remained unchanged. Myocardial oxygen uptake was not influenced by cardiac ischaemia. CONCLUSIONS: Ischaemia of the human heart in vivo is associated with an enhanced outflow of neuropeptide Y and noradrenaline from the heart. Since arterial blood concentrations of these substances were also increased on reperfusion, their release is probably due to increased sympathetic nerve activity, though other mechanisms such as temperature change and local metabolite formation could also participate. Local release of neuropeptide Y during cardiac ischaemia may be involved in the regulation of coronary vascular tone as well as in the release of noradrenaline and acetylcholine.

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

Myocardial outflow of calcitonin gene-related peptide in relation to metabolic stress during coronary artery bypass grafting without cardiopulmonary bypass.

OBJECTIVE: Because of adverse effects of cardiopulmonary bypass and the prospect of shortening intensive care and hospital stay, coronary artery bypass grafting without cardiopulmonary bypass is gaining increased attention. The impact of the localized myocardial ischemia that is inherent in these procedures has not been thoroughly investigated in human beings. We have investigated metabolic changes, possible myocardial damage, and myocardial outflow of the vasodilator calcitonin gene-related peptide during coronary artery bypass grafting without cardiopulmonary bypass. METHODS: Coronary sinus and arterial blood was sampled before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 consecutive patients (mean age 70 +/- 5 years) who had an anastomosis performed to the left anterior descending artery without cardiopulmonary bypass. RESULTS: No perioperative myocardial infarctions occurred. The arteriovenous difference in lactate decreased during ischemia, to reach a minimum after 1 minute of reperfusion (-0.17 +/- 0.25 vs 0.15 +/- 0.25 mmol/L before ischemia; P =.008). Myocardial lactate extraction decreased (from 11.2 +/- 13.6 micromol/min before ischemia to -3.0 +/- 7.0 micromol/min after 1 minute of reperfusion; P =.012), that is, a net production of lactate. The arteriovenous difference in calcitonin gene-related peptide decreased from -0.1 +/- 2.6 pmol/L before ischemia to -30.5 +/- 26.5 pmol/L (P =.008) after 1 minute of reperfusion. CONCLUSIONS: The localized myocardial ischemia associated with these procedures causes metabolic changes in the myocardium, but no myocardial damage. The ischemia-related outflow of calcitonin gene-related peptide indicates that the vasodilating and cardioprotective properties of this peptide that are known from animal studies may be of importance in myocardial ischemia in human beings.

Myocardial outflow of prostacyclin in relation to metabolic stress during off-pump coronary artery bypass grafting.

BACKGROUND: The metabolic changes, possible myocardial damage, and influence on the vascular endothelium during off-pump coronary artery bypass grafting have been investigated. METHODS: Coronary sinus and arterial blood samples were obtained before coronary arterial occlusion, after 10 minutes of ischemia, and after 1 and 10 minutes of reperfusion in 9 patients who had an anastomosis performed to the left anterior descending coronary artery off-pump bypass RESULTS: The mean ischemic time was 14 +/- 1 minutes. The arteriovenous difference in lactate decreased during ischemia to reach a minimum at 1 minute of reperfusion (-0.15 +/- 0.06 micromol/L compared to 0.21 +/- 10 micromol/L before ischemia; p < 0.01). Myocardial lactate extraction decreased from 14.2 +/- 6.8 micromol/min before ischemia to -10.9 +/- 6.5 micromol/min after 1 minute of reperfusion (p < 0.01). Simultaneously, the arteriovenous difference in 6-keto-PGF(1alpha), the stable metabolite of prostacyclin, decreased from -30 +/- 26 pg/mL to -258 +/- 80 pg/mL at 1 minute of reperfusion (p < 0.05), and the 6-keto-PGF(1alpha) extraction over the heart decreased -556 +/- 466 pg/min to -18,560 +/- 5,683 pg/min (p < 0.01). CONCLUSIONS: The localized myocardial ischemia associated with these procedures causes changes in the myocardium and endothelial influence. Coronary bypass surgery performed on the beating heart may not be superior in preventing cardiac ischemia and endothelial disturbance, compared with conventional bypass surgery.

Is endothelin-1 release at reperfusion of the ischaemic human heart due to cold-induced displacement of endothelin from binding sites?

Following reperfusion of ischaemic human hearts subjected to cold (4 degrees C) cardioplegia during coronary bypass surgery, there was an increase in cardiac outflow of endothelin-1 but not the pro-peptide big endothelin-1. Furthermore, specific endothelin-1 binding in human lung membrane preparations was displaced by incubation in buffer medium at 4 degrees C. The present results thus indicate that cold-induced displacement of endothelin-1 binding, rather than increased synthesis, may explain the cardiac release of endothelium-1 following ischaemia during heart surgery in which cold cardioplegia has been used.

Plasma concentrations following repeated rectal or intravenous administration of paracetamol after heart surgery.

BACKGROUND: Paracetamol is commonly used for post-operative pain management in combination with more potent analgesics. The best route of paracetamol administration after major surgery, when oral intake may not be optimal, is not known. Our primary purpose was to study plasma concentrations after the 1st and 4th dose of 1 g of paracetamol given either rectally or intravenously (i.v.) after major surgery. METHODS: In this prospective, randomized study, 48 patients undergoing heart surgery were randomized upon arrival to the intensive care unit (ICU) to receive paracetamol every 6th hour either as suppositories or intravenous injections. In half the patients (n = 24), blood samples for paracetamol concentration were obtained before and 20, 40 and 80 min after the first dose. In the other patients (n = 24), additional samples were taken prior to, and at 20, 40, 80 min and 4 and 6 h after, the 4th dose. RESULTS: Plasma paracetamol concentration peaked (95 +/- 36 micromol/l) within 40 min after initial i.v. administration but did not increase within 80 min after the 1st suppository. Plasma concentration before the 4th dose was 74 +/- 51 and 50 +/- 27 in the rectal and i.v. groups, respectively. Paracetamol concentration peaked 20 min after the 4th dose for the i.v. patients (210 +/- 84 micromol/l) and declined to 99 +/- 27 micromol/l at 80 min as compared with the rectal patients 69 +/- 44 to 77 +/- 48 micromol/l. CONCLUSION: Both time course and peak plasma concentrations of paracetamol given rectally differ from the one seen after intravenous administration. The clinical impact of these differences needs further investigation.

Are even impaired fasting blood glucose levels preoperatively associated with increased mortality after CABG surgery?

AIMS: Impaired fasting glucose (IFG) below the diagnostic threshold for diabetes mellitus (DM) is associated with macrovascular pathology and increased mortality after percutaneous coronary interventions. The study goal was to determine whether pre-operative fasting blood glucose (fB-glu) is associated with an increased mortality after coronary artery bypass grafting (CABG). METHODS AND RESULTS: During 2001-03, 1895 patients underwent primary CABG [clinical DM (CDM) in 440/1895; complete data on fB-glu for n=1375/1455]. Using pre-operative fB-glu, non-diabetics were categorized as having normal fB-glu (<5.6 mmol/L), IFG (5.6< or =fB-glu<6.1 mmol/L), or suspected DM (SDM) (> or =6.1 mmol/L). fB-glu was normal in 59%. The relative risks of 30 day and 1 year mortality compared with patients with normal fB-glu was 1.7 [95% confidence interval (CI): 0.5-5.5] and 2.9 (CI: 0.8-11.2) with IFG, 2.8 (CI: 1.1-7.2) and 1.9 (CI: 0.5-6.3) with SDM vs. 1.8 (CI: 0.8-4.0) and 1.6 (CI: 0.6-4.3) if CDM, respectively. The receiver operator characteristic area for the continuous variable fB-glu and 1 year mortality was 0.65 (P=0.002). CONCLUSION: The elevated risk of death after CABG surgery known previously to be associated with CDM seems also to be shared by a group of similar size that includes patients with IFG and undiagnosed DM.

Effects of thoracic epidural analgesia on glucose homeostasis after cardiac surgery in patients with and without diabetes mellitus.

BACKGROUND AND OBJECTIVE: Even moderate hyperglycaemia increases mortality/morbidity after coronary artery bypass grafting, stroke and myocardial infarction. The goal of this prospective study was to determine if using thoracic epidural analgesia from start of surgery until the end of the third postoperative day would blunt postoperative hyperglycaemia. METHODS: Forty-four patients had diabetes mellitus, 60 did not; half of each group had an epidural with continuous local anaesthetics. All patients received continuous insulin infusions during the initial 24 h period beginning with surgery. Blood glucose was measured four times daily (fasting or 2-3 h post-prandial) until end of the third postoperative day. RESULTS: For patients without diabetes, the epidural group had lower mean blood glucose and insulin requirements (P < 0.02) than controls during the initial 24 h period beginning with surgery. For patients with diabetes mellitus, thoracic epidural analgesia reduced mean blood glucose (P = 0.017) with unchanged insulin requirements. Epidural did not diminish the increase (vs. preoperative) in fasting blood glucose on the third postoperative day (32% vs. 22%, P < 0.001) for non-diabetics. Epidural analgesia was not able to attenuate hyperglycaemia during the first 3 postoperative days. CONCLUSIONS: Epidural analgesia improved glucose homeostasis minimally during the initial 24 postoperative hours but did not attenuate hyperglycaemia during the subsequent 3 postoperative days.

Clinical comparison of three different anaesthetic depth monitors during cardiopulmonary bypass.

The lack of a gold standard complicates the evaluation and comparison of anaesthetic depth monitors. This randomised study compares three different depth-of-anaesthesia monitors during cardiopulmonary bypass (CPB) at 34 degrees C with fentanyl/propofol anaesthesia adjusted clinically and blinded to the monitors. Coronary artery bypass grafting patients (n = 21) were randomly assigned to all three possible paired combinations of three monitors: Bispectral Index (Aspect Medical), AAI auditory evoked potential (Danmeter), Entropy (Datex-Ohmeda). Indices were manually recorded every 5 min during CPB. Agreement between paired indices was classified as good, non-, or disagreement. Anaesthesia was classed as adequate, inadequate, or excessive according to recommended index values. Of the 255 paired indices recorded, 62% showed good agreement, 33% showed non-agreement, and 5% showed disagreement. Using good agreement between two monitors as a gold standard, a quarter of the measurements indicate inappropriate anaesthetic depth monitoring during CPB with clinically titrated anaesthetic depth.

Myocardial effects of adenosine- and sodium nitroprusside-induced hypotension: a comparative study in patients anaesthetized for abdominal aortic aneurysm surgery.

The effects of adenosine and sodium-nitroprusside (SNP) on central and myocardial haemodynamics and metabolism were evaluated during fentanyl anaesthesia (100 micrograms.kg-1) in six patients with peripheral vascular disease. The investigation was performed during stable anaesthesia, before scheduled abdominal aortic graft surgery. Adenosine and SNP were infused intravenously in random order over 20 min, leaving a 30-min control period in between. The vasodilators were titrated in order to reduce mean arterial pressure by approximately 25%. Adenosine (90 +/- 20 micrograms.kg-1.min-1) reduced mean arterial pressure from 10.9 +/- 0.3 to 8.4 +/- 0.4 kPa (82 +/- 3 to 63 +/- 3 mmHg), and SNP (0.7 +/- 0.1 micrograms.kg-1.min-1) from 11.0 +/- 0.2 to 8.4 +/- 0.3 kPa (83 +/- 3 mmHg to 63 +/- 3 mmHg), during the hypotension period. Cardiac index remained unaffected during induced hypotension with both vasodilators, while heart rate increased during SNP infusion (8 +/- 3%) and remained unaffected with adenosine. Left ventricular stroke work index and myocardial oxygen consumption decreased during SNP infusion (33 +/- 3% and 17 +/- 5%, respectively), while these parameters were unchanged with adenosine. Adenosine hypotension increased coronary sinus flow 1-2 fold (128 +/- 26%), together with increased coronary sinus oxygen content (96 +/- 11%). In contrast, coronary sinus flow decreased during SNP hypotension (-15 +/- 4%) with unaffected coronary sinus oxygen content. It is concluded that adenosine, in contrast to SNP, is associated with a hyperkinetic myocardial circulation.

Effects of adenosine-induced hypotension on myocardial hemodynamics and metabolism during cerebral aneurysm surgery.

The effects of adenosine-induced hypotension on central as well as myocardial hemodynamics and metabolism were studied in five neurolept-anesthetized patients without known heart or lung diseases, who were undergoing cerebral aneurysm surgery. Adenosine (217 +/- 32 micrograms.kg-1.min-1) decreased mean arterial pressure 30% from 77 +/- 5 to 54 +/- 3 mm Hg. Cardiac filling pressures and heart rate remained unchanged during hypotension. Adenosine decreased systemic vascular resistance 50 +/- 5% while cardiac index increased 39 +/- 10%. Coronary sinus blood flow increased by 73 +/- 13% from 128 +/- 18 to 224 +/- 36 ml/min with a concomitant decrease in calculated coronary vascular resistance (66 +/- 4%). Both systemic and myocardial arteriovenous oxygen content differences decreased, and myocardial oxygen consumption decreased 42 +/- 9%. There were no alterations in myocardial fractional lactate extraction. Arterial plasma renin activity and arterial catecholamine levels were unaffected by hypotension. It is concluded that adenosine hypotension in this group of patients produced a hyperkinetic circulation in the systemic as well as in the myocardial vascular bed. Cardiac output and coronary sinus blood flow increased at the same time as myocardial oxygen consumption decreased.

Incidence of sore throat and patient complaints after intraoperative transesophageal echocardiography during cardiac surgery.

To evaluate the incidence of postoperative side effects and patient complaints following transesophageal echocardiography (TEE), 57 patients were interviewed by questionnaire and examined by pharyngeal inspection, preoperatively. The patients were randomized to undergo surgery with or without intraoperative TEE, and a second interview and examination were performed in 48 patients on the second postoperative day using a double-blind protocol. Twenty-four of the patients were investigated by TEE over a period of 5.4 +/- 2.3 hours and 24 had surgery without TEE. The intubation time for the two groups did not differ. There was no difference between controls and TEE patients with regard to painful swallowing evaluated by a visual analog scale. Furthermore, there was no difference between the controls and TEE patients regarding nausea or time elapsed from extubation to the first oral intake. No differences between the groups were found regarding the findings on pharyngeal inspection and no major complication attributable to the use of TEE occurred. A sore throat with painful swallowing was not a great problem for the patients in the present study; this indicates that endotracheal intubation rather than TEE caused the minor complaints. It is concluded that intraoperative TEE can be used without harmful postoperative pharyngeal side effects.

Influence of adenosine and prostacyclin on hypoxia-induced pulmonary hypertension in the anaesthetized pig.

The effects of adenosine and prostacyclin (PGI2) infusions on hypoxia-induced pulmonary hypertension in the pulmonary and systemic circulatory systems of nine pigs were compared. The animals received the drugs in random order, and they were allowed to recover between each experimental sequence. Hypoxia was induced by reducing FiO2 to 0.12-0.13 so as to result in an arterial PO2 of approximately 6 kPa. Dose rates of adenosine or PGI2 during hypoxia were individualized in order to achieve a maximal reduction of 15% in the mean arterial blood pressure. Adenosine and PGI2 produced a fall in pulmonary vascular resistance of 36 +/- 4% (s.e.mean P less than 0.01) and 37 +/- 6% (P less than 0.01), respectively. The mean pulmonary artery pressure was reduced by 19 +/- 3% (P less than 0.01) during adenosine infusion and by 36 +/- 4% (P less than 0.01) during PGI2 infusion. The systemic haemodynamic responses to the two drugs were similar but adenosine produced a 7 +/- 2% (P less than 0.01) increase in cardiac output. Arterial PO2 during hypoxia and vasodilator treatment did not differ from the hypoxic situation without drug infusion. It is concluded that adenosine and PGI2 counteract hypoxia-induced increases in pulmonary vascular resistance similarly, but the reduction in pulmonary artery pressure was greater with PGI2 at infusion rates, causing minor systemic haemodynamic changes.

Entropy during propofol hypnosis, including an episode of wakefulness.

Depth of anaesthesia has proved to be a complex process to quantify. Monitors based on bispectral analysis of the electroencephalogram and auditory evoked potential have been available, but only recently has a monitor based on entropy become available. This study determined state entropy and response entropy in nine healthy volunteers during propofol hypnosis with a brief intervening period of wakefulness. Both the calculated entropy indices decreased with increasing levels of sedation (r2 = 0.58 and 0.61, respectively) and they showed a high correlation with each other (r2 = 0.94). However, an overlap was observed in real time indices between different stages of the Observer's Assessment of Alertness/Sedation Scale. Only three of the nine volunteers had explicit memories from the episode of wakefulness. Electroencephalographic entropy monitors seem to have potential for staging clinical hypnotic effects.

Influence of adenosine-induced hypotension on the canine myocardium rendered acutely ischaemic by artificial stenosis.

An open-chest preparation was carried out in 14 pentobarbitone anaesthetized dogs in order to evaluate the myocardial effects of controlled hypotension induced by adenosine in the presence of a severe coronary stenosis that caused ischaemia of the left anterior ventricular wall. Myocardial performance, blood flow and metabolism were studied before and during a 78 +/- 3% reduction of flow in the left anterior descending coronary artery (LAD) and during adenosine-induced hypotension (approximately 40% reduction of the mean arterial pressure) in the presence of the LAD stenosis. The LAD stenosis decreased the myocardial lactate uptake (P less than 0.01), increased ST-T segment depression (P less than 0.05) of the left ventricular subendocardial ECG, and reduced cardiac output by 10% (P less than 0.05). In the presence of stenosis, the mean arterial pressure was reduced by adenosine from 10.4 +/- 0.6 kPa to 6.3 +/- 0.2 kPa for 15 min. Heart rate decreased by 22% (P less than 0.01). There was no change in cardiac output during hypotension, while the rate-pressure product decreased by 47% (P less than 0.01) and myocardial oxygen consumption decreased by 30 +/- 7%. Adenosine increased the coronary sinus blood flow by 52% (P less than 0.01), while the LAD flow distal to the stenosis was not significantly reduced. Myocardial lactate uptake was not further reduced and subendocardial ECG signs of ischaemia were not aggravated by the hypotension. In conclusion, adenosine-induced hypotension did not aggravate the subendocardial ECG signs of acute poststenotic myocardial ischaemia. Nor did myocardial lactate determinations indicate aggravation of myocardial ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelin infusion reduces hypoxic pulmonary hypertension in pigs in vivo.

Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pulmonary circulation after hypoxia-induced hypertension. Pits under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled O2 from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion through the Swan-Ganz catheter in the right ventricle. Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET-1 (10, 25 and 50 ng kg-1 min-1) dose-dependently decreased MPAP and PVR; at a higher dose (100 ng kg-1 min-1), the PVR returned to the level observed at hypoxia. ET-infusions at 50 and 100 ng kg-1 min-1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET-1 infusion. Infusion of ET-3 evoked effects similar to those of ET-1 infusions, although the response to ET-3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET-1 (25 ng kg-1 min-1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET-infusion. ET-1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia. It is concluded that in the pig, short-term ET-infusion reduces the pulmonary hypertension associated with acute hypoxia.

Effect of adenosine-induced controlled hypotension on canine myocardial performance, blood flow and metabolism.

The effect of adenosine-induced controlled hypotension (CH) on myocardial performance, blood flow, and metabolism was studied in nine pentobarbital-anaesthetized, open-chest dogs. Adenosine was continuously infused i.v. (0.69 +/- 0.06 and 1.36 +/- 0.11 mg/kg/min) at two stepwise increased rates (12-14 min-periods) in order to induce approximately 20 and 40% reduction of the mean arterial pressure (MAP 62 +/- 4 and 43 +/- 1 mmHg, respectively). The reduction of MAP was associated with decreases in heart rate (6 +/- 2%, P less than 0.05 and 21 +/- 4%, P less than 0.01), left intraventricular systolic pressure (14 +/- 3%, P less than 0.01 and 32 +/- 3%, P less than 0.01), left ventricular end-diastolic pressure (23 +/- 9%, P less than 0.05 and 42 +/- 9%, P less than 0.01) and ventricular intramyocardial systolic pressure (15 +/- 6% n.s. and 27 +/- 6%, P less than 0.01). The rate pressure product was markedly reduced by 49 +/- 3% (P less than 0.01) at the highest infusion rate. The mean coronary vein pressure (20.3 +/- 2.8 mmHg) was unaffected by the adenosine infusion. The systolic pressure time index (SPTI) was decreased by 33 +/- 3% (P less than 0.01) during the highest infusion rate of adenosine, while the diastolic perfusion time index (DPTI) was 15.4 +/- 2.2 mmHg X s and remained unchanged. The DPTI:SPTI ratio increased by 40 +/- 13% (P less than 0.05), suggesting a sufficient endocardial oxygen supply.(ABSTRACT TRUNCATED AT 250 WORDS)

Early bioavailability of paracetamol after oral or intravenous administration.

BACKGROUND: Paracetamol is a peripherally acting analgesic commonly used in multimodal post-operative pain management to reduce the need for more potent analgesics with their unwanted side-effects. The dose and optimal galenical form for achieving analgesic concentrations is not well defined. The primary aim of this pilot project was to study the early bioavailability for two fixed doses of orally administrated paracetamol and one dose of intravenous propacetamol, all of which were given after minor surgery. METHODS: Thirty-five patients undergoing day surgery were divided into five groups, seven patients each. Groups received either 1 g of an ordinary paracetamol tablet, 2 g of an ordinary paracetamol tablet, 1 g of a bicarbonate paracetamol tablet, 2 g of a bicarbonate paracetamol tablet or 2 g intravenously of prodrug propacetamol. We studied the plasma concentration of paracetamol during the first 80 min after administration. RESULTS: Within 40 min, intravenous propacetamol gave a median plasma paracetamol concentration of 85 micromol/l (range 65-161) and decreased thereafter. After oral administration, median plasma paracetamol concentration increased with increasing dose and time, but there were huge inter-individual differences at all time points studied. At 80 min after oral paracetamol the median plasma concentrations were 36 and 129 micromol/l for the 1- and 2-g groups, respectively, with an overall range between 0 and 306 micromol/l. CONCLUSION: Oral administration of paracetamol as part of multimodal pain management immediately post-operatively resulted in a huge and unpredictable variation in plasma concentration compared with the intravenous administration.

Myocardial ischaemia as judged from transoesophageal echocardiography and ECG in the early phase after coronary artery bypass surgery.

The incidence of myocardial ischaemia, as diagnosed by transoesophageal echocardiography (TEE) versus ECG, and the relationship between ischaemic events and haemodynamic parameters were studied in 30 patients in the early phase after coronary artery bypass grafting. Information comprising invasive haemodynamics, TEE measurements, and 12-lead ECG was obtained on arrival of the patient in the intensive care unit (ICU), and then hourly in the ICU for 5 h. In the ICU, TEE signs of ischaemia were found in 14 patients and ECG signs of ischaemia in six patients. The ischaemic events were not related to levels of blood pressure or heart rate. Three patients showed signs of myocardial infarction postoperatively. All three of these patients showed both TEE and ECG signs of ischaemia in the ICU. It was concluded that TEE reveals more ischaemic events than ECG in the early postoperative period and that these ischaemic events do not correlate with the haemodynamic indices.