Hyperventilation reverses the nitrous oxide-induced increase cerebral blood flow velocity in human volunteers

Because hypocapnia is routine during general anaesthesia forintracranial procedures, we have compared, in 1 3 healthy volunteers,the effect of normocapnia (PE'_CO2 5.3 kPa) and hypocapnia (PE'_CO23.3 kPa) on mean blood flow velocity in the middle cerebralartery (Vmca) during normoventilation and hyperventilation withair and with 50% nitrous oxide in oxygen. After replacementof air with 50% nitrous oxide in oxygen, there was an increasein mean Vmca during normoventilation (air: mean 68.23 (SD 16.98)cm s^–1 vs nitrous oxide in oxygen: 90.69 (20.41) cm s^–1;P < 0.01), whereas during hyperventilation mean Vmca valueswere similar regardless of the inhaled gas mixture (air: 43.46(9.97) cm s^–1 vs nitrous oxide in oxygen: 41.69 (8.08)cm s^–1 Our data suggest that the nitrous oxide-inducedincrease in mean Vmca can be blocked by hyperventilation. (Br.J. Anaesth. 1995; 74: 616–618)     

Comparison of 1% and 2% lidocaine epidural anaesthesia combined with sevoflurane general anaesthesia utilizing a constant bispectral index

Background. The authors compared the effects of epidural anaesthesiawith lidocaine 1% and lidocaine 2% on haemodynamic variables,sevoflurane requirements, and stress hormone responses duringsurgery under combined epidural/general anaesthesia with bispectralindex score (BIS) kept within the range 40–50. Methods. Thirty-three patients undergoing lower abdominal surgerywere randomly divided into two groups to receive lidocaine 1%or 2% by epidural with sevoflurane general anaesthesia. Sevofluranewas adjusted to achieve a target BIS of 40–50 during maintenanceof anaesthesia with nitrous oxide 60% in oxygen. Measurementsincluded the inspired (FI_SEVO) and the end-tidal sevofluraneconcentrations (E'_SEVO), blood pressure (BP), and heart rate(HR) before surgery and every 5 min during surgery for2 h. Plasma samples were taken immediately before and duringsurgery for measurements of catecholamines, cortisol, and lidocaine. Results. During surgery, both groups were similar for HR, BPand BIS, but FI_SEVO and E'_SEVO were significantly higher andmore variable with lidocaine 1% than with 2%. Intraoperativeplasma concentrations of epinephrine and cortisol were foundto be higher with lidocaine 1% as compared with 2%. Conclusions. To maintain BIS of 40–50 during combinedepidural/general anaesthesia for lower abdominal surgery, sevofluraneconcentrations were lower and less variable with lidocaine 2%than with 1%. In addition, the larger concentration of lidocainesuppressed the stress hormone responses better. Br J Anaesth 2003; 91: 825–9     

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     

Effect of two anaesthetic regimens on airway nitric oxide production in horses

There is evidence that halothane inhibits nitric oxide synthasein vitro, but the effect of intravenous anaesthetic agents isless clear. This study was undertaken to compare the rate ofexhaled nitric oxide production (V_NO) in spontaneously breathinghorses anaesthetized with halothane or an intravenous regimen.Seven adult horses were studied twice in random order. Afterpremedication with romifidine 100 µg kg^–1,anaesthesia was induced with ketamine 2.2 mg kg^–1and maintained with halothane in oxygen (HA) or by an intravenousinfusion of ketamine, guaiphenesin and romifidine (IV). Inhaledand exhaled nitric oxide (NO) concentrations, respiratory minuteventilation (V_E), pulmonary artery pressure (P_PA), fractionalinspired oxygen concentration (FI_O2), end-tidal carbon dioxideconcentration (E'_CO2), cardiac output (Q) and partial pressuresof oxygen and carbon dioxide in arterial blood (Pa_O2, Pa_CO2)were measured. Exhaled nitric oxide production rate was significantlylower (40 min, P<0.01; 60 min, P<0.02) duringHA [40 min, 1.4 (SD 1.4) pmol l^–1 kg^–1 min^–1;60 min, 0.7 (0.7) pmol l^–1 kg^–1 min^–1]than during IV [40 min, 9.3 (9.9) pmol l^–1 kg^–1min^–1; 60 min, 12.5 (13.3) pmol l^–1 kg^–1min^–1). Mean pulmonary artery pressure was significantlyhigher (40 min, P<0.01; 60 min, P<0.001) during HA[40 min, 5.9 (1.1) kPa; 60 min, 5.9 (0.9) kPa] comparedwith IV (40 min, 4.4 (0.4) kPa; 60 min, 4.4 (0.5) kPa].NO is reduced in the exhalate of horses anaesthetized with halothanecompared with an intravenous regimen. It is suggested that increasedmean pulmonary artery pressure during halothane anaesthesiamay be linked to the differences in NO production. Br J Anaesth 2001; 86: 127–30     

Preoxygenation: a comparison of three different breathing systems

An end-tidal expiratory oxygen concentration (FE'_O2) greaterthan 0.90 is considered to be adequate for preoxygenation. Thisis generally achieved using a face mask, but this can be unsatisfactoryin some patients. We compared preoxygenation in 30 healthy volunteersusing a face mask, the NasOral system, which is a novel preoxygenationdevice, and a mouthpiece with a nose-clip. We measured the maximalFE'_O2, the FE'_O2 after 2 min and the time to reach maximalFE'_O2 and recorded the subjective judgement of the volunteers.The maximal FE'_O2 with face mask and mouthpiece was significantlygreater than with the modified NasOral system (P<0.05 andP<0.01). With the former devices, a FE'_O2 of 0.90 was achievedin 73% of the volunteers vs 46% with the modified NasOral system.Using the mouthpiece, the FE'_O2 after 2 min was significantlyhigher than using the face mask (P<0.01) or the modifiedNasOral system (P<0.01). The time to maximal FE'_O2 was significantlyshorter using the modified NasOral system than with the facemask or mouthpiece (P<0.001 and P=0.0001). The volunteersgave more positive ratings to the face mask and mouthpiece thanto the modified NasOral system (P<0.001 and P<0.01). Weconclude that the use of a mouthpiece can improve preoxygenationin some patients. The results obtained with the modified NasOralsystem do not justify its introduction into clinical practice. Br J Anaesth 2001; 87: 928–31     

Randomized,double-blind comparison of different inspired oxygen fractions during general anaesthesia for Caesarean section

Background. The optimal inspired oxygen fraction FI_O2 for fetaloxygenation during general anaesthesia for Caesarean sectionis not known. Methods. We randomized patients having elective Caesarean sectionto receive one of the following: FI_O2 0.3, FI_N2O 0.7 and end-tidalsevoflurane 0.6% (Group 30, n=20); FI_O2 0.5, FI_N2O 0.5 and end-tidalsevoflurane 1.0% (Group 50, n=20), or FI_O2 1.0 and end-tidalsevoflurane 2.0% (Group 100, n=20) until delivery. Neonataloutcome was compared biochemically and clinically. Results. At delivery, for umbilical venous blood, mean PO₂ wasgreater in Group 100 (7.6 (SD 3.7) kPa) compared with both Group30 (4.0 (1.1) kPa, P<0.0001) and Group 50 (4.7 (0.9) kPa,P=0.002) and oxygen content was greater in Group 100 (17.2 (1.6)ml dl^–1) compared with both Group 30 (12.8 (3.6) ml dl^–1,P=0.0001) and Group 50 (13.8 (2.6) ml dl^–1, P=0.0001).For umbilical arterial blood, PO₂ was greater in Group 100 (3.2(0.4) kPa) compared with Group 30 (2.4 (0.7) kPa, P=0.003),and in Group 50 (2.9 (0.8) kPa) compared with Group 30 (2.4(0.7) kPa, P=0.04); oxygen content was greater in Group 100(10.8 (3.5) ml dl^–1) than in Group 30 (7.0 (3.0) ml dl^–1,P<0.01). Apgar scores, neonatal neurologic and adaptive capacityscores, and maternal arterial plasma concentrations of epinephrineand norepinephrine before induction and at delivery were similaramong groups. No patient reported intraoperative awareness. Conclusions. Use of FI_O2 1.0 during general anaesthesia forelective Caesarean section increased fetal oxygenation. Br J Anaesth 2002; 89: 556–61     

Randomized study comparing the effects of hydroxyethyl starch solution with Gelofusine on pulmonary function in patients undergoing abdominal aortic aneurysm surgery

Background. Restoring blood flow to ischaemic tissue can causelung damage with pulmonary oedema. Hydroxyethyl starch (HES)solution, when used for volume replacement, may modify and reducethe degree of ischaemia–reperfusion injury. We comparedthe effects of HES solution with those of Gelofusine solutionon pulmonary function, microvascular permeability and neutrophilactivation in patients undergoing elective infrarenal abdominalaortic aneurysm surgery. Methods. Forty patients were randomized into two groups. Theanaesthetic technique was standardized. Lung function was assessedwith the PO₂/FI_O2 ratio, respiratory compliance, chest x-rayand a score for lung injury. Microvascular permeability wasdetermined by measuring microalbuminuria. Neutrophil activationwas determined by measurement of plasma elastase. Results. Four hours after surgery, the median (quartile values)PO₂/FI_O2 ratio was 40.3 (37.8, 53.1) kPa for the HES-treatedpatients compared with 33.9 (31.2, 40.9) kPa for the Gelofusine-treatedpatients (P<0.01, Mann–Whitney test). The respiratorycompliance was 80 (73.5, 80) ml cm^–1 H₂O inthe HES-treated patients compared with 60.1 (50.8, 73.3) mlcm^–1 H₂O in the Gelofusine-treated patients (P<0.01,Mann–Whitney test). The lung injury score 4 h after surgerywas less for the patients treated with HES compared with thepatients treated with Gelofusine (0.33 vs 0.71, P=0.01, Wilcoxonrank sum test). Mean (SD) plasma elastase was less in the HES-treatedpatients on the first postoperative day (1.96 (0.17) vs 2.08(0.24), P<0.05). The log mean microalbuminuria was less inthe HES-treated patients (0.41 vs 0.91 mg mmol^–1,P<0.05). This difference in microvascular permeability wasassociated with different volumes of colloid required to maintainstable cardiovascular measurements in the two groups of patientsstudied (3000 vs 3500 ml, P<0.01, Mann–Whitney test). Conclusion. Compared with Gelofusine, the perioperative pulmonaryfunction of patients treated with HES after abdominal aorticaneurysm surgery was better. Br J Anaesth 2004; 92: 61–6     

Xenon increases total body oxygen consumption during isoflurane anaesthesia in dogs

Background. This study was designed to examine whether the couplingbetween oxygen consumption (V^·O₂) and cardiac output(CO) is maintained during xenon anaesthesia. Methods. We studied the relationship between V^·O₂ (indirectcalorimetry) and CO (ultrasound flowmetry) by adding xenon toisoflurane anaesthesia in five chronically instrumented dogs.Different mixtures of xenon (70% and 50%) and isoflurane (0–1.4%)were compared with isoflurane alone (1.4% and 2.8%). In addition,the autonomic nervous system was blocked (using hexamethonium)to study its influence on V^·_O2 and CO during xenon anaesthesia. Results. Mean (SEM) V^·O₂ increased from 3.4 (0.1) ml kg^–1 min^–1during 1.4% isoflurane to 3.7 (0.2) and 4.0 (0.1) ml kg^–1 min^–1after addition of 70% and 50% xenon, respectively (P<0.05),whereas CO and arterial pressure remained essentially unchanged.In contrast, 2.8% isoflurane reduced both, V^·O₂ [from3.4 (0.1) to 3.1 (0.1) ml kg^–1 min^–1]and CO [from 96 (5) to 70 (3) ml kg^–1 min^–1](P<0.05). V^·O₂ and CO correlated closely during isofluraneanaesthesia alone and also in the presence of xenon (r²=0.94and 0.97, respectively), but the regression lines relating COto V^·_O2 differed significantly between conditions, withthe line in the presence of xenon showing a 0.3–0.6 ml kg^–1 min^–1greater V^·O₂ for any given CO. Following ganglionic blockade,50% and 70% xenon elicited a similar increase in V^·O₂,while CO and blood pressure were unchanged. Conclusions. Metabolic regulation of blood flow is maintainedduring xenon anaesthesia, but cardiovascular stability is accompaniedby increased V^·O₂. The increase in V^·_O2 is independentof the autonomic nervous system and is probably caused by directstimulation of the cellular metabolic rate. Br J Anaesth 2002; 88: 546–54     

Estimation of pulmonary blood flow from sinusoidal gas exchange during anaesthesia: a theoretical study

We simulated the use of simultaneous sinusoidal changes of inspiredO₂ and N₂O (Williams et al., J Appl Physiol, 1994; 76: 2130–9)at fractional concentrations up to 0.3 and 0.7, respectively,to estimate FRC and pulmonary blood flow (PBF) during anaesthesia,using O₂ as an insoluble indicator. Hahn’s approximateequations, which neglect the effect of pulmonary uptake and excretionon expiratory flow, estimate dead space and alveolar volume (V_A)with systematic errors less than 10%, but yield systematic errorsin PBF which are approximately proportional to FI_N2O in magnitude.A correction factor (1 – )^–1 forHahn’s equations for PBF (where is the mean partial pressure of the soluble indicator) reducesthe dependence of PBF estimates on FI_N2O, and the solution ofequations describing the simultaneous mass balance of both indicatorsyields accurate results for a wide range of mean FI_N2O. However,PBF estimates are sensitive to measurement errors and a thirdgas must be present to ensure that the indicator gases behave independently. Br J Anaesth 2000; 85: 371–8     

Comparison of end-tidal and transcutaneous measures of carbon dioxide during general anaesthesia in severely obese adults

Background. Patients with severe obesity (body mass index (BMI)greater than 35 kg m^–2) present difficulties for end-tidalcarbon dioxide (FE'_CO2) monitoring. Previous studies suggestthat transcutaneous (TC) carbon dioxide measurements could bevaluable, so we compared FE' and TC measures with Pa_CO2 in severelyobese patients during anaesthesia. Methods. We studied patients with severe obesity (BMI     

Accuracy of feedback-controlled oxygen delivery into a closed anaesthesia circuit for measurement of oxygen consumption

Background. Oxygen consumption (V^·>O₂) is rarely measuredduring anaesthesia, probably because of technical difficulties.Theoretically, oxygen delivery into a closed anaesthesia circuit(V^·>O₂-PF; PhysioFlex^TM Draeger Medical Company, Germany)should measure V^·>O₂. We aimed to measure V^·>O₂-PFin vitro and in vivo. Methods. Three sets of experiments were performed. V^·>O₂-PFwas assessed with five values of V^·>O₂ (0–300 mlmin^–1) simulated by a calibrated lung model (V^·>O₂-Model)at five values of FI_O2 (0.25–0.85). The time taken forV^·>O₂-PF to respond to changes in V^·>O₂-Modelgave a measure of dynamic performance. In six healthy anaesthetizeddogs we compared V^·>O₂-PF with V^·>O₂ measuredby the Fick method (V^·>O₂-Fick) during ventilationwith nine values of FI_O2 (0.21–1.00). V^·>O₂-PFand V^·>O₂-Fick were also compared in three dogs whenV^·>O₂ was changed pharmacologically [102 (SD 14),121 (17) and 200 (57) ml min^–1]. In patients during surgery,we measured V^·>O₂-PF and V^·>O₂-Fick simultaneouslyafter induction of anaesthesia (n=21) and during surgery (n=17)(FI_O2 0.3–0.5). Results. Compared with V^·>O₂-Model, V^·>O₂-PFvalues varied from time to time so that averaging over 10 minis recommended. Furthermore, at an FI_O2 >0.8, V^·>O₂-PFalways overestimated V^·>O₂. With FI_O2 <0.8, averagedV^·>O₂-PF corresponded to V^·>O₂-Model andadapted rapidly to changes. Averaged V^·>O₂-PF alsocorresponded to V^·>O₂-Fick in dogs at FI_O2 <0.8.V^·>O₂ measured by the two methods gave similar resultswhen V^·>O₂ was changed pharmacologically. In contrast,V^·>O₂-PF systematically overestimated V^·>O₂-Fickin patients by 52 (SD 40) ml min^–1 and this bias increasedwith smaller arteriovenous differences in oxygen content. Conclusion. V^·>O₂-PF measures V^·>O₂ adequatelywithin specific conditions. Br J Anaesth 2003; 90: 281–90     

Extrapolation to zero-flow pressure in cerebral arteries to estimate intracranial pressure

Background. Cerebral perfusion pressure (CPP) is commonly calculatedfrom the difference between arterial blood pressure (AP) andintracranial pressure (ICP). ICP can be considered the effectivedownstream pressure of the cerebral circulation. Consequently,cerebral circulatory arrest would occur when AP equals ICP.Estimation of AP for zero-flow pressure (ZFP) may thus allowestimation of ICP. We estimated ZFP from cerebral pressure–flowvelocity relationships so that ICP could be measured by transcranialDoppler sonography. Methods. We studied 20 mechanically ventilated patients withsevere head injury, in whom ICP was monitored by epidural pressuretransducers. AP was measured with a radial artery cannula. Bloodflow velocity in the middle cerebral artery (V_MCA) ipsilateralto the site of ICP measurement was measured with a 2 MHz transcranialDoppler probe. All data were recorded by a microcomputer fromanalogue–digital converters. ZFP was extrapolated by regressionanalysis of AP–V_MCA plots and compared with simultaneousmeasurements of ICP. Results. ZFP estimated from AP–V_MCA plots was linearlyrelated to ICP over a wide range of values (r=0.93). There wasno systematic difference between ZFP and ICP. Limit of agreement(2 SD) was 15.2 mm Hg. Short-term variations in ICP wereclosely followed by changes in ZFP. Conclusion. Extrapolation of cerebral ZFP from instantaneousAP–V_MCA relationships enables detection of severely elevatedICP and may be a useful and less invasive method for CPP monitoringthan other methods. Br J Anaesth 2003; 90: 291–5     

Cerebrovascular carbon dioxide reactivity in children anaesthetized with sevoflurane

Background. To determine the effects of sevoflurane on cerebrovascularcarbon dioxide reactivity (CCO₂R), middle cerebral artery bloodflow velocity (CBFV) was measured at different levels of PE'_CO2by transcranial Doppler sonography in 16 ASA I or II children,aged 18 months to 7 yr undergoing elective urological surgery. Methods. Anaesthesia comprised 1.0 MAC sevoflurane and air in30% oxygen delivered through an Ayre’s T piece by intermittentpositive-pressure ventilation, and a caudal epidural block with0.25% bupivacaine 1.0 ml kg^–1 without epinephrine.PE'_CO2 was randomly adjusted to 25, 35, 45 and 55 mm Hg(3.3, 4.6, 5.9 and 7.2 kPa) with an exogenous source ofCO₂, while maintaining ventilation variables constant. Results. CBFV increased as PE'_CO2 increased from 25 to 35, andto 45 mm Hg (P<0.001), but did not increase significantlywith an increase in PE'_CO2 from 45 to 55 mm Hg. Meanheart rate and arterial pressure remained constant. Conclusion. CCO₂R is preserved in healthy children anaesthetizedwith 1.0 MAC sevoflurane. Br J Anaesth 2002; 88: 357–61     

Regional response of cerebral blood volume to graded hypoxic hypoxia in rat brain

Background. The response of cerebral blood flow to hypoxic hypoxiais usually effected by dilation of cerebral arterioles. However,the resulting changes in cerebral blood volume (CBV) have receivedlittle attention. We have determined, using susceptibility contrastmagnetic resonance imaging (MRI), changes in regional CBV inducedby graded hypoxic hypoxia. Methods. Six anaesthetized rats were subjected to incrementalreduction in the fraction of inspired oxygen: 0.35, 0.25, 0.15,and 0.12. At each episode, CBV was determined in five regionsof each hemisphere after injection of a contrast agent: superficialand deep neocortex, striatum, corpus callosum and cerebellum.A control group (n=6 rats) was studied with the same protocolwithout contrast agent, to determine blood oxygenation leveldependent (BOLD) contribution to the MRI changes. Results. Each brain region exhibited a significant graded increasein CBV during the two hypoxic episodes: 10–27% of controlvalues at 70% Sa_O2, and 26–38% at 55% Sa_O2. There wasno difference between regions in their response to hypoxia.The mean CBV of all regions increased from 3.6 (SD 0.6) to 4.1(0.6) ml (100 g)^–1 and to 4.7 (0.7) ml (100 g)^–1during the two hypoxic episodes, respectively (SchefféF-test; P<0.01). Over this range, CBV was inversely proportionalto Sa_O2 (r²=0.80). In the absence of the contrast agent, changesdue to the BOLD effect were negligible. Conclusions. These findings imply that hypoxic hypoxia significantlyraises CBV in different brain areas, in proportion to the severityof the insult. These results support the notion that the vasodilatoryeffect of hypoxia is deleterious in patients with reduced intracranialcompliance. Br J Anaesth 2002; 89: 287–93     

Arterial to end-tidal carbon dioxide tension difference in children with congenital heart disease

In children with congenital cyanotic heart disease, right-to-leftintracardiac shunting causes an obligatory difference betweenarterial and end-tidal carbon dioxide tension (Pa_CO2–PE'_CO2)as venous blood, rich in carbon dioxide, is added to the arterialcirculation. This obligatory Pa_CO2–PE'_CO2 difference,which can be predicted from knowledge of oxygen saturation,haemoglobin concentration and Pa_CO2, increases as oxygen saturationdecreases, most markedly when the haemoglobin concentrationis high. A second possible cause of the Pa_CO2–PE'_CO2 differenceis the effect of pulmonary hypoperfusion caused by the shunt.We studied 60 children undergoing cardiac surgery and comparedthe predicted the Pa_CO2–PE'_CO2 difference with measuredvalues to investigate the extent to which additional factorsinfluence the clinically observed Pa_CO2–PE'_CO2. In manychildren, observed values were much greater than predicted,which is compatible with some degree of pulmonary hypoperfusion.However, this was not felt to represent the complete picturein all patients. Another cause of ventilation–perfusionmismatch was suspected in those children who showed a considerableimprovement in oxygen saturation during ventilation with anincreased FI_O2. We believe that pulmonary congestion causedby large left-to-right shunts may further increase the Pa_CO2–PE'_CO2difference. Br J Anaesth 2001; 86: 349–53     

Effects of sustained post-traumatic shock and initial fluid resuscitation on extravascular lung water content and pulmonary vascular pressures in a porcine model of shock

Background. The temporal evolution of lung injury followingpost-traumatic shock is poorly understood. In the present studywe have tested the hypothesis that manifestations of pulmonaryvascular dysfunction may be demonstrable within the first hourafter the onset of shock. Methods. Twenty-nine anaesthetized pigs (mean weight 27.4 kg;(SD) 3.2) were randomly allocated to three groups: control (C,n=9), shock resuscitated with either NaCl 0.9% (S, n=10), or4% gelatine (G, n=10). Shock was maintained for 1 h followedby fluid resuscitation with either normal saline or 4% gelatinesolution. Cardiac output (CO), mean arterial pressure (MAP),mixed venous saturation (Sv_O2), blood lactate concentration,mean pulmonary artery pressure (MPAP), MPAP/MAP, pulmonary vascularresistance (PVR), extravascular lung water index (EVLWi), Pa_O2/FI_O2,venous admixture (Q^·_S/Q^·_T), and dynamic lung compliance(C_dyn) were measured at baseline, beginning of shock phase,end of shock phase, and post-resuscitation. Results. At the end of volume resuscitation CO was restoredto control values in both shock groups. MAP remained significantlybelow control values (95% CI: C=70–95, S=28–52,G=45–69 mm Hg) in both shock groups. MPAP/MAP was significantlygreater in both shock groups at the end of the shock phase (95%CI; C=0.15–0.24, S=0.28–0.38, G=0.32–0.42)and at the post-resuscitation phase (95% CI: C=0.12–0.30,S=0.43–0.61, G=0.32–0.49) indicating the presenceof relative pulmonary hypertension. This was associated witha significant increase in PVR in Group S (F=3.9; P<0.05).There were no significant changes in Pa_O2/FI_O2, Q^·_S/Q^·_T,EVLWi, or C_dyn. In a small cohort of animals a measurable increasein EVLWi (>30%) and reduction in C_dyn (>10%) were observed. Conclusions. Pulmonary vascular injury manifesting as relativepulmonary hypertension and increased PVR may occur within thefirst hour after the onset of shock. These changes may not beaccompanied by overt changes in oxygenation, compliance, orEVLWi. Br J Anaesth 2003; 91: 224–32     

Predicted values of propofol EC50 and sevoflurane concentration for insertion of laryngeal mask Classic and ProSeal

Background. A new laryngeal mask airway, the ProSeal^TM (PLMA),is said to be more difficult to insert than the laryngeal maskairway Classic^TM (CLMA) using propofol anaesthesia. Therefore,we expected a greater dose of propofol and sevoflurane to berequired to insert the PLMA compared with the CLMA. We determinedthe effective concentration 50% (EC₅₀) of propofol and end-tidalsevoflurane to allow insertion of the PLMA and the CLMA. Methods. Seventy-six elective female patients (aged 20–60yr and ASA I–II) were randomly assigned to one of fourgroups. Either a PLMA or a CLMA was inserted using either propofoltarget controlled infusion or sevoflurane. Both propofol andsevoflurane targets were determined with a modified Dixon’sup-and-down method. After equilibration between the predeterminedblood and effect site concentrations, which had been held steadyfor more than 10 min, LMA insertion was attempted without neuromuscularblock. Results. The predicted EC_50CLMA and EC_50PLMA for propofol were3.14 (0.33) and 4.32 (0.67) µg ml^–1. E'_CLMAand E'_PLMA of sevoflurane (mean (SD)) were 2.36 (0.22) and 2.82(0.45)% (P<0.01 and 0.05, respectively). Conclusions. The estimated concentration of propofol and thesevoflurane concentration needed to allow insertion of the ProSeal^TMare respectively 38 and 20% greater than those needed for insertionof the Classic LMA. Br J Anaesth 2004; 92: 242–5     

Influence of tramadol on the ventilatory response to hypoxia in humans

We studied the effect of tramadol on the ventilatory responseto 7 min acute isocapnic hypoxia (Sp_O2 85.1 (SD 0.4)%)during steady mild hypercapnia (PE'_co2 0.7 kPa above normoxicbaseline) in 14 healthy volunteers (seven male). The acute hypoxicresponse was measured before and 1 h after oral placeboor tramadol (100 mg). After tramadol, ventilation duringmild hypercapnia (mean 11.28 litres min^–1) wassignificantly less (P<0.05) than during placebo baseline(13.93 litres min^–1), tramadol baseline (14.63 litres min^–1),or after placebo (14.95 litres min^–1), confirmingthat tramadol has a small depressive effect on the hypercapnicventilatory response. There was no significant difference inthe hypoxic ventilation/Sp_O2 response (l min^–1 %^–1)measured during the placebo baseline (0.99), placebo (1.18),tramadol baseline (0.78) or tramadol (0.68) runs. These datasuggest that tramadol does not depress the hypoxic ventilatoryresponse. Br J Anaesth 2000; 85: 211–6 ^* Correspondingauthor     

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

BACKGROUND: The arterial pharmacokinetics of ketamine and norketamine enantiomersafter racemic ketamine or S-ketamine i.v. administration wereevaluated in seven gelding ponies in a crossover study (2-monthinterval). METHODS: Anaesthesia was induced with isoflurane in oxygen via a face-maskand then maintained at each pony's individual MAC. Racemic ketamine(2.2 mg kg^–1) or S-ketamine (1.1 mg kg^–1)was injected in the right jugular vein. Blood samples were collectedfrom the right carotid artery before and at 1, 2, 4, 8, 16,32, 64, and 128 min after ketamine administration. Ketamineand norketamine enantiomer plasma concentrations were determinedby capillary electrophoresis. Individual R-ketamine and S-ketamineconcentration vs time curves were analysed by non-linear leastsquare regression two-compartment model analysis using PCNonlin.Plasma disposition curves for R-norketamine and S-norketaminewere described by estimating AUC, C_max, and T_max. Pulse rate(PR), respiratory rate (R_f), tidal volume (V_T), minute volumeventilation (V_E), end-tidal partial pressure of carbon dioxide(PE'_CO2), and mean arterial blood pressure (MAP) were also evaluated. RESULTS: The pharmacokinetic parameters of S- and R-ketamine administeredin the racemic mixture or S-ketamine administered separatelydid not differ significantly. Statistically significant higherAUC and C_max were found for S-norketamine compared with R-norketaminein the racemic group. Overall, R_f, V_E, PE'_CO2, and MAP weresignificantly higher in the racemic group, whereas PR was higherin the S-ketamine group. CONCLUSIONS: Norketamine enantiomers showed different pharmacokinetic profilesafter single i.v. administration of racemic ketamine in poniesanaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonaryvariables require further investigation.     

Liver tissue partial pressure of oxygen and carbon dioxide during partial hepatectomy

Background. Data on tissue oxygen partial pressure (Pt_O2) andcarbon dioxide partial pressure (Pt_CO2) in human liver tissueare limited. We set out to measure changes in liver Pt_O2 andPt_CO2 during changes in ventilation and a 10 min period of ischaemiain patients undergoing liver resection using a multiple sensor(Paratrend^® Diametrics Medical Ltd, High Wycombe, UK). Methods. Liver tissue oxygenation was measured in anaesthetizedpatients undergoing liver resection using a sensor insertedunder the liver capsule. Pt_O2 and Pt_CO2 were recorded with FI_O2values of 0.3 and 1.0, at end-tidal carbon dioxide partial pressuresof 3.5 and 4.5 kPa and 10 min after the onset of liver ischaemia(Pringle manoeuvre). Results. Data are expressed as median (interquartile range).Increasing the FI_O2 from 0.3 to 1.0 resulted in the Pt_O2 changingfrom 4.1 (2.6–5.4) to 4.6 (3.8–5.2) kPa, but thiswas not significant. During the 10 min period of ischaemia Pt_CO2increased significantly (P<0.05) from 6.7 (5.8–7.0)to 11.5 (9.7–15.3) kPa and Pt_O2 decreased, but not significantly,from 4.3 (3.5–12.0) to 3.3 (0.9–4.1) kPa. Conclusion. Pt_O2 and Pt_CO2 were measured directly using a Paratrend^®sensor in human liver tissue. During anaesthesia, changes inventilation and liver blood flow caused predictable changesin Pt_CO2. Br J Anaesth 2004; 92: 735–7