EFFECT OF ADRENALINE ON PLASMA CONCENTRATIONS OF BUPIVACAINE FOLLOWING LOWER LIMB NERVE BLOCK

Twenty-two patients undergoing total knee arthroplasty receivedcombined sciatic plus femoral "3 in 1" blocks as adjuncts togeneral anaesthesia. Eleven patients received 0.375% bupivacaine45 ml (168.75 mg) with adrenaline 1 in 200000 and the remaining11 received plain solution according to a previously prepared,randomized list. The mean maximum plasma bupivacaine concentrationwas significantly greater with plain solution than when adrenalinewas added (1.66 µg ml^–1 compared with 0.98 µgml^–1) (P < 0.05). Bupivacaine concentrations were greaterat all times in the plain group compared with the group receivingadrenaline. These differences were statistically significantat 10, 15 and 20 min (P < 0.05). The greatest peak concentrationrecorded was 3.13 µg ml^–1 in one patient receivingplain bupivacaine. No patient developed signs of systemic toxiceffects. Peak plasma concentrations were related inversely tobody weight in patients receiving solution containing adrenaline(P < 0.005), but no relationship existed in patients whoreceived plain solution.     

EFFECT OF ADRENALINE ON VENOUS PLASMA CONCENTRATIONS OF BUPIVACAINE AFTER INTERPLEURAL ADMINISTRATION

Bupivacaine 2.5 mg kg^–1 (0.5 ml kg^–1 of 0.5% solution),with or without adrenaline 5 µg ml^–1, was administeredby interpleural injection to 12 patients after elective cholecystectomy.Non-compartmental analysis indicated that the addition of adrenalinehad no effect on total body clearance, apparent volume of distributionat steady state or elimination half-life of bupivacaine. However,peak plasma concentrations were lower in the adrenaline group(mean (SD) [range]: 2.57 (0.61) [1.52–3.11] VS 3.22 (0.27)[2.84–3.53] µg ml^–1, P < 0.05) and thetime to maximum concentration was delayed (median [range]: 25[15–30] VS 15 [10–20] min, P < 0.05). Analgesiawas variable and no differences were detected between the twogroups. The addition of adrenaline appears prudent to minimizepossible bupivacaine toxicity.     

EFFECT OF ADRENALINE ON PLASMA CONCENTRATIONS OF BUPIVACAINE FOLLOWING INTRA-ARTICULAR INJECTION OF BUPIVACAINE FOR KNEE ARTHROSCOPY

We administered 0.5% bupivacaine 30 ml either with or withoutadrenaline 5 ug ml^–1 randomly to 16 healthy outpatients,to determine the efficacy of local and intra-articular localanaesthesia for knee arthroscopy and whether or not adrenalineshould be added to intra-articular bupivacaine. Bupivacaineconcentrations were measured in plasma obtained 15, 30, 45 and60 min after intra-articular injection. Patients receiving bupivacainewith adrenaline had significantly smaller plasma concentrationsof bupivacaine at all times than did patients receiving plainbupivacaine. The maximal concentrations of bupivacaine in theplain group (median 515 ng ml^–1, range 46–875 ngml^–1) were greater than those in the adrenaline group(median 33 ng ml^–1, range 7–125 ng ml^–1) (P= 0.001). All patients found the anaesthetic satisfactory. Weconclude that intra-articular/local anaesthesia is satisfactoryfor outpatient arthroscopic surgery, and that adrenaline shouldprobably be added to bupivacaine before intra-articular injection.     

PLASMA CONCENTRATIONS OF BUPIVACAINE AFTER STELLATE GANGLION BLOCK USING TWO VOLUMES OF 0.25% BUPIVACAINE PLAIN SOLUTION

Plasma concentrations of bupivacaine were measured in patientsafter stellate ganglion block using either 10 or 20 ml of 0.25%plain solution. The mean peak concentrations were greater inthe larger volume group, but this was not statistically significant.From 30 min after injection, there was a significantly greaterplasma concentration in the larger volume group. The concentrationsapproached the limit of detection in the smaller volume groupat 2 h after block. Present address, for correspondence: Pain Clinic, GloucestershireRoyal Hospital, Great Western Road, Gloucester GL1 3NN.     

PLASMA CONCENTRATIONS OF BUPIVACAINE AND ITS ENANTIOMERS DURING CONTINUOUS EXTRAPLEURAL INTERCOSTAL NERVE BLOCK

Plasma concentrations of bupivacaine have been measured in 12patients given bupivacaine through a paravertebral catheterplaced under direct vision at thoracotomy. After an initialbolus of 0.5% bupivacaine 20 ml, mean (SEM) CPmax was 1.45 (0.32)fig mt1 and median (range) tCPmax was 25 (10-60) min. A concentrationof 4.43 ug mt' measured in one patient was not associated withtoxic signs. During continuous infusion of bupivacaine for 120h, CPmax was 4.9 (0.7) fig mt' and tCPmax 48 (5–96) h.No symptoms or signs of toxicity occurred. Separate measurementof R- and S-bupivacaine concentrations demonstrated significantlydifferent concentration-time profiles. (Br. J. Anaesth. 1993;70: 201–204)     

PLASMA CONCENTRATIONS OF BUPIVACAINE AFTER INTERCOSTAL NERVE BLOCK IN PATIENTS AFTER ORTHOTOPIC LIVER TRANSPLANTATION

Bilateral intercostal nerve blocks were performed on 12 occasionsin 11 patients after liver transplantation. Group 1 (six patients)received bupivacaine 2 mg kg^–1 on one occasion; in group2 (five patients) bupivacaine 2 mg kg^–1 with adrenaline1: 200000 was injected on two occasions separated by 6 h. Arterialblood was sampled repeatedly and analysed for total bupivacaineconcentrations by high performance liquid chromatography (HPLC).Six patients had bupivacaine concentrations within the putativetoxic threshold of 2–4 ug ml^–1. The use of adrenaline-containingsolutions neither slowed absorption reliably nor decreased peakconcentrations of bupivacaine. Cumulation of bupivacaine occurredin group 2. No patient had adverse effects attributable to thebupivacaine.     

PLASMA CONCENTRATIONS OF BUPIVACAINE AND TWO OF ITS METABOLITES DURING CONTINUOUS INTERSCALENE BRACHIAL PLEXUS BLOCK

An interscalene brachial plexus block was performed via a catheterwith 20–28 ml of 0.75% bupivacaine plus adrenaline forsurgery of the shoulder region in 12 patients. Constant infusionof 0.25% bupivacaine 0.25 mg kg^–1 h^–1 was continuedfor 24 h. During surgery light general anaesthesia, withoutanalgesics, was maintained. Plasma concentrations of total andunbound (free fraction) bupivacaine, desbutylbupivacaine (DBB),4-hydroxybupivacaine (4-OHB) and alpha₁-acid glycoprotein (AAG)were measured at predetermined intervals during the continuousblock. The greatest mean plasma concentrations of bupivacainewere measured at 30 min (1.63 (SD 0.55) µg ml^–1)and 60 min (1.38 (0.48) µg ml^–1). There was a smallbut statistically significant increase in the plasma concentrationof bupivacaine between 12 and 24 h of infusion. The mean unboundconcentration of bupivacaine in plasma decreased from 0.044(0.015) µg ml^–1 (3.6 (1.1)% of total bupivacaineconcentration) at 3 h to 0.023 (0.011) µg ml^–1 (2.1(1.0)%) at 24 h. The AAG concentration in plasma increased by38% in 24 h. The metabolites DBB and 4-OHB were detectable inplasma from 30 min, with a gradual increase during infusion.At 24 h the mean concentrations of DBB and 4-OHB were 0.33 (0.22)µg ml^–1 and 0. 13 (0.04) µg ml^–1, respectively.There were no toxic reactions during the blocks.     

PLASMA DIAZEPAM CONCENTRATIONS FOLLOWING PROLONGED ADMINISTRATION

Plasma diazepam and N–desmethyl diazepam concentrationswere measured in patients receiving diazepam 5 mg or 10 mg i.v.at 4–h intervals for periods of 6–22 days. At bothdoses there was an accumulation of both diazepam and its metabolite,the latter reaching concentrations of up to two to three timesthat of the parent drug. Plasma diazepam concentrations reacheda plateau after 8 days while the concentration of N-desmethylmetabolite continued to increase throughout the period of drugadministration. On discontinuation of diazepam therapy bothdiazepam and N-desmethyl diazepam concentrations decreased slowly,the former with a half-life of 2–4 days and the latterwith a half-life of 4–8 days.     

SERUM CONCENTRATIONS OF PRILOCAINE FOLLOWING RETROBULBAR BLOCK

Retrobulbar block for eye surgery is associated with adversereactions. We performed retrobulbar block in 10 patients usingprilocaine (Citanest) and found mean (SD) peak serum concentrationsof 851 (165.6) ng ml^–1 (range 540–1100 mg ml^–1).Peak serum concentrations occurred 3–7 min after the endof administration of the block, and in all cases were less thanthose associated with toxicity.     

PLASMA CONCENTRATIONS OF BUPIVACAINE FOLLOWING COMBINED SCIATIC AND FEMORAL 3 IN 1 NERVE BLOCKS IN OPEN KNEE SURGERY

We administered combined femoral 3 in 1 and sciatic nerve blocksto provide postoperative pain relief in 22 consecutive patientsundergoing elective knee replacement surgery under spinal anaesthesia.The patients were allocated randomly to two groups. In groupA (n=11) the blocks were performed with 0.5% bupivacaine (withadrenaline) 3 mg/kg body weight and in group B (n=11) 0.5% plainbupivacaine in the same dose was used. Serial plasma concentrationsof bupivacaine were measured for up to 2 h and the durationof postoperative analgesia was measured in both groups. No significantdifferences were found between the two groups. There were noclinical signs or symptoms of bupivacaine toxicity in each group.This study demonstrated that, after combined sciatic and 3 in1 femoral block, concentrations of bupivacaine associated withtoxicity were not reached, even though the dose of bupivacaineadministered exceeded the manufacturer's recommended dose by50%.     

COMPARISON OF PLASMA BUPIVACAINE CONCENTRATIONS DURING CONTINUOUS EXTRADURAL INFUSION FOR LABOUR

Twenty patients who requested extradural analgesia for labourwere allocated randomly to receive an infusion of either 0.25%or 0.08% solutions of bupivacaine. Following an initial bolusdose of 50 mg, the infusions were given at a rate of 20 mg h^–1.Both solutions provided acceptable pain relief, but plasma concentrationswere significantly lower with the weaker concentration.     

PLASMA LIGNOCAINE CONCENTRATIONS FOLLOWING ENDOTRACHEAL SPRAYING WITH AN AEROSOL

Plasma concentrations of lignocaine were measured in three groupsof anaesthetized patients following spraying of the tracheaand larynx with a lignocaine 10% aerosol spray. Greater venousplasma concentrations occurred in patients who were paralysedwith suxamethonium. A mean plasma concentration of 0.1 µg/mlof lignocaine resulted from each 10 mg of lignocaine used inspontaneously breathing patients, and 0.15 µg/ml in paralysedpatients. In individual patients a concentration 50% in excessof the mean value may occur. The use of lignocaine 100 mg asa 10% aerosol spray can be considered safe.     

PLASMA CONCENTRATIONS OF CATECHOLAMINES FOLLOWING INTRAOCULAR IRRIGATION WITH ADRENALINE

Plasma concentrations of adrenaline and nor-adrenaline weremeasured in 13 patients under going cataract surgery after intraocularirrigation with an adrenaline-containing solution. Venous bloodsamples were withdrawn before, during and after intraocularirrigation with a solution of adrenaline 1:500000. Plasma concentrationsof both adrenaline and noradrenaline did not differ significantlyfrom those noted before induction of anaesthesia. ^*Present address: Manchester Royal Eye Hospital Oxford Road,Manchester M13 9WH     

PLASMA CONCENTRATIONS OF CATECHOLAMINES FOLLOWING ADRENALINE INFILTRATION DURING GYNAECOLOGICAL SURGERY

High pressure liquid chromatography with electrochemical detectionhas been used to measure plasma catecholamine concentrationsin six gynaecological patients undergoing halothane anaesthesiafor cervical cone biopsy. Mean catecholamine concentrationsbefore infiltration were 1.01 $ 0.23 (SEM) nmollitre-1 (185±43pgml-1)for adrenaline, and 2.2±0.25nmollitre-1 (364±41pgml-1)fornoredrenaline. Following infiltration with 0.5% bupivacaine15ml with adrenaline 1:200000, plasma adrenaline concentrationsincreased to a mean peak concentration of 18.6±3.7nmollitre-1(3.4±0.69ngtitre-1). The lack of sympathoncuronal responsewas confirmed by simultaneous measurements of plasma noradrenalineconcentrations, which did not change significantly. The proportionof the injected adrenaline measured in the intravaSCUlar Compartmentwas 21.8%. Discussed in relation to the use of halothane anamthnriaand the concurrent injection of a local anaesthetic solution     

THE MATERNAL PLASMA LEVELS AND PLACENTAL TRANSFER OF BUPIVACAINE FOLLOWING EPIDURAL ANALGESIA

The maternal plasma levels of bupivacaine following epiduraladministration of 0.5 per cent solution with 1/200,000 adrenalinewere determined in twelve patients in labour. After 10 ml (50mg) peak concentrations occurred 15–30 min later and rangedfrom 0.22 µg/ml to 0.60 µg/ml. Plasma levels fellgradually with time after the peak until by 3 hours after injectionthey were all well below 0.2 µg/ml. Maternal and umbilicalplasma levels of bupivacaine were determined at delivery. Theratio of the foetal to maternal levels varied from 0.14 to 0.86.The highest foetal plasma level obtained in the series was 0.25µg/ml and the highest maternal level was 0.68 µg/ml.This value was reached after three 10-ml injections of 0.5 percent bupivacaine with 1/200,000 adrenaline. The 1-min Apgarscores ranged from 7 to 10.     

PLASMA CONCENTRATIONS OF LOCAL ANAESTHETICS AFTER INTERSCALENE BRACHIAL PLEXUS BLOCK

Plasma concentrations of local anaesthetic agents have beenmeasured after 40 interscalene brachial plexus blocks in 39patients, using lignocaine, prilocaine, bupivacaine and etidocaine.Lignocaine produced greater concentrations than prilocaine,and bupivacaine greater concentrations than etidocaine. Theaddition of adrenaline resulted in much lower concentrationsin the case of all four agents.     

EFFECT OF ADRENALINE ON EXTRADURAL ANAESTHESIA AND PLASMA BUPIVACAINE CONCENTRATIONS DURING CAESAREAN SECTION

The effect of adrenaline on the efficacy of extradural blockand plasma bupivacaine concentrations was investigated in womenundergoing elective (n = 40) and emergency (n = 40) Caesareansection. Patients were randomly allocated within these two groupsto receive 0.5% bupivacaine 20 ml either plain or with adrenaline1 in 200000, as a single fractionated extradural injection.The elective plain group needed significantly more supplementaryanalgesia compared with the other three groups (P <0.05).In the elective group, plasma bupivacaine concentrations weresignificantly lower in the subgroup receiving extradural adrenalinethan in the plain subgroup. This effect was not observed whencomparing only those who received bupivacaine 100 mg. In theemergency group, there were no significant differences in plasmabupivacaine concentrations between the plain and adrenalinesubgroups. Maximum plasma concentrations correlated significantly(P < 0.0001) with dose of bupivacaine (mg kg^–1). Itis concluded that extradural adrenaline does not usefully reducesystemic absorption of 0.5% bupivacaine, but may improve itsefficacy in extradural anaesthesia for elective Caesarean section.     

CONTINUOUS EXTRADURAL INFUSION OF 0.125% BUPIVACAINE FOR PAIN RELIEF AFTER LOWER ABDOMINAL SURGERY

Twenty women, undergoing lower abdominal surgery, were allocatedrandomly to receive a continuous extradural infusion of either0.125% bupivacaine or placebo at a rate of 15 ml h^–1.All had received an intra-operative extradural block. Pain scoreswere recorded at 30, 60, 90, 120, 150, 180, 240 and 360 minafter surgery. From 150 min onwards there was a significantbenefit for those receiving the active drug. Six of nine patientsin this group had adequate analgesia over the 6-h study period,while all patients in the placebo group required further painrelief.     

PLASMA CONCENTRATIONS OF BUPIVACAINE DURING CONTINUOUS EPIDURAL ANALGESIA IN LABOUR: THE EFFECT OF ADRENALINE

Continuous epidural analgesia has been provided for eighteenpatients during the first and second stages of labour. Ninepatients received bupivacaine 0.5 per cent with adrenaline 5µg/ml, and nine bupivacaine alone, using a double-blindtechnique. The initial dose of bupivacaine was 30 mg, repeatedand increased as necessary. A total of fifty-nine doses wasgiven. Plasma concentrations of bupivacaine were measured inthe mother throughout the blockade, and in the baby at delivery.The duration of action of bupivacaine was not significantlyprolonged by adrenaline, though plasma concentrations were significantlyreduced 20 minutes after the first dose and 40 minutes afterthe second. In neither treatment group did bupivacaine accumulatemarkedly in maternal plasma unless the second stage necessitatedincreased doses. Neonatal bupivacaine concentrations were alwayslow and neonatal: maternal ratios increased by the use of adrenaline.It is thus uncertain whether adrenaline offered a significantadvantage except with large doses of bupivacaine, when it reducedthe likelihood of maternal intoxication.