Coronary blood flow

The heart has the highest oxygen consumption per tissue massof all human organs. The resting coronary blood flow is 250ml min^–1 (0.8 ml min^–1 g^–1 of heart muscle);this represents 5% of cardiac output.¹ Ischaemia results whenoxygen demand outstrips supply.     

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.     

PHARMACOKINETICS OF GALANTHAMINE (A LONG-ACTING ANTICHOLINESTERASE DRUG) IN ANAESTHETIZED PATIENTS

The pharmacokinetics of the long-acting anti-cholinesterasedrug, galanthamine, were investi-gated in eight patients. Afteri.v. injection of 0.3 mg kg^–1, the decrease in the serumconcen-tration of galanthamine followed a biexponential curve.The serum concentration decreased rapidly from 543±47ng ml^–1 to 128±14 ng ml^–1 be-tween 2 and30 min with a T of 6.42 ± 2.15 min, and then declinedmore slowly with a T^ß of 264±28min. Total serumclearance of galanthamine amounted to 5.37±0.87ml min^–1kg^–1, and the renal clearance was 1.36±0.10 mlmin^–1 kg^–1. The cumulative urinary excretion ofgalanthamine between 0 and 48 h after injection amounted to28.0±5.4% of the administered dose. The biliary excretionof galanthamine during 24 h amounted to 0.2 ±0.1% ofthe dose. There was no evidence of glucuronide or sulphate conjugationof galanthampine.     

VARIATION IN THE DISPOSITION OF MORPHINE AFTER I.M. ADMINISTRATION IN SURGICAL PATIENTS

The disposition of morphine when administered by i.m. injectionwas studied in 36 patients receiving morphine as part of premedicationbefore general anaesthesia, and in five patients who receivedmorphine as a postoperative analgesic after median sternotomyfor coronary artery surgery (PCA group). Maximum plasma concentrationof morphine (Cp_max) was 75.3 ± 6.0 (mean±standarderror (SEM)) ng ml^–1 (range 30–160 ng ml(^–1),mean elimination rate constant (k) 4.85 x 10^–3 min^–1and half-life (T₁₂) = 143 min for the preanaesthetic group.The corresponding values for PCA group were Cp_max = 58.0 ±18.0 ng ml^–1 (range 30–130 ng ml^–1), k = 5.63x 10^–3 min^–1 and T₁₂ = 123 min. Analysis of varianceshowed no differences between the groups. Within the preanaestheticgroup, there was a significant difference in k between males(k = 4.01 x 10^–3 min^–1) and females (6.30 x 10^–3min^–1, P<0.01). The corresponding T₁₂ for males was173 min; and 110 min for females. The variation in the dispositionof morphine is thought to be the result of variations in restingmuscle blood flow and inadvertent injection into adipose tissue.There were no significant differences between males and femalesin the preanaesthetic group with respect to age, CP_max timefrom injection to Cp_max.     

EFFECTS OF NITROUS OXIDE ON CEREBRAL METABOLIC RATE IN RATS ANAESTHETIZED WITH ISOFLURANE

It has been demonstrated in several species that a significantincrease in cerebral blood flow (CBF) occurs when nitrous oxideis added to a volatile anaesthetic. This blood flow responsecould result from an increase in cerebral metabolic rate orfrom a direct effect of nitrous oxide on cerebral vessels. Toinvestigate this, the cerebral metabolic rate for glucose (CMRglu)was determined autoradiographically in rats receiving isofluraneanaesthesia with or without nitrous oxide. An increase in anaestheticdepth from 0.5 to 1.0 MAC achieved with isoflurane alone causeda significant reduction in CMRglu (52 (SD11) µmol/100gmin^–1 vs 39 (8) µmol/100 g min^–1). In contrast,the addition of 70% nitrous oxide (0.5 MAC) to 0.5 MAC isofluraneanaesthesia (1 MAC total) left CMRglu unchanged (54 (4) µmol/100g min^–1). We conclude that 70% nitrous oxide does notalter cerebral metabolic rate when administered with 0.5 MACisoflurane. Because CBF increases substantially under very similarconditions, our data indicate that the CBF effects of nitrousoxide, when administered with a volatile agent, were directand mediated by factors other than changes in cerebral metabolicrate. Presented at the American Society of Anesthesiologists AnnualMeeting 1989, New Orleans, U.S.A.     

INCREASED VENTILATION REQUIREMENTS DURING OBSTETRIC GENERAL ANAESTHESIA

The inspiratory fresh gas flow rate (FGF) required to producean end-tidal carbon dioxide tension (PE' _CO2)of 4kPa duringgeneral anaesthesia, neuromuscular blockade and artificial ventilation,was compared in a group of 46 obstetric patients and a matchedgroup of 50 non-pregnant female patients. The non-pregnant patientsrequired a mean (SD) inspiratory FGF of 77 (10.6) ml kg^–1min^–1, whereas the pregnant patients required a mean FGFof 121 (24.6) ml kg^–1 min^–1 before delivery (inthose who reached a stable state), and 109 (19.3) ml kg^–1min^–1 after delivery. These represent significant (P <0.0001) increases of 57% and 42%, respectively, over the non-pregnantstate. ^*Anaesthetics Unit, The London Hospital, Whitechapel, LondonEl IBB. 335, Southampton Road, Titchfield, Hants PO14 4AX. Northampton General Hospital, Whitechapel, London E1 1BB.     

ERRATA

Delete: "During infusions of alfentanil... can be derived". Insert: "During infusions of fentanyl at 3 µg kg^–1h^–1,the plasma concentration was 3.28±0.54 ng ml^–1,from which a clearance of 15.2 litre kg^–1 min^–1can be derived." Page 123. Formula for A (ml min^–1) should be: A (ml min^–1) = Page 258, line 13. The dose of pancuronium should have been0.1 ng kg^–1 and not 0.001 ng kg^–1 as printed.      

Actions of morphine on noradrenaline efflux in the rat locus coeruleus are mediated via both opioid and {alpha}2 adrenoceptor mechanisms

A recent report showed that morphine inhibited [³H]clonidinebinding to human platelet ₂ receptors. As the analgesic effectsof morphine and clonidine are clinically additive, we investigatedthe possibility that morphine might stimulate ₂ receptors or₂ mechanisms in rat locus coeruleus (LC) slices. StimulatedLC noradrenaline efflux was measured by fast cyclic voltammetry.Cumulatively applied morphine 10^–8–10^–4mollitre^–1 had no effect on noradrenaline efflux evoked bypseudo-single-pulse stimulations (20 pulses at 100 Hz) whilethe ₂ agonist dexmedetomidine 2 x 10^–10–10^–7mol litre^–1 decreased efflux of noradrenaline in a concentration-dependentmanner. Administration of single concentrations of morphine10^–6–10^–4 mol litre^–1 significantlydecreased efflux of noradrenaline (by 22% and 17%, respectively)and attenuated the effect of dexmedetomidine in a concentration-dependentfashion. Morphine 10^–6–10^–4mol litre^–1also decreased efflux of noradrenaline on long stimulus trains(50 pulses at 50 Hz). These data suggest that the analgesicpotentiation of ₂ and opioid agonists is not mediated via LC₂ receptors.     

PHARMACOKINETICS OF ATRACURIUM IN ANAESTHETIZED INFANTS AND CHILDREN

The pharmacokinetics of atracurium were studied in infants andchildren anaesthetized with isoflurane and nitrous oxide inoxygen. There were no significant differences in volume of distribution(area) (139 v. 152 ml kg^–1), clearance (5.1 v. 5.3 mlkg^–1 min^–1), T (2.1 v. 2.0 mim), or T^ß(19.1 v. 20.3 min) between children with normal hepatic andrenal function and those with moderately impaired hepatic functionpresenting for hepatic transplantation. There were significantdifferences in volume of distribution (area) (176 v. 139 mlkg^–1) and in clearance of atracurium (9.1 v.5.1 ml kg^–1min^–1) between infants and children with normal excretoryfunction. In infants the clearance of atracurium in ml m^–1min^–1 (153 v. 133) tended to be greater and the T andT^ß tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1)than in children with normal excretory function; however, thesetrends did not reach statistical significance. Plasma laudanosineconcentration was around 100 ng ml^–1 greater in patientswith liver disease than in normal children from 15–45min following a bolus of atracurium 0.5 mg kg^–1.     

TOTAL I.V. ANAESTHESIA WITH PROPOFOL AND ALFENTANIL: DOSE REQUIREMENTS FOR PROPOFOL AND THE EFFECT OF PREMEDICATION WITH CLONIDINE

We determined in 51 healthy patients undergoing body surfacesurgery the dose requirements for propofol, as part of a totali.v. anaesthesia technique with an alfentanil infusion. Afterpremedication with temazepam, patients received alfentanil 50µg kg^–1 followed by an infusion of 50 µg kg^–1h^–1. Patients were anaesthetized with a loading dose ofpropofol followed by a three-stage infusion designed to reachone of five preselected blood concentrations of propofol. Themotor response to the initial surgical incision was noted andprobit analysis was used to derive the ED₅₀ (2.94 mg kg^–1h^–1; 95% confidence limits: 2.35–3.37 mg kg^–1h^–1). and ED₉₅ (4.98 mg kg^–1 h^–1; 95% limits:4.13–8.8 mg kg^–1 h^–1) for the final propololinfusion rate under these conditions. Whole blood concentrationof propofol at the time of the incision was related linearlyto the infusion rate and the EC₅₀ and EC₉₅ (probit analysis)were derived as 1.44 (95% confidence limits 0.62–1.87)and 4.05 (95% confidence limits 2.78–30.5) µg ml^–1,respectively. Postoperative recovery was rapid, uncomplicatedand uneventful. In a subgroup of eight patients, the additionof clonidine 0.6mg to the premedication significantly decreasedthe requirement for propofol (P <0.05) during surgery, butresulted in prolonged recovery times. Pilot study presented to the Anaesthetic Research Society, June24, 1988 [1].     

Effects of levobupivacaine and ropivacaine on rat sciatic nerve blood flow

Background. Ischaemia is one of the causative mechanisms ofperipheral nerve injury, a documented complication of regionalanaesthesia. Local anaesthetics per se and/or vasopressor adjuvantsmay account for changes in peripheral nerve blood flow. Theaim of this study was to test the effects of levobupivacaineand ropivacaine in a rat sciatic nerve model with respect tolocal blood flow and histopathological changes. Methods. Forty-eight female Sprague–Dawley rats were anaesthetizedfor left sciatic nerve exposure. After baseline nerve bloodflow measurement with a laser Doppler flowmeter, 0.2 ml of oneof the following solutions was applied topically to the nervein a random fashion: saline 0.9%; lidocaine 10 mg ml^–1;levobupivacaine 2.5 mg ml^–1; levobupivacaine 5 mg ml^–1;levobupivacaine 7.5 mg ml^–1; ropivacaine 2 mg ml^–1;ropivacaine 7.5 mg ml^–1; and ropivacaine 7.5 mg ml^–1plus epinephrine 5 µg ml^–1; all in saline 0.9%.Nerve blood flow was evaluated at 5-min intervals up to 30 minafter local application of anaesthetic solution. Three animalsper group were killed for histological evaluation 48 h later.Multiple one-way analyses of variance followed by Scheffé'spost hoc test was used for statistical analysis. P<0.05 wasconsidered significant. Results. Local anaesthetics at all concentrations tested causedsignificant reduction in nerve blood flow. The combination ofropivacaine 7.5 mg ml^–1 plus epinephrine did not reducenerve blood flow to a greater extent than ropivacaine 7.5 mgml^–1 alone. Low concentrations of levobupivacaine (2.5and 5 mg ml^–1) reduced nerve blood flow to the same extentas lidocaine 10 mg ml^–1. No significant histological changeswere observed at 48 h. Conclusion. Despite acute reductions in peripheral nerve bloodflow, significant histopathological changes were not observedin this rat sciatic nerve model after topical application oflevobupivacaine and ropivacaine at concentrations relevant toclinical practice.     

A SYSTEM FOR THE CONTINUOUS MEASUREMENT OF OXYGEN UPTAKE AND CARBON DIOXIDE OUTPUT IN ARTIFICIALLY VENTILATED PATIENTS

A continuous, non-invasive system is described for measuringoxygen uptake () and carbon dioxide output () in mechanically ventilated patients. Inspiratory and mixed expiratory gas sampleswere pumped through fine-bore tubing to a remote mass spectrometerfor analysis. The expiratory flow transducer of a Siemens Servo900B ventilator was used for expiratory flow measurement andinspiratory flow was calculated from this using the Haldanetransformation. A desk-top computer calculated , and respiratory quotient. The system has been validated against standard methodsof gas analysis and flow measurement ( mean difference –lOml min^–1: SD9.13; mean difference 8.12ml min^–1:SD4.66). Comparison with Douglas bag measurements in patientshas been made ( mean difference 10.7ml min^–1: SD9.8; mean difference –1.07ml min^–1: SD4.7).     

HEPATIC AND EXTRAHEPATIC DISPOSITION OF PROPOFOL IN PATIENTS UNDERGOING CORONARY BYPASS SURGERY

In order to clarify the relative contribution of the liver tothe short term disposition of propofol, hepatic blood flow wasmeasured during induction of anaesthesia with an i.v. bolusdose of propofol 2 mg kg^–1. Total clearance of the drugwas 2390 (SD 340) ml min^–1, hepatic extraction 82% andhepatic clearance 1060 (260) ml min^–1. During the 60-minperiod of observation, hepatic extraction of propofol increasedfrom 79% to 92%. It is concluded that, within 1 h, only 44%of the administered dose is removed by the liver. Consequently,drug accumulation may occur with repeated dosing or infusionof propofol. The increase in extraction results presumably fromslow release of propofol from the soy-bean emulsion. Results presented in part at the 29th Spring Meeting of theGerman Association of Pharmacology, March 8–11, Mainz,FRG. (Abstract (No. 490) in Naunyn-Schmiedebergs Archives ofPharmacology 1988; 337 (Suppl.): R123.)     

Thenar muscle blood flow and neuromuscular effects of vecuronium in patients receiving balanced or isoflurane anaesthesia

We have tested the hypothesis that isoflurane potentiates non-depolarizingneuromuscular block via an increase in muscle blood flow. Anaesthesiawas induced with thiopentone 4–5 mg kg^–1 in 30 adultmale patients of ASA physical status I or II and was maintainedwith 70% nitrous oxide in oxygen supplemented with either abolus dose of fentanyl 4µg kg^–1 followed by an infusionof 1 7µg kg^–1 h^–1 (balanced anaesthesia group,n=15) or 1.1% end-tidal isoflurane (isoflurane group, n=15).Vecuronium 0.1 mg kg^–1 was given for neuromuscular block.The force of contraction of the adductor pollicis of the thumbin response to ulnar nerve stimulation was recorded. Thenarmuscle blood flow was measured continuously with a laser Dopplerflowmeter. Times required for the first twitch in the train-of-four(T1) to recover to 25%, 75% and 90% of its control value weremean 26.3 (SD 5), 35.3 (10), 43.5 (7) min and 39.2 (15), 53(12.5), 61.2 (10) min in the balanced anaesthesia and isofluranegroups, respectively (P<0.01). Recovery index (time betweenT1 25% and 75%) was prolonged significantly in the isofluranegroup. Administration of thiopentone significantly increasedthenar muscle blood flow from 2.6 (1.9) and 2.2 (1.5) ml min^–1/100g to 19.2 (14) and 21.7 (16) ml min^–11100 g in the balancedanaesthesia and isoflurane groups, respectively (P<0.001).The addition of fentanyl (balanced) or isoflurane to the anaestheticmixture produced further increases in thenar muscle blood flowto reach, respectively, 26.2 (16) and 26.8 (13.6) ml min^–1/1100g during steady state anaesthesia. Thenar muscle blood flowwas comparable in the two groups throughout the study. We concludethat isoflurane prolonged vecuronium-induced neuromuscular block.This prolongation was not related primarily to increase in muscleblood flow.     

OESOPHAGEAL CONTRACTILITY DURING TOTAL I.V. ANAESTHESIA WITH AND WITHOUT GLYCOPYRRONIUM

Somatic movement and spontaneous and provoked oesophageal contractionswere noted at time of incision in 51 patients receiving totali.v. anaesthesia with alfentanil and propofol. Probit analysisof the dose of propofol required to prevent spontaneous movementrevealed an ED₅₀ (95% confidence limits) of 2.5 (1.8-2.9) mgkg^–1 h^–1 and ED₉₅ of 4.7 (4.0-7.5) mg kg^–1h^–1. Corresponding venous blood concentrations gave anEC₅₀ of 1.2 (0.4-1.6) µg ml^–1 and an EC₉₅ of 4.0(2.8-18.5) µg ml^minus;1. ED₅₀ of propofol for preventingspontaneous oesophageal contraction was 3.0 (1.9-3.6) mg kg^–1h^–1. ED₉₅ was 6.9 (5.0-27.3) mg kg^–1 h^–1;EC₅₀ for oesophageal contractions was 1.7 (0.7-2.3) µgml^–1 and EC₉₅ was 5.9 (3.7-70.6) µg ml^–1.Another group of 10 patients were given glycopyrronium 5 µgkg^–1 at induction; oesophageal contractility was significantlyreduced in this group. Preliminary results of this research were presented to the AnaestheticResearch Society, Nottingham, July 1990. ^*Department of Anaesthesia, Derriford Hospital, Plymouth, DevonPL6 8DH. Department of Anaesthesia, Darlington Memorial Hospital, Darlington,Durham DL3 6HX.     

Antagonism of pancuronium- and pipecuronium-induced neuromuscular block

We have compared the antagonism of neuro muscular block producedby pipecuronium with pancuronium in 80 anaesthetized surgicalpatients using mechanomyography and electromyography. Pancuronium0.1 mg kg or pipecuronium 0.07 mg kg^–1 was given afterinduction of anaesthesia and neuromuscular block was adjustedto 75% twitch depression at the time of antagonism. The followingregimens were used: edrophonium 0.5 and 1.0 mg kg^–1, neostigmine0.04 mg kg^–1 pyridostigmine 0.3 mg kg^–1 and edrophonium0.25 mg kg^–1 with pyridostigmine 0.15 mg kg^–1. Antagonismwas evaluated also by the head lift test. There was no differencebetween the reversibility of neuromuscular block produced bypancuronium or pipecuronium. Edrophonium produced a significantlyfaster antagonism than neostigmine or pyridostigmine but onsetof action was not significantly faster than that of edrophoniumwith pyridostigmine. All regimens produced 100% (or near 100%)antagonism of twitch response within 15 min. However, TOF fadeantagonism was more complete with pyridostigmine, neostigmineand edrophonium 1.0 mg kg^–1 than with edrophonium 0.5mg kg^–1. The head lift test indicated somewhat less antagonismwith edrophonium 0.5 and 1.0 mg kg^–1. Using five monitoringmethods, the rank order of reversal potency was: pyridostigmine neostigmine > edrophonium 1.0 mg kg^–1 edrophonium+ pyridostigmine > edrophonium 0.5 mg kg^–1.     

FENTANYL PHARMACOKINETICS IN ANAESTHETIZED PATIENTS WITH CIRRHOSIS

Fentanyl kinetics were studied in patients with cirrhosis andin patients with normal hepatic and renal function undergoingsurgery under general anaesthesia, the latter group served asthe controls. Plasma fentanyl concentrations declined bi-exponentiallyin the controls with an average elimination half-life (T^ß)of 263 mm; total plasma clearance (C7) was 10.8mlmin^–1kg^–1,and total apparent volume of distribution (V^ß) 3 81litre kg^–1. No significant change was observed in patientswith cirrhosis: T( T^ß) was 304mm, Cl 11.3 ml min^–1kg^–1 and V^ß 4.41 litre kg^–1. These datasuggest that the elimination half-life of fentanyl is not primarilyinfluenced by the rate at which it is metabolized in the liver.     

HEPATIC AND RENAL DISPOSITION OF PANCURONIUM AND GALLAMINE IN PATIENTS WITH EXTRAHEPATIC CHOLESTASIS

The plasma clearance of pancuronium in patients with extrahepaticcholestasis was 16% lower than in a control group (1.47±0.11ml min^–1 kg^–1 v. 1.76±0.21 ml min^–1kg^–1), but the difference was not significant. A significantincrease in the elimination half-life T^ß of pancuronium(from 141 to 224 min) and a significant increase in the volumeof the peripheral compartment (V₂ was found in patients withextrahepatic cholestasis when compared with control patients.There was a significantly lower cumulative biliary excretionof pancuronium (0.3±0.3% v. 10.9±3.2% in the controls)during the 48-h period of observation. The biotransformationand cumulative urinary excretion patterns of pancuronium revealedno significant differences between the two groups of patients.The increase of T^ß pancuronium in patients with extrahepaticcholestasis was mainly a consequence of the increase in thevolume of distribution. No significant differences in the plasmaclearance, T^ß or in the volume of distribution wereobserved with gallamine in the patients with extrahepatic cholestasiswhen compared with the control patients. The cumulative urinaryexcretion of gallamine during 48 h in both groups of patientswas approximately 100%. We concluded that in patients with cholestasisand normal glomerular filtration, gallamine is probably morereliable than pancuronium for neuromuscular blockade.     

EFFECTS OF DIFFERENT HEPATIC PATHOLOGIES ON DISPOSITION OF ALFENTANIL IN ANAESTHETIZED PATIENTS

We have studied the influence of different hepatic pathologieson the disposition of alfentanil in 23 unpremedicated patients(six healthy control subjects, six patients with liver dysfunctionof alcoholic aetiology and 11 patients with non-alcohol relatedliver disease). All patients received a bolus of alfentanil500 fig i.v. as supplement to 67% nitrous oxide and isofluranein oxygen anaesthesia. Plasma drug concentrations were measuredin venous blood samples at intervals up to 24 h by radio-immunoassayand protein binding was determined by equilibrium dialysis.Kinetic estimates were determined using non-compartmental analysis.Patients with non-alcoholic liver disease had lesser plasmaclearance (114.8 (range 66.8–213.5) ml min^–1) thanthe alcoholic group (158.8 (100.0–220.7) ml min^–1)or controls (187.4 (125.2–269.5) ml min^–1). In allthree groups, there was considerable intersubject variability,with a bimodal distribution in the non-alcoholic group. Thisgroup also had a smaller apparent volume of distribution atsteady state. Mean residence time was prolonged in the alcoholicgroup compared with controls (284.9 (217.8–362.2) minvs 226.8 (201.2–250) min). Protein binding was decreasedin the alcoholic group compared with controls (84.9 (SD 4.2)%vs 89.3 (2.1)%); this was attributable to a lesser plasma a,-acidglycoprotein concentration (0.55 (0.18) g litre^–1 vs 0.89(0.21) g litre^–1). Free drug clearance was reduced inboth liver dysfunction groups compared with controls. ^*Department of Anesthesiology, Bowman-Gray Medical School, WinstonSalem, North Carolina, U.S.A. Department of Anaesthesia, Freeman Hospital, Newcastle uponTyne. Presented in part at the Anaesthetic Research Society meeting,Cardiff July 1989 [1].     

IN VITRO DISPLACEMENT OF VASOACTIVE MEDIATORS FROM PLASMA PROTEINS: A POSSIBLE MECHANISM FOR PSEUDO-ALLERGIC REACTIONS TO NEUROMUSCULAR BLOCKING DRUGS

We have studied the re/ease of prostaglandin F₂ (PGF₂ and histaminefrom serum proteins by neuromuscular blocking drugs using equilibriumdialysis, with tracer quantities of radio-labelled mediatorsas probes. Small concentrations (0.05–0.25 mmol litre^–1)of competitive neuromuscular blocking drugs displaced 16–67%of bound histamine. Greater concentrations of suxamethonium(2 mmol litre^–1) were required for histamine displacement(19%). There was a significant release of PGF2^* by atracurium1 mmol litre^–1 and pan–curonium 0.69 mmol litre^–1.These findings suggest an alternative mechanism of histaminerelease by neuromuscular blocking drugs which may be relevantto adverse reactions during use. (Br. J. Anaesth. 1992;69:508–510)