Comparison of closed circuit and Fick-derived oxygen consumption in patients undergoing simultaneous aortocaval occlusion.

Agreement between continuously measured oxygen consumption during quantitative closed system anaesthesia and intermittently Fick-derived calculated oxygen consumption was assessed in 11 patients undergoing simultaneous occlusion of the aorta and inferior vena cava for hypoxic treatment of pancreatic cancer. All patients were mechanically ventilated using a quantitative closed system anaesthesia machine (PhysioFlex) and had pulmonary and radial artery catheters inserted. During the varying haemodynamic conditions that accompany this procedure, 73 paired measurements were obtained. A significant correlation between Fick-derived and closed system-derived oxygen consumption was found (r = 0.78, p = 0.006). Linear regression showed that Fick-derived measure = [(1.19 x closed system derived measure) - 72], with the overall closed circuit-derived values being higher. However, the level of agreement between the two techniques was poor. Bland-Altman analysis found that the bias was 36 ml.min(-1), precision 39 ml.min(-1), difference between 95% limits of agreement 153 ml.min(-1). Therefore, we conclude that the two measurement techniques are not interchangeable in a clinical setting.

Increased airway resistance during xenon anaesthesia in pigs is attributed to physical properties of the gas.

BACKGROUND: In this study we investigated the effects of the physical properties of xenon on respiratory mechanisms in pigs. METHODS: With institutional approval, 10 female pigs (mean 25.2 (SD 2.5) kg) were anaesthetized with thiopental, remifentanil, and pancuronium. Gas flow and pressure were recorded continuously at the proximal end of the tracheal tube during constant flow ventilation for control, with 100% oxygen (control), followed by 1.5% isoflurane in 70/30% nitrogen/oxygen, 1.0% isoflurane in 70/30% nitrous oxide/oxygen, and 70/30% xenon/oxygen in random order. Compliance (C) and resistance (R) were calculated using a single compartment model. Resistance was corrected for gas viscosities eta and also for densities pho and viscosities eta as (pho*eta)(1/2) to compare assumptions of laminar and mixed flow in the airways. RESULTS: With constant flow ventilation, xenon increases inspiratory pressure compared with other gas mixtures. There were no significant differences in resistance, corrected for laminar or mixed flow, between the gas mixtures. Xenon anaesthesia did not affect compliance. CONCLUSIONS: The increase in airway pressure observed with xenon anaesthesia is attributed completely to its higher density and viscosity. Therefore, determination of airway resistance must take into account the physical properties of the gas. Xenon does not exert any major effect on airway diameter.

Cardiovascular effects of simultaneous occlusion of the inferior vena cava and aorta in patients treated with hypoxic abdominal perfusion for chemotherapy.

BACKGROUND: Animal studies suggest less cardiovascular disturbance if the aorta and vena cava are occluded simultaneously. We set out to establish the effects of simultaneous clamping in humans, because oncologists suggested that perfusion for chemotherapy could be done under local anaesthesia without invasive haemodynamic monitoring. METHODS: We studied the cardiovascular effects of the onset and removal of simultaneous occlusion of the thoracic aorta and inferior vena cava, in seven ASA II patients. Two stop-flow catheters positioned in the aorta and in the inferior vena cava were inflated to allow hypoxic abdominal perfusion to treat pancreatic cancer. We measured the arterial pressure, heart rate (HR), right atrial pressure (RAP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and cardiac output (CO), and calculated systemic vascular resistance index (SVRi), pulmonary vascular resistance index (PVRi), left ventricular stroke work index (LVSWi) and right ventricular stroke work index (RVSWi). Three patients were studied with transoesophageal echocardiography. RESULTS: Six patients needed intravenous nitroprusside during the occlusion because mean arterial pressure (MAP) increased to more than 20% of baseline (SVRi increased by 87%). One minute after occlusion release, all patients had a 50% decrease in MAP, and mPAP increased by 50%. The procedure had severe cardiovascular effects, shown by a 100% increase in cardiac index at occlusion release with increases in left and right ventricular stroke work indices of 75% and 147%. Left ventricular wall motion abnormalities were seen on transoesophageal echocardiography. CONCLUSIONS: Serious haemodynamic changes occur during simultaneous occlusion of the thoracic aorta and inferior vena cava, which may need invasive haemodynamic monitoring.

Xenon anaesthesia for laparoscopic cholecystectomy in a patient with Eisenmenger's syndrome.

There are few reports on anaesthesia for patients with Eisenmenger's syndrome requiring non-cardiac surgery and none of the use of xenon. We describe the use of xenon with a closed-circuit system in a patient with Eisenmenger's syndrome having a laparoscopic cholecystectomy.

Angiotensin-converting enzyme activity is increased in lungs of rats with pulmonary hypoplasia and congenital diaphragmatic hernia.

Lung hypoplasia (LH) and pulmonary hypertension are responsible for the high mortality rate in congenital diaphragmatic hernia (CDH) patients. Angiotensin-converting enzyme (ACE) plays a role in the regulation of pulmonary vascular resistance in the postnatal period and might be involved in the development of pulmonary hypertension of the newborn. A study was made of the development of ACE activity spectrophotometrically in a rat model of LH and CDH. It was previously shown that the lungs in this model are hypoplastic and the muscularization of the pulmonary vascular bed is increased. CDH was induced in fetal rats by oral administration of 115 mg/kg Nitrofen to the mother on day 10.5 of pregnancy. Fetuses were delivered by hysterotomy on days 19, 20, 21, and 22. Nitrofen-exposed rats showed significantly lower lung weights and not statistically significant lower total ACE activities than in controls. ACE activity expressed per milligram lung wet weight and per milligram protein was significantly increased compared to controls. ACE converts angiotensin I to the vasoconstrictor angiotensin II, and it inactivates the vasodilator bradykinin. Increased ACE activity may therefore contribute to pulmonary hypertension. Whether ACE and angiotensin II levels are increased in human newborns with a diaphragmatic defect and whether they contribute to the development of persistent pulmonary hypertension has not been studied up till now.

Transesophageal echocardiographic monitoring of preoperative acute hypervolemic hemodilution.

BACKGROUND: Preoperative acute hypervolemic hemodilution is used in anesthesia to reduce the loss of blood cells during intraoperative bleeding. Indications for use of the technique might be broadened if it can be shown to be safe in older as well as younger patients. Few data are available describing heart function in humans subjected to hypervolemic hemodilution. METHODS: Nineteen anesthetized Jehovah's Witnesses (ages 22-70 yr) without evidence of heart disease had hypervolemic hemodilution before surgery in three stages, each consisting of an infusion of 500 ml dextran 40 (50 g/l) and 500 ml Ringer's lactate over a 10-min period. After each stage, the size and function of the left ventricle were recorded by transesophageal cross-sectional echocardiography in the short-axis view. Simultaneously heart rate, arterial blood pressure, pulmonary arterial and wedge pressures and cardiac output were recorded, to compare the echocardiographic and hemodynamic data. RESULTS: No complications occurred. Hypervolemic hemodilution resulted in an increased cardiac output by increasing the stroke volume from 48 ml in basal conditions to 67, 71, and 72 ml over the three stages, whereas heart rate did not increase. There was an initial increase in end-diastolic volume of the left ventricle, as assessed from the cross-sectional end-diastolic area from 12.9 to 15.5, 16.6, and 16.9 cm2 followed by a decrease in the in cross-sectional end-systolic area from 6.3 to 6.8, 6.0, and 5.7 cm2. The increase in wedge pressures (from 5.9 to 12.4, 17.9, and 22.6 mmHg) did not lead to progressive cardiac dilation. There was a curvilinear relation between wedge pressure and cross-sectional end-diastolic area. Stroke volume did not decrease, nor did cross-sectional end-systolic area increase; instead, a decrease in end-systolic area was a common observation. CONCLUSIONS: The described regimen of acute hypervolemic hemodilution is well tolerated during anesthesia by patients without heart disease and does not lead to cardiac failure. It leads to an increase in stroke volume that is generated initially from an increase in end-diastolic volume, followed in many patients by a decrease in end-systolic volume, the mechanism of which is as yet unclear.

Evaluation of lung function changes before and after surfactant application during artificial ventilation in newborn rats with congenital diaphragmatic hernia.

Patients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research into optimal ventilatory regimen is essential to improve survival rate and to prevent ongoing lung damage. Against this background, the effect of exogenous surfactant application is evaluated. In newborn rats, CDH was induced after a single dose of 2,4 dichloro-4'-nitrophenyl (Nitrofen) (400 mg/kg) on day 10 of gestation. The newborn rats were intubated immediately after hysterotomy, transferred to a heated multichambered body plethysmograph, and artificially ventilated. Inspiratory peak pressures were initially set at 17 cm H2O, with positive end-expiratory pressure at 0 cm H2O and FIO2 at 1.0. The pressure was raised in steps of 5 cm H2O, from 5 to 30 cm H2O, to obtain pressure-volume diagrams at 0, 1, and 6 hours of artificial ventilation. These measurements were obtained in controls and in CDH rats with and without endotracheal installation of bovine surfactant (n = 4 to 10 in each group). Significant differences in lung volume between CDH and control rats were observed at all time-points. Surfactant application had a positive effect on lung volume, especially in control rats at t = 1 hour. No significant differences were observed between the CDH groups at t = 1 or t = 6 hours. In this animal model, the effect of artificial ventilation as well as the beneficial short-term effect of exogenous surfactant application have been evaluated. A continued positive effect on lung volume in CDH lungs could not be determined. Routine administration of exogenous surfactant in human CDH patients is not supported by these experimental results.

The natural history of congenital diaphragmatic hernia and pulmonary hypoplasia in the embryo.

Up to now, descriptions of the natural history of congenital diaphragmatic hernia (CDH) associated with pulmonary hypoplasia (PH) are based exclusively on observations made in the fetal period. However, nothing is known about the events that take place in an embryo with CDH. Recently, an animal model of CDH and PH has been established in rat embryos to study the embryology and natural history of this lesion. We exposed 36 pregnant Sprague-Dawley rats to a single dose of 100 mg nitrofen on day 11 of pregnancy. A total of 356 staged embryos and fetuses from day 13 to day 21 were studied by light and scanning electronmicroscopy. The litters of 9 untreated rats (124 normal age-matched embryos and fetuses) served as controls. The abnormal development of the diaphragmatic anlage was first seen in embryos aged 13 to 14 days. A defect appeared in the dorsal part of the diaphragm, normally on the right side. The liver grew through this defect early on. Gut was found in an intrathoracic position only in the very late stages (day 21/22) and newborns. Compared to controls, lungs of nitrofen-embryos with CDH were smaller, depending on the size of liver found in the thoracic cavity. Histologically, compression of lung was absent at these stages. Most authors speculate that CDH results because the pleuroperitoneal canals fail to close at the end of the embryonic period (ie, week 8 to 10 in human development) leading to a defect in the dorsolateral region of the diaphragm. However, contradictory to this assumption, our findings indicate that diaphragmatic defects develop in early embryonic life.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities.

We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.

Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats.

In infants with congenital diaphragmatic hernia (CDH), abnormalities of the pulmonary arteries are present consisting of increased medial wall thickness and decreased external diameter. This forms the morphological substrate for persistent pulmonary hypertension, one of the leading causes of the high mortality in these patients. To elucidate the significance of these abnormalities, experimental models are required that mimic as close as possible the human situation. In our rat model we are able to study the hypoplastic CDH lungs extensively. In this study we performed a histological evaluation of the pulmonary arterial bed in the control group and the nitrofen-treated group in which the latter was divided into two subgroups, CDH and normal diaphragm. We examined the newborn rats after perfusion of the pulmonary arteries with barium gelatine and subsequent fixation. At the level of the respiratory bronchioles significant differences in the vessels were found consisting of decreased external diameter and increased wall thickness as percentage of the external thickness in CDH lungs compared with controls. Abnormal muscularization of the peripheral branches of the CDH pulmonary arteries was also found. We concluded that the rat model strongly resembles the human situation concerning the arterial bed in the lungs.

Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia.

The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated. In these animals which developed PCP with severe respiratory failure after s.c. administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2. Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated. These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations.

In vivo and in vitro inactivation of bovine surfactant by an anti-surfactant monoclonal antibody.

In this study the importance of a low-weight surfactant protein (11 kDa) is demonstrated by selectively blocking this protein with a monoclonal antibody. In adult rats respiratory failure was induced by repeated bronchoalveolar lavage to remove all pulmonary surfactant. It was shown that surfactant mixed with the antibody was not capable of restoring lung function when compared with surfactant alone or surfactant mixed with control serum. Using the pulsating bubble surfactometer, it could be demonstrated that surfactant mixed with this antibody had a significant higher minimum surface tension when compared with surfactant alone, or surfactant mixed with an unrelated mouse immunoglobulin G (IgG). The inhibition of surfactant function by the monoclonal antibody suggests the importance of the 11 kDa protein for normal surfactant function.

Accuracy of a mixed venous saturation catheter during acutely induced changes in hematocrit in humans.

OBJECTIVE: To determine the accuracy of in vivo mixed venous hemoglobin saturation (Svo2) measurements with a fiber optic thermodilution catheter during acute changes in hematocrit. DESIGN: Comparison of fiberoptic in vivo Svo2 values with in vitro Svo2 values obtained with a multiwavelength spectrophotometer. SETTING: Operating room in a university hospital. PATIENTS: Six consecutive patients who are Jehovah's Witnesses. MEASUREMENTS AND MAIN RESULTS: Before and after each step of hypervolemic hemodilution and after every 500 mL of blood loss, blood gases were analyzed and hemodynamic, hemoglobin, hematocrit, and in vitro and in vivo Svo2 measurements were made. Hematocrit values were measured in the range of 40% to 18%. Plotting all in vivo Svo2 values (n = 74) against the in vitro Svo2 measurements obtained during the entire study period gives r2 = .86. The accuracy of in vivo Svo2 measurements was not affected by changes in hematocrit or cardiac output. The Svo2 catheter value at the beginning of the study differed from the in vitro Svo2 value by -0.86 +/- 2.56% and at the end of the study period of 8 to 10 hrs by 0.71 +/- 3.04%. CONCLUSIONS: The accuracy of the studied fiberoptic continuous measuring Svo2 system was not affected by changes in hematocrit or cardiac output. No significant drift in the in vitro Svo2 measurements was observed.

Effect of surfactant replacement on Pneumocystis carinii pneumonia in rats.

The effect of intratracheal surfactant instillation on pulmonary function in rats with Pneumocystis carinii pneumonia (PCP) was investigated. In those animals which developed PCP with severe respiratory failure after administration of cortisone acetate s.c. over 8-12 weeks, pulmonary function was improved by surfactant instillation. PaO2 values 30 min after surfactant instillation were significantly higher compared to pretreatment values and also compared to PaO2 values of rats 30 min after receiving saline (482.9 mmHg +/- 44.7, 170.7 mmHg +/- 39.3 and 67.2 mmHg +/- 17.4, respectively). Histological examination showed that alveoli of rats with PCP which received no exogenous surfactant are filled with foamy edema, whereas after exogenous surfactant alveoli are stabilized and well-aerated. These results indicate that exogenous surfactant may help patients with severe PCP to overcome an acute stage of respiratory distress.