H. Stephan

Effects of one minimum alveolar anesthetic concentration sevoflurane on cerebral metabolism, blood flow, and CO2 reactivity in cardiac patients.

UNLABELLED We investigated the cerebral hemodynamic effects of 1 minimum alveolar anesthetic concentration (MAC) sevoflurane anesthesia in nine male patients scheduled for elective coronary bypass grafting. For measurement of cerebral blood flow (CBF), a modified Kety-Schmidt saturation technique was used with argon as an inert tracer gas. Measurements of CBF were performed before the induction of anesthesia and 30 min after induction under normocapnic, hypocapnic, and hypercapnic conditions. Compared with the awake state under normocapnic conditions, sevoflurane reduced the mean cerebral metabolic rate of oxygen by 47% and the mean cerebral metabolic rate of glucose by 39%. Concomitantly, CBF was reduced by 38%, although mean arterial pressure was kept constant. Significant changes in jugular venous oxygen saturation were absent. Hypocapnia and hypercapnia caused a 51% decrease and a 58% increase in CBF, respectively. These changes in CBF caused by variation of Paco2 indicate that cerebrovascular CO2 reactivity persists during 1 MAC sevoflurane anesthesia. IMPLICATIONS We used a modified Kety-Schmidt saturation technique to investigate the effects of 1 minimum alveolar anesthetic concentration (MAC) sevoflurane on cerebral blood flow, metabolism, and CO2 reactivity in cardiac patients. We found that the global cerebral blood flow and global cerebral metabolic rate of oxygen remained coupled and that cerebrovascular CO2 reactivity is not impaired by the administration of 1 MAC sevoflurane.

Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease

Background Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO (2) on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery. Methods In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety‐Schmidt technique with argon as a tracer. End‐diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer‐tipped catheter. Results The cardiac index significantly changed with varying PaCO (2) levels (hypocapnia, ‐ 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying Pa (CO)2 levels. Conclusions In anesthetized patients with coronary artery disease, short‐term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.

Bedside Assessment of Cerebral Blood Flow by Double-indicator Dilution Technique

Background Currently, quantitative measurement of global cerebral blood flow (CBF) at bedside is not widely performed. The aim of the present study was to evaluate a newly developed method for bedside measurement of CBF based on thermodilution in a clinical setting. Methods The investigation was performed in 14 anesthetized patients before coronary bypass surgery. CBF was altered by hypocapnia, normocapnia, and hypercapnia. CBF was measured simultaneously by the Kety-Schmidt inert-gas technique with argon and a newly developed transcerebral double-indicator dilution technique (TCID). For TCID, bolus injections of ice-cold indocyanine green were performed via a central venous line, and the resulting thermo-dye dilution curves were recorded simultaneously in the aorta and the jugular bulb using combined fiberoptic thermistor catheters. CBF was calculated from the mean transit times of the indicators through the brain. Results Both methods of measurement of CBF indicate a decrease during hypocapnia and an increase during hypercapnia, whereas cerebral metabolic rate remained unchanged. Bias between CBFTCID and CBFargon was −7.1 ± 2.2 (SEM) ml · min−1 · 100 g−1; precision (± 2 · SD of differences) between methods was 26.6 ml · min−1 · 100 g−1. Conclusions In the clinical setting, TCID was feasible and less time-consuming than alternative methods. The authors conclude that TCID is an alternative method to measure global CBF at bedside and offers a new opportunity to monitor cerebral perfusion of patients.

Cerebral effects of anaesthesia and hypothermia.

Cerebral blood flow, cerebral oxygen and glucose consumption, and cerebral lactate and pyruvate release were measured; spectral analysis of the EEG was recorded in 10 male patients who had coronary artery bypass surgery. The measurements were taken to evaluate the effects of fentanyl–midazolam anaesthesia during normothermia and during hypothermic nonpulsatile cardiopulmonary bypass at 26°C venous blood temperature, when a temperature‐corrected Paco2‐value of 5.3 kPa was maintained. Anaesthesia with fentanyl 7 μg/kg and midazolam 200 μg/kg as induction doses, followed by infusions of fentanyl 0.15 μg/kg/minute and midazolam 3 μg/kg/minute, was characterised by a decrease in fast‐wave activity and an increase in high‐amplitude, slow‐wave activity in the EEG. There was also a decrease in cerebral blood flow (38%), oxygen consumption (22%) and glucose consumption (25%), while lactate and pyruvate production remained unchanged. Hypothermia of 26°C venous blood temperature suppressed EEG almost completely and decreased oxygen and glucose consumption by a further 61% and 54%, respectively, with no changes in lactate and pyruvate production while cerebral blood flow increased by 145%. These results show that the effects of fentanyl–midazolam anaesthesia on cerebral metabolism are enhanced during hypothermic cardiopulmonary bypass while the influence of anaesthesia on cerebral blood flow is overshadowed by the practice of a temperature‐corrected acid‐base management.

[The effect of nitroglycerin on cerebrovascular circulation, cerebrovascular CO2-reactivity and blood flow rate in basal cerebral arteries].

ZusammenfassungZiel dieser prospektiven kontrollierten Studie war es, 1.) den Einfluß von Nitroglyzerin (NTG) auf den globalen zerebralen Blutfluß (CBF) und die zerebrovaskuläre CO2-Reaktivität zu untersuchen, und 2.) den Einfluß von NTG auf den Zusammenhang zwischen CBF und der Flußgeschwindigkeit in der A. cerebri media (VMCA) zu bestimmen. Bei 10 kardiochirurgischen Patienten wurde zunächst während einer Kontrollphase in randomisierter Reihenfolge eine Hypo- und Hyperkapnie (paCO2≈30 bzw. 50 mmHg) induziert. Anschließend wurden alle Messungen unter einer Infusion von 1,5·μg·kg−1·min−1 NTG bei identischen paCO2-Niveaus wiederholt. Die Bestimmung des CBF erfolgte mittels der Kety-Schmidt-Technik. Simultan wurde jeweils die VMCA mittels eines 2-MHz-Dopplersystems aufgezeichnet. Unter NTG-Infusion nahm der zerebrale Perfusionsdruck um 15–17% ab, dennoch zeigte sich aufgrund einer Reduktion des zerebrovaskulären Widerstands eine erhebliche Zunahme des CBF um 96 bzw. 69%, während die VMCA geringfügig abfiel. Die CO2-Reaktivität des CBF zeigte keine signifikante Änderung. Die Ergebnisse der vorliegenden Untersuchung zeigen zum einen, daß NTG zu einer ausgeprägten Zunahme der globalen Hirndurchblutung führt, sofern kein kritischer Abfall des zerebralen Perfusionsdrucks eintritt. Zum anderen legen die Ergebnisse des durchgeführten Methodenvergleichs nahe, daß auch die proximalen Segmente der A. cerebri media (MCA) unter dem Einfluß von NTG eine Vasodilatation aufweisen, die zu einer methodisch relevanten Diskrepanz zwischen relativen Änderungen der Hirndurchblutung und der MCA-Strömungsgeschwindigkeit führt.AbstractThe cerebral haemodynamic effects of vasodilators are of clinical interest because a decrease in mean arterial pressure (MAP) might alter global cerebral blood flow (CBF). Luxury perfusion of the brain, in contrast, might be unfavourable in patients with reduced intracranial compliance. Despite the widespread use of nitroglycerine (NTG), little is known about the cerebral haemodynamic consequences of NTG infusions in humans. This prospective, controlled study was designed: (1) to investigate the effects of NTG on CBF and cerebrovascular CO2 reactivity and (2) to compare reference measurements o

Effect of ketanserin on global cerebral blood flow and middle cerebral artery flow velocity

The aim of this study was to examine the influence of ketanserin, a 5-hydroxytryptamine antagonist antihypertensive agent, on the relationship between cerebral blood flow (CBF) and middle cerebral artery flow velocity (Vmean MCA) and to compare Doppler-sonographic indices of downstream resistance (pulsatility index, PI; resistance index, RI) with calculations of cerebrovascular resistance (CVR) in 17 male patients under fentanyl/midazolam anesthesia. CBF was measured with the Kety-Schmidt technique using argon as a tracer. Cerebral perfusion pressure (CPP) was calculated as the difference between mean arterial pressure (MAP) and jugular bulb pressure. Measurements of Vmean MCA and determinations of PI and RI were performed by use of a 2-MHz transcranial Doppler ultrasound device. All variables were measured at normo- and moderate hypocapnia before and after intravenous (IV) bolus administration of 0.3 mg/kg ketanserin followed by an infusion of 0.06 mg centered dot kg-1 centered dot h-1. Ketanserin changed neither average CBF nor Vmean MCA. The CO2 reactivity of Vmean MCA was significantly lower than the CO2 reactivity of CBF (P < 0.01); however, ketanserin did not change the relationship between CBF and Vmean MCA. During hypocapnia, CVR as well as PI and RI significantly increased (P <or=to 0.01), indicating consistent directional changes in arteriolar resistance and flow velocity pulsatility. In contrast, after IV administration of ketanserin, CVR decreased (P < 0.05), whereas both Doppler-derived indices increased (P < 0.01). These results suggest that ketanserin in a clinically relevant dose does not alter the validity of serial Vmean MCA measurements as an index of global CBF and that ketanserin does not change the diameter of middle cerebral arteries (MCAs). Doppler-derived indices of pulsatility and resistance, which are supposed to estimate changes in downstream resistance, reflect changes, after administration of ketanserin, in systemic hemodynamics rather than changes in CVR. (Anesth Analg 1995;80:64-70)

Hepatic disposition of sufentanil in patients undergoing coronary bypass surgery

In order to clarify the relative contribution of the liver to the short‐term disposition of sufentanil, hepatic blood flow was measured during induction of anaesthesia with a 10 μg/kg i.v. bolus dose of sufentanil followed by a continuous infusion of 0.3 μg/kg/min of sufentanil. The hepatic clearance of the drug was 0.57 1/min after induction and 0.55 1/min at sternotomy, its hepatic extraction 92% and 91%, respectively. As a consequence of the high hepatic extraction, the hepatic clearance of sufentanil was closely dependent on hepatic plasma flow. Comparing the hepatic clearance of sufentanil with data from the literature for total body clearance of sufentanil, there is a significant difference of more than 0.3 1/min. It is concluded that there is evidence for a relevant extrahepatic disposition of sufentanil.

Messung der menschlichen Hirndurchblutung

ZusammenfassungIn der vorliegenden Untersuchung wurde die Hirndurchblutung simultan sowohl mit der intravenösen 133Xenon-Clearancetechnik als auch mit der Kety-Schmidt-Technik gemessen. Unter Standardanästhesiebedingungen wurden Hirndurchblutung, zerebraler Stoffwechsel und die CO2-Reaktivität der Hirndurchblutung miteinander verglichen. Untersucht wurden 13 männliche Patienten, unmittelbar bevor sie sich einer aortokoronaren Bypassoperation unterzogen. Die Hirndurchblutungsmessungen wurden simultan durchgeführt und zwar jeweils unter normokapnischen (paCO2 43±3 mm Hg), hypokapnischen (paCO2 31±3 mm Hg) und hyperkapnischen (paCO2 54±4 mm Hg) Bedingungen. Mit der Xenonmethode wurden unter allen Ventilationsbedingungen signifikant niedrigere Hirndurchblutungswerte gemessen als mit der Kety-Schmidt-Technik. Eine signifikante Korrelation zwischen den Hirndurchblutungswerten beider Methoden wurde nicht gefunden (y=1,82x−8,58, r=0,76, p=0,357). Die CO2-Antwortkurven der Hirndurchblutung zeigten für beide Verfahren einen exponentiellen Verlauf. Die CO2-Reaktivität war jedoch bei der Kety-Schmidt-Technik deutlichgrößer als bei der Xenonmethode (y=8,14e0,039xvs. y=10,75 e0,023x). Wahrscheinlich aufgrund einer Miterfassung langsam perfundierter extrazerebraler Areale ist die intravenöse Xenonmethode unter Verwendung von CBF15 als Durchblutungsparameter mit einer deutlichen Unterschätzung von Hirndurchblutung, -stoffwechsel und zerebrovaskulärer CO2-Reaktivität behaftet.AbstractIn this study cerebral blood flow (CBF) was simultaneously measured with the Kety-Schmidt method and the intravenous 133Xe clearance technique. CBF, cerebral metabolic rate of oxygen (CMRO2), and CO2 reactivity of CBF were compared under fentanyl-midazolam anaesthesia and varying paCO2 levels. Methods. Thirteen male patients were studied before they underwent coronary artery bypass surgery. For measurement of CBF with the Kety-Schmidt inert gas saturation technique, argon was used as indicator instead of nitrous oxide, because argon is less soluble in water and lipid such that arterial and hence organ saturation is attained earlier. Wash-in periods of 10 min were used for all measurements. For measurement of CBF with the intravenous xenon method 10 scintillation detectors placed lateral to the skull and an air detector for calculation of tracer recirculation were used. 10–15 mCi of 133Xe dissolved in physiological saline was injected via a peripheral i.v. cannula. For comparison with the Kety-Schmidt technique CBF15-values representing the flow of the grey and white matter were chosen. CBF was measured simultaneously with both methods under normocapnic (paCO2 43±3 mmHg), hypocapnic (paCO2 31±3 mmHg), and under hypercapnic (paCO2 54±4 mmHg) conditions. Results. All CBF15 values obtained with the intravenous xenon method were significantly lower than the corresponding CBF-values measured with the Kety-Schmidt technique: by 36% under normocapnic, 23% under hypocapnic, and 39% under hypercapnic conditions, respectively. Hence, CMRO2 values calculated from CBF values obtained with the xenon method were reduced to about the same degree as those derived from CBF values measured with the Kety-Schmidt technique. There was no significant correlation between the CBF values of either method (y=1.82x−8.58,r=0.76 P=0.357). Non-linear curve-fitting procedures yielded exponential CBF−paCO2 relationships for both methods, although the relative carbon dioxide reactivity was higher with the Kety-Schmidt technique than with the xenon method (y=8.14 e0.039x vs y=10,75 e0.023x). Conclusions. Most probably due to contamination with radioactivity from slowly perfused extracerebral tissues the intravenous 133Xe-clearance technique underestimates CBF, CMRO2, and cerebrovascular CO2 reactivity, at least when CBF15 values are used as flow parameters.

Is cerebral venous oxygen saturation an indicator of cerebral circulation

ZusammenfassungIn der klinischen Routine stellt die Bestimmung der Hirndurchblutung häufig ein Problem dar. Leichter meßbar ist die arteriovenöse Sauerstoffgehaltsdifferenz (avDO2) des Gehirns, die abhängig ist von dessen O2-Verbrauch (CMRO2) und dem zerebralen Blutfluß (CBF). Bei gleichbleibendem Sauerstoffangebot ist die avDO2 umgekehrt proportional zur hirnvenösen O2-Sättigung (ShvO2). Damit erlaubt die Bestimmung der hirnvenösen Sättigung nicht nur eine Aussage über die Sauerstoffausschöpfung des Gehirns, sondern könnte bei einer konstanten O2-Aufnahme eine Einschätzung des CBF ermöglichen. In der vorliegenden Untersuchung wurde an 62 männlichen Patienten im Alter von 41–60 Jahren im Rahmen von aorto-koronaren Bypassoperationen dieser Zusammenhang untersucht. Zu vier definierten Meßpunkten wurden die arterielle und hirnvenöse Sauerstoffsättigung sowie die zerebrale Durchblutung gemessen. Die erhaltenen Werte wurden gepoolt. Es konnte eine lineare Abhängigkeit zwischen der avDO2 und ShvO2 bestätigt werden; eine hinreichend enge Verknüpfung zwischen ShvO2 und CBF lag unter diesen klinischen Bedingungen jedoch nicht vor. Die Ursache lag in der hohen Variabilität des CMRO2. Ohne Kenntnis der CMRO2 dürfen aus Sättigungsänderungen keine Rückschlüsse auf perioperative Veränderungen der Hirndurchblutung gezogen werden.AbstractThe arteriovenous oxygen content difference (avDO2) of the brain is dependent on O2 consumption (CMRO2) and cerebral blood flow (CBF). With unchanging arterial O2 content, avDO2 is inversely related to cerebral venous O2 saturation (SO2). Measurement of SO2 in the jugular bulb not only provides information about the O2 balance of the brain, but may give an important estimation of CBF if a clinically useful correlation is proven. The aim of the present study was to verify this aspect. Methods. Sixty-two male patients undergoing coronary revascularisation were investigated. The study was approved by the local Ethical Committee and each patient gave written informed consent on the preoperative day. At four points during the perioperative course arterial and cerebral venous SO2 and CBF were measured. Cerebral venous blood was sampled from a catheter in the superior bulb of the right internal jugular vein. CBF was measured using the argon wash-in technique. All sampled data were pooled and evaluated. Results. As expected from theory, cerebral venous SO2 and avDO2 showed a close linear relationship (r=−0.892). However, only a weak hyperbolic relationship was found between cerebral venous SO2 and CBF. In addition, no direct correlation between CMRO2 and SO2 in the jugular bulb could be demonstrated. Conclusions. In this clinical study, a close relationship between cerebral venous SO2 and CBF was not found. This was primarily due to the high variability of cerebral O2 uptake. Changes in cerebral venous SO2 may therefore not be used as an estimate of perioperative changes in CBF.

Hämodynamische Effekte neuerer Phosphodiesterase-III-Hemmer bei Patienten mit koronarer Herzkrankheit Ein Vergleich zwischen Enoximon und R80122

ZusammenfassungIn dieser Untersuchung wurden die hämodynamischen Effekte einer Bolusinjektion von 1,0 mg/kg KG Enoximon bzw. 0,3 mg/kg KG R80122 bei jeweils 10 Patienten mit koronarer Herzkrankheit und normaler linksventrikulärer Funktion gemessen und miteinander verglichen. Die einzelnen Messungen erfolgten präoperativ nach Narkoseeinleitung unter steady state-Bedingungen. Der Herzindex stieg bereits 5 min nach Gabe des jeweiligen PDE-III-Hemmers maximal an, in der Enoximongruppe im Mittel um 31%, in der R80122-Gruppe im Mittel um 26% über die jeweiligen Ausgangswerte. Der Anstieg des Herzindex basierte bei beiden Gruppen sowohl auf einem Anstieg des Schlagvolumens, nach Enoximongabe im Mittel um 13%, nach Gabe von R80122 im Mittel um 14%, wie auch der Herzfrequenz, nach Enoximongabe im Mittel um 15%, nach Gabe von R80122 im Mittel um 10%. Gleichzeitig kam es zu einem Abfall des arteriellen Mitteldrucks, nach Enoximongabe im Mittel um 19%, nach Gabe von R80122 im Mittel um 21%. Ursache für den Abfall des arteriellen Mitteldrucks war in beiden Gruppen die Erniedrigung des peripheren Gefäßwiderstands, in der Enoximongruppe im Mittel um 38%, in der R80122-Gruppe im Mittel um 36%. Ein signifikanter Unterschied zwischen den hämodynamischen Parametern beider Gruppen lag zu keinem Meßzeitpunkt vor. Beide Substanzen zeigen in der vorgegebenen Dosierung vergleichbare hämodynamische Effekte, einen Anstieg von Herzindex, Herzfrequenz und Schlagvolumen bei gleichzeitigem Abfall des peripheren Gefäßwiderstands. Die in tierexperimentellen Untersuchungen nachgewiesene höhere Kardioselektivität von R80122 konnte unter den klinischen Bedingungen dieser Studie nicht nachgewiesen werden.AbstractAt present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotropic and lusitropic effects, these drugs are still under discussion because of certain adverse effects like thrombopaenia, elevation of transaminases, abdominal disregulation, and excessive periphereal vasodilatation. As a consequence, more cardioselective phosphodiesterase inhibitors were developed with the aim of reducing these adverse effects. One of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole derivative, has nearly no influence on platelets and abdominal organ function. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig. 1), was developed. First experimental studies showed high cardioselectivity of this substance. The aim of this study was to compare the haemodynamic effects of enoximone and R80122 in patients with ischaemic heart disease. Methods. This study was thoroughly discussed and approved by the local Ethics Committee; all patients gave written informed consent. Twenty male patients (Table 1) with normal left ventricular function who were about to undergo elective coronary artery bypass surgery were randomly allocated to receive a bolus of either 1.0 mg/kg enoximone or 0.3 mg/kg R80122 after induction of anaesthesia. Premedication consisted of 2 mg flunitrazepam orally the evening before and in the morning 1 h before operation. Anaesthesia was induced with 0.007 mg/kg fentanyl, 0.2 mg/kg etomidate, and 0.1 mg/kg pancuronium bromide and maintained by a continuous infusion of 0.02 mg/min fentanyl and 0.3 mg/min midazolam. After induction of anaesthesia haemodynamic measurements were performed and blood gas samples were taken preoperatively under steady-state conditions before and 5, 30, and 60 min after drug administration. Results. The results of both groups are shown in Table 2 as mean values with standard deviations. Individual changes of cardiac index (CI), mean arterial pressure (MAP), and systemic vascular resistance (SVR) are depicted in Fig. 2. Peak percentage changes of the haemodynamic parameters are shown in Fig. 3. Both substances improved cardiac function; 5 min after drug administration CI increased by 31% and 26%, respectively. This was accompanied by increases in stroke volume (13% and 14%, respectively) and heart rate (15% and 10%, respectively). At the same time, there were declines in SVR (38% and 36%, respectively) and MAP (19% and 21%, respectively). Although mean values of pulmonary arterial and wedge pressure decreased after drug administration, these changes were inconsistent and not of clinical relevance. There were no statistically significant differences between the haemodynamic effects of both substances at any time in this study. Conclusions. Both enoximone and R80122 showed the expected inotropic effects. Nevertheless, both substances have a distinct vasodilative effect, which leads to a decline in MAP. R80122 does not have higher cardioselectivity than enoximone.