Effects of milrinone on jugular bulb oxygen saturation and cerebrovascular carbon dioxide reactivity in patients undergoing coronary artery bypass graft surgery

Background. Jugular bulb oxygen saturation () is a surrogate marker for global cerebral oxygenation. The effectof milrinone on and the cerebrovascular carbon dioxide reactivity (CCO2R) was investigated. Methods. Thirty patients scheduled for coronary artery bypassgraft surgery (CABG) were studied prospectively. After sternotomy,normoventilation (at T₁; =4.7–5.0 kPa) and hyperventilation (at T₂; =3.3–3.7 kPa) were induced and the changes in () and (), and (CCO₂R) were measured. After normoventilationwas re-established (at T₃), milrinone 50 µg kg^–1was given (at T₄), followed by hyperventilation (at T₅), and, and CCO₂R were measured. Results. After milrinone administration at normoventilation(T₃ and T₄), cardiac index and mixed venous oxygen saturationincreased, while mean arterial pressure and systemic vascularresistance index decreased, without a significant change in. Before milrinone administration (T₁ andT₂), hyperventilation decreased and , and showed positive linear correlation with . After milrinone administration (T₄ and T₅), hyperventilation decreased and , and showed positive linear correlation with . There was no significant difference in CCO₂R before and after milrinone administration(13.3 (5.7)% kPa^–1 and 12.3 (3.9)% kPa^–1, respectively). Conclusions. Although milrinone induced significant haemodynamicchanges, and CCO₂R were unchanged duringits administration.     

Pressure support ventilation during fibreoptic intubation under propofol anaesthesia

Goal of the study. To assess the benefit of pressure supportventilation during fibreoptic intubation performed under propofolanaesthesia in patients having an anticipated difficult intubation. Procedures. Thirty-two patients with ENT cancer, and havingat least two criteria for anticipated difficult intubation wereprospectively included. All patients received topical lidocaine2% and propofol by plasma target control infusion (initial targetconcentration 3 µg ml^–1, then adjusted to maintainloss of consciousness without apnoea). They were randomly assignedbetween two groups: spontaneous breathing (SB) or pressure supportventilation (with a support level set at 10 cm H₂O) both usingFI_O2=1. Conditions for fibreoptic intubation, respiratory parameters(pulse oxymetry, ventilatory frequency, tidal volume and after intubation) and haemodynamicparameters were recorded. Results. Patient characteristic data and intubation conditionswere similar between both groups. All patients had a successfulfibreoptic intubation and none needed a rescue procedure becauseof desaturation. In spite of a longer duration of intubation, after intubation was lower and tidal volume during intubation was higher with pressuresupport ventilation than in SB patients [38.1 (4.2) vs 42.3(4.7) mm Hg and 371 (139) vs 165 (98) ml, respectively]. Desaturationepisodes were observed in two SB patients conversely to no episodeduring pressure support ventilation, probably because of thehigher minute ventilation. Conclusion. Pressure support represents a useful method to improveventilation during fibreoptic intubation under propofol anaesthesiain patients with an anticipated difficult intubation. Presented in abstract at the ASA meeting 2003.     

One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study

Background: One-lung ventilation (OLV) increases mechanical stress in thelung and affects ventilation and perfusion (V, Q). There areno data on the effects of OLV on postoperative / matching. Thus, thiscontrolled study evaluates the influence of OLV on / distribution in a pigmodel using a gamma camera technique [single-photon emissioncomputed tomography (SPECT)] and relates these findings to lunghistopathology after OLV. Methods: Eleven anaesthetized and ventilated pigs (V_T=10 ml kg^–1,FI_O2=0.40, PEEP=5 cm H₂O) were studied. After lung separation,OLV and thoracotomy were performed in seven pigs (OLV group).During OLV and in a two-lung ventilation (TLV), control group(n=4) ventilation settings remained unchanged. SPECT with ^81mKr(ventilation) and ^99mTc-labelled macro-aggregated albumin (perfusion)was performed before, during, and 90 min after OLV/TLV. Finally,lung tissue samples were harvested and examined for alveolardamage. Results: OLV affected ventilation and haemodynamic variables, but therewere no differences between the OLV group and the control groupbefore and after OLV/TLV. SPECT revealed an increase of perfusionin the dependent lung compared with baseline (49–56%),and a corresponding reduction of perfusion (51–44%) innon-dependent lungs after OLV. No perfusion changes were observedin the control group. This resulted in increased low / regions anda shift of /areas to 0.3–0.5 (10^–0.5–10^–0.3) independent lungs of OLV pigs and was associated with an increaseddiffuse alveolar damage score. Conclusions: OLV in pigs results in a substantial / mismatch, hyperperfusion, and alveolar damagein the dependent lung and may thus contribute to gas exchangeimpairment after thoracic surgery.     

Do fluid administration and reduction in norepinephrine dose improve global and splanchnic haemodynamics?

We studied global and splanchnic haemodynamics in patients withseptic shock, while reducing norepinephrine doses by progressivefluid loading administration. Ten patients (six female, fourmale, aged 39–86 yr, mean 61 yr) were assessed using atranspulmonary thermo-dye dilution technique to measure cardiacoutput, intrathoracic blood volume and total blood volume. Splanchnicblood flow was measured by the steady state indocyanine greentechnique using a hepatic venous catheter. Gastric mucosal bloodflow was estimated by regional carbon dioxide tension (P_CO2). Hydroxyethylstarch was infused in two stageswhile maintaining mean arterial pressure, allowing a reductionin norepinephrine dose from 0.54 to 0.33 to 0.21 µg kg^–1min^–1. Mean () heart rate significantly decreased, from 104 (13) to 94 (15) beats min^–1. Totalblood volume index (mean ()) increased from 2650 (638) to 3655 (885) ml m^–2, intrathoracic blood volumeindex from 888 (204) to 1050 (248) ml m^–2 and cardiacindex from 3.6 (1.0) to 4.0 (0.9) litres min^–1 m^–2.Splanchnic blood flow did not change significantly–eitherabsolute (from 0.81 to 0.98 litres min^–1 m^–2) orfractional (from 22.3% to 23.9%). Gastric mucosal (P_CO2) increased from 7.5 (2.5) to 9.0 (2.8) kPa. TheP₂ gap, i.e. the difference between regionaland end-tidal P₂, increased from 3.1 (2.5)to 4.0 (2.9) kPa. Marked individual variation in responses suggeststhat norepinephrine dose reduction by fluid loading in patientswith stabilized septic shock does not necessarily increase globalor splanchnic blood flow.     

Ephedrine and phenylephrine for the treatment of maternal hypotension in a chronic sheep model of increased placental vascular resistance

Background. We hypothesized that ephedrine and phenylephrineare equal with respect to uterine and placental haemodynamicsand fetal acid–base status after exposure to maternalhypoxaemia and hypotension in a chronic sheep model of increasedplacental vascular resistance (R_UA). Methods. At 114–135 days gestation, chronically instrumentedfetal sheep underwent placental embolization leading to increasedR_UA. Twenty-four hours after embolization, the ewes were anaesthetizedand randomized to receive boluses of ephedrine (n=7) or phenylephrine(n=6) for epidural-induced hypotension after maternal hypoxaemia.Uterine (Q_UtA) and placental (Q_UA) volume blood flows and uterinevascular resistance (R_UtA) and R_UA were recorded. Uterine (PI_UtA)and umbilical artery (PI_UA) pulsatility indices were obtainedby Doppler ultrasonography. Fetal arterial blood samples wereanalysed for acid–base values and lactate concentrations. Results. During hypotension, Q_UtA, fetal pH, BE, and decreased whereas R_UtA, PI_UtA, R_UA,and fetal lactate concentration increased. With ephedrine, Q_UtA,R_UtA, PI_UtA, R_UA, and fetal returned to baseline. Fetal pH, BE, and lactate concentrationdid not change from hypotensive values. With phenylephrine,Q_UtA remained lower (P=0.007) and R_UtA (P=0.007), PI_UtA (P=0.013),and R_UA (P=0.050) higher than at baseline. Fetal returned to baseline and fetal pH and BE did notchange from hypotensive values. However, fetal lactate concentrationincreased further (mean difference 1.49, 95% confidence interval0.72–2.26 mmol litre^–1; P=0.004). Conclusions. In a chronic sheep model of increased placentalvascular resistance, compared with ephedrine administration,phenylephrine administration was associated with impaired uterineand placental haemodynamics and increased fetal lactate concentrations. Presented in part at the Euroanaesthesia 2005 Meeting, Vienna,Austria, May 28–31, 2005.     

Blood/gas partition coefficients of halothane,isoflurane and sevoflurane in horse blood

Background. Blood/gas partition coefficients (_b/g) for volatileagents in horse blood are reported for halothane but not forisoflurane and sevoflurane. We measured the _b/g of halothane,isoflurane and sevoflurane in the blood of fasted horses. Thecorrelation with age, weight and some haematological and biochemicalvariables was studied. The temperature correction factor forisoflurane solubility was calculated. Methods. Twenty-four horses were randomly allocated to halothane(n=8), isoflurane (n=8) or sevoflurane (n=8). Blood sampleswere taken after 10 h’ fasting. Calculation of _b/g wasbased on the measurement of anaesthetic partial pressures inblood at 37 °C, which was achieved with tonometer equilibrationand headspace gas chromatography. Results. Mean _b/g was 1.66 (SD 0.06) for halothane, 0.92 (0.04)for isoflurane, and 0.47 (0.03) for sevoflurane. The _b/g valueswere all significantly lower than in humans (P<0.001). Nocorrelation was found between _b/g and weight, age, haematocrit,plasma triglycerides, cholesterol or total bilirubin. The changein isoflurane solubility per 1 °C temperature increase was–2.63 (0.13)%. Conclusion. The _b/g values of halothane, isoflurane and sevofluranein fasted horses are significantly lower than those reportedin humans. The _b/g for halothane in this study agrees with valuesreported in the literature but a positive correlation with plasmatriglycerides could not be confirmed. Knowledge of _b/g can refinemodels of anaesthetic uptake. Br J Anaesth 2003; 91: 276–8     

RELATIONSHIP OF VENTILATORY DEPRESSION TO STEADY-STATE BLOOD PETHIDINE CONCENTRATIONS

An i.v. infusion regimen was developed to permit rapid attainmentof steady-state blood pethidine concentrations (C_p26). In 10adult volunteers (12 studies) the relationship of pethidineC_p26 to the ventilatory effects of the drug were examined. Meanpethidine C_p26 ranged from 170 to 1320 ng ml_–1, with amedian C_p26 of 480 ng ml^–1. Increased end-tidal (PE' _co2)and mixed venous and decreased slope (I/Pco₂) and position(ISO-I) of the carbon dioxide response wereall significant (P<0.001) for C_P26. (1) 480 and (2) >480ng ml^-1. The averaged changes in PE'_co2, ,I/Pco₂, and ISO-I expressed as a per cent of respectivecontrol variables, were shown to be linear functions of C_P26.It is concluded that, under conditions of C_P26, significantventilarory depression occurs at blood pethidine concentrationsless than those required for analgesia. The possible significanceof these findings in volunteers is discussed in terms of thisapplication to the clinical setting of postoperative pain andits management after general anaesthesia.     

Tissue oxygenation response to mild hypercapnia during cardiopulmonary bypass with constant pump output

Background. Tissue oxygenation is the primary determinant ofwound infection risk. Mild hypercapnia markedly improves cutaneous,subcutaneous (s.c.), and muscular tissue oxygenation in volunteersand patients. However, relative contributions of increased cardiacoutput and peripheral vasodilation to this response remainsunknown. We thus tested the hypothesis that increased cardiacoutput is the dominant mechanism. Methods. We recruited 10 ASA III patients, aged 40–65yr, undergoing cardiopulmonary bypass for this crossover trial.After induction of anaesthesia, a Silastic tonometer was inserteds.c. in the upper arm. S.C. tissue oxygen tension was measuredwith both polarographic electrode and fluorescence-based systems.Oximeter probes were placed bilaterally on the forehead to monitorcerebral oxygenation. After initiation of cardiopulmonary bypass,in random order patients were exposed to two arterial CO₂ partialpressures for 30 min each: 35 (normocapnia) or 50 mm Hg (hypercapnia).Bypass pump flow was kept constant throughout the measurementperiods. Results. Hypercapnia during bypass had essentially no effecton , mean arterial pressure, or tissue temperature. and pH differed significantly. S.C. tissue oxygenation was virtuallyidentical during the two periods [139 (50–163) vs 145 (38–158), P=0.335] [median(range)]. In contrast, cerebral oxygen saturation (our positivecontrol measurement) was significantly less during normocapnia[57 (28–67)%] than hypercapnia [64 (37–89)%, P=0.025]. Conclusions. Mild hypercapnia, which normally markedly increasestissue oxygenation, did not do so during cardiopulmonary bypasswith fixed pump output. This suggests that hypercapnia normallyincreases tissue oxygenation by increasing cardiac output ratherthan direct dilation of peripheral vessels.     

LOW VENTILATORY RESPONSE TO CARBON DIOXIDE NOT ASSOCIATED WITH INCREASED DEPRESSION BY MORPHINE

Ventilation (E), end-tidal (P')_co2 mixed venous Pco₂ (P_co2andthe ventilatory response to carbon dioxide (E/Pco₂) were measured before and within 90 min asgtermorphine 0.15 mg kg^–1 i.m. given to 17 adult patientsundergoing elective surgery under general anaesthesia. The hypothesisthat pastients with a low ventilastory response to carbon dioxideare more susceptible to the ventilatory depressant effecstsof morphine was tested. Morephine induced increases in PE'_co2andP_co2 were not correlasted witheither the slope or the position of the preinjection responseto carbon dioxide. Mean E/Pco₂was depressed after morphine (P <0.05), but individual responsesvaried widely. Seven pastients whose control E/Pco₂ was 9.9 litre min^–1kPa^–1 or lessdecreased E/Pco₂ after morphine.In four patients, E/Pco₂ increasedafter morphine; however, in each case, PE'co₂ and Pco₂ increased also. Morphine disphine displaced thecarbon dioxide response to the right (P < 0.001) but no correlationwas found between either the magnitude of the displacement orchange in slope and control E/Pco₂.The results suggest that patients with a low value for E/Pco₂ are not more susceptible tothe ventilatory depressant action of morphine.     

PULMONARY BLOOD FLOW DURING CLOSED HEART SURGERY: Use of a Modified Formula Ratio to Assess Adequacy of Palliation of Systemic-Pulmonary Artery Shunts

The ability to assess changes in pulmonary blood flow, usinga modified ratio (), was evaluated in 12 infants withcongenital heart disease and complete intracardiac mixing whounderwent modified Blalock-Taussig shunt procedures. At thevarious measuring stages there were no major changes in meanarterial pressure or heart rate. Arterial oxygen tensions andsaturation increased (P < 0.01) and the arterial to end-tidalcarbon dioxide difference (Pa_CO2–PE'_CO2) was significantlyreduced (P < 0.001) after completion of the shunt procedure.There was a significant increase in mean after chest closure (P < 0.001), which was seento correlate well with early clinical outcome. Two patientswho did not demonstrate any increase in over the course of the procedure had failed shunts.The limitations of use of the are discussed. A modified ratio of less than unity after surgery is strongly indicativeof inadequate palliation. Present address: Department of Anaesthesiology, University ofTexas Health Science Center at Dallas, 5323 Harry Hines Blvd,Dallas, Texas 75235, U.S.A.     

An investigation to show the effect of lung fluid on impedance cardiac output in the anaesthetized dog

Background. Accumulation of lung fluid in the critically illpatient is believed to attenuate impedance cardiac output (CO_IC)measurements. However, this phenomenon has never been shownexperimentally. Methods. In eight anaesthetized and ventilated dogs (weight15–22 kg) a high-precision flow probe was placed on theascending aorta via a left thoracotomy incision and the directcardiac output (CO_FP) was measured. Simultaneous CO_IC measurementswere made using a RheoCardioMonitor (ACMA, Singapore). Lungoedema was induced by intravenous oleic acid 0.1 mg kg^–1.Lung fluid was assessed by the decrease in basal thoracic impedance(Z_b). Percentage errors between the two methods (CO_IC–CO_FP)were calculated and compared as Z_b decreased at 1 intervals. Results. During the experiment mean Z_b decreased from 35.9 (SD5.2) to 27.8 (6.5) (P=0.0037). This occurred over a periodof 225 (range 112–338) min and Z_b decreased by 1 every51 (22–68) min. The presence of excessive lung fluid wasconfirmed at post-mortem. Before lung oedema was induced, CO_ICwas 1.5 (0.6) litre min^–1 and the corresponding valueof CO_FP was1.5 (0.7) litre min^–1 (data from eight dogs).As Z_b decreased, and lung fluid accumulated, the error betweenCO_IC and CO_FP widened (P<0.0001, ANOVA for repeated measures).Eventually, CO_IC decreased to 0.7 (0.3) litre min^–1 andthe corresponding value of CO_FP was1.2 (0.3) litre min^–1(Z_b=5 , data from six dogs). Mean arterial pressure, centralvenous pressure and systemic vascular resistance were kept constant. Conclusion. The presence of lung fluid attenuates CO_IC measurementswith respect to CO_FP.     

Inhibition of active sodium absorption leads to a net liquid secretion into in vivo rabbit lung at two levels of alveolar hypoxia

Active sodium transport across alveolar epithelium is knownto contribute to the resolution of pulmonary oedema. We haveattempted to assess whether sodium transport is essential toprevent liquid accumulation in healthy pulmonary alveoli exposedto mild hypoxia, and whether its contribution to liquid absorptiondiffers between mild and moderate levels of hypoxia. In twenty-fouranaesthetized adult rabbits we used direct bronchial cannulationto measure liquid movement from the liquid-filled left lungover 3.5 h. Half of the rabbits were studied at a level of mixedvenous (and alveolar) oxygen partial pressure, P_O2, of 6.5 kPaand half at 4.5 kPa. P_O2 was altered by changing the inspiredoxygen fraction in the ventilated right lung. Alveolar hydrostaticpressure was 0.3 kPa. In each group of 12, six animals withinhibitors of sodium transport in the isosmotic instillate werecompared with six controls. We have shown an alveolar liquidsecretion (approximately 0.6 µl min^–1 (kg bodyweight)^–1) in the presence of inhibitors of active transportand an absorption (approximately 4 µl min^–1 (kgbody weight)^–1) in controls. Changing P_O2 had no influenceon these movements. We conclude that, in this model of pulmonaryoedema, active sodium transport appears to be essential forprevention of alveolar liquid accumulation via secretion. Furthermore,the contribution of active sodium transport to liquid absorptionremains constant at oxygen tensions between 4.5 and 6.5 kPa. Br J Anaesth 2001; 87: 897–904     

VENTILATORY EFFECTS AND PLASMA CONCENTRATION OF MORPHINE IN MAN

The relationship between the plasma concentration of morphineand morphine-induced changes in ventilation and the ventilatoryresponse to carbon dioxide was studied in 17 healthy adultsundergoing elective surgery under general anaesthesia. Eachsubject was given morphine sulphate 0.15 mg kg^–1 i.m.;ventilation (E), end-tidal Pco₂(PE'_CO2), mixed venous PV_CO2(P_CO2)and ventilatory response to carbon dioxide (E/P_CO2) were measured before and within 90 min afterinjection. Mixed venous P_CO2 and E/P_CO2were measured by standard rebreathing methods; plasma morphineconcentration was measured by radioimmunoassay. Maximum plasmamorphine ranged from 30 to 120 ng ml^–1, between 4 and60 min after injection. There was a significant increase inmixed venous PE'_CO2 (P<0.001), and PE'_CO2 (P<0.01) aftermorphine while E decreased insignificantly. Morphine displaced the carbon dioxide responsecurve to the right (P<0.01) and E/P_CO2decreased from 12.3 to 10.0 litre min^–1 kPa^–1 (P<0.05).The magnitude of changes in E and E/P_CO2 were not relatedto the peak plasma concentration of morphine or to the meanconcentration immediately before and after the carbon dioxideresponse measurement. Plasma concentrations of morphine, underthe conditions of the present study, are not an objective indicatorof pharmacological activity between one patient and another. Presented in part at the VI World Congress of Anaesthesiology,MexicoCity, Mexico, April 1976     

VENTILATORY RESPONSES TO CARBON DIOXIDE IN CHILDREN DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA

The ventilatory response to carbon dioxide was studied in 12unpremedicated children, aged 20–68 months, weighing between10 and 20 kg, under nitrous oxide-halothane anaesthesia. Tidalvolume (VT) and end-tidal carbon dioxide tension (PE'_CO2) werecontinuously measured by pneumotachograph and capnograph. Minuteventilation (), respiratory rate (f), mean in-spiratory flow (VT) and effective inspiratorycycle (T1/T^tot) were calculated during anaesthesia at threedifferent inspired halothane concentrations (0.5, 7 and 1.5%).The ventilatory response to carbon dioxide was determined byrelating the increase in ventilation during exposure to 2% carbondioxide to the change in end-tidal carbon dioxide concentration.When the inspired concentration of halothane increased, therewere significant decreases in , VT, , and a significant increase in PE'_CO2 The slope of the carbon dioxide response under lightnitrous oxide-halothane anaesthesia (0.5% halothane) was relativelyflat (18.64 ml min^–1 kg^– mm Hg^-1) when comparedwith the mean values published for anaesthetized adults, childrenor neonates. When the inspired concentration of halothane wasincreased, the slope decreased significantly (39% of initialvalue at 1 % inspired halothane, 26% at 1.5%). The additionof carbon dioxide produced significant increases in , VT and but no change in respiratory rate. No statistical differencewas observed in the slope of carbon dioxide response betweenthe initial and "control" periods which were measured at thesame inspired halothane concentration (0.5%).     

THE CONCEPT OF DEADSPACE WITH SPECIAL REFERENCE TO THE SINGLE BREATH TEST FOR CARBON DIOXIDE

We present a review and a theoretical analysis of factors determiningairway deadspace (VD^aw) and alveolar deadspace (VD^alv), thetwo constituents of physiological deadspace (VD^phys). VD^aw isthe volume of gas between the lips and the alveolar/fresh gasinterface, the location of which is determined by inspiratoryflow pattern and airway geometry. VD^alv can be caused by incompletealveolar gas mixing and associated / mismatching within the terminal respiratoryunits, temporal / mismatching within units, spatial / mismatching between units, and venous admixture. Most causes of VD^phys are influencedby inspiratory flow pattern and the time available for gas diffusionand distribution. Analysis can be made from the single breathtest for carbon dioxide (SBT–CO₂) which is the plot offraction of carbon dioxide in expired gas against expired volume.The common causes of VD^alv are associated with a sloping SBT-CO₂phase III. Combination of SBT-CO₂ with PaCO₂ yields VD^phys andVD^alv. A sloping phase III with a negative arterial-end-tidalPco₂ gradient implies compensation by perfusion for early emptying,overventilated alveoli.     

EFFECTS OF INCREASED CARDIAC OUTPUT ON PULMONARY BLOOD FLOW DISTRIBUTION DURING LOBAR VENTILATION HYPOXIA AND COLLAPSE

Electromagnetic flow probes were placed around the pulmonaryartery and left lower lobe artery in anaesthetized open-chestdogs in order to measure possible changes in the ratio of lobar-to-totalpulmonary blood flow (l/t) in response to changes in cardiacoutput produced by the opening of arterio-venous fistulae orfluid loading. Ventilation of the lobe with 7% oxygen or lobarcollapse reduced l/t by 35% and 42%, respectively, butthere were no significant changes in l/t in response to increases in t of 29–133%. It is concludedthat the changes in t, pulmonary vascular pressures and mixed venous PO₂ within the range studieddid not influence l/t.     

Characterization and comparison of recombinant human and rat TRPV1 receptors: effects of exo- and endocannabinoids

Background. TRPV1 is a ligand-gated ion channel whose activationby capsaicin increases intracellular Ca²⁺ ([Ca²⁺]_i). TRPV1 andcannabinoid CB₁ receptor activation are capable of elicitinganalgesia. In this study, using recombinant human (h) and rat(r) TRPV1 receptors expressed in HEK293 cells, we have performeda comparison of both TRPV1 species at 22 and 37°C and comparedendo- and exocannabinoid activity at both receptors. Methods. [Ca²⁺]_i was measured in Fura-2-loaded HEK293_hTRPV1and HEK293_rTRPV1 cells. To assess native CB₁ receptor activity,[³⁵S]GTPS binding to membranes prepared from rat cerebellumwas measured. Results. Both capsaicin (pEC₅₀ rat 6.9 and pEC₅₀ human 6.8 at37°C) and anandamide (pEC₅₀ rat 5.3 and pEC₅₀ human 5.8at 37°C) produced a concentration-dependent increase in[Ca²⁺]_i in rat and human systems and at 22 and 37°C. InHEK293_rTRPV1 cells, anandamide appeared to be a partial agonist.Capsazepine demonstrated competitive antagonism at both humanand rat TRPV1 receptors and at both temperatures studied. Capsazepineeffects were not temperature dependent: pK_B at rTRPV1 was 5.98at 22°C and 6.02 at 37°C, and pK_B at hTRPV1 was 6.76at 22°C and 6.75 at 37°C. However, there was a consistent6-fold increase in capsazepine potency for hTRPV1 relative torTRPV1. The exocannabinoid ⁹-tetrahydrocannabinol failed toincrease [Ca²⁺]_i, although its solvent ethanol was an effectiveTRPV1 activator. In the [³⁵S]GTPS binding assay using rat cerebellarmembranes, anandamide (pEC₅₀ 5.8) and ⁹-tetrahydrocannabinol(pEC₅₀ 7.1), but not capsaicin, stimulated binding. ⁹-tetrahydrocannabinolwas a partial agonist. pEC₅₀ values for anandamide at rTRPV1and rCB₁ were similar. Conclusions. There were small differences in the pharmacologyof rat and human TRPV1 receptors. Whilst capsaicin activatedTRPV1 and ⁹-tetrahydrocannabinol activated CB₁, anandamide isan endogenous agonist for both receptor systems. Presented in abstract form in the following publications: LamPMW, Smart D, Lambert DG. Anandamide but not ⁹-tetrahydrocannabinolactivates recombinant human vanilloid receptors. Br J Anaesth2003; 90: 418P; Lam PMW, Smart D, Lambert DG. Differences inthe affinity of capsazepine at recombinant rat and human VR1receptors. Br J Pharmacol 2003; 138: 220P.     

EFFECT OF AGE, GENDER AND ANAESTHETIC TECHNIQUE ON THE PHARMACODYNAMICS OF ATRACURIUM

We have measured in 38 patients the plasma concentration profileof atracurium and its effect on the electromyographic firstresponse of the train-offour. One of three techniques was usedto supplement anaesthesia with 66% nitrous oxide in oxygen,0.9% isoflurane (end-tidal), 0.5% halothane (end-tidal) or midazolam3–10mg. A fourparameter threshold pharmacodynamic modelwasfitted to the data in each patient. Compared with a groupof patients anaesthetized with an i.v. technique, the steady-stateplasma concentration producing 50% block was reduced by halothane, and to a greater extentby isoflurane. The rate constant for exit from the effect compartment(k_o correlated negatively with age and was greater in femalepatients, but unaffected by anaesthetic technique. The valuesof , the slope of the concentration-response curve, and of thethreshold were not affected significantly by age, sex or anaesthetic technique. (Br. J.Anaesth. 1993; 70: 38–41)     

Increased concentrations of L-lactate in the rectal lumen in patients undergoing cardiopulmonary bypass

Background. Gut ischaemia may contribute to morbidity in patientsafter cardiopulmonary bypass (CPB), but little is known aboutthe metabolic state of the large bowel in such patients. Thereforewe estimated the concentrations of L-lactate and in rectal mucosa in patients undergoing cardiac surgery withor without the use of CPB. Methods. Patients undergoing coronary artery bypass grafting(CABG) (n=12) or off-pump CABG (n=10) were subjected to equilibriumdialysis of the rectal lumen during the procedure and in thefirst 4 h afterwards. Dialysate concentrations of L-lactateand were measured using an auto-analyser and compared with values obtained in healthy subjects (n=10). Results. During CPB, a 2- to 3-fold increase in luminal concentrationsof L-lactate was observed (CABG vs off-pump CABG, P=0.05; CABGvs healthy subjects, P<0.01). The dialysate concentrationsof L-lactate were higher than the mean systemic values (luminal–arterialgradient mean (SD) 0.9 (1.0) mmol litre^–1, P<0.05),and the two values were positively correlated (P<0.05). LuminalL-lactate concentrations remained elevated 4 h after the operation.In contrast, dialysate was equally high in patient and control groups and substantially higher thanvalues observed in arterial blood. Conclusions. Uncomplicated CPB is associated with moderate butsustained increases in luminal concentrations of L-lactate inthe rectum, indicating metabolic dysfunction of the mucosa inthe large bowel. Part of this study was presented at the 27th Congress of theScandinavian Society of Anaesthesiology and Intensive Care Medicine,Helsinki, Finland, 2003.     

Absorption of carbon dioxide during laparoscopy in children measured using a novel mass spectrometric technique

Background. Carbon dioxide (CO₂) is absorbed during pneumoperitoneumand may cause adverse haemodynamic effects. The aim of thisstudy was to measure the elimination of exogenous CO₂ duringlaparoscopy in children. Methods. Ten children [27.6 (56.5) months; mean (SD)] undergoinglaparoscopic and nine [24.5 (17.3) months] undergoing open surgerywere studied. Breath samples were collected at the line forend-tidal CO₂ and analysed for ¹³CO₂/¹²CO₂ ratio expressed asPDB (difference from standard), by isotope-ratio mass spectrometry.The proportion of absorbed CO₂ was calculated comparing exhaled¹³CO₂/¹²CO₂ before and during CO₂ pneumoperitoneum. Results. ¹³CO₂/¹²CO₂ in medical CO₂ was –32.7 (2.1) PDB.¹³CO₂/¹²CO₂ in breath of patients undergoing open procedureswas –24.3 (2.4) PDB at the start of operation and didnot change during the operation (P > 0.2). ¹³CO₂/¹²CO₂ inbreath of patients undergoing laparoscopy was –21.5 (5.4)PDB at the start of insufflation, and decreased during pneumoperitoneumby 2.5 (1.6) PDB, indicating absorption of exogenous CO₂. Thepercentage of expired CO₂ absorbed rose to 15.5 (7.7)% after30 min of pneumoperitoneum and decreased rapidly after desufflation. Conclusion. After 10 min of laparoscopy 10–20% of expiredCO₂ derives from the exogenous CO₂. CO₂ absorption can be measuredusing a simple mass spectrometric technique.