THE CARDIORESPIRATORY EFFECTS OF HAEMORRHAGE AND OVERTRANSFUSION IN DOGS

Changes in cardiorespiratory function resulting from haemorrhageand overtransfusion were measured in forty-seven dogs duringcontrolled ventilation. In the animals bled to a mean arterialpressure of 70 mm Hg there were significant reductions in arterialPco₂, carbon dioxide output and oxygen consumption, cardiacoutput and total venous admixture. In the animals transfusedto a mean central venous pressure of 15 mm Hg there was a significantfall in total thoracic compliance and arterial Po₃ and significantincreases in the alveolar-arterial Po₃, difference and carbondioxide output. ^*Radcliffe Infirmary, Oxford. Western Infirmary, Glasgow. Mount Sinai School of Medicine, New York, U.S.A. Vancouver General Hospital, Vancouver, Canada.     

THE EFFECTS OF VARIATIONS IN END-EXPIRATORY INFLATION PRESSURE ON CARDIORESPIRATORY FUNCTION IN NORMO-, HYPO AND HYPERVOLAEMIC DOGS

The effects of altering end-expiratory inflation pressure werestudied in mechanically ventilated dogs in the normo-, hypo-and hypervolaemic state. The mean fall in cardiac output resultingfrom an increase in end-expiratory pressure was smaller in thehypervolaemic group than in the other two groups. A positiveend-expiratory pressure increased the mean deadspace/tidal volumeratio in all groups. A negative end-expiratory pressure increasedvenous admixture, particularly in the over-transfused animals,but the increase was not significant in the hypovolaemic group.A negative end-expiratory pressure did not affect deadspace/tidalvolume ratio. ^*Radcliffe Infirmary, Oxford Western Infirmary, Glasgow St George's Hospital, London Paddington Green Technical College, London     

VOLTAGE FIELDS SURROUNDING NEEDLES USED IN REGIONAL ANAESTHESIA

Using a bench model, we have studied the voltage fields surroundingboth insulated and uninsulated needles used in regional anaesthesia.The findings were compared with earlier computer predictionswhich suggested that the fields would be markedly differentfor the two types of needle. The results confirm that the fieldsdiffer markedly and suggest that the use of insulated needlesmay not necessarily improve the accuracy of nerve location andthat uninsulated needles may be more appropriate. ^*Present addresses: Department of Anaesthetics, Hull Royal Infirmary,Hull, Humberside. Droitwich Knee Foundation, Saga House, SansomePlace, Worcester Present addresses: Droitwich Knee Foundation, Saga House, SansomePlace, Worcester.     

METHOXYFLURANE ANALGESIA FOR BURNS DRESSINGS: EXPERIENCE WITH THE ANALGIZER

Methoxyflurane has been used to provide analgesia for burnsdressings on sixty occasions in eleven patients. It was administeredby way of a new, disposable vaporizer, the Analgizer, whichis described. Three patients required either supplementary analgesicsor tranquillizers. No side effects were noted, and patient acceptanceof the Analgizer was good. This method is thought to representan advance over previous methods of analgesia for burns dressings,since there is no undue sedation, pre-operative starvation isunnecessary, and venepunctures are avoided. ^*This device is not yet marketed in the United Kingdom. Present address:Department of Anaesthesia, Royal HampshireCountyHospital, Romsey Road,Winchester Present address:Department of Surgery, University of Chicago,Chicago,Illinois 60637     

EFFECTS OF ANAESTHETIC TECHNIQUE ON DEEP VEIN THROMBOSIS: A Comparison of Subarachnoid and General Anaesthesia

Forty patients with fractured neck of femur were allocated randomlyto undergo surgery under general anaesthesia (GA) or subarachnoidanaesthesia (SAB). After operation, the incidence of deep veinthrombosis (DVT), assessed by venography, was found to be 40%in the SAB group, which was significantly lower than the incidence(76.2%) in the GA group. These observations may account forthe previously reported effect of SAB, in comparison with GA,in reducing early postoperative mortality in this category ofpatient. ^*Nuffield Department of Anaesthetics, Radcliffe Infirmary,OxfordOX2 6HE. Department of Orthopaedic Surgery, Royal Liverpool Hospital,LiverpoolL7 8XP. University Department of Anaesthesia, Leicester Royal Infirmary,Leicester LEI 5WW.     

THE EFFECTS OF VARIATIONS OF INSPIRATORY FLOW WAVEFORM ON CARDIORESPIRATORY FUNCTION DURING CONTROLLED VENTILATION IN NORMO-, HYPO- AND HYPERVOLAEMIC DOGS

The effects of changes in applied positive pressure waveformduring inspiration were studied in anaesthetized dogs mechanicallyventilated with air in the normo-, hypo- and hypervolaemic states.Four waveforms were used (sine, square, late peak and earlypeak flow patterns), these being delivered from a speciallyconstructed ventilator which behaved as a volume preset machinein the inspiratory phase. Controlled ventilation was performedat a constant frequency of 20 respirations per minute at a fixedinspiratory: expiratory ratio of 1:2. None of the waveformsused was found to produce significant changes in cardiorespiratoryfunction within any of the three states of blood volume. ^*Radcliffe Infirmary, Oxford. Paddington Green Technical College, London. Western Infirmary, Glasgow.     

THE EFFECTS OF VARIATIONS IN INSPIRATORY: EXPIRATORY RATIO ON CARDIORESPIRATORY FUNCTION DURING CONTROLLED VENTILATION IN NORMO-, HYPO- AND HYPERVOLAEMIC DOGS

Changes in cardiorespiratory function resulting from the useof three different inspiratory: expiratory ratios (1:2, 0.5:2.5,and 2:1) have been studied in normo-, hypo- and hypervolaemicdogs. Deadspace/tidal volume ratio increased slightly with the0.5:2.5 ratio in all the states of blood volume but the changeswere not statistically significant. There was a significantincrease in arterial-alveolar Pco₂ difference on the 0.5:2.5ratio in the hypervolaemic state and there was a significantreduction in the Pco₂ difference with the 2:1 ratio in the normovolaemicstate. There was a significant reduction in arterial Po₂ anda significant increase in venous admixture on the 0.5:2.5 ratioin the hypervolaemic state. Cardiac output was reduced afterhaemorrhage and increased after overtransfusion but there wereno significant changes resulting from changes in the I: E ratiowithin each state of blood volume. ^*Present addresses:Western Infirmary, Glasgow, Scotland Present addresses:Mount Sinai School of Medicine, New York,U.S.A. Present addresses:Radcliffe Infirmary, Oxford.     

A NEW TECHNIQUE FOR DOMICILIARY FLYING SQUAD ANAESTHESIA

A technique of domiciliary midwifery anaesthesia using Entonoxon a demand basis and minimal trichloroethylene is described.The method employs apparatus using the drawover principle, andalso includes facilities for neonatal resuscitation. ^*Liverpool Maternity Hospital, Liverpool 7. Department of Anaesthetics, Bristol University. Whiston Hospital, Prescot, Lanes.     

HAEMODYNAMIC RESPONSES TO ENFLURANE ANAESTHESIA AND HYPOVOLAEMIA IN THE DOG, AND THEIR MODIFICATION BY PROPRANOLOL

The haemodynamic responses to minumum equipotent concentrationsof halothane and enflurance were compared in seven dogs. Thehaemodynamic responses to increasing concentrations of enflurane,and to induced hypovolaemia during enflurane anaesthesia, werestudied in the same dogs, both before and after administrationof propranolol 0.3 mg kg^-1 i.v. In equipotent concentrations,enflurane caused marginally greater impairment of left ventricularfunction than halothane, and caused a dose-dependent reductionof arterial pressure, cardiac output and myocardial contractility.Following administration of propranolol, these haemodynamiceffects of enflurane were marked, and withdrawal of 20% of estimatedblood volume was tolerated poorly. ^*Present addresses :Department of Anaesthetics, St Vincent'sHospital,Darlinghurst, N.S.W. 2010, Australia. Present addresses :Department of Anaesthesia, University ofBristol,Royal Infirmary, Bristol BS2 8HW. Present addresses :Department of Anesthesiology, Universityof California,San Francisco Medical Center, San Francisco, U.S.A. Present addresses :Department of Anaesthesia, Flinders Universityof South Australia, Bedford Park, South Australia 5042.     

DELAYED EXCITATORY REACTION FOLLOWING INTERACTION OF COCAINE AND MONOAMINE OXIDASE INHIBITOR (PHENELZINE)

A case report is presented in which a patient receiving themonoamine oxidase inhibitor, phenelzine, developed a delayedexcitatory reaction following administration of topical cocainespray during anaesthesia for vocal cordsurgery. The pharmacologicalbasis of the drug interaction is discussed. ^*Department of Anaesthesia, St Bartholomew's Hospital, WestSmithfield, London EC1A 7BE. Shackleton Department of Anaesthetics, Southampton General Hospital,Tremona Road, Southampton S09 4XY. Harefield Hospital, Uxbridge, Middx UB9 6JH.     

USE OF REGIONAL ANAESTHESIA IN A PATIENT WITH ACUTE PORPHYRIA

The porphyrias are inherited disorders of haemmetabolism, acuteattacks of which may be precipitated by anaesthesia, surgeryand pregnancy. The principal clinical feature of the diseaseis an acute neuropathy. A patient with acute intermittent porphyriawas given bupivacaine as part of a regional anaesthetic forCaesarean section. The course of anaesthesia was uneventful. ^*Department of Anaesthesia, Royal Infirmary, 84 Castle Street,Glasgow. Department of Anaesthesia, University of Uppsala, Uppsala, Sweden.     

EFFECTS OF TEMPERATURE ON THE INTERACTION OF MORPHINE WITH OPIOID RECEPTORS

The electrically stimulated guineapig ileum preparation wasused to determine the effects of temperature on the affinityof morphine for opioid receptors. The potency of morphine (expressedas the concentration which produces 50% inhibition—IC₅₀)was significantly decreased at 30C (IC₅₀ 41.0x10^–8 mollitre^–1) and increased at 40C (IC₅₀ 5.1x10^–1 mollitre^–1) when compared with its potency at 37C (IC₅₀,8.8x10^–8 mol litre^–1). Experiments carried out inthe presence of naloxone (a competitive opioid antagonist) indicatedthat the affinity of opioid receptors for this antagonist wasnot affected by temperature. Further studies using B-funaltrexamine(a mu-specific, non-reversible opioid antagonist) revealed anincrease in morphine receptor affinity when temperature wasincreased from 30 to 37C. The data demonstrated that the potencyof morphine increased with temperature; the affinity of naloxonefor opioid receptors was unaltered by temperature; and the affinityof morphine for mu-receptors reached an optimal value withinthe range 30–37C. Presented in part to the American Society of AnesthesiologistsAnnual Meeting, Las Vegas, Nevada, U.S.A., 1986.     

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     

COMPLICATIONS OF TRACHEOTOMY

A patient underwent elective tracheotomy before resection ofthe floor of the mouth. After operation, several life-threateningcomplications arose from this tracheotomy, including surgicalemphysema of the tracheal mucosa which has not been describedpreviously. (Br. J. Anaesth. 1993; 71: 898–901) ^*Division of Anaesthesia, Royal Infirmary, Glasgow, G31 3ER St John's Hospital at Howden, Howden West, Livingston, WestLothian EH54 6PP     

A CASE OF MASSIVE ASPIRATION OF GASTRIC CONTENTS DURING OBSTETRIC ANAESTHESIA: Treatment by Tracheostomy and Prolonged Intermittent Positive Pressure Ventilation

A case is described of massive aspiration of liquid gastriccontents into the lungs of an obstetric patient undergoing generalanaesthesia. Pre-operative treatment with oral alkali to neutralizegastric acid did not prevent a severe reaction in the lungs.Treatment was by general supportive measures and long-term intermittentpositive pressure ventilation via a tracheostomy. Great difficultywas experienced in ventilating the lungs because of their lowcompliance and the large physiological deadspace. Recovery wascomplicated by a severe reduction in pulmonary diffusing capacityand by the development of tracheal stenosis. The factors influencingthe treatment and complications are discussed. ^*Present addresses:United Oxford Hospitals Present addresses:Tottenham Group of Hospitals Present addresses:St. George's Hospital, London     

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.     

CARDIOVASCULAR EFFECTS OF KETAMINE IN THE PITHED RAT, RABBIT AND CAT

The effects of i.v. ketamine on arterial pressure and heartrate were examined in pithed rats, rabbits and cats. In allthree species ketamine caused a brief decrease in arterial pressureand heart rate. In the rat, but not in the other two species,this initial decrease in arterial pressure was followed by apressor response which was resistant to -adrenoceptor blockade,depletion of tissue noradrenaline stores and adrenalectomy.It is concluded that the peripherally mediated pressor responsefound in the pithed rat is specific to this species, is nota result of liberation of peripheral catecholamines and doesnot explain the pressor effect of ketamine found in man andseveral animal species. ^*Department of Pharmacology, University of Alberta, Edmonton,Alberta, Canada. Institute of Physiology, University of Glasgow, Glasgow G128QQ.     

VENTILATION, VENTILATORY CARBON DIOXIDE AND HORMONAL RESPONSE DURING HALOTHANE ANAESTHESIA AND SURGERY IN CHILDREN AFTER MIDAZOLAM PREMEDICATION

In 14 intubated, spontaneously breathing children with bodyweight (bw) ranging from 8.3 to 25.6 kg, the influence of midazolam0.1 mg kg^–1 i.m. (group M_0.1', n = 7) and 0.2 mg kg^–1i.m. (group M_0.2' n = 7) as pre-medication, on sedation, ventilation,ventilatory response to carbon dioxide and hormonal stress responsewas studied in connection with minor surgical procedures duringhalothane anaesthesia. The concentrations of catecholamines,ACTH and cortisol were measured immediately after induction,during undisturbed anaesthesia, during surgery and 15 min afterthe end of the surgical procedure. Sedation was better and plasmacatecholamine concentrations during undisturbed anaesthesiawere less in children receiving the larger dose of midazolam.During surgery and in recovery there were no differences inhormone concentrations. In recovery, the concentrations of allhormones were significantly greater compared with during undisturbedanaesthesia. During surgery, VE and respiratory rate were somewhatlower in group M_0.2 while E'_CO2, was similar. A dose dependentdepression of the response to carbon dioxide was found. However,clinically, the response to carbon dioxide after surgery wasconsidered to be adequate in both groups. ^*Department of Anaesthesia, Manchester Royal Infirmary, OxfordRoad, Manchester Ml3 9WL. Department of Anaesthesia, University Hospital, S-221 85 Lund,Sweden Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden Department of Anesthesiology, Vanderbilt University, Nashville,Tennessee 37232, U.S.A.     

EFFECTS OF VARYING INSPIRATORY FLOW WAVEFORM AND TIME IN INTERMITTENT POSITIVE PRESSURE VENTILATION I: INTRODUCTION AND METHODS

A general review of the physiological alterations with artificialventilation is presented with particular emphasis on the alterationof inspiratory time and flow waveform. The general methods andphysiological calibration procedures used in a more elaboratestudy of inspiratory time and waveform effects are described,with the results of testing these methods showing that the modelis satisfactory. ^*Present addresses:Department of Anaesthesia, University ofOtago, New Zealand. Present addresses:Princess Margaret Hospital, Swindon, Wilts. Present addresses:St Vincent's Hospital, Melbourne, Australia.     

POSSIBLE INVOLVEMENT OF INOSITOL-LIPID METABOLISM IN MALIGNANT HYPERTHERMIA

-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [³H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP₃)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP₃ content. As 1,4,5-IP₃,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH. ^*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany. Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn.