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Healthy vascular endothelium is luminally coated by an endothelial glycocalyx, which interacts with the bloodstream and assumes a filter function on the vascular wall. Although this structure was discovered nearly 70 years ago, its physiological importance has been underestimated for a long time. Recent findings indicate that the glycocalyx is, in addition to the endothelial cells themselves, a main constituent part of the vascular barrier. The existence of different colloid osmotic gradients within and beneath this structure has now led to a modification of the Starling equation. In many vascular beds the interstitial space features a protein concentration similar to that of the plasma. The inwardly directed gradient, which retains water and proteins in the vascular system, is generated beneath the glycocalyx by selective protein filtration over this structure. The endothelial glycocalyx, as an additional competent vascular permeability barrier has, therefore, not only a key role for perioperative fluid and protein shifts into the interstitial space, but it seems to be intimately involved in the pathophysiology of diabetes, arteriosclerosis, sepsis and ischemia/reperfusion, especially with respect to associated vascular dysfunctions. The fragile glycocalyx can be destroyed in the course of surgery, trauma, ischemia/reperfusion and sepsis and by inflammatory mediators such as TNF-alpha, causing leukocyte adhesion, platelet aggregation and edema formation. Recent studies have shown that protecting this structure not only maintains the vascular barrier, but constitutes an important component of a rational perioperative fluid therapy. [ABSTRACT FROM AUTHOR]

Acid-base disturbances are commonly found in critically ill patients and are often associated with fatal complications. The basis of a successful treatment is a thorough understanding of the causes of these disorders. The "classical methods" to explain acid-base disorders--pH, base excess and bicarbonate concentration--mostly do not provide a causal correlation to the underlying pathology. An unusual case of a combined respiratory-metabolic disorder with hyperlactatemia and hypercapnia is presented. An acidosis masked by hypochloremic and hypoalbuminemic alkalosis was identified with the help of Stewart's concept and finally permitted a successful therapy. The modern Stewart concept provides enhanced information, enabling an exact diagnosis and causal therapy even in complex cases. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

About twenty years ago, Peter Stewart had already published his modern quantitative approach to acid-base chemistry. According to his interpretations, the traditional concepts of the mechanisms behind the changes in acid-base balance are considerably questionable. The main physicochemical principle which must be accomplished in body fluids, is the rule of electroneutrality. There are 3 components in biological fluids which are subject to this principle: a)Water, which is only in minor parts dissociated into H+ and OH-, b)"strong", i.e. completely dissociated, electrolytes, which thus do not interact with other substances, and body substances, such as lactate, and c)"weak", i.e. incompletely dissociated, substances. Peter Stewart strictly distinguished between dependent and independent variables and thus indeed described a new order of acid-base chemistry. The 3 dependent variables (bicarbonate concentration [Bic(-)], pH, and with this also hydrogen ion concentration [H(+)]) can only change if the 3 independent variables allow this change. These 3 independent variables are: 1. Carbon dioxide partial pressure, 2.the total amount of all weak acids ([A-] (Stewart called these ATOT), and 3.strong ion difference (SID). [A(-)] can be calculated from the albumin (Alb) and the phosphate concentration (Pi): [A(-)]=[Alb x (0.123 x pH - 0.631)] + [Pi x (0.309 x pH - 0.469)]. An apparent SID (or "bedside" SID) can be calculated using measurable ion concentrations: SID=[Na(+)] + [K(+)] - [Cl(-)]-lactate. Regarding the metabolic disturbances of acid-base chemistry, according to Stewart's terminology, changes in pH, [H(+)], and [Bic(-)] are only possible if either SID or [A(-)] itself changes. If, for example, SID decreases (e.g. in case of hyperchloremia), this increase in independent negative charges leads to a decrease in dependent negative charges in terms of [Bic(-)] resulting in acidosis (and vice versa). Therefore, according to Stewart, the decrease in SID during hyperchloremic acidosis results from the increase in serum chloride concentration and is the causal mechanism behind this acidosis. Contrary for example, a decrease in [A(-)] (e. g. during hypoalbuminemia) leads to an increase in [Bic(-)] and therefore to an alcalosis (and vice versa). Thus, by Stewart's approach, completely new acid-base disturbances, like "hyperchloremic acidosis" or "hypoalbuminemic alcalosis" (which, of course, can also exist in combination) can be detected, which had been unrecognised by the classic acid-base concepts. Consequently, Stewart's analysis can lead to a better understanding of the mechanisms behind the changes in acid-base balance. [ABSTRACT FROM AUTHOR]

None of the currently available inhaled anesthetics has all of the properties of an "ideal" inhaled agent. The exceptionally low solubility of desflurane and sevoflurane offers a significantly greater precision of control over maintenance of anesthesia and a potential for a more rapid recovery from anesthesia than other inhaled anesthetics. Sevoflurane appears to offer some advantages regarding cardiovascular stability. Products of metabolism or degradation can be associated with potential organ-specific toxic effects. Renal toxicity is discussed for enflurane and sevoflurane. Breakdown products of volatile agents with carbon dioxide absorbents have to be mentioned especially for sevoflurane (compound A) and desflurane (CO). In contrast to intravenous anesthetics, volatile anesthetics are associated with cardio- and cerebroprotection. [ABSTRACT FROM AUTHOR]

The alkali hydroxide content in soda lime induces Compound A formation from Sevoflurane (Sevo). This study was designed to answer the question if the use of potassium hydroxide-free Soda Lime (SL) would lead to lower Compound A levels as compared to Sodasorb (SO). A total of 30 patients scheduled for elective laparoscopic cholecystectomy received Sevo anaesthesia under low-flow conditions (0.8 l/min fresh gas flow). Each absorbent was used in 15 patients, but 3 patients of the SO group were excluded due to technical problems with Compound A analysis. Hemodynamic parameters, parameters of ventilation and gas concentrations were documented. Compound A concentrations were measured by gas chromatography from gas samples before Sevo application and 20, 40, 60, 90 and 120 min after low-flow start. Mean endtidal Sevo concentrations were 1.94 +/- 0.17 (SO) and 1.97 +/- 0.15 (SL) vol %, the total anaesthetic exposition was 1.52 +/- 0.36 (SO) and 1.64 +/- 0.47 (SL) MAC-h (n.s). The maximum Compound A concentration was significantly higher in SL group (19.6 +/- 2.8 vs. 11.7 +/- 4.1 ppm, p < 0.001). Therefore, elimination of potassium hydroxide from carbon dioxide absorbents alone did not lead to a reduction of Compound A formation during low-flow anaesthesia. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease. [ABSTRACT FROM AUTHOR]

Unlabelled: Eltanolone is a new steroid anaesthetic agent that is 5-beta reduced derivative of progesterone. In the present study we investigated the haemodynamic effects of eltanolone or thiopentone in patients scheduled for coronary artery bypass grafting.Methods: After obtaining approval of the institutional ethics committee and informed patient consent, 40 patients (age 45-70 years, ASA III and IV, ejection fraction > 50%, cardiac index > 2.5 l/min per m2) were randomly assigned to four groups, each containing 10 patients: After premedication with 2 mg flunitrazepam, anaesthesia was induced with 3 mg/kg thiopentone in group 1, 0.5 mg/kg eltanolone in group 2, 0.75 mg/kg eltanolone in group 3, 1.0 mg/kg eltanolone in group 4. Each patient additionally received 3 mirograms/kg fentanyl after induction and 0.1 mg/kg pancuronium. Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure and cardiac output were recorded in the awake state, 2 min after induction of anaesthesia, and 1 and 5 min after intubation. Cardiac index and systemic vascular resistance were calculated.Results: Two minutes after induction, mean arterial pressure was significantly lower than the baseline (P < 0.05) in each group. Mean arterial pressure changes were more prominent in the case of eltanolone, but intergroup tests did not reveal significant differences between the four groups. There was a fall in cardiac index in all groups, and these changes reached the level of significance only in the thiopentone patients. The most obvious difference between eltanolone and thiopentone was systemic vascular resistance. It dropped significantly 2 min after induction with eltanolone at all dosages. In contrast, there was an increase in systemic vascular resistance following induction of anaesthesia with thiopentone. Intergroup tests also showed significantly (P < 0.05) lower systemic vascular resistance 1 and 5 min after intubation with eltanolone compared to thiopentone.Discussion: Mean arterial pressure reduction induced by eltanolone is most likely the result of the combination of a decrease in cardiac contractility and peripheral vasodilatation. In contrast, mean arterial pressure reduction in the case of thiopentone seems to be exclusively related to the negative inotropic properties of the drug. Results of a dosage finding study [5] with eltanolone revealed an AD50 of 0.33 mg/kg. In our study 0.5 mg/kg eltanolone brought all the patients to sleep within 2 minutes. The haemodynamic results do not show any significant difference up to twofold dosage. Therefore, the therapeutic margin seems to be large. Because of considerable interindividual variability additional studies in larger collectives are required for definitive evaluation of the drug. [ABSTRACT FROM AUTHOR]

Unlabelled: Desflurane is a new volatile anaesthetic with an extremely low blood/gas partition coefficient of 0.42. This should provide a rapid recovery from anaesthesia.Methods: We studied 100 adult patients, ASA class I or II, undergoing elective orthopaedic surgery randomly assigned to anaesthesia with desflurane (n = 50) or isoflurane (n = 50) supplemented by nitrous oxide in oxygen. Clorazepat was given for premedication, fentanyl and thiopental for induction of anaesthesia, followed by maintenance with desflurane or isoflurane as clinically appropriate. Emergence from anaesthesia was measured as well as return of cognitive functions (extended Aldrete score, digit symbol substitution test, and visual analogue scales [VAS]).Results: While the demographic characteristics and administrated doses of fentanyl and thiopental were comparable, the recovery profiles in both groups were different. After discontinuation of the volatile anaesthetics, times to extubation and ability to follow simple commands were significantly shorter after desflurane than after isoflurane. Extended Aldrete scores, estimation of the patients' physical condition, results of the digit symbol substitution test, measuring cognitive functions, and rates of drowsiness and weakness on VAS showed better recovery with less impairment of cognitive function in the desflurane group than in isoflurane patients even 120 min after anaesthesia. VAS pain scores and doses of analgesic drugs given within the first 2 postoperative hours, however, showed no significant differences. Desflurane patients were also judged fit for discharge from the recovery room significantly faster.Conclusions: Our results demonstrate that desflurane anaesthesia, even when supplemented by premedication, intraoperative opioids, and nitrous oxide may offer clinical advantages over isoflurane as far as the post-anaesthetic recovery profile is concerned. [ABSTRACT FROM AUTHOR]

Inhalational anesthetics have been used for induction and maintenance of general anesthesia for more than 150 years. All of the currently used inhalational anesthetics are chlorinated and fluorinated derivatives of ether. Dosing is carried out using the minimal alveolar concentration (MAC) concept. The pharmacokinetic properties of the various inhalational anesthetics are governed by the specific distribution coefficients. Mechanisms of action include specific modulations of various receptors of the central nervous system as well as an unspecific interaction with the cell membrane. Organ toxicity of modern inhalational anesthetics is considered to be minimal. The role of inhalational anesthetics in the context of postoperative nausea and vomiting (PONV) has been reassessed in recent years. The superiority of inhalational anesthetics over intravenous hypnotics with respect to intraoperative awareness is undisputed. The organ protective mechanism of preconditioning is an exclusive property of inhalational anesthetics among all the currently available hypnotics.

Background: With broad acceptance of Stewart's acid-base model "hyperchloremic acidosis" is regarded as an independent form of metabolic disorder. It is unknown whether hypernatremia plays a corresponding role with respect to the development of alkalosis., Methods: A total of 201 artificially ventilated, critically ill patients were monitored for hypernatremic episodes. Inclusion criterion was a serum sodium concentration above 145 mmol/l., Results: In 20 patients a total of 78 periods of elevated plasma sodium levels lasting at least 24 h were observed. In 86% of these cases sodium and chloride concentrations were simultaneously increased. The development of alkalosis correlated with the strong ion difference (r=0.80, p<0.01) but not with the serum sodium concentration (r=-0.031, p=0.78). In cases without accompanying hyperchloremia (13%) metabolic alkalosis regularly occurred and a correlation between serum sodium concentration and base excess could be verified (r=0.66, p=0.03). Alkalosis occurred in 84.8% of cases where the strong on difference exceeded 39 mmol/l., Conclusion: From the available data hypernatremic alkalosis could not be defined as an independent metabolic disorder. In would seem more appropriate to use the term "strong ion alkalosis" in this context.

Healthy vascular endothelium is luminally coated by an endothelial glycocalyx, which interacts with the bloodstream and assumes a filter function on the vascular wall. Although this structure was discovered nearly 70 years ago, its physiological importance has been underestimated for a long time. Recent findings indicate that the glycocalyx is, in addition to the endothelial cells themselves, a main constituent part of the vascular barrier. The existence of different colloid osmotic gradients within and beneath this structure has now led to a modification of the Starling equation. In many vascular beds the interstitial space features a protein concentration similar to that of the plasma. The inwardly directed gradient, which retains water and proteins in the vascular system, is generated beneath the glycocalyx by selective protein filtration over this structure. The endothelial glycocalyx, as an additional competent vascular permeability barrier has, therefore, not only a key role for perioperative fluid and protein shifts into the interstitial space, but it seems to be intimately involved in the pathophysiology of diabetes, arteriosclerosis, sepsis and ischemia/reperfusion, especially with respect to associated vascular dysfunctions. The fragile glycocalyx can be destroyed in the course of surgery, trauma, ischemia/reperfusion and sepsis and by inflammatory mediators such as TNF-alpha, causing leukocyte adhesion, platelet aggregation and edema formation. Recent studies have shown that protecting this structure not only maintains the vascular barrier, but constitutes an important component of a rational perioperative fluid therapy.

Acid-base disturbances are commonly found in critically ill patients and are often associated with fatal complications. The basis of a successful treatment is a thorough understanding of the causes of these disorders. The "classical methods" to explain acid-base disorders--pH, base excess and bicarbonate concentration--mostly do not provide a causal correlation to the underlying pathology. An unusual case of a combined respiratory-metabolic disorder with hyperlactatemia and hypercapnia is presented. An acidosis masked by hypochloremic and hypoalbuminemic alkalosis was identified with the help of Stewart's concept and finally permitted a successful therapy. The modern Stewart concept provides enhanced information, enabling an exact diagnosis and causal therapy even in complex cases.

Accurate perioperative fluid balance is the basis of a targeted infusion regimen. However, neither the initial status nor perioperative changes of the fluid compartments can be reliably measured in daily routine. In particular, insensible losses are not consistently assessed, so that substitution therapy is generally empirical. The object of this paper is to communicate the scientific data on this topic. Preoperative fasting (10 h) does not per se cause intravascular hypovolemia. In adults, total basal evaporation by way of the skin and airways and of any wounds during major abdominal interventions is usually less than 1 ml/kg/h. An inconstant fluid and protein shift towards the interstitial space perioperatively seems to be associated with hypervolemia, which suggests it should be preventable. The decisive factor in this context seems to be deterioration of the endothelial glycocalyx, whose further patho-physiological impact is currently only partially known. Clinical studies have revealed a link between fluid restriction and improved outcome after major abdominal surgery.

About twenty years ago, Peter Stewart had already published his modern quantitative approach to acid-base chemistry. According to his interpretations, the traditional concepts of the mechanisms behind the changes in acid-base balance are considerably questionable. The main physicochemical principle which must be accomplished in body fluids, is the rule of electroneutrality. There are 3 components in biological fluids which are subject to this principle: a)Water, which is only in minor parts dissociated into H+ and OH-, b)"strong", i.e. completely dissociated, electrolytes, which thus do not interact with other substances, and body substances, such as lactate, and c)"weak", i.e. incompletely dissociated, substances. Peter Stewart strictly distinguished between dependent and independent variables and thus indeed described a new order of acid-base chemistry. The 3 dependent variables (bicarbonate concentration [Bic(-)], pH, and with this also hydrogen ion concentration [H(+)]) can only change if the 3 independent variables allow this change. These 3 independent variables are: 1. Carbon dioxide partial pressure, 2.the total amount of all weak acids ([A-] (Stewart called these ATOT), and 3.strong ion difference (SID). [A(-)] can be calculated from the albumin (Alb) and the phosphate concentration (Pi): [A(-)]=[Alb x (0.123 x pH - 0.631)] + [Pi x (0.309 x pH - 0.469)]. An apparent SID (or "bedside" SID) can be calculated using measurable ion concentrations: SID=[Na(+)] + [K(+)] - [Cl(-)]-lactate. Regarding the metabolic disturbances of acid-base chemistry, according to Stewart's terminology, changes in pH, [H(+)], and [Bic(-)] are only possible if either SID or [A(-)] itself changes. If, for example, SID decreases (e.g. in case of hyperchloremia), this increase in independent negative charges leads to a decrease in dependent negative charges in terms of [Bic(-)] resulting in acidosis (and vice versa). Therefore, according to Stewart, the decrease in SID during hyperchloremic acidosis results from the increase in serum chloride concentration and is the causal mechanism behind this acidosis. Contrary for example, a decrease in [A(-)] (e. g. during hypoalbuminemia) leads to an increase in [Bic(-)] and therefore to an alcalosis (and vice versa). Thus, by Stewart's approach, completely new acid-base disturbances, like "hyperchloremic acidosis" or "hypoalbuminemic alcalosis" (which, of course, can also exist in combination) can be detected, which had been unrecognised by the classic acid-base concepts. Consequently, Stewart's analysis can lead to a better understanding of the mechanisms behind the changes in acid-base balance.

None of the currently available inhaled anesthetics has all of the properties of an "ideal" inhaled agent. The exceptionally low solubility of desflurane and sevoflurane offers a significantly greater precision of control over maintenance of anesthesia and a potential for a more rapid recovery from anesthesia than other inhaled anesthetics. Sevoflurane appears to offer some advantages regarding cardiovascular stability. Products of metabolism or degradation can be associated with potential organ-specific toxic effects. Renal toxicity is discussed for enflurane and sevoflurane. Breakdown products of volatile agents with carbon dioxide absorbents have to be mentioned especially for sevoflurane (compound A) and desflurane (CO). In contrast to intravenous anesthetics, volatile anesthetics are associated with cardio- and cerebroprotection.

The alkali hydroxide content in soda lime induces Compound A formation from Sevoflurane (Sevo). This study was designed to answer the question if the use of potassium hydroxide-free Soda Lime (SL) would lead to lower Compound A levels as compared to Sodasorb (SO). A total of 30 patients scheduled for elective laparoscopic cholecystectomy received Sevo anaesthesia under low-flow conditions (0.8 l/min fresh gas flow). Each absorbent was used in 15 patients, but 3 patients of the SO group were excluded due to technical problems with Compound A analysis. Hemodynamic parameters, parameters of ventilation and gas concentrations were documented. Compound A concentrations were measured by gas chromatography from gas samples before Sevo application and 20, 40, 60, 90 and 120 min after low-flow start. Mean endtidal Sevo concentrations were 1.94 +/- 0.17 (SO) and 1.97 +/- 0.15 (SL) vol %, the total anaesthetic exposition was 1.52 +/- 0.36 (SO) and 1.64 +/- 0.47 (SL) MAC-h (n.s). The maximum Compound A concentration was significantly higher in SL group (19.6 +/- 2.8 vs. 11.7 +/- 4.1 ppm, p < 0.001). Therefore, elimination of potassium hydroxide from carbon dioxide absorbents alone did not lead to a reduction of Compound A formation during low-flow anaesthesia.

The new inhalational anesthetic sevoflurane is biotransformed by approximately 5%. Serum fluoride concentrations resulting from transformation mainly depend on rate of hepatic defluorination, total amount of anesthetic given and the solubility of the volatile anesthetic, as expressed by its blood gas partition coefficient. Enflurane is metabolized by 5-11%. However subsequent peak fluoride levels are lower than after sevoflurane which is a consequence of its lower rate of hepatic defluorination. To date numerous studies have examined the nephrotoxic potential of the sevoflurane degradation product fluoride. However, fluoride-related toxicity was not observed, neither in clinical or in animal studies, nor after prolonged administration or in patients with preexisting renal disease. New insights into intrarenal metabolisation of volatile anesthetics may well explain absence of nephrotoxicity after sevoflurane. The threshold of fluoride nephrotoxicity of 50 mumol/l, which has been empirically found after methoxyflurane, and which is still listed in many medical textbooks, can not be assumed a marker of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore also, the elevated serum fluoride concentrations, as regularly obtained after anesthesia with sevoflurane are devoid of clinical significance. In addition, exposure to sevoflurane or its metabolites is not associated with hepatic toxicity.

Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease.

Unlabelled: Eltanolone is a new steroid anaesthetic agent that is 5-beta reduced derivative of progesterone. In the present study we investigated the haemodynamic effects of eltanolone or thiopentone in patients scheduled for coronary artery bypass grafting., Methods: After obtaining approval of the institutional ethics committee and informed patient consent, 40 patients (age 45-70 years, ASA III and IV, ejection fraction > 50%, cardiac index > 2.5 l/min per m2) were randomly assigned to four groups, each containing 10 patients: After premedication with 2 mg flunitrazepam, anaesthesia was induced with 3 mg/kg thiopentone in group 1, 0.5 mg/kg eltanolone in group 2, 0.75 mg/kg eltanolone in group 3, 1.0 mg/kg eltanolone in group 4. Each patient additionally received 3 mirograms/kg fentanyl after induction and 0.1 mg/kg pancuronium. Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure and cardiac output were recorded in the awake state, 2 min after induction of anaesthesia, and 1 and 5 min after intubation. Cardiac index and systemic vascular resistance were calculated., Results: Two minutes after induction, mean arterial pressure was significantly lower than the baseline (P < 0.05) in each group. Mean arterial pressure changes were more prominent in the case of eltanolone, but intergroup tests did not reveal significant differences between the four groups. There was a fall in cardiac index in all groups, and these changes reached the level of significance only in the thiopentone patients. The most obvious difference between eltanolone and thiopentone was systemic vascular resistance. It dropped significantly 2 min after induction with eltanolone at all dosages. In contrast, there was an increase in systemic vascular resistance following induction of anaesthesia with thiopentone. Intergroup tests also showed significantly (P < 0.05) lower systemic vascular resistance 1 and 5 min after intubation with eltanolone compared to thiopentone., Discussion: Mean arterial pressure reduction induced by eltanolone is most likely the result of the combination of a decrease in cardiac contractility and peripheral vasodilatation. In contrast, mean arterial pressure reduction in the case of thiopentone seems to be exclusively related to the negative inotropic properties of the drug. Results of a dosage finding study [5] with eltanolone revealed an AD50 of 0.33 mg/kg. In our study 0.5 mg/kg eltanolone brought all the patients to sleep within 2 minutes. The haemodynamic results do not show any significant difference up to twofold dosage. Therefore, the therapeutic margin seems to be large. Because of considerable interindividual variability additional studies in larger collectives are required for definitive evaluation of the drug.

In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. Based upon the clinical experience with methoxyflurane, serum fluoride concentrations exceeding 50 mumol/l were considered to be nephrotoxic. Without further reevaluation, this 50 mumol/l threshold was subsequently applied to other fluorinated anaesthetics as well. Enflurane and even isoflurane may, when used during prolonged operations, also yield anorganic fluoride levels in excess of 50 mumol/l. Nevertheless, no cases of renal dysfunction attributable to prolonged use of these anesthetics have been reported. About 4% of the new inhalational anaesthetic sevoflurane is metabolized, and fluoride concentrations exceeding those after enflurane are frequently measured. Numerous studies have examined the nephrotoxic potential of sevoflurane degradation products. However, fluoride-related toxicity has been observed neither in animal nor in clinical studies, including prolonged administration and patients with pre-existing renal disease. New insights into the intrarenal metabolisation of volatile anaesthetics may well explain the absence of nephrotoxicity after sevoflurane. The threshold for fluoride nephrotoxicity of 50 mumol/l, still given in many medical text-books, can no longer be applied as an indicator of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore, the elevated serum fluoride concentrations consistently recorded following anaesthesia with sevoflurane are devoid of clinical significance.

Unlabelled: Desflurane is a new volatile anaesthetic with an extremely low blood/gas partition coefficient of 0.42. This should provide a rapid recovery from anaesthesia., Methods: We studied 100 adult patients, ASA class I or II, undergoing elective orthopaedic surgery randomly assigned to anaesthesia with desflurane (n = 50) or isoflurane (n = 50) supplemented by nitrous oxide in oxygen. Clorazepat was given for premedication, fentanyl and thiopental for induction of anaesthesia, followed by maintenance with desflurane or isoflurane as clinically appropriate. Emergence from anaesthesia was measured as well as return of cognitive functions (extended Aldrete score, digit symbol substitution test, and visual analogue scales [VAS])., Results: While the demographic characteristics and administrated doses of fentanyl and thiopental were comparable, the recovery profiles in both groups were different. After discontinuation of the volatile anaesthetics, times to extubation and ability to follow simple commands were significantly shorter after desflurane than after isoflurane. Extended Aldrete scores, estimation of the patients' physical condition, results of the digit symbol substitution test, measuring cognitive functions, and rates of drowsiness and weakness on VAS showed better recovery with less impairment of cognitive function in the desflurane group than in isoflurane patients even 120 min after anaesthesia. VAS pain scores and doses of analgesic drugs given within the first 2 postoperative hours, however, showed no significant differences. Desflurane patients were also judged fit for discharge from the recovery room significantly faster., Conclusions: Our results demonstrate that desflurane anaesthesia, even when supplemented by premedication, intraoperative opioids, and nitrous oxide may offer clinical advantages over isoflurane as far as the post-anaesthetic recovery profile is concerned.

Midlatency auditory evoked potentials (MLAEP) are suppressed dose-dependently during anaesthesia with a variety of general anaesthetics. Therefore, MLAEP have been proposed to measure depth of anaesthesia and to indicate intraoperative awareness. Several studies give evidence of a close relationship between MLAEP and motor signs of wakefulness, intraoperative awareness, and explicit and implicit memory functions during general anaesthesia. Summarising these data, one may conclude that there is a close hierarchical relation between cognitive function, memory and wakefulness during anaesthesia, and MLAEP latencies. A short Nb latency below 45 ms is consistent with conscious awareness and unimpaired memory function with explicit recall and adequate response to commands. When Nb latency increases to 45-50 ms, it may be associated with conscious awareness. Patients still respond to commands, but memory formation is impaired and explicit recall is lost. A further increase of Nb latencies seems to be consistent with unconscious awareness, characterised by implicit memory of intraoperative events; 60 ms seems to be the threshold value for motor signs of wakefulness during anaesthesia. With a further increase of MLAEP latency during anaesthesia, conscious awareness and memory formation, explicit and implicit recall, response to commands, and spontaneous purposeful movements during anaesthesia are blocked. The new volatile anaesthetic sevoflurane leads to a dose-dependent increase in MLAEP peak latencies and a decrease in MLAEP amplitudes. At about 1.5 vol.% end-expiratory sevoflurane concentration, MLAEP are significantly suppressed and Nb latency is in the range of 68-80 ms. Therefore, from the present data and those from the literature, one may expect that sevoflurane at concentrations greater than 1.5 vol.% for general anaesthesia would be able to suppress awareness phenomena such as purposeful movements, auditory perception, intraoperative wakefulness and awareness, memory formation, and explicit and implicit recall of intraoperative events.

Sevoflurane breaks down in basic environments to form a vinyl ether known as Compound A. This compound is toxic in the rat, with an LC50 of about 400 ppm after 3 h exposure and with renal damage evident between 50 and 100 ppm. There is no valid current evidence that Compound A is toxic in man, and the rat may not be an appropriate model for determination of this breakdown product's toxic potential in humans. The main factors influencing the degree of patient exposure to Compound A include fresh gas flow, sevoflurane concentrations, absorber temperature and composition, and the patient's carbon dioxide production.

Background: Propanidid, an ultra-short-acting i.v. anaesthetic agent, was widely used in the 1960s. Reports of anaphylactoid reactions in patients associated with release of histamine following administration of the drug, however, led to withdrawal of this useful anaesthetic. Since the adverse side effects of the former solution could be attributed to the solvent cremophor, attempts have recently been made to produce a propanidid solution without addition of the solvent. We report on comparative investigations employing a new liposomal solution (B. Braun, Melsungen, FRG) and the conventional cremophor preparation with regard to anaesthetic properties, haemodynamic side effects, and electroencephalographic effects (EEG)., Methods: Sprague-Dawley rats (n = 46) were implanted with venous and arterial lines and epidural EEG electrodes during chloral-hydrate anaesthesia. The following day, arterial blood pressure (ABP), heart rate (HR), and EEG were monitored in awake animals and then after induction of anaesthesia by a bolus of the respective propanidid preparation, followed by an infusion period of 15 min in six different experimental groups. Animals of groups L-60, L-90, L-120, or C-60, C-90, or C-120 groups received 60, 90, or 120 mg.100 g-1.h-1 of the liposomal (L) or cremophor (C) preparation. During anaesthesia, the corneal reflex and nociception to tail-clamping were also tested. At termination of the infusion, blood samples were drawn for determination of plasma propanidid concentrations., Results: Both preparations were similarly effective in induction and maintenance of anaesthesia in a dose-dependent manner; both similarly lowered ABP and HR. The corneal reflex and nociceptive responses to tail clamping were also comparably suppressed. However, whereas the liposomal preparation was well tolerated at higher dose levels, the cremophor preparation caused considerable dose-dependent mortality of 11%, 86%, and 86% in animals in groups C-60, C-90, and C-120, respectively. Both preparations were found to induce a burst-suppression pattern in the EEG associated with clonic seizures, with a lower incidence with the liposomal preparation (22% and 50% in groups L-90 and L-120) as compared to the cremophor preparation (100% and 89% in groups C-90 and C-120). A remarkable variability in propanidid plasma concentrations was found at the end of the infusion period, although no differences were observed between both preparations. Discontinuation of infusion of propanidid resulted in rapid awakening (less than 5 min), irrespective of whether the liposomal or conventional preparation was employed., Conclusion: The present findings demonstrate largely identical anaesthetic potencies of a new liposomal solution as compared to the conventional cremophor preparation of propanidid. The liposomal preparation, however, was superior as far as tolerance and incidence of clonic seizures was concerned. The present findings should prompt further studies on the suitability of liposomal propanidid as a short-acting anaesthetic agent in patients.

Treatment of reactions. The treatment of reactions to protamine is still symptomatic. Hypotension resulting from systemic vasodilation (anaphylactoid reaction) is treated by volume infusion, and alpha-stimulating catecholamines may be necessary. The combination of increased right ventricular afterload and systemic hypotension (anaphylactic/anaphylactoid reaction) requires primarily the improvement of coronary perfusion pressure and, thus, of O2 delivery to the right ventricular myocardium. To this end, catecholamines with alpha-stimulating action should be administered. Nitroglycerin is indicated when pulmonary hypertension persists in the presence of essentially normal systemic pressure. In the acute situation, steroids and antihistamines have no beneficial effect. Prevention of protamine reactions. For prevention of systemic hypotension by vasodilatation, protamine should be infused very slowly and not during hypovolemia. General prophylaxis using H1/H2 antagonists is not justified. Reliable preoperative identification of patients who would suffer an anaphylactic/anaphylactoid reaction to protamine, for example by skin tests or by measuring specific anti-protamine IgE or IgG antibodies, is not possible. This prevents individual prophylaxis in risk patients. In view of the low incidence of severe protamine reactions and the lack of better alternatives to the heparin/protamine regimen, general prevention is not indicated. For patients who are potentially at risk (insulin-dependent diabetics, prior protamine exposure), the side-effects of preventive measures must be weighed against their benefits. Only known sensitivity to protamine justifies certain preventive actions. In vascular surgery prostacyclin can be used instead of heparin/protamine or can be withheld (fading out of heparin action). Administration of steroids and/or antihistamines should be avoided. In cardiac surgery the use of hexadimethrine (if available) or total avoidance of protamine is paramount. Corticosteroids may be considered. Aortic administration of protamine and anticoagulation with ancrod are not recommended. The most promising compounds for rpharmacologic prevention of anaphylactic/anaphylactoid reactions in the future are thromboxane receptor antagonists.

Protamine is a strongly alkaline polypeptide with a molecular weight of about 4500. Protamine solutions contain paraben compounds as antimicrobial agents. Rapid neutralization of heparin by protamine may cause an anaphylactoid reaction characterized by a non-immunogenic histamine release and by unknown mediators mechanisms. This response is associated with systemic peripheral vasodilation resulting in slight to moderate hypotension. Weak negative inotropic effects by mechanisms different from the reduction of ionized calcium concentrations may also contribute to systemic hypotension. Apart from these mostly slight reactions, severe reactions may occur with life-threatening systemic hypotension, bronchospasm and, in rare cases, death. They are caused by anaphylactic/anaphylactoid reactions resulting in catastrophic pulmonary vasoconstriction which induces right and eventually global ventricular failure. Sensitization to protamine (anaphylactic) and anaphylactoid reactions are the underlying mechanisms. The majority of anaphylactic/anaphylactoid reactions are associated with complement activation and the release of anaphylatoxins C3a and C5a. These activate the cyclo-oxygenase pathway of the arachidonic acid metabolism in yet unidentified cells, probably within the lung. As a result, thromboxane and prostaglandins are released. Thromboxane is the pivotal mediator responsible for the pulmonary vasoconstriction and, presumably, also for the bronchospasm during protamine reactions. The pronounced activation of polymorphonuclear leukocytes and the decrease in platelet counts may reflect a mere epiphenomenon. The degree of right ventricular afterload increase at which systemic hypotension requiring immediate therapy would occur depends mainly on the contractile state of the heart. Potential risk patients for severe protamine reactions are depot insulin-dependent diabetics and patients with prior exposure to protamine.

A review of the myocardial effects of the volatile anesthetics halothane (HAL), enflurane (ENF) and isoflurane (ISO) is presented. In the first part the effects on cardiac rhythm, myocardial contractility and oxygen supply are discussed. In the second part the pathophysiology of myocardial ischemia during anesthesia and surgery is summarized. Finally the role of inhalation anesthetics in inducing or preventing myocardial ischemia is considered, with special regard to the "coronary steal" phenomenon.

The effects of a pyridoxalated polyhaemoglobin (SFH-PLP)n-solution on haemodynamics were investigated in a model of partial (hct = 12%) and total blood exchange (hct less than 1%) in 7 dogs. Partial blood exchange resulted in a slight increase in right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) and in a marked decrease in heart rate (HR). Cardiac output (CO) did not increase as would be expected from haemodilution. After total blood exchange, arterial pressure, HR, RAP, PCWP and CO were unchanged compared to the pre-exchange values during the 90 minutes of observation. However, pronounced pulmonary vasoconstriction was observed in 4 dogs. The beneficial effects on haemodynamics are due to the long intravascular persistance of the polymerized haemoglobin molecules (plasma half-disappearance time = 36 hours) and the addition of albumin supplying a sufficient colloid-osmotic pressure of the solution. These characteristics and the good oxygen unloading capacity of the pyridoxalated polyhaemoglobin resulted in longterm survival of three dogs. These results demonstrate a better haemodynamic efficacy of the (SFH-PLP)n-solution compared to previous investigations with unmodified haemoglobin solutions. However, there are still many problems, which have to be clarified prior to its clinical application.