A surgical technique for a terminal intracranial hypertension model in pigs.

The life-threatening effects of intracranial hypertension on brain perfusion and cerebral metabolism are the subject of current research in different animal models. The purpose of this study was to describe an efficient, reliable and inexpensive surgical method for temporary elevation of intracranial pressure (ICP) in acutely instrumented pigs in a research setting. Therefore, a balloon catheter was inserted into the left lateral ventricle and an ICP sensor was placed in the parenchyma of the right cerebral hemisphere. Ten acutely instrumented pigs were studied while under deep terminal general anaesthesia. The step-by-step inflation of the intraventricular balloon allows one to achieve the desired ICP up to 46 mmHg and maintain it at this level. ICP values ranged from a median of 2 (1-2) mmHg to 43 (29-45) mmHg. To the authors' knowledge, this is the first detailed description of a minimally invasive surgical technique for temporary ICP elevation in pigs via stepwise inflation of an intraventricular balloon.

Clinical evaluation of a simultaneous closed-loop anaesthesia control system for depth of anaesthesia and neuromuscular blockade*.

We developed a closed-loop system to control the depth of anaesthesia and neuromuscular blockade using the bispectral index and the electromyogram simultaneously and evaluated the clinical performance of this combined system for general anaesthesia. Twenty-two adult patients were included in this study. Anaesthesia was induced by a continuous infusion of remifentanil at 0.4 µg.kg(-1) .min(-1) (induction dose) and then 0.25 µg.kg(-1) .min(-1) (maintenance dose) and propofol at 2 mg.kg(-1) 3 min later. The combined automatic control was started 2 min after tracheal intubation. The depth of anaesthesia was recorded using bispectral index monitoring using a target value of 40. The target value of neuromuscular blockade, using mivacurium, was a T1/T1(0) twitch height of 10%. The precision of the system was calculated using internationally defined performance parameters. Twenty patients were included in the data analysis. The mean (SD) duration of simultaneous control was 129 (69) min. No human intervention was necessary during the computer-controlled administration of propofol and mivacurium. All patients assessed the quality of anaesthesia as 'good' to 'very good'; there were no episodes of awareness. The mean (SD) median performance error, median absolute performance error and wobble for the control of depth of anaesthesia and for neuromuscular blockade were -0.31 (1.78), 6.76 (3.45), 6.32 (2.93) and -0.38 (1.68), 3.75 (4.83), 3.63 (4.69), respectively. The simultaneous closed-loop system using propofol and mivacurium was able to maintain the target values with a high level of precision in a clinical setting.

[Feedback control of depth of anesthesia during propofol administration. Bispectral index as the controlled variable]. / Regelkreisgesteuerte Narkosetiefe bei Propofolapplikation. Verwendung des Bispektralindex als Regelungsgrösse.

BACKGROUND: The objective of this study was to evaluate the performance of a new system for closed-loop control of propofol administration using the bispectral index (BIS) under total intravenous anesthesia in the index values of middle-to-deep depth of anaesthesia. METHODS: In this study 20 adult patients anesthetized with propofol and remifentanil were investigated. The propofol infusion was carried out using a fuzzy-PD+I controller with a target BIS value of 40. RESULTS: Closed-loop control was able to provide maintenance of anesthesia and adequate operating conditions for all patients. The following quality control criteria were calculated: median performance error (MDPE; 0.16%, SD +/-1.4%), median absolute performance error (MDAPE; 6.9%, SD +/-2.8%) and wobble (6.8%, SD +/-2.5%). CONCLUSION: The present study showed the clinical feasibility of the controller compared to existing devices regarding a high level of quality criteria of a model with an implemented fuzzy-PD+I structure controlling depth of hypnosis.

Xenon anesthesia impairs hepatic oxygenation and perfusion in healthy pigs.

BACKGROUND: Over the last 15 years, there has been growing interest in the noble gas xenon as a new inhalational anesthetic. This is due to its favorable pharmacological properties such as short onset and offset, as well as its hemodynamic stability. However, most volatile anesthetics appear to play an important role in the multi-factorial etiology of perioperative liver injury by decreasing liver blood flow with a subsequent reduction of hepatic oxygen supply. However, the effects of the anesthetic gas xenon on hepatic perfusion and oxygenation have not been completely investigated. METHODS: Following ethical approval, 18 anesthetized and acutely monitored pigs were randomly assigned to the two following groups: 9 animals received xenon anesthesia in increasing inspiratory concentrations of 0%, 20%, 50%, and 65% in addition to their basic intravenous anesthesia; 9 animals served as a control group. Measurement points for systemic and regional hemodynamic and oxygenation parameters were performed 30 min after changing the xenon concentration. RESULTS: Xenon elicited dose-dependent systemic hemodynamic changes such that the mean arterial pressure did not change, while the heart rate and cardiac output decreased by about 30%, thereby indicating an increase in the systemic vascular resistance. Portal venous blood flow decreased, while hepatic arterial blood flow was unchanged. The oxygen supply of the liver was reduced, but not the rate of indocyanine plasma disappearance from the liver. Furthermore, the increase of liver surface pO2 to systemic hyperoxia was absent, and hepatic lactate uptake was reduced. CONCLUSION: Xenon, in addition to basic intravenous anesthesia, elicited a decrease in heart rate and cardiac output and an increase in mean arterial pressure. Similar to volatile anesthetics, xenon does reduce portal venous flow and influences hepatic tissue oxygenation. In contrast, hepatic arterial blood flow remains stable in the presence of xenon, and no changes in the hepatic arterial buffer responses were evident. Xenon does affect hepatic perfusion and oxygenation.

Are women more sensitive to a pre-curarization dose of rocuronium than men?

BACKGROUND: There is increasing evidence that there are gender-related differences in the pharmacodynamics of neuromuscular blocking drugs. However, it is not known whether gender influences the pharmacodynamics of a pre-curarizing dose. METHODS: In the first part, we measured the neuromuscular blockade after administration of rocuronium 0.03 mg/kg (10% of ED(95)) after induction of anaesthesia in 20 patients (10 female and 10 male patients) by electromyography. In the second part, 40 female and 40 male patients were observed for signs and symptoms of muscle weakness 2.5 min after injection of rocuronium 0.03 mg/kg before loss of consciousness. Succinylcholine-associated post-operative myalgia (POM) was also assessed. RESULTS: Median twitch heights were comparable between the two groups: 95.5 (range: 85-97; female) vs. 96.0 (range: 85-99; male), (NS). Train-of-four ratios were 97.5 (range: 64-100; female) vs. 99.0 (range: 52-100; male) (NS). Signs and symptoms of muscle weakness were observed in 64 (80%) patients, but there were no gender-related differences. The incidence and severity of POM did not differ significantly between the study groups. CONCLUSIONS: Pre-curarization with rocuronium 0.03 mg/kg affected men and women equally. Nor was the incidence and the severity of muscle weakness affected by gender.

[Influence of clonidine-induced systemic sympathicolysis on oxygenation and perfusion of the liver. Investigations with healthy pigs under general anesthesia]. / Einfluss der Clonidin-induzierten systemischen Sympathikolyse auf die Oxygenierung und Perfusion der Leber. Untersuchungen am gesunden Hausschwein in Allgemeinanästhesie.

BACKGROUND: Increased sympathetic nervous activity which induces vasoconstriction and decreases perfusion may be an underlying mechanism behind the development of perioperative liver damage. This animal study was designed to assess how clonidine-induced systemic sympathicolysis affects liver oxygenation with respect to induced hypotension and vasodilatation under physiological conditions. METHODS: Following ethical approval 17 anesthetized and acutely instrumented pigs were randomly assigned to 2 groups. Group 1 consisted of 8 animals receiving intravenous clonidine (2 microg x kg(-1) bolus and 2 microg x kg(-1) x h(-1) for induction of sympathicolysis and group 2 consisted of 9 animals serving as controls. After obtaining baseline values, measurements were repeated 90 and 250 min after starting to reduce systemic sympathetic nervous activity. RESULTS: Clonidine-induced systemic sympathicolysis was associated with decreased mean arterial blood pressure, cardiac output and heart rate. Portal venous and hepatic arterial blood flow, oxygen delivery to the liver, oxygen uptake and liver tissue oxygen partial pressure remained unchanged. The plasma indocyanine green disappearance rate increased. CONCLUSION: We concluded that despite decreased mean arterial pressure and cardiac output, clonidine-induced systemic sympathicolysis did not affect liver oxygenation or perfusion.

Protective effects of PARP inhibition on liver microcirculation and function after haemorrhagic shock and resuscitation in male rats.

OBJECTIVE: The aim of this study was to investigate the impact of the water-soluble poly-(ADP)-ribose-polymerase (PARP) inhibitor 5-aminoisoquinolinone (5-AIQ) on liver microcirculation and function after haemorrhagic shock and resuscitation. DESIGN: Controlled, randomized animal study. SETTING: University animal care facility and research laboratory. SUBJECT: Male Sprague-Dawley rats were subjected to haemorrhagic shock for 1 h, followed by resuscitation with shed blood and crystalloid solution for a total of 5 h. INTERVENTIONS: The PARP inhibitor 5-AIQ (3 mg/kg; n=7) or vehicle (n=7) was administered 5 min prior to resuscitation. Sham-operated animals without induction of shock served as controls (n=7). MEASUREMENTS AND RESULTS: Using intravital fluorescence microscopy hepatic microcirculation was assessed at baseline, end of shock phase as well as 1 h and 5 h after resuscitation. Systemic arterial blood pressure and bile flow were continuously monitored. 5-AIQ treatment attenuated shock/resuscitation-induced increase of intrahepatic leukocyte-endothelial cell interaction with a marked reduction of both sinusoidal leukostasis and venular leukocyte adherence. Moreover, nutritive perfusion was found improved, guaranteeing sufficient oxygen supply to tissue, as indicated by low NADH autofluorescence, which was not different to that in controls. Most notably, excretory liver function reached baseline level over 5 h of reperfusion in 5-AIQ-treated animals. CONCLUSIONS: In the present setting of shock/resuscitation in male rats the PARP inhibitor 5-AIQ proved to be very effective in ameliorating compromised liver microcirculation and function. Further research has to confirm that PARP inhibition is a suitable tool in the acute treatment of patients suffering from reduced circulating blood volume and thus microcirculatory organ dysfunction.

Comparison of invasive and less-invasive techniques of cardiac output measurement under different haemodynamic conditions in a pig model.

BACKGROUND AND OBJECTIVE: Despite the introduction of various less-invasive concepts of cardiac output measurement, pulmonary arterial thermodilution is still the most common measurement technique. METHODS: This prospective controlled study was designed to compare different methods of cardiac output measurement simultaneously. Pulmonary arterial thermodilution, transpulmonary thermodilution (PiCCO), trans-oesophageal echo-Doppler probe (HemoSonic) and partial carbon dioxide rebreathing technique (NICO monitor) were evaluated against a peri-aortic transit-time flow-probe as reference method in a clinically relevant animal model. After approval from the Local Ethics Committee on Animal Research, the investigations were conducted in nine anesthetized domestic pigs. Systemic haemodynamics were modulated systematically by the application of catecholamines, caval occlusion and exsanguination. Statistical analysis was performed with Bland-Altman and linear regression. RESULTS: A total of 366 paired cardiac output measurements were carried out at a reference cardiac output between 0.5 and 7 L min(-1). The correlation coefficients for pulmonary arterial and transpulmonary thermodilution against reference were 0.93 and 0.95, for trans-oesophageal Doppler and partial rebreathing technique 0.84 and 0.77. Pulmonary arterial thermodilution and transpulmonary thermodilution showed comparable bias and limits of agreement. Where HemoSonic showed an overestimation of cardiac output at a higher precision, NICO overestimated low and underestimated higher cardiac output values. CONCLUSIONS: Our data suggest that pulmonary arterial thermodilution and PiCCO may be interchangeably used for cardiac output measurement even under acute haemodynamic changes. The method described by Bland and Altman demonstrated an overestimation of cardiac output for both thermodilution methods. HemoSonic and NICO offer non-invasive alternatives and complementary monitoring tools in numerous clinical situations. Trend monitoring and haemodynamic optimizing can be applied sufficiently, when absolute measures are judged critically in a clinical context. The use of the NICO system seems to be limited during acute circulatory changes.

Effects of systemically applied clonidine on intestinal perfusion and oxygenation in healthy pigs during general anaesthesia and laparotomy.

BACKGROUND AND OBJECTIVE: Clonidine, which is used for induction of sympatholysis and prevention or treatment of alcohol withdrawal in anaesthesia and intensive care medicine, may have deleterious effects on intestinal mucosal perfusion. This study was designed to investigate the effects of clonidine on intestinal perfusion and oxygenation. METHODS: Following ethical approval 17 anaesthetized, and acutely instrumented pigs were randomly assigned to two groups: eight animals received intravenous clonidine (2 microg kg(-1) bolus and 2 microg kg(-1) h(-1)), nine animals served as a control group. Measurement points for systemic and regional haemodynamic and oxygenation parameters were 135 and 315 min after starting the clonidine application. RESULTS: Clonidine elicited systemic haemodynamic changes (median [25-75th interquartile range]): heart rate (106 [91, 126] to 84 [71, 90] beats min(-1)) cardiac output (147 [123, 193] to 90 [87, 107] mL min(-1) kg(-1)) and mean arterial pressure (77 [72, 93] to 69 [61, 78] mmHg) decreased. Despite systemic haemodynamic changes, the superior mesenteric artery blood flow did not change in the clonidine group. The vascular resistance of the superior mesenteric artery decreased. The small intestinal oxygen supply, the mucosal and the serosal tissue oxygen partial pressure did not change. CONCLUSIONS: Systemic sympatholysis induced by intravenously applied clonidine in addition to basic intravenous anaesthesia elicited a decrease in cardiac output and mean arterial pressure. However, regional macrohaemodynamic perfusion was maintained and intestinal oxygenation did not change. Clonidine does not impair intestinal mucosal and serosal oxygenation under physiological conditions.

Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients.

A well-defined relationship has to exist between substance concentrations in blood and in breath if blood-borne volatile organic compounds (VOCs) are to be used as breath markers of disease or health. In this study, the impact of inspired substances on this relationship was investigated systematically. VOCs were determined in inspired and expired air and in arterial and mixed venous blood of 46 mechanically ventilated patients by means of SPME, GC/MS. Mean inspired concentrations were 25% of expired concentrations for pentane, 7.5% for acetone, 0.7% for isoprene and 0.4% for isoflurane. Only if inspired concentrations were <5% did substance disappearance rates from blood and exhalation rates correlate well. Exhaled substance concentrations depended on venous and inspired concentrations. Patients with sepsis had higher n-pentane and lower acetone concentrations in mixed venous blood than patients without sepsis (2.27 (0.37-8.70) versus 0.65 (0.33-1.48) nmol L-1 and 69 (22-99) versus 18 (6.7-56) micromol L-1). n-Pentane and acetone concentrations in breath showed no differences between the patient groups, regardless whether or not expired concentrations were corrected for inspired concentrations. In mechanically ventilated patients, concentration profiles of volatile substances in breath may considerably deviate from profiles in blood depending on the relative amount of inspired concentrations. A simple correction for inspired substance concentrations was not possible. Hence, substances having inspired concentrations>5% of expired concentrations should not be used as breath markers in these patients without knowledge of concentrations in blood and breath.

[Extracorporeal blood purification in severe liver failure with the albumin dialysis MARS -- impact on relevant intensive care parameters]. / Extrakorporale Blutreinigung im schweren Leberversagen mit der Albumindialyse MARS -- Einfluss auf intensivmedizinisch relevante Parameter.

Extracorporeal liver support methods have been tested for over 50 years now. Standard techniques of blood purification like dialysis, adsorption, hemo- and plasma filtration as well as bioreactor-based approaches using liver cells or tissues have been used. Most clinical experience, however, is limited to use in acute liver failure (ALF). Since 1993, the Molecular Adsorbent Recirculating System (MARS) has been used clinically -- a system that combines dialysis, filtration and adsorption in a biocompatible method. Human serum albumin (HSA) acts as a selective molecular adsorbent binding protein-bound compounds like bile acids or bilirubin. These substances can contribute to the maintenance or even further aggravation of liver failure. They are linked with the pathogenesis of hyperdynamic hypotonic circulation, hepatic encephalopathy, hepatorenal syndrome, impaired hepatic protein synthesis, and intractable pruritus seen in chronic liver failure. HSA takes over the toxic substances from a patient's blood and passes through a remote detoxification process including bicarbonate-dialysis and a two-step adsorption. It is then recirculated in the patient's blood. Up to today, more than 4000 patients have been treated in approximately 16,000 single sessions. Thus, MARS represents the most frequently used liver support method at the present time. In addition to ALF, mainly acute decompensations of chronic liver failures (ACLF) have been treated. The impact of the extracorporeal treatment on relevant medical parameters of intensive care medicine is discussed with regard to the specific situation of the liver-failure patient (susceptibility to infection, atypical picture and course of infection, coagulation disorders and bleeding tendencies).

Effects of xenon anaesthesia on intestinal oxygenation in acutely instrumented pigs.

BACKGROUND: Xenon is a narcotic gas that might be able to replace volatile anaesthetics or nitrous oxide due to its favourable pharmacological properties, such as providing haemodynamic stability. Intestinal oxygenation is affected by most volatile anaesthetics as a result of cardiodepressive effects. Reducing oxygenation of the gut might be a factor leading to perioperative organ dysfunction. This animal study was designed to assess the effects of xenon on intestinal oxygenation. METHODS: After ethical approval, 24 anaesthetized, acutely instrumented pigs were randomly assigned to three groups: nine animals received xenon anaesthesia with inspiratory concentrations of 0, 20, 50 and 65% in addition to their basic i.v. anaesthesia, nine animals served as a study control group, and five animals were used to assess model stability. Measurement of systemic and regional haemodynamic and oxygenation parameters was made 30 min after changing the xenon concentration. RESULTS: Xenon elicited dose-dependent systemic haemodynamic changes: heart rate and cardiac output decreased by 30%, while mean arterial pressure was stable. Superior mesenteric artery blood flow was lower in the xenon group. Vascular resistance of the superior mesenteric artery increased. The small intestinal oxygen supply decreased with increasing xenon concentration; the mucosal tissue oxygen partial pressure decreased but did not reach hypoxic (<5 mm Hg) values. Serosal tissue oxygen partial pressure was maintained. CONCLUSIONS: Xenon, in addition to basic i.v. anaesthesia, elicited a decrease in cardiac output and maintained mean arterial pressure. Intestinal oxygenation was maintained, although regional macrohaemodynamic perfusion decreased. Xenon does not impair intestinal oxygenation under physiological conditions.

[Remifentanil analgesia for aspiration of follicles for oocyte retrieval]. / Remifentanil-Analgezien zur Follikelpunktion für In-Vitro-Fertilisation.

Remifentanil is an esterase-metabolized ultra-short acting mu-agonist opioid with a rapid clearance. The aim of this study was to determine the efficacy of remifentanil infusion for the short-lasting, but painful, transvaginal puncture for oocyte retrieval. Eighty consenting adult women (ASA I and II) aged 30.5 +/- 5 years and with a body weight of 69.1 +/- 9.1 kg were enrolled in this prospective study. After an oral premedication with 7.5 mg midazolam, all patients received 3 l/min oxygen. Subsequently, the remifentanil infusion was started with a rate of 0.3 microg/kg/min. Remifenanil doses were adjusted as needed for painless puncture and sufficient oxygen saturation in steps of 0.05 microg/kg/min. Dosage requirements, blood pressure, heart rate, oxygen saturation (pulse oxymetry, SaO2) and the level of analgesia were recorded every 3 minutes. Follicular aspiration lasted 11.8 +/- 4.1 min and the time of remifentanil infusion was 18.7 +/- 4.6 min. Dosage requirements of remifentanil were 0.3 microg/kg/min in 48.7% of all patients, but 27.8% needed only 0.25 microg/kg/min and 16.6% needed only 0.2 microg/kg/min. However, 4.2% of patients needed 0.35 microg/kg/min and 2.7% of all cases needed 0.4 microg/kg/min. Vital parameters remained nearly unchanged. Oxygen saturation decreased significantly from 99.2 +/- 0.7% to 98.2 +/- 2.4% after 3 min and to 94.9 +/- 7.2% after 10 min. Nine women showed motoric reactions to puncture. In many cases, the infusion of remifentanil after premedication with midazolam provided a suitable and satisfying anaesthesia for oocyte retrieval. Some patients, however, showed motoric reactions to vaginal puncture, while in other cases significant and clinical relevant decreases in Hb-oxygen saturation occurred. Therefore, we no longer carry out remifentanil infusion for transvaginal oocyte retrieval. We now prefer a remifentanil infusion of 0.2 microg/kg/min and propofol (1 mg/kg initially with intermittent doses of 0.5 mg/kg) combined with assisted ventilation by mask.

[Cricoid pressure--safety necessity or unnecessary risk?]. / Krikoid-Druck--Sicherheitsnotwendigkeit oder unnötiges Sicherheitsrisiko?

Cricoid pressure is a simple and effective measure to prevent regurgitation of gastric juice and content. This procedure, which prevents a possible reflux by compression of the oesophagus between the cricoid cartilage and the cervical vertebral bodies, is generally acknowledged in clinical practice, although there is lack of scientific evidence regarding its effect on the outcome of patients at risk of aspiration. However, there is only a rare incidence of complications as long as cricoid pressure is used with exact indication, considering the contraindications and correct performance. Especially important are the optimal force applied on the cricoid and the duration of application. However, there is a lot of evidence in the literature that the knowledge of anaesthetists about the method and technique of cricoid pressure is rather unsatisfactory. Thus, the starting point for improving the efficiency and safety of cricoid pressure seems to be better teaching and training.