Arterial and mixed venous xenon blood concentrations in pigs during wash-in of inhalational anaesthesia

There are no data available on the kinetics of blood concentrationsof xenon during the wash-in phase of an inhalation anaesthesiaaiming at 1 MAC end-expiratory concentration. Therefore, weanaesthetized eight pigs with continuous propofol and fentanyland measured arterial, mixed venous and end-expiratory xenonconcentrations by gas chromatography–mass spectrometry1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 60 and 120 min afterstarting the anaesthetic gas mixture [67% xenon/33% oxygen;3 litre min^–1 during the first 10 min,thereafter minimal flow with 0.48 (SD 0.03) litre min^–1].End-expiratory xenon concentrations plateaued (defined as <5%change from the preceding value) at 64 (6) vol% after 7 min,and arterial and mixed venous xenon concentrations after 5 and15 min respectively. The highest arterio-venous concentrationdifference occurred after 3 min. Using the Fick principle,we calculated a mean xenon uptake of 3708 (829) and 9977 (3607)ml after 30 and 120 min respectively. Br J Anaesth 2001; 87: 497–8     

Effects of xenon anaesthesia on intestinal oxygenation in acutely instrumented pigs

Background. Xenon is a narcotic gas that might be able to replacevolatile anaesthetics or nitrous oxide due to its favourablepharmacological properties, such as providing haemodynamic stability.Intestinal oxygenation is affected by most volatile anaestheticsas a result of cardiodepressive effects. Reducing oxygenationof the gut might be a factor leading to perioperative organdysfunction. This animal study was designed to assess the effectsof xenon on intestinal oxygenation. Methods. After ethical approval, 24 anaesthetized, acutely instrumentedpigs were randomly assigned to three groups: nine animals receivedxenon anaesthesia with inspiratory concentrations of 0, 20,50 and 65% in addition to their basic i.v. anaesthesia, nineanimals served as a study control group, and five animals wereused to assess model stability. Measurement of systemic andregional haemodynamic and oxygenation parameters was made 30min after changing the xenon concentration. Results. Xenon elicited dose-dependent systemic haemodynamicchanges: heart rate and cardiac output decreased by 30%, whilemean arterial pressure was stable. Superior mesenteric arteryblood flow was lower in the xenon group. Vascular resistanceof the superior mesenteric artery increased. The small intestinaloxygen supply decreased with increasing xenon concentration;the mucosal tissue oxygen partial pressure decreased but didnot reach hypoxic (<5 mm Hg) values. Serosal tissue oxygenpartial pressure was maintained. Conclusions. Xenon, in addition to basic i.v. anaesthesia, eliciteda decrease in cardiac output and maintained mean arterial pressure.Intestinal oxygenation was maintained, although regional macrohaemodynamicperfusion decreased. Xenon does not impair intestinal oxygenationunder physiological conditions.      

Comparison of xenon with propofol for supplementary general anaesthesia for knee replacement: a randomized study

Background. Xenon anaesthesia is associated with rapid recoveryand may also offer protection against neuronal damage. The aimof this study was to compare xenon with propofol for supplementarygeneral anaesthesia in patients undergoing knee replacementin spinal anaesthesia. Methods. In total, 39 patients aged 60 or over were randomizedto xenon 50–70% or propofol 3–5 mg kg^–1 h^–1.Vital signs and emergence time were recorded and cognitive functionwas assessed before operation, at discharge between the thirdand the fifth day and at 3 months using four neuropsychologicaltests. Results. Propofol supplementation was necessary in six xenonpatients (29%) because of detectable movement of the upper body.Emergence time was significantly shorter with xenon (260 s forxenon and 590 s for propofol, P=0.001). There was no significantdifference between the groups in blood pressure, heart rate,ventilatory frequency or end-tidal carbon dioxide concentration.No difference could be detected in cognitive function, whichmay be attributed to insufficient sample-size rather than theabsence of a true difference. Conclusions. Xenon was well tolerated for supplementary generalanaesthesia in elderly spontaneously breathing patients butsupplementation may be necessary. Compared with propofol, emergencewas faster with xenon. A larger sample-size is needed if cognitivefunction is to be addressed.     

Emergence and early cognitive function in the elderly after xenon or desflurane anaesthesia: a double-blinded randomized controlled trial

Background: Postoperative cognitive impairment after general anaesthesia,especially in the elderly, is a well-recognized problem. Xenon,known to be an N-methyl-D-aspartate antagonist, may be advantageous.In this study, the early cognitive function in the elderly aftergeneral anaesthesia with xenon was compared with that afterdesflurane. Methods: After approval by the local ethical committee and after obtainingwritten informed consent, patients were enrolled in this randomized,double-blinded, controlled study. Thirty-eight patients (65–75yr old, ASA status I–III) undergoing an elective surgerywith a planned duration of 60–180 min were allocated toeither the xenon (n = 18) or the desflurane (n = 20) anaesthesiagroup. The primary outcome was the cognitive Test for AttentionalPerformance (TAP) with its subtests Alertness, Divided Attention,and Working Memory. After baseline assessment 12–24 hbefore operation, patients were followed-up 6–12 and 66–72h after operation. Secondary outcomes were emergence times fromanaesthesia and the modified Aldrete score. Results: No difference was found between the groups in the TAP at 6–12and 66–72 h after operation. In the xenon group, emergencetime was significantly faster for the following parameters:time to open eyes (P = 0.001), to react on demand (P = 0.001),to extubation (P = 0.001), and for time and spatial orientation(P = 0.007). The modified Aldrete score was significantly higherafter 30, 45 and 60 min in the xenon group. Conclusions: There was no difference in the postoperative cognitive testingat 6–12 and 66–72 h. Xenon was associated in theelderly with a faster emergence from general anaesthesia thandesflurane.     

Positron emission tomography study of regional cerebral blood flow and flow-metabolism coupling during general anaesthesia with xenon in humans

Background: The effects of xenon on regional cerebral blood flow (rCBF)are controversial. Moreover, the precise sites of action atwhich xenon exerts its effects in the human brain remain tobe established. Methods: rCBF was sequentially assessed by H₂¹⁵O positron emission tomographyin six volunteers. rCBF was determined at baseline and duringgeneral anaesthesia induced with propofol and maintained withone minimum alveolar concentration xenon. rCBF measurementswere started after the calculated plasma concentration of propofolhad decreased to subanaesthetic levels (<1.0 µg ml^–1).Changes in rCBF were calculated for 13 cerebral volumes of interestby measurement of a semi-quantitative perfusion index (PI).In addition, voxel-wise changes in rCBF were analysed usingstatistical parametric mapping. Results: Xenon had only minor effects on PI in grey matter volumes ofinterest. In contrast, PI was increased in white matter [from1.01 (0.11) to 1.24 (0.15) kcnt ml^–1 MBq^–1, P=0.05,mean (SD)]. Voxel-based analysis showed an increase of rCBFin white matter and a relative decrease of rCBF during xenonanaesthesia in distinct grey matter regions, particularly theorbito- and mesiofrontal cortex, cingulate gyrus, thalamus,hippocampus and bilateral cerebellum (P<0.05 corrected).When correlating PI with cerebral metabolic rate of glucose(previously obtained in another group of six volunteers using¹⁸F-fluorodeoxyglucose as tracer), the flow–metabolismcoupling was preserved during xenon anaesthesia. Conclusions: Xenon exerted distinct regional effects on CBF: relative decreasesin several cortical, subcortical, and cerebellar areas wereaccompanied by an increase in white matter. Flow–metabolismcoupling was not impaired during xenon anaesthesia.     

Cerebral and regional organ perfusion in pigs during xenon anaesthesia

Little is known about the haemodynamic effects of inhaled xenon on regional organ perfusion. The aim of this study was to investigate the effect of 79% xenon ventilation on organ perfusion in pigs. We investigated 10 pigs, which were randomly allocated to receive either xenon 79% or total intravenous anaesthesia (TIVA)/oxygen anaesthesia. Microspheres were used to determine organ perfusion. The following regions of interest were investigated: cerebral cortex, medulla oblongata, brainstem, cerebellum, liver, kidney, small intestine, colon, muscle, skin and heart. The results demonstrated a significant increase in regional perfusion in the brainstem (+63%), cerebral cortex (+38%), medulla oblongata (+35%) and cerebellum (+34%). All other organs showed no significant change in regional perfusion. We conclude that xenon should be used with caution in clinical situations associated with pathological increases in intracranial pressure, e.g. neurosurgical procedures, head injury, cerebral mass lesions or stroke.     

Asynchronous administration of xenon and hypothermia significantly reduces brain infarction in the neonatal rat

BACKGROUND: Neonatal asphyxia causes long-term neurological and behaviouralimpairment in the developing brain. Concurrent administrationof xenon and hypothermia synergistically reduces long-term damagein a rat model of neonatal asphyxia. This study sought to investigatewhether asynchronous administration of xenon and hypothermiais capable of combining synergistically to provide neuroprotection. METHODS: Seven-day-old rats were subjected to right common carotid arteryocclusion followed by 90 min hypoxia with 8% oxygen. Aftera 1 h recovery period, rats received asynchronous administrationof mild hypothermia (35°C) and xenon (20%) with a 1 or 5 hgap between interventions, xenon (20%) alone, or mild hypothermia(35°C) alone. Infarct volume in the brain was measured 4days after injury. RESULTS: Administration of hypothermia or xenon alone, 1 and 6 hafter the hypoxic ischaemic insult, respectively, provided noneuroprotection. Asynchronous administration of xenon and hypothermiaat a 1 h interval produced a significant reduction in infarctvolume [93 (7) vs 74 (8); P < 0.05]. Reduction in infarctvolume was also present when hypothermia and xenon were asynchronouslyadministered with an intervening gap of 5 h [97 (5) vs83 (3); P < 0.05]. CONCLUSIONS: This finding provides a rationale for investigating the combineduse of hypothermia and xenon in a progressive manner for themanagement of neonatal asphyxia. Thus, hypothermia can be administratedat the site of delivery and xenon can be administered later.     

The effects of subanaesthetic concentrations of xenon in volunteers

This study reports the subjective, psychomotor and physiological properties of subanaesthetic concentrations of xenon. Ten healthy male volunteers received either xenon or nitrous oxide in a randomised crossover study design. The subjects breathed either xenon (Xe) or nitrous oxide (N2O) from a closed circuit breathing system, according to a randomised, double-blind protocol. The concentration of xenon required to produce sedation, ranged between 27 and 45% (median 35%). All subjects completed the xenon protocol. Subjects were tested using the Critical Flicker Fusion test and derived electroencephalogram parameters, however, neither test was found to reliably predict sedation. The respiratory rate decreased markedly during sedation with xenon. The subjects did not experience any airway irritability (coughing, breath-holding or laryngospasm) during administration of either gas. One subject required anti-emetic treatment in the N2O group compared to none in the Xe group. Eight subjects reported that they found sedation with xenon pleasant and preferable to nitrous oxide. Xenon sedation was well tolerated and was not associated with any adverse physiological effects, however, it was reported to be subjectively dissimilar to nitrous oxide.     

Differential electroencephalographic response to tracheal intubation between young and elderly during isoflurane and sevoflurane nitrous oxide anaesthesia

BACKGROUND: Age-associated differences in the electroencephalographic (EEG) response to noxious stimuli with the presence of nitrous oxide (N(2)O) are unknown. We compared the EEG response with tracheal intubation between young and elderly. METHODS: Sixty young (<40 yr) and elderly (>70 yr) patients were randomly allocated to one of the four groups. Anaesthesia was induced with 66% N(2)O and isoflurane in oxygen (Young-isoflurane and Elderly-isoflurane groups) or 66% N(2)O and sevoflurane in oxygen (Young-sevoflurane and Elderly-sevoflurane groups). Inhaled isoflurane and sevoflurane concentrations were gradually increased and the end-tidal concentrations were maintained at 1.1% and 1.7%, respectively. Tracheal intubation was performed 12 min after induction of anaesthesia. RESULTS: There were significant differences in the overall changes in bispectral index (BIS) and 95% spectral edge frequency (SEF95) between young and elderly (P<0.001 for both), but not between patients receiving isoflurane and sevoflurane (P=0.4 and 0.3, respectively). Both BIS and SEF95 were significantly decreased after tracheal intubation in Young-isoflurane and Young-sevoflurane groups (P<0.05 for all). In sharp contrast, BIS and SEF95 remained unchanged in Elderly-isoflurane and Elderly-sevoflurane groups (P>0.7 for all). These results suggest that both BIS and SEF95 significantly decreased, despite the presence of increased sympathetic activity after tracheal intubation in young patients. CONCLUSIONS: A significant difference was detected in EEG response to tracheal intubation between young and elderly. BIS does not reflect the depth of anaesthesia after tracheal intubation during anaesthesia with isoflurane or sevoflurane with 66% of N(2)O in young patients.     

Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation

Background: One-lung ventilation (OLV) induces a pro-inflammatory responseincluding cytokine release and leucocyte recruitment in theventilated lung. Whether volatile or i.v. anaesthetics differentiallymodulate the alveolar inflammatory response to OLV is unclear. Methods: Thirty patients, ASA II or III, undergoing open thoracic surgerywere randomized to receive either propofol 4 mg kg^–1 h^–1(n = 15) or 1 MAC desflurane in air (n = 15) during thoracicsurgery. Analgesia was provided by i.v. infusion of remifentanil(0.25 µg kg^–1 min^–1) in both groups. The patientswere mechanically ventilated according to a standard protocolduring two-lung ventilation and OLV. Fibre optic bronchoalveolarlavage (BAL) of the ventilated lung was performed before andafter OLV and 2 h postoperatively. Alveolar cells, protein,tumour necrosis factor (TNF), interleukin (IL)-8, soluble intercellularadhesion molecule-1 (sICAM), IL10, and polymorphonuclear (PMN)elastase were determined in the BAL fluid. Data were analysedby parametric or non-parametric tests, as indicated. Results: In both groups, an increase in pro-inflammatory markers wasfound after OLV and 2 h postoperatively; however, the fractionof alveolar granulocytes (median 63.7 vs 31.1%, P < 0.05)was significantly higher in the propofol group compared withthe desflurane group. The time courses of alveolar elastase,IL-8, and IL-10 differed between groups, and alveolar TNF (7.4vs 3.1 pg ml^–1, P < 0.05) and sICAM-1 (52.3 vs 26.3ng ml^–1, P < 0.05) were significantly higher in thepropofol group. Conclusions: These data indicate that pro-inflammatory reactions during OLVwere influenced by the type of general anaesthesia. Differentpatterns of alveolar cytokines may be a result of increasedgranulocyte recruitment during propofol anaesthesia.     

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

There are few reports on anaesthesia for patients with Eisenmenger’ssyndrome requiring non-cardiac surgery and none of the use ofxenon. We describe the use of xenon with a closed- circuit systemin a patient with Eisenmenger’s syndrome having a laparoscopiccholecystectomy. Br J Anaesth 2001; 86: 882–6     

Suppressive effect of nitrous oxide on motor evoked potentials can be reversed by train stimulation in rabbits under ketamine/fentanyl anaesthesia, but not with additional propofol

The effect of nitrous oxide on myogenic motor evoked potentials(MEPs) after multipulse stimulation is controversial. We investigatedthe effects of propofol in this paradigm. MEPs were elicitedelectrically by a single pulse and by trains of three and fivepulses in rabbits anaesthetized with ketamine and fentanyl.Nitrous oxide 30–70% was given and MEPs were recorded.After washout of nitrous oxide, propofol was given as a bolusof 10 mg kg^–1 followed by 0.8 (n=9) or 1.6 mg kg^–1 min^–1(n=8) as a continuous infusion. Nitrous oxide was then readministeredand MEPs were recorded. Without propofol, nitrous oxide significantlyreduced the amplitude of MEPs dose-dependently, but this effectwas reversed by multipulse stimulation. Administration of low-dosepropofol enhanced nitrous oxide-induced suppression, and thiseffect was reversed by five-pulse stimulation. However, high-dosepropofol produced a greater increase in suppression, such thateven five-pulse stimulation did not overcome the suppression.The results suggest that the degree of reversal of nitrous oxide-inducedMEP suppression produced by multipulse stimulation is affectedby the administration of propofol. Br J Anaesth 2001; 86: 395–402     

Influence of xenon on pulmonary mechanics and lung aeration in patients with healthy lungs

Background

The anaesthetic xenon shows potent organ-protective properties. Due to high density and dynamic viscosity, peak inspiratory pressure (P_max) increases during xenon application. Thus, barotrauma may counteract organ protection. Accordingly, we investigated the influence of xenon on lung mechanics and lung aeration in patients with normal and reduced thoracic wall compliance.

Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia

Xenon anaesthesia appears to have minimal haemodynamic effects. The purpose of this randomised prospective study was to compare the cardiovascular effects of xenon and nitrous oxide in patients with known ischaemic heart disease. In 20 patients who were due to undergo coronary artery bypass graft surgery, 30 min following induction of anaesthesia with fentanyl 30 microg x kg(-1) and midazolam 0.1 mg x kg(-1) but prior to the start of surgery, xenon or nitrous oxide 60% was administered for 15 min. The results showed that xenon caused a minimal decrease in the mean arterial pressure (from 81 (7) to 75 (8) mmHg, mean (SD)), but did not affect the systolic function of the left ventricle, as demonstrated by unchanged left ventricular stroke work index (LVSWI) and the fractional area change of the left ventricle (FAC) derived from transoesophageal echocardiography (TOE). However, in contrast, nitrous oxide was found to decrease the mean arterial pressure (from 81 (8) to 69 (7) mmHg), the LVSWI, and the FAC. The cardiac index, central venous and pulmonary artery occlusion pressures, systemic and pulmonary vascular resistances, and the TOE-derived E/A ratio through the mitral valve were unchanged by xenon or nitrous oxide. We conclude that xenon provides improved haemodynamic stability compared with nitrous oxide, conserving the left ventricular systolic function.     

Effects of isoflurane and xenon on Ba2+-currents mediated by N-type calcium channels

Background. Isoflurane and xenon are inhalation general anaestheticswith differing clinical profiles and contrasting synaptic actions.Both agents have been shown to depress excitatory synaptic responses.Whether this is via pre-synaptic or post-synaptic mechanismshas not been determined clearly. N-type calcium channels area putative pre-synaptic target for these agents. We tested whetherN-type calcium channels were sensitive to isoflurane and xenonand whether there was any stereoselectivity in the effect ofisoflurane. Methods. We used patch-clamp electrophysiology on isolated HEK293cells stably expressing N-type calcium channels to investigatethe effects of isoflurane and xenon on barium currents mediatedby N-type calcium channels. Results. Racemic isoflurane caused a concentration-dependentreduction (11–35%) in the peak current through the N-typechannels in the concentration range 0.15–1.22 mM. In theclinically relevant concentration range the inhibition was small.At an isoflurane concentration of 0.31 mM (equivalent to 1 MAC),the peak N-type current was inhibited by 14 (1)%. The opticalisomers of isoflurane were found to be equally potent at inhibitingcurrents through N-type channels. The inert gas anaestheticxenon was found to have no measureable effect on N-type channelsat a concentration of 3.4 mM (1 MAC). Conclusions. These results suggest that N-type calcium channelsare not the targets mediating general anaesthesia with thesetwo inhalation agents. Declaration of interest. Professor Franks is a board memberof an Imperial College spin-out company, Protexeon Ltd, thatis interested in developing clinical applications for medicalgases, including xenon. Professor Franks is a paid consultantin this activity. In addition Air Products have funded workin the authors' laboratories that bears on the actions of xenonas an anaesthetic and neuroprotectant. Air Products has a financialstake in Protexeon Ltd.     

Effect of nitrous oxide on cerebrovascular reactivity to carbon dioxide in children during sevoflurane anaesthesia

Background. Sevoflurane and nitrous oxide have intrinsic cerebralvasodilatory activity. To determine the effects of nitrous oxideon cerebrovascular reactivity to carbon dioxide (CCO₂R) duringsevoflurane anaesthesia in children, middle cerebral arteryblood flow velocity (V_mca) was measured over a range of end-tidalcarbon dioxide concentrations (E'_CO2), using transcranial Doppler(TCD) ultrasonography. Methods. Ten children aged 1.5–6 yr were anaesthetizedwith sevoflurane and received a caudal block. Patients wereallocated randomly to receive either air–nitrous oxideor nitrous oxide–air. Further randomization determinedthe sequence of E'_CO2 (25, 35, 45, and 55 mm Hg) and sevoflurane(1.0 then 1.5 MAC or 1.5 then 1.0 MAC) concentrations. Oncesteady state had been reached, three measurements of V_mca, meanarterial pressure (MAP), and heart rate (HR) were recorded. Results. Cerebrovascular carbon dioxide reactivity was reducedin the 25–35 mm Hg E'_CO2 range on the addition of nitrousoxide to 1.5 MAC, but not 1.0 MAC sevoflurane. A plateau inCCO₂R of 0.4–0.6% per mm Hg was seen in all groups betweenE'_CO2 values of 45 and 55 mm Hg. Mean HR and MAP remained constantthroughout the study period. Conclusions. Cerebrovascular carbon dioxide reactivity is reducedat and above an E'_CO2 of 45 mm Hg during 1.0 and 1.5 MAC sevofluraneanaesthesia. The addition of nitrous oxide to 1.5 MAC sevofluranediminishes CCO₂R in the hypocapnic range. This should be takeninto consideration when hyperventilation techniques for reductionof brain bulk are being contemplated in children with raisedintracranial pressure. Br J Anaesth 2003; 91: 190–5     

Recovery characteristics of propofol anaesthesia, with and without nitrous oxide: a comparison with halothane/nitrous oxide anaesthesia in children

Few studies have examined whether nitrous oxide influences the recovery characteristics of propofol anaesthesia. The present study examined the effect of nitrous oxide on the recovery characteristics of propofol anaesthesia, and compared these data with those for halothane/nitrous oxide anaesthesia. Sixty children aged 3–12 years were assigned at random to receive one of three maintenance regimens: propofol with or without nitrous oxide (70%) or halothane/nitrous oxide (70%). During propofol/N₂O anaesthesia, the infusion rate of propofol (180±39 μg·kg⁻¹·min⁻¹) required to maintain the mean arterial pressure and heart rate within 20% of the baseline values was significantly less than that during propofol/O₂ (220±37 μg·kg⁻¹·min⁻¹; P <0.005). The time from discontinuation of anaesthesia to eye-opening (11±6 min), to response to commands (12±6 min), and to return of full wakefulness (21±10 min) after propofol/N₂O were similar to those after propofol/O₂, but significantly less (by approximately 30%) than those after halothane ( P <0.05). The overall incidence of emesis after propofol/N₂O (53%) was greater than that after propofol/O₂ (17%, P <0.05) and comparable to that after halothane/N₂O (58%). These data suggest that N₂O has little effect on the rate of recovery after propofol, but significantly increases the incidence of postoperative emesis, thereby attenuating one of the main attributes of propofol anaesthesia.     

Effects of increased intra-abdominal pressure on central circulation

Background. In an experimental model we investigated the effectsof a gradual increase in intra-abdominal pressure (IAP) on thecentral circulation. Methods. Seven pigs were anaesthetized, mechanically ventilatedand instrumented. IAP was gradually increased by 5 mm Hg upto 30 mm Hg by abdominal banding in normovolaemic animals, andthen they were made hypovolaemic after blood withdrawal. Rightatrial pressure (RAP) and left ventricular end-diastolic pressure(LVEDP) at each step and aortic, femoral and inferior vena cavablood flows were measured. Left ventricular end-diastolic area(LVEDA) was determined using epicardial echocardiography. Results. Cardiac output maintained at mild IAP was reduced to76 (24)% of the initial value at 30 mm Hg IAP [mean (SD)] innormovolaemic animals, and 72 (22)% (P<0.001) in hypovolaemicanimals. In normovolaemic animals the LVEDA and LVEDP were significantlyincreased at an IAP of 10 and 15 mm Hg by 26 (24)% and 38 (23)%,respectively. At these IAP values, the difference between theRAP and IAP was positive. When this gradient became negative,that is beyond 15 mm Hg in normovolaemia and for all IAP valuesin hypovolaemic animals, the LVEDA declined, reaching 78 (16)%and 62 (22)% (P<0.05) of the initial values in normovolaemicand hypovolaemic groups at the highest IAP value. Conclusions. These results showed that a gradual increase inIAP led to a redistribution of abdominal blood volume towardsthe thoracic compartment, at IAP lower than 15 mm Hg in normovolaemia,and at its expense at higher values of IAP. In hypovolaemiathere was no thoracic compartment gain. Whereas the absoluteor transmural RAPs were not informative of the direction ofthis blood shift, an RAP greater than IAP was associated withan intrathoracic compartment gain.