Starting from the observation that the specific minimal metabolic rate of hibernating mammals, including that attained by winter sleeping black bears, equals the specific basal metabolic rate of the very largest mammals, and that this lower metabolic level coincides both with the limit of hypothermia tolerance in larger mammals and with the metabolism of structural maintenance in ischemic tissues, the hypothesis is put forward that there is a uniform specific minimal metabolic rate (MMR) in all mammals, and that a fall below this MMR, irrespective of its cause, is not compatible with long-term survival. This hypothesis is reinforced by the fact that it allows correct prediction of several apparently unconnected biological and clinical phenomena, concerning the hypothermia tolerance of nonhibernating and hibernating mammals, the size limitation of homeothermic and poikilothermic vertebrates, and the interaction between hypothermia and ischemia in organ preservation. With regard to the latter point, a theoretical model is developed which may explain the different protectibility of tissues from different species and different organs. Complementary to the varying metabolic starting position, the MMR is supposed to represent a relatively uniform lower metabolic limit, below which the osmotic and ionic dysequilibria of mammalian cells cannot be maintained and which therefore represents a thermodynamic end point of beneficial metabolic reduction.

Introduction:The present investigation was designed to investigate the accuracy and precision of lactate measurement obtained with contemporary biosensors (Chiron Diagnostics, Nova Biomedical) and standard enzymatic photometric procedures (Sigma Diagnostics, Abbott Laboratories, Analyticon).Materials and Methods: Measurements were performed in vitro before and after the stepwise addition of 1molar sodium lactate solution to samples of fresh frozen plasma to systematically achieve lactate concentrations of up to 20 mmol/l.Results: Precision of the methods investigated varied between 1% and 7%, accuracy ranged between 2% and -33% with the variability being lowest in the Sigma photometric procedure (6%) and more than 13% in both biosensor methods. Conclusion:Biosensors for lactate measurement provide adequate accuracy in mean with the limitation of highly variable results.A true lactate value of 6 mmol/l was found to be presented between 4.4 and 7.6 mmol/l or even with higher difference.Biosensors and standard enzymatic photometric procedures are only limited comparable because the differences between paired determinations presented to be several mmol.The advantage of biosensors is the complete lack of preanalytical sample preparation which appeared to be the major limitation of standard photometry methods.

This study was designed to assess the pCO(2) accuracy of portable mainstream (Tidal Wave, Novametrix; Propaq 106, Protocol) and sidestream capnometers (Capnocheck 8200, BCI; Capnocount mini, Weinmann; NPB-75, Nellcor Puritan Bennett; SC-210, Pryon) with respect to international standards and preclinical emergency conditions. Measurements were performed under temperature conditions of +22 degrees C and -20 degrees C using dry gas mixtures with different CO(2) concentrations (STPD) and in patients ventilated with pure oxygen (BTPS). Accuracy presented to be between +1% (Capnocheck) and +12% (Propaq) (STPD) and between -0.4% (Capnocheck) and +11% (Tidal Wave) (BTPS). The measurements were affected by low ambient temperature only in the NPB-75 (+15%). Our results indicate that portable quantitative capnometers are able to fulfill accuracy requirements as requested by international standards but can be affected by changing ambient temperatures.

Background: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. Microcirculation‐dependent alteration of the gut mucosal barrier with subsequent translocation of endotoxins is a postulated mechanism for this inflammatory response. This study was designed to elucidate whether two different approaches to modulate splanchnic perfusion may influence systemic inflammation to CPB. Methods: We examined 40 patients scheduled for elective coronary bypass surgery in a prospective, randomized study. One group (DPX) received dopexamine (1 µg · kg −1 · min −1 ) continuously after induction of anesthesia until 18 h after CPB. The control group (CON) received equal volumes of NaCl 0.9% in a time‐matched fashion. In a third group (EPI) a continuous epidural infusion of bupivacaine 0.25% [(body height (cm) – 100) · 10 −1 =ml·h −1 ] was administered for the whole study period. Procalcitonin (PCT), tumor necrosis factor (TNF‐α), soluble TNF receptor, human soluble intercellular adhesion molecule‐1, C‐reactive protein (CRP) and leukocyte count were measured as parameters of inflammation. Results: All parameters significantly increased following CPB. Increases of PCT, TNF‐α and leukocyte count were significantly attenuated in the DPX and EPI groups at different time points. However, neither splanchnic blood flow nor oxygen delivery and consumption were different when compared with the CON‐group. Conclusion: These results do suggest that mechanisms other than an improved splanchnic blood flow by DPX and EPI treatment have to be considered for the anti‐inflammatory effects.

UNLABELLED:We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L) obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald, Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen, Denmark). A total of 134 measurements per analyzer were obtained in arterial and venous blood samples from 10 patients undergoing cardiac surgery and 65 measurements per analyzer in venous blood samples from 2 healthy volunteers. The blood samples were equilibrated in a tonometer with gases of known composition (37 degrees C). Additional theoretical studies were performed to evaluate the relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using the formulas of the various analyzers. The standard deviations of repeated measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the other 4 analyzers. The maximal systematic difference between the average of all measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to differences in measuring pH, and, to a lesser extent, to differences in calculation and determination of PCO(2). Comparison of the results from samples with different oxygen saturation showed that the relative alkalinity of deoxygenated hemoglobin (Haldane effect) can also influence the determinations of BE(ecf). IMPLICATIONS:A clinically useful way to quantify nonrespiratory disturbances of the acid-base balance is calculation of the base excess of extracellular fluid by using blood gas analyzers. In this study, we found significant variability in estimates of base excess of extracellular fluid obtained with five analyzers from different manufacturers. This variability is attributable to multiple factors, including lack of correction for deoxygenated hemoglobin (Haldane effect).

Background: Nitrous oxide (N2O) has been suggested to contribute to bowel distension, resulting in worsened operating conditions for laparoscopic surgery, and to increase incidence of postoperative nausea and vomiting. Therefore, our objective was to assess the feasibility of two remifentanil‐based anaesthetic regimens free from N2O with special regard to recovery profile, postoperative analgesic demand and side effects in patients undergoing laparoscopic cholecystectomy.Methods: Fifty patients (ASA I–II, 23–65 yr) were randomly assigned to receive remifentanil‐based anaesthesia in conjunction with propofol (group R/P) or desflurane (group R/D). After standardised induction of anaesthesia, analgesia was continued with remifentanil in all patients. For maintenance of hypnosis, propofol or desflurane were used in concentrations to ensure loss of consciousness, lack of awareness, and maintenance of heart rate and blood pressure within ±25% of initial values. At the end of surgery all anaesthetics were discontinued without tapering and early emergence and recovery were recorded. Pain scores were assessed by using a visual analogue scale. Patient‐controlled analgesia with i.v. piritramide was used for treatment of postoperative pain and recorded for 90 min in the postanaesthesia care unit (PACU). In addition, side effects were noted.Results: Early emergence from anaesthesia did not differ between the groups. In group R/P, time to eye opening, spontaneous respiration and extubation was 4.4±2.9 min, 5.2±3.4 min and 5.5±3.3 min respectively, compared with 4.7±2.7 min, 5.3±2.4 min and 5.7±2.5 min in group R/D. While pain scores did not differ between both groups on admission to the PACU, patients receiving desflurane required more i.v. piritramide as compared to those receiving propofol, 22.0±6.5 mg and 17.9±7.0 mg, respectively (P<0.05). Nausea was less frequent after propofol (16% vs. 48%, P<0.05).Conclusion: In patients undergoing laparoscopic cholecystectomy, remifentanil‐based anaesthetic regimens in conjunction with propofol or desflurane are suitable and allow for rapid recovery from anaesthesia. However, the use of propofol results in less postoperative analgesic consumption and nausea as compared to desflurane.

BACKGROUND:Patients with heparin-induced thrombocytopenia type II require an alternative to standard heparin anticoagulation. However, in patients with renal impairment, anticoagulation during cardiopulmonary bypass with agents such as danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation with unfractionated heparins combined with prostacyclin, a potent platelet aggregation inhibitor, is associated with severe hypotension. The authors investigated a new concept using unfractionated heparins after platelet inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist tirofiban.METHODS:Ten patients with heparin-induced thrombocytopenia type II and renal impairment were enrolled in the investigation. All had heparin-induced thrombocytopenia type II antibodies present as proved by the heparin-induced platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked immunosorbent assay, or both. In all patients, preoperative anticoagulation to an activated partial thromboplastin time of 40-60 s was performed with r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10 microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1) x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional unfractionated heparins were only administered if activated clotting time decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer concentrations, as a marker of venous thromboembolism, were measured before and 12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started immediately with r-hirudin to anticoagulation to an activated partial thromboplastin time of 40-60 s.RESULTS:The postoperative blood loss ranged from 110 to 520 ml. No patient needed reexploration. In no patient was there clinical evidence of thrombosis or embolism in the postoperative period or of a critical increase of the D-dimer concentrations, suggesting venous thromboembolism. Transfusion of platelets was necessary in only two patients.CONCLUSIONS:The protocol is easy to perform and no increased postoperative bleeding and no thromboembolic complications occurred. The combination of unfractionated heparins and tirofiban may be an alternative to other anticoagulation strategies in patients with heparin-induced thrombocytopenia.

European Society of Anaesthesiologists; 8th Annual Meeting with the Austrian International Congress; Vienna, Austria, 1-4 April 2000

European Society of Anaesthesiologists; 8th Annual Meeting with the Austrian International Congress; Vienna, Austria, 1-4 April 2000

In der vorliegenden Studie wurde der Einfluß von Dopexamin auf die Splanchnikusperfusion und die allgemeine Hämodynamik während einer aortokoronaren Bypassoperation untersucht.

Procalcitonin (PCT) is an inflammatory peptide of still unknown origin. In this study we investigated a potential source for circulating PCT in patients undergoing coronary artery bypass grafting.To determine PCT concentrations, arterial, liver-venous and mixed-venous blood samples were collected time matched perioperatively in 20 patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB).PCT concentrations significantly increased 4 hours postoperatively compared to baseline values (0.74 +/- 0.45 vs. 0.16 +/- 0.04 ng/ml). The highest concentrations were measured 18 hours postoperatively (1.44 +/- 1.01 ng/ml). PCT concentrations in liver venous samples were significantly higher (1.67 +/- 1.29 ng/ml) than in time matched collected arterial samples (1.44 +/- 1.01 ng/ml).These results provide evidence, that hepatosplanchnicus is a source for PCT synthesis in patients following CPB. The mechanism of PCT induction remains unclear. A loss of gut mucosal barrier function with translocation of endotoxins and the inflammatory response with release of cytokines following cardiopulmonary bypass has to be discussed.

Der Syntheseort für das inflammatorische Peptid Procalcitonin (PCT) ist bisher nicht bekannt. In der vorliegenden Studie wurde bei kardiochirurgischen Patienten nach Hinweisen für einen Syntheseort nach extrakorporaler Zirkulation (EKZ) gesucht.

Gastrointestinal complications following major surgery, including cardiac surgery requiring cardiopulmonary bypass (CPB), have been associated with splanchnic ischemia. Because of the annual increase in the number of CPB procedures including elderly patients with a higher incidence of existing diseases, the importance of CPB-related gastrointestinal complications has become more pronounced. Severe intestinal complications after CPB such as nonocclusive mesenteric ischemia are, fortunately, rare but seem to be a trigger mechanism for mucosal barrier breakdown, translocation of endotoxin, and systemic inflammatory response. Therefore, a severe course of intestinal ischemia is associated with high mortality [1, 2].

The haemodynamic effects of anaesthesia with gamma-hydroxybutyrate (GHB)/sufentanil for elective coronary artery bypass grafting (CABG) were investigated and compared in patients with unimpaired left ventricular function (ejection fraction > or = 45%, left ventricular end diastolic pressure < or = 16 mmHg) and patients with impaired left ventricular function. In 38 consecutive patients scheduled for CABG (21 with unimpaired and 17 with impaired left ventricular function), anaesthesia was induced with etomidate, sufentanil and pancuronium. After tracheal intubation, the lungs were normoventilated (end tidal Pco2 4.9-5.6 kPa) with an oxygen-air mixture (Fio2 0.5). Total intravenous anaesthesia was maintained with GHB (20 mg kg-1 h-1 after a 'priming dose' of 40 mg kg-1) and sufentanil (2 micrograms kg-1 h-1). Haemodynamic measurements were made after induction of anaesthesia and at various times in the prebypass period. Patients in both groups showed similar haemodynamic trends. Mean arterial pressure showed a maximum reduction of 10%, whereas heart rate and right- and left-sided filling pressures remained unchanged within the groups after the induction of anaesthesia. Cardiac index remained unchanged in both groups, although values differed between the groups. A total of 14 out of 21 patients (67%) with unimpaired and 10 out of 17 patients (59%) with impaired ventricular function required supplementary administration of opioids to control temporary hypertension after sternotomy. No episodes of myocardial ischaemia were detected during the study period using ST segment analysis (leads II and V5). The results of this study suggest that GHB provides adequate haemodynamic conditions in the prebypass period and may be a suitable agent for TIVA also in patients with impaired left ventricular function undergoing CABG.

Backround and Methods: Alteration of the hepatocellular function following ischemic damage may play a crucial role in the limited recovery after reperfusion. In spite of numerous efforts, finding a simple technique for predicting recovery of the liver after ischemic damage is still an unresolved problem. During ischemic storage of isolated rat livers at 25°C tissue concentrations of high energy phosphates and lactate were determined photometrically and interstitial pH was measured by glass electrodes. In comparison, the metabolic rate was measured continuously by direct calorimetry. In a second series of experiments these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25°C for 60, 120 or 240 min, the isolated livers were reperfused for 30 min in a non‐recirculating system with a constant flow rate. During reperfusion functional recovery, as assessed by oxygen consumption and bile flow, was determined. At the end of reperfusion tissue samples were taken for biochemical analysis of adenine nucleotides. Furthermore, morphologic integrity was determined by electron microscopy.Results: Whereas the ATP concentration drops within 60 min of ischemia to 6.9% of the control value without further significant change, the continuously measured metabolic rate as assessed by direct calorimetry decreases in an exponential manner. Accordingly, a better correlation of hepatocellular secretory function and calorimetrically measured heat output (r2=0.85; P<0.001) was observed than with high energy phosphates (r2=0.56; P<0.001).Conclusions: These data suggest that if the metabolism of the ischemic rat liver falls below a critical level, recovery is incomplete or impossible. Therefore, assessment of the global metabolic rate by direct calorimetry seems not only to be a very good predictor of recovery after ischemic damage but also a good tool in the laboratory for studies concerning the sequelae of ischemic metabolism and for improvement of tissue protection.

Size effects on metabolic rate include the effects of body size (biological) and sample size (methodological) and are to be found in cell, tissue, and body calorimetry. The biological size effect, known as Kleiber's rule and consisting of a metabolic reduction with increasing body mass, is demonstrated by the size relationship of blood heat output in several mammalian species (cellular level) and by the differing metabolic behaviour of cardioplegic rat and dog heart samples (tissue level). The methodological size effect, known as the crowding effect and consisting of a metabolic decrease with increasing sample size, is demonstrated in human renal carcinoma cells (cellular level) and ischemic rat liver samples (tissue level) and is explained by a simple mathematical simulation. With respect to body calorimetry, it is stressed that metabolic size allometry may be temporarily inactivated in special biological adaptations (neonatal period, mammalian hibernation), and weight correction of metabolic rates may produce methodological problems when mass differences are mainly due to varying body fat content (circannual rhythms). In conclusion, careful size standardization is a prerequisite of comparability in biomedical calorimetry.

Alteration of the hepatocellular function following ischemic damage may play a crucial role in the limited recovery after reperfusion. In spite of numerous efforts, finding a simple technique for predicting the recovery of the liver after ischemic damage is still an unresolved problem. During the ischemic storage of isolated rat livers at 25 degrees C, tissue concentrations of high energy phosphates, glycogen and lactate were determined photometrically and, in comparison, the metabolic rate was measured continuously by direct calorimetry. In addition, interstitial pH was measured with microelectrodes. In a second series of experiments these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25 degrees C for 60, 120 and 240 min, the isolated livers were reperfused for 30 min in a non-recirculating system with a constant flow rate. During reperfusion, functional recovery as assessed by oxygen consumption and bile flow was determined. At the end of reperfusion, tissue samples were taken for biochemical analysis of adenine nucleotides and tissue lactate. Though the ATP concentration drops within 60 min of ischemia to 6.94% of the control value without further significant change, the metabolic rate measured continuously by direct calorimetry decreases in an exponential manner. According to the calorimetrically measured heat output, functional hepatic metabolism as assessed by oxygen consumption, bile flow and restoration of high energy phosphates during reperfusion, recovered to an extent depending on the duration of ischemia. It is concluded that the metabolic rate of the ischemic rat liver, as determined continuously by direct calorimetry, is a good predictor for recovery after ischemic damage.