Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation

Background. Lung resistance increases after induction of anaesthesia.We hypothesized that prophylactic bronchodilation with i.v.carperitide before tracheal intubation would decrease airwayresistance and increase lung compliance after placement of thetracheal tube in both smokers and nonsmokers. Methods. Ninety-seven adults aged between 24 and 59 yr wererandomized to receive i.v. normal saline (0.9% saline) (control)or carperitide, 0.2 µg kg^–1 min^–1 throughoutthe study. The 97 patients included smokers and nonsmokers.Thus the patients were allocated to one of the four groups:smokers who received normal saline (n=21), nonsmokers who receivednormal saline (n=27), smokers who received carperitide (n=19)or nonsmokers who received carperitide (n=30). Thirty minutesafter starting normal saline or carperitide infusion, we administeredthiamylal 5 mg kg^–1 and fentanyl 5 µg kg^–1to induce general anaesthesia and vecuronium 0.3 mg kg^–1for muscle relaxation. Continuous infusion of thiamylal 15 mgkg^–1 h^–1 followed anaesthetic induction. Mean airwayresistance (R_awm), expiratory airway resistance (R_awe) and dynamiclung compliance (C_dyn) were determined 4, 8, 12 and 16 min aftertracheal intubation and compared between the four groups. Results. At 4 min after intubation, R_awm and R_awe were higherand C_dyn lower in smokers than in nonsmokers in the controlgroup. R_awm and R_awe were lower and C_dyn higher in smokers inthe carperitide group than in smokers in the control group.R_awm and R_awe were lower in nonsmokers in the carperitide groupthan in nonsmokers in the control group. Conclusions. Marked bronchoconstriction occurred in the controlgroups (smokers and nonsmokers) 4 min after tracheal intubation.Prophylactic treatment with carperitide before induction ofanaesthesia and tracheal intubation was advantageous, particularlyin smokers.     

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     

Phenotyping malignant hyperthermia susceptibility by measuring halothane-induced changes in myoplasmic calcium concentration in cultured human skeletal muscle cells

Background. Malignant hyperthermia (MH) is a potentially lethaldisease triggered by volatile anaesthetics and succinylcholinein genetically predisposed individuals. Because of the heterogeneticnature of MH, a simple genetic-based diagnostic test is notfeasible and diagnosis requires an invasive open muscle biopsyfollowed by the in vitro contracture test (IVCT). Our aim wasto establish if measurements of halothane-induced increasesin intracellular calcium ion concentration [Ca²⁺]_i in culturedhuman skeletal muscle cells can be used to phenotype MH susceptibilityand if different mutations in the ryanodine receptor (RYR1)gene affect halothane-induced increases in [Ca²⁺]_i. Methods. Primary cultures of human skeletal muscle cells wereestablished from 54 individuals diagnosed by the IVCT accordingto the protocol of the European MH Group as: MH susceptible(n=22), MH negative (n=18) or MH equivocal (n=14). All individualswere screened for the presence of the most common mutationsin the RYR1 gene. [Ca²⁺]_i was measured by fluorescent digitalmicroscopy using fura-2/AM in 10 cells from each patient atfive different halothane concentrations. Results. The halothane-induced increase in [Ca²⁺]_i differedsignificantly between the three diagnostic groups. Differentmutations of the RYR1 gene did not have a specific impact onhalothane-induced increases in [Ca²⁺]_i. Conclusions. Measurements of [Ca²⁺]_i in human skeletal musclecells can be used to phenotype MH susceptibility; however, wedid not observe a specific effect of any mutation in the RYR1gene on the halothane-induced increase in [Ca²⁺]_i. Br J Anaesth 2002; 89: 571–9     

Derivation of preliminary three-dimensional pharmacophoric maps for chemically diverse intravenous general anaesthetics

Background. The molecular basis of i.v. general anaestheticactivity was investigated using comparative molecular fieldanalysis (CoMFA). Methods. The free plasma concentrations that abolish movementto a noxious stimulus for 14 structurally diverse i.v. anaestheticswere obtained from the literature. The compounds were randomlydivided into a training set (n=10) to derive the activity model,and a separate test set (n=4) used to assess its predictivecapability. The anaesthetic structures were aligned so as tomaximize their similarities in molecular shape and electrostaticpotential to conformers of the most active agent in the group,eltanolone. The conformers and alignments that showed the maximumsimilarity (calculated using combined Carbo indices) were retained,and used to derive the CoMFA models. Results. The final model explained 94.0% of the variance inthe observed activities of the training set (n=10, P<0.0001)and was a good predictor of test set activity (n=4, r²=0.799).In contrast, a model based on non-polar solubility (LogP) explainedonly 78.3% of the variance in the observed activities of thetraining set (n=10, P=0.0007) and was a poor predictor for thetest set (n=4, r²=0.272). Further analysis of the CoMFA resultsidentified the spatial distribution of key areas where stericand electrostatic interactions are important in determiningthe activity of the 14 anaesthetics considered. Conclusions. A single activity model can be formulated for i.v.general anaesthetics and preliminary pharmacophoric maps derived,which describe the molecular basis of their in vivo potency. Br J Anaesth 2004; 92: 45–53     

Increased carbon dioxide absorption during retroperitoneal laparoscopy

Background. Retroperitoneoscopy for renal surgery is now a commonprocedure. We compared carbon dioxide absorption in patientsundergoing retroperitoneoscopy for adrenal or renal surgerywith that of patients undergoing laparoscopic cholecystectomy. Methods. We measured carbon dioxide elimination with a metabolicmonitor in 30 anaesthetized patients with controlled ventilation,undergoing retroperitoneoscopy (n=10), laparoscopy (n=10) ororthopaedic surgery (n=10). Results. Carbon dioxide production increased by 38, 46 and 63%at 30, 60 and 90 min after insufflation (P<0.01) in patientshaving retroperitoneoscopy. Carbon dioxide production (mean(SD)) increased from 92 (21) to 150 (43) ml min^–1 m^–260–90 min after insufflation and remained increased afterthe end of insufflation. During laparoscopy, V^·_CO2 increasedless (by 15%) (P<0.05 compared with retroperitoneoscopy)and remained steady throughout the procedure. Conclusion. Retroperitoneal carbon dioxide insufflation causesmore carbon dioxide absorption than intraperitoneal insufflation,and controlled ventilation should be increased if hypercapniashould be avoided. Br J Anaesth 2003; 91: 793–6     

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     

Agitation and changes of Bispectral Index and electroencephalographic-derived variables during sevoflurane induction in children: clonidine premedication reduces agitation compared with midazolam

Background. This double-blind randomized study was undertakento assess agitation, Bispectral Index^TM (BIS^TM) and EEG changesduring induction of anaesthesia with sevoflurane in childrenpremedicated with midazolam or clonidine. Methods. Children were allocated randomly to receive rectalmidazolam 0.4 mg kg^–1 (n=20) or oral clonidine 4µg kg^–1 (n=20) as premedication. Rapid inductionof anaesthesia was achieved with inhalation of sevoflurane 8%in nitrous oxide 50%–oxygen 50%. After tracheal intubation,the children’s lungs were mechanically ventilated andthe inspired sevoflurane concentration was adjusted to achievean end-tidal fraction of 2.5%. The EEG and BIS^TM were recordedduring induction until 10 min after tracheal intubation. TheEEG was analysed using spectral analysis at five points: baseline,loss of eyelash reflex, 15 s before the nadir of the BIS^TM (BIS_nadir),when both pupils returned to the central position (immediatelybefore intubation), and 10 min after intubation. Results. Agitation was observed in 12 midazolam-treated andfive clonidine-treated patients (P=0.05). At baseline, EEG rhythmswere slower in the clonidine group. Induction of anaesthesiawas associated with similar EEG changes in the two groups, withan increase in total spectral power and a shift towards lowfrequencies; these changes were maximal around the end of thesecond minute of induction (BIS_nadir). When the pupils had returnedto the central position, fast EEG rhythms increased and BIS^TMwas higher than BIS_nadir (P<0.05). In both groups, agitationwas associated with an increase in slow EEG rhythms at BIS_nadir. Conclusions. Compared with midazolam, clonidine premedicationreduced agitation during sevoflurane induction. During inductionwith sevoflurane 8% (oxygen 50%–nitrous oxide 50%), thenadir of the BIS^TM occurred at the end of the second minuteof inhalation. Agitation was associated with a more pronouncedslowing of the EEG rhythms at BIS_nadir compared with inductionsin which no agitation was observed. The BIS^TM may not followthe depth of anaesthesia during sevoflurane induction in children. Br J Anaesth 2004; 92: 504–11     

Cytochrome P4502B6 and 2C9 do not metabolize midazolam: kinetic analysis and inhibition study with monoclonal antibodies

We determined the contribution of cytochrome P450 (CYP) isoformsto the metabolism of midazolam by kinetic analysis of humanliver microsomes and CYP isoforms and by examining the effectof chemical inhibitors and monoclonal antibodies against CYPisoforms in vitro. Midazolam was metabolized to 1'-hydroxymidazolam(1'-OH MDZ) by human liver microsomes with a Michaelis–Mentenconstant (K_m) of 4.1 (1.0) (mean (SD)) µmol litre^–1and a maximum rate of metabolism (V_max) of 5.5 (1.1) nmol min^–1mg protein^–1 (n=6). Of the nine representative human liverCYP isoforms, CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and3A5, three (CYP2B6, 3A4 and 3A5) showed midazolam 1'-hydroxylationactivity, with K_ms of 40.7, 1.7 and 3.0 µmol litre^–1,respectively, and V_max values of 12.0, 3.3 and 13.2 nmol min^–1nmol P450^–1, respectively (n=4). Midazolam 1'-hydroxylationactivity of human liver microsomes correlated significantlywith testosterone 6ß-hydroxylation activity, a markerof CYP3A activity (r²=0.77, P=0.0001), but not with S-mephenytoinN-demethylation activity, a marker of CYP2B6 activity (r²<0.01,P=0.84) (n=11). Troleandomycin and orphenadrine, chemical inhibitorsof CYP isoforms, inhibited the formation of 1'-OH MDZ by humanliver microsomes. Monoclonal antibody against CYP3A4 inhibitedthe formation of 1'-OH MDZ by 79%, whereas monoclonal antibodyagainst CYP2B6 had no effect on midazolam 1'-hydroxylation byhuman liver microsomes (n=5). These results indicate that onlyCYP3A4, but not CYP2B6 or CYP2C, is involved in the metabolismof midazolam in vitro. Br J Anaesth 2001; 86: 540–4     

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     

Comparison of hyperbaric and plain ropivacaine 15 mg in spinal anaesthesia for lower limb surgery

Background. Previously, plain ropivacaine 15 mg given intrathecallyhas been shown to be feasible for ambulatory surgery of lower-extremities.Hypothetically, hyperbaric solution could improve and shortenthe block. Methods. This prospective, randomized, double-blind study included56 patients undergoing surgery of lower extremities. They receivedintrathecally either 1.5 ml of ropivacaine 10 mg ml^–1and 0.5 ml of glucose 300 mg ml^–1 (HYP) or 2 ml of ropivacaine7.5 mg ml^–1 (PL). Results. All patients in Group HYP achieved T₁₀ dermatome analgesiabut only 64% (18/28) of Group PL. T₁₀ analgesia was reachedin 5 min (median, range 5–20 min) in the HYP group vs10 min (5–45 min) in the PL group (P=0.022), and fullmotor block in 10 min (5–45 min) vs 20 min (5–60min) (P=0.003), respectively. Group HYP had a longer durationof analgesia at T₁₀; 83 min (5–145 min) vs 33 min (0–140min) (P=0.004). Duration of sensory block from injection ofthe anesthetic to complete recovery was shorter in Group HYPthan in Group PL, 210 min (120–270 min) vs 270 min (210–360min) (P<0.001), as was duration of motor block, 120 min (5–150min) vs 210 min (120–330 min) (P<0.001). Patients ofGroup HYP attained discharge criteria earlier than those ofGroup PL (P=0.009). Conclusion. In comparison with the plain solution, 15 mg ofintrathecal hyperbaric ropivacaine produced a faster onset,greater success rate of analgesia at the level of T₁₀ dermatome,and faster recovery of the block.     

Comparability of Narcotrend index and bispectral index during propofol anaesthesia

Background. The dimensionless Narcotrend^TM (NCT) index (MonitorTechnik,Germany, version 4.0), from 100 (awake) to 0, is a new indexbased on electroencephalogram pattern recognition. Transferringguidelines for titrating the Bispectral Index^TM (BIS, AspectMedical Systems, USA, version XP) to the NCT index depends ontheir comparability. We compared the relationship between BISand NCT values during propofol anaesthesia. Methods. Eighteen adult patients about to have radical prostatectomywere investigated. An epidural catheter was placed in the lumbarspace and electrodes for BIS and NCT were applied as recommendedby the manufacturers. After i.v. fentanyl 0.1 mg, anaesthesiawas induced with a propofol infusion. After intubation, patientsreceived bupivacaine 0.5% 15 ml via the epidural catheter. Forty-fiveminutes after induction, the propofol concentration was increasedto substantial burst suppression pattern and then decreased.This was done twice in each patient, and BIS and Narcotrendvalues were recorded at intervals of 5 s. The efficacy of NCTand BIS in predicting consciousness vs unconsciousness was evaluatedusing the prediction probability (P_K). Results. We collected 38 629 artefact-free data pairs of BISand NCT values from the respective 5-s epochs. Because of artefacts,another 5008 epochs had been excluded from data analysis (3855epochs for the NCT index alone, 245 epochs for the BIS aloneand 908 epochs for both indices). Mean (SD) values in awakepatients were 94 (6) for Narcotrend and 91 (8) for BIS. Withloss of the eyelash reflex, both values were significantly reduced,to 72 (9) for NCT (P<0.001) and to 77 (11) for the BIS index(P<0.001). The P_K value for loss of eyelash reflex was similarfor BIS (0.95) and NCT (0.93). Decreasing BIS values coincidedwith decreasing NCT values. A sigmoid model [NCT index=52.8+26.8/(1+exp(–(BIS–78.3)/4.8))^0.4;r=0.52] described the correlation between BIS and NCT indexin a BIS range between 100 and 50. For BIS values lower than50, a second sigmoid model with a correlation of r=0.83 wasapplied [NCT index=6.6+45.3/(1+exp(–(BIS–29.8)/2.4))^0.6 r=0.83]. The relationship between burst suppression ratio(BSR) and NCT index was best described by the following sigmoidmodel: NCT index=265/(1+exp((–BSR+108)/–49); r=0.73. Conclusions. We found a sufficient correlation between BIS andNCT index, but deviations from the line of identity in someranges require attention. Therefore, a simple 1:1 transfer fromBIS to NCT values is not adequate. Our results might serve asa blueprint for the rational translation of BIS into NCT values.     

Sevoflurane preconditions stunned myocardium in septic but not healthy isolated rat hearts

Background. Recent evidence indicates that sevoflurane treatmentbefore prolonged ischaemia reduces infarct size in normal hearts,mimicking ischaemic preconditioning. We examined whether exposureto sevoflurane before brief ischaemia, inducing a ‘stunnedmyocardium’, provided such protective effects in an isolatedworking heart from normal or septic rats. Methods. With institutional approval, 91 rats were randomlyallocated into one of either caecal-ligation and perforation(CLP: n=50) or sham (Sham: n=41) procedure groups 24 h beforethe study. After determination of baseline measurements, includingcardiac output (CO), myocardial oxygen consumption (mV^·O₂)and cardiac efficiency (CE; COxpeak systolic pressure/mV^·O₂),each isolated heart was perfused with or without 2% sevofluranefor 15 min before global ischaemia (pre-ischaemia). After 15min ischaemia and 30 min reperfusion, all hearts were assessedfor functional recovery of myocardium (post-reperfusion). Results. During the pre-ischaemia period, 2% sevoflurane causeda significant reduction of CO in the CLP group compared withthe Sham group. During the post-reperfusion period, both CO(16.9 vs 11.0 ml min^–1) and CE (11.2 vs 7.7 mm Hg ml^–1(µl O₂)^–1) was higher in the sevoflurane-treatedvs -untreated hearts from CLP rats, and was accompanied by lowerincidence of reperfusion arrhythmia compared with control hearts(8 vs 32%). In contrast, 2% sevoflurane did not provide cardioprotectiveeffects in normal rats. Conclusions. The current study demonstrates that pre-treatmentwith sevoflurane minimizes myocardial dysfunction and the incidenceof reperfusion arrhythmia after brief ischaemic insults in septichearts. Br J Anaesth 2002; 89: 896–903     

Impact of peripheral elimination on the concentration-effect relationship of remifentanil in anaesthetized dogs

Background. This study elucidates the impact of sampling sitewhen estimating pharmacokinetic-pharmacodynamic (PK-PD) parametersof drugs such as remifentanil that undergo tissue extractionin the biophase. The interrelationship between the concentrationsof remifentanil predicted for the effect compartment and thosemeasured in arterial, venous, and cerebrospinal fluid were investigatedunder steady-state conditions. Methods. Following induction of anaesthesia with pentobarbital,an arterial cannula (femoral) and two venous catheters (jugularand femoral) were inserted. Electrodes were placed for EEG recordingof theta wave activity. Each dog received two consecutive 5-mininfusions for the PK-PD study and a bolus followed by a 60-mininfusion was started for the steady-state study. Cerebrospinalfluid, arterial and venous blood samples were drawn simultaneouslyafter 30, 40, and 50 min. At the end of the infusion, arterialblood samples were collected for pharmacokinetic analysis. Results. Remifentanil PK-PD parameters based on theta wave activitywere as follows: apparent volume of distribution at steady-state(V_ss) (231±37 ml kg^–1), total body clearance (Cl)(63±16 ml min^–1 kg^–1), terminal eliminationhalf-life (t_1/2ß) (7.71 min), effect compartment concentrationat 50% of maximal observed effect (EC₅₀) (21±13 ng ml^–1),and equilibration rate constant between plasma and effect compartment(k_e0) (0.48±0.24 min). The mean steady-state cerebrospinalfluid concentration of 236 ng ml^–1 represented 52 and74% of that in arterial and venous blood, respectively. Conclusions. Our study re-emphasizes the importance of a samplingsite when performing PK-PD modelling for drugs undergoing eliminationfrom the effect compartment. For a drug undergoing tissue eliminationsuch as remifentanil, venous rather than arterial concentrationswill reflect more exactly the effect compartment concentrations,under steady-state conditions. Declaration of interest. Remifentanil was provided by AbbottLaboratories.     

Effects of xenon anaesthesia on the circulatory response to hypoventilation

Background. Circulatory response to hypoventilation is aimedat eliminating carbon dioxide and maintaining oxygen delivery(DO₂) by increasing cardiac output (CO). The hypothesis thatthis increase is more pronounced with xenon than with isofluraneanaesthesia was tested in pigs. Methods. Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil0.5 µg kg^–1 min^–1 (group X, n=10) or isoflurane0.55 MAC/remifentanil 0.5 µg kg^–1min^–1 (groupI, n=10). CO, heart rate (HR), mean arterial pressure (MAP)and left ventricular fractional area change (FAC) were measuredat baseline, after 5 and 15 min of hypoventilation and after5, 15 and 30 min of restored ventilation. Results. CO increased by 10–20% with both anaesthetics,with an equivalent rise in HR, maintaining DO₂ in spite of a20% reduction in arterial oxygen content. Decreased left ventricular(LV) afterload during hypoventilation increased FAC, and thiswas more marked with xenon (0.60–0.66, P<0.05 comparedwith baseline and isoflurane). This difference is attributedto negative inotropic effects of isoflurane. Increased pulmonaryvascular resistance during hypoventilation was found with bothanaesthetics. Conclusion. The cardiovascular effects observed in this modelof moderate hypoventilation were sufficient to maintain DO₂.Although the haemodynamic response appeared more pronouncedwith xenon, differences were not clinically relevant. An increasein FAC with xenon is attributed to its lack of negative inotropiceffects.     

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     

Comparison of lactated Ringer's, gelatine and blood resuscitation on intestinal oxygen supply and mucosal tissue oxygen tension in haemorrhagic shock

Objectives. To evaluate the effects on intestinal oxygen supply,and mucosal tissue oxygen tension during haemorrhage and afterfluid resuscitation with either blood (B; n=7), gelatine (G;n=8), or lactated Ringer's solution (R; n=8) in an autoperfused,innervated jejunal segment in anaesthetized pigs. Methods. To induce haemorrhagic shock, 50% of calculated bloodvolume was withdrawn. Systemic haemodynamics, mesenteric venousand systemic acid–base and blood gas variables, and lactatemeasurements were recorded. A flowmeter was used for measuringmesenteric arterial blood flow. Mucosal tissue oxygen tension(PO₂muc), jejunal microvascular haemoglobin oxygen saturation(HbO₂) and microvascular blood flow were measured. Measurementswere performed at baseline, after haemorrhage and at four 20min intervals after fluid resuscitation. After haemorrhage,animals were retransfused with blood, gelatine or lactated Ringer'ssolution until baseline pulmonary capillary wedge pressure wasreached. Results. After resuscitation, no significant differences inmacrohaemodynamic parameters were observed between groups. Systemicand intestinal lactate concentration was significantly increasedin animals receiving lactated Ringer's solution [5.6 (1.1) vs3.3 (1.1) mmol litre^–1; 5.6 (1.1) vs 3.3 (1.2) mmol litre^–1].Oxygen supply to the intestine was impaired in animals receivinglactated Ringer's solution when compared with animals receivingblood. Blood and gelatine resuscitation resulted in higher HbO₂than with lactated Ringer's resuscitation after haemorrhagicshock [B, 43.8 (10.4)%; G, 34.6 (9.4)%; R, 28.0 (9.3)%]. PO₂mucwas better preserved with gelatine resuscitation when comparedwith lactated Ringer's or blood resuscitation [20.0 (8.8) vs13.8 (7.1) mm Hg, 15.2 (7.2) mm Hg, respectively]. Conclusion. Blood or gelatine infusion improves mucosal tissueoxygenation of the porcine jejunum after severe haemorrhagewhen compared with lactated Ringer's solution.     

Effects of temperature gradient correction of carbon dioxide absorbent on carbon dioxide absorption

Background. The effects of temperature gradients in CO₂ absorbentson water content and CO₂ absorption are not clear. We constructeda novel temperature gradient correction (TGC) canister, andinvestigated the effects of temperature gradient correctionon the water content and longevity (time to exhaustion) of CO₂absorbent using a simulated anaesthesia circuit. Methods. Experiments were divided into two groups accordingto the type of canister used: the TGC canister (n=6) or theconventional canister (n=6). One kilogram of fresh CO₂ absorbentwas placed into the canister. The anaesthetic ventilator wasconnected to a 3 litre bag and 300 ml min^–1 of CO₂ wasintroduced. Oxygen (500 ml min^–1) was used as fresh gas.The anaesthetic ventilator was set at a ventilatory frequencyof 12 bpm, and tidal volume was adjusted to 700 ml. Results. Before the experiment, the water content of the freshCO₂ absorbent in the conventional canister and TGC canisterwas 16.1 (0.9)% and 15.7 (1.1)%, respectively. After the experiment,the water content of CO₂ absorbent near the upper outer rimof the canister increased to 32.4 (0.7)% in the conventionalcanister, but increased to only 20.6 (1.3)% in the TGC canister(P<0.01). The longevity of CO₂ absorbent in the conventionalcanister and TGC canister was 434 (9) min and 563 (13) min (P<0.01). Conclusions. Temperature gradient correction prevented a localexcessive increase in water content and improved the longevityof CO₂ absorbent.      

Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction

Background. The effects of anaesthetics on left ventricular(LV) diastolic function in patients with pre-existing diastolicdysfunction are not well known. We hypothesized that propofolbut not sevoflurane will worsen the pre-existing LV diastolicdysfunction. Methods. Of 24 randomized patients, 23 fulfilled the predefinedechocardiographic criterion for diastolic dysfunction. Theyreceived general anaesthesia with sevoflurane 1 MAC (n=12) orpropofol 4 µg ml^–1 (n=11). Echocardiographic examinationswere performed at baseline and in anaesthetized patients underspontaneous breathing and under positive pressure ventilation.Analysis focused on peak early diastolic velocity of the mitralannulus (E_a). Results. During spontaneous breathing, E_a was higher in thesevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9–8.1)vs 5.5 (4.7–6.3) cm s^–1; P<0.05], reflectingan increase of E_a from baseline only in the sevoflurane group(P<0.01). Haemodynamic findings were similar in both groups,but the end-tidal carbon dioxide content was more elevated inthe propofol group (P<0.01). During positive pressure ventilation,E_a was similarly low in the sevoflurane and propofol groups[5.3 (4.2–6.3) and 4.4 (3.6–5.2) cm s^–1, respectively]. Conclusions. During spontaneous breathing, early diastolic functionimproved in the sevoflurane but not in the propofol group. However,during positive pressure ventilation and balanced anaesthesia,there was no evidence of different effects caused by the twoanaesthetics.     

Effect site concentrations of remifentanil and pupil response to noxious stimulation

Background. Opioid drugs block reflex pupillary dilatation inresponse to noxious stimulation. The relationship between thetarget effect site concentration (Ce_T) of remifentanil and thepupil diameter and reactivity in response to a standard noxiousstimulus were evaluated. Methods. Anaesthesia was induced with propofol TCI to obtainloss of consciousness (LOC) in 12 ASA I/II patients. Thereafter,remifentanil Ce_T was titrated by increments of 1 up to 5 ngml^–1. In the awake state, at LOC and at each plateau levelof remifentanil Ce_T, arterial pressure, heart rate, and BIS(A2000) were recorded. Pupil size and dilatation after a 100Hz tetanic stimulation (T100) were measured at LOC and at eachplateau level of remifentanil Ce_T. Results. LOC was observed at a mean propofol Ce_T of 3.53 (SD0.43) µg ml^–1. Arterial pressure and heart ratedecreased progressively from LOC to 5 ng ml^–1 remifentanilCe_T without any statistical difference between each incrementaldose of remifentanil. Mean BIS values decreased from 96 (2)in the awake state, to 46 (12) at LOC (P<0.05) and then remainedunchanged at all remifentanil Ce_T. Pupil dilatation in responseto 100 Hz tetanic stimulation decreased progressively from 1.55(0.72) to 0.01 (0.03) mm and was more sensitive than pupil diametermeasured before and after 100 Hz tetanus. An inverse correlationbetween pupil dilatation in response to 100 Hz tetanus and anincrease in remifentanil Ce_T from 0 to 5 ng ml^–1 was found(R²=0.68). Conclusions. During propofol TCI in healthy patients, the decreasein pupil response to a painful stimulus is a better measurementof the progressive increase of remifentanil Ce_T up to 5 ng ml^–1than haemodynamic or BIS measurements. Br J Anaesth 2003; 91: 347–52     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503