Background: Patients with liver failure have an increased incidence of a prolonged QTc interval which is associated with increased morbidity. The etiology of the increase in QTc interval is unknown. We looked for a correlation between the QTc interval and three possible contributors: estradiol, progesterone and hyperventilation. Methods: Arterial blood gases, estradiol, progesterone, and electrolytes were obtained from 50 patients with cirrhosis presenting for possible liver transplantation. QTc and QT dispersion were measured on electrocardiograms from the patients and age and sex matched with controls. Results: The male and female patients with cirrhosis had an increase in QTc compared to controls. There was no increase in QT dispersion in the patients. There was no correlation between QTc interval and estradiol or progesterone. However, there was a negative correlation between the QTc interval and PaCO2 in male patients. Conclusion: Our results raise the possibility that hyperventilation contributes to the prolonged QTc interval found in patients with cirrhosis.
Introduction: Bispectral index (BIS) is a promising method for monitoring anaesthetic depth in humans. Inhalational and intravenous anaesthetics produce dose-dependent effects on electroencephalogram-derived parameters, such as bispectral index (BIS). Significant correlations between decrease of BIS values in humans and end-tidal concentrations of volatile anaesthetics halothane, isoflurane, desflurane and sevoflurane and plasma propofol concentrations have been reported in several investigations. We have investigated the effect of xenon anaesthesia on bispectral index (BIS) in pigs. Materials and Methods: BIS index was measured under total intravenous, xenon and halothane anaesthesia: in 8 pigs. Each animal received 1 MAC halothane before or after xenon anaesthesia in randomized cross over design to eliminate systemic errors. Between xenon and halothane anaesthesia total intravenous anaesthesia was applied to eliminate the effects of the anaesthetic gas first applied. Surgical stimuli were not present during xenon and halothane anaesthesia, surgical preparations were completed in TIVA. BIS levels measured during preparation phase were used as reference values to assure adequate level of anaesthesia. BIS was measured using an BIS EEG monitor (Aspect A 2000, Aspect Medical Systems Inc., Natick, MA, USA). Results: We found no significant difference between BIS scores in anaesthetized pigs with I MAC of halothane or 70% xenon or in total intravenous anaesthesia. In addition, we found no significant difference in BIS during the whole anaesthesia with halothane or xenon. BIS levels during halothane and xenon anaesthesia were comparable to those measured under TIVA and surgical preparation. BIS values remained unchanged during xenon anaesthesis as compared with TIVA and halothane anaesthesia. Conclusion: As a conclusion the BIS EEG is a very promising tool for measuring depth of xenon, halothane and total intravenous anaesthesia also in animals.
ARDS is under continuous investigation as today's proposed therapies are not able to reduce mortality. Total liquid ventilation or partial liquid ventilation using perfluorocarbons appear to offer an alternative treatment both in animals and humans, not only in RDS in premature babies and ARDS in adults, due to the possibility to eliminate air/liquid interfaces and reduce surface tension, but also in meconium aspiration syndrome where they facilitate the removal of the meconium and eliminate inhomogeneous lung ventilation. In other lung pathologies liquid ventilation appears useful even though the number of patients treated is limited. While the improvement in gas exchange and the elimination of matter from the lung have been clearly demonstrated, improved survival rates and complications in prolonged treatment need further research and confirmation.
This paper presents a new technological solution for a long standing problem: how to recycle nitrous oxide or xenon in a closed low-flow anaesthetic circuit. For a nitrous oxide anaesthetic circuit, a CMS hollow fiber membrane module, where the permeate side is filled with a diamine, is proposed to remove carbon dioxide and simple CMS hollow fiber membrane module is proposed to remove nitrogen, methane and acetone. Some oxygen ends up also being lost. In a xenon anesthetic circuit, carbon dioxide can be removed using a CMS hollow fiber membrane module and nitrogen with a Pressure Swing Adsorption (PSA) unit packed with a special CMS adsorbent. Some of the acetone is also removed. In both cases (nitrous oxide and xenon recycling), the halogenated anesthetics remain in the closed circuit. Both the adsorbents and the membranes are sterilizable in-situ by rising the temperature up to 121 degrees C.
Similar pharmacokinetic principles apply to intravenous and inhaled anaesthetic drugs so that dosing principles are also similar. Opioids and inhaled agents interact synergistically, therefore simultaneous administration of these drugs gives rise to anaesthesia at reduced dosage, thereby minimizing side-effects. Computer-assisted technology exists for target-controlled administration of both agents by targeting plasma or effect-site concentrations (target-controlled anaesthesia, TCA). With suitable background knowledge of the pharmacokinetic properties of these drugs, it is also possible to practice TCA by manual control of vaporizer and infusion pump. Future developments will expand TCA techniques and evolvement of complete closed-loop anaesthesia is envisaged.
Background: Ventricular diastolic function is an important determinant of overall cardiovascular performance and is a sensitive marker of cardiac dysfunction. It is dependent on structural changes as well as functional abnormalities. Patients and methods: 12 patients with hypoxaemic cor pulmonale 69(3) years with normal left ventricular systolic function were treated with 60% oxygen for 30 minutes. Indices of left ventricular diastolic function and pulmonary haemodynamics were measured using Doppler echocardiography. Results: Treatment with 60% oxygen significantly increased oxygen saturation from 90 (0.9) to 98 (0.3) %. Hyperoxia compared to baseline had no significant effects on left ventricular diastolic filling parameters reflected by its lack of effect on left ventricular isovolumic relaxation time IVRT: 82 (4) vs 84 (3) ms and transmitral E/A ratio: 0.77 (0.06) vs 0.72 (0.05), respectively. Hyperoxia significantly reduced heart rate (HR): 70 (3) vs 74 (2) bpm, mean pulmonary artery pressure (MPAP): 27 (1) vs 32 (2) mmHg, total pulmonary vascular resistance (PVR): 376 (21) vs 432 (18) dyne.s.cm(-5) but had no significant effects on either cardiac output (CO): 5.68 (0.19) vs 5.88 (0.14) l/min or mean arterial blood pressure(MAP): 104 (5) vs 103 (4) mmHg, respectively compared to baseline. Conclusions: Although short term administration of high flow oxygen has beneficial pulmonary haemodynamic effects it appears to have no significant effects on left ventricular diastolic filling. This suggests that abnormalities other than myocyte hypoxaemia are responsible for impairment of left ventricular diastolic filling in established hypoxaemic cor pulmonale and that oxygen therapy when given acutely does not improve myocardial relaxation.
Objective: To assess whether acute hypercapnia affects hepatic tissue oxygen tension as measured at the surface of the rat liver. Design: Prospective, controlled study. Setting: University medical school laboratory. Subjects: Male Sprague-Dawley rats weighing 250-450 grams. Interventions: An 8-point surface oxygen electrode was used to measure tissue oxygen tension (P1O2) in the rat liver during normocapnia (PaCO2 33-49 mmHg), while breathing 5% CO2 (PaCO2 54-70 mmHg), and while breathing 10% CO2 (PaCO2 74-101 mmHg). Measurements were made at baseline in all 3 groups, following which 5% or 10% carbon dioxide was added to the inhaled gas mixture in the two hypercapnic groups. Measurements were then taken again at 10, 15, 30, 40, and 50 minutes. Measurements and Main Results: There were no significant differences between the groups at baseline with mean P1O2 being 29.4 +/- 2.1 mmHg in the control group, 30.2 +/- 5.7 mmHg in the 5% group, and 29.7 +/- 5.5 mmHg in the 10% group. At 10 minutes there was an increase in mean P1O2 to 38.7 +/- 4.4 mmHg in the 5% group (p < .005), and to 48 +/- 3.0 mmHg in the 10% group (p < .001). The mean P1O2 values for both hypercapnic groups remained significantly elevated when compared to the control group for the remaining 50 minutes of the experiment. Conclusion: We conclude that acute hypercapnia leads to increased hepatic tissue oxygen tension as measured at the surface of the liver.
The surface tension of blood may play a role in intravascular bubble formation after decompression. This study involves surface tension in serum derived from two different populations; 25 individuals (group A) and 29 individuals with a high lipid level in blood (group B). The surface tension was measured at 21 - 23 degrees C with a drop-volume method. The mean surface tension in 25 healthy individuals was 68.8 +/- 0.70 dynes/cm. A significant intraindividual variation (1.11 +/- 0.73%) was observed in surface tension over a period of 6 months. The effect of freezing the serum samples resulted in a mean decline in surface tension of 2.2 +/- 0.8 dynes/cm, which was significant. The surface tension in the individuals with a high blood lipid level was 63.8 +/- 1.6 dynes/cm, which is significantly lower than that of the normal group. We conclude that serum surface tension varies over time within each individual. The effect of freezing and storing the samples had a significant impact on surface tension. High lipid level in serum causes a lower surface tension compared to normal serum.
Introduction: Biologic half life and pharmacokinetics of xenon are known from application of xe(133) in nuclear medicine. In these investigations washout time constants were calculated after relatively short exposure times of 10-20 minutes. Investigations using xenon concentrations and exposure times as used in anaesthesia have not yet been carried out. We have investigated xenon uptake, distribution and elimination under conditions of experimental anaesthesia. Materials and methods: 7 pigs were anaesthetized with a combination of intravenous pentobarbital and buprenorphine and an inspiratory concentration of xenon 70%. Radioactive xenon(133) was used as tracer for inert xenon(134). Washin and washout of xenon was observed under a gamma camera. Washin time was 4 hours, washout time was 2 hours. Kinetic curves for all body compartments revealing different activity curves as the whole body were calculated separately. Statistics were calculated using an empiric regression model. Mean residence times (MRT), terminal half lives (t 1/2), biologic half lives (t(50%)) and t(90%) were calculated for the compartments whole body, lung, fatty tissue and bowel. Results: As known from previous investigations, the fastest compartment was the lung. The slowest compartments were fatty tissue and bowel, respectively. No other compartments revealed delays of excretion as compared to whole body. Discussion: Time constants like mean residence times and half lives were different as reported from investigations from nuclear medicine. The slowest compartments were found to be fatty tissue and bowel. The reason for that finding is that in short exposures slow compartments are not saturated. Washout time constants calculated after short exposures cannot be easily transferred to conditions of xenon anaesthesia.
Knowledge of the surfactant system has grown immensely in the past decade. A variety of investigative strategies, including manipulation of surfactant protein gene expression in mice, has contributed dramatically to our understanding of the role of surfactant components in lung function. These approaches have fostered investigations that will further our knowledge of the role of lung surfactant in host defense and will provide information that should lead to improved strategies for the treatment of lung disease.
Respiratory alkalosis from hyperventilation is seen frequently in patients with hepatic cirrhosis. Although the etiology is unknown, we previously demonstrated that estradiol and progesterone concentrations correlated with a decreased PaCO2 in cirrhotic patients, suggesting that hormonal changes might stimulate respiratory centers in the brain. The present study explores the possibility that hormonal changes induced by end stage liver disease mediate hyperventilation through the upregulation of brainstem progesterone receptors. Sprague-Dawley rats received CCL4 to induce cirrhosis; control animals were given mineral oil. PaCO2, serum estradiol, and progesterone levels were measured. Cirrhosis was documented by liver biopsy. RT-PCR was used to determine progesterone receptor mRNA expression. CCL4 treatment resulted in decreased serum progesterone (2.5 ng/mL vs 18.8, P=0.002) and increased estradiol (57.8 +/- 8.47 pg/mL vs 31.9 +/- 6.96, P < 0.001). CCL4 treated animals had significantly increased brainstem progesterone receptor expression ratios (0.1502 +/- 0.0637 vs 0.0853 +/- 0.0348, P=0.04). There was no statistically significant decrease in PaCO2 among cirrhotic rats (35.3 vs 39.2, P=0.18). This is the first study to show estradiol induced upregulation of progesterone receptors in the brainstem of cirrhotic animals. Further study is needed to determine if this upregulation is responsible for the hyperventilation common in cirrhotic patients.
