VENOUS REACTIONS FOLLOWING ETOMIDATE

BRITISH JOURNAL OF ANAESTHESIA

932

PETER SUPPAN

Nyon, Switzerland REFERENCES

Frynn, P. J., Hughes, R., Walton, B., and JothQingham, S. (1983). Use of atracurium infusions for general surgical procedures including rardiar surgery with induced hypothermia. Br. J. Anaesth., 55, (Suppl. 1). 135S. Sear, J. W., and Prys-Roberts, C. (1979). Plasma concentrations of alphaxalone during continuous infusions of Althesin. Br. J. Anaetth., 51,861. Sir,—A single case report on the use of atracurium and pneumatic tourniquets has been published recently (Alegesan, 1983), the conclusions drawn from it being quite different to my own. It is difficult to explain this discrepancy except perhaps by the fact that the patient described was an 18-months-old child in whom the dose of atracurium may have been insufficient from the onset if a marked age-related dose requirement does exist, as suggested by Nightingale and Bush (1983), who used a dose of 0.6 mg kg' 1 compared with 0.3mgkg"' by Alegesan, and Brandom, Rudd and Cook (1983) who estimated the ED93 in infants and small children as 65% higher than in adults. It may be, also, that too much reliance has been placed on a single patient; we recently encountered in this hospital a similar situation with alcuronium in an adult patient (limb movement resulting from surgical stimulation in spite of apnoea, atracurium 17.5 mg for 60 kg), the first such occurrence after several hundred uneventful anaesthetics. It is likely that similar cases occur with all neuromuscular blocking agents from time to time. PETER SUPPAN

Nyon, Switzerland

REFERENCES

Alegesan, K. (1983). Unwanted isolated limb. Anaesthesia, 38, 1230. Brandom, B. W., Rudd, G. D . , and Cook, D. R. (1983). Clinical pharmacology of atracurium in paediatric patients. Br. J.

Anaesth., S5.WS.

Nightingale, D. A., and Bush, G. H. (1983). Atracurium in paediatric anaesthesia. Br. J. Anaesth., 55,115S.

ANGIONEUROTIC OEDEMA FOLLOWING ATRACURIUM

Sir,—A fit, 30-year-old female weighing 55 kg presented for a laparoscopic sterilization. There was no history of asthma or allergy to any drugs. She was premedicated with papaveretum 10 mg and hyoscine 0.2 mg. A 23-gauge butterfly needle was placed in a vein in the back of her hand and anaesthesia was induced with thiopentone 300mg. Atracurium 25mg was administered. Her lungs were hyperventilated with 50% nitrous oxide in oxygen. Tracheal intubation was carried out with an 8.5-mm Magill's endotracheal tube. Soon after intubation, cyanosis was noticed on the lips and swelling appeared on the eyelids and soon spread all over the face and hands. There were large skin weals along the injected vein. The position of the tracheal tube was verified: there was air entry in both lungs, so artificial ventilation was commenced with 100% oxygen. The patient's radial pulse could be felt very feebly and the systolic arterial pressure was recorded at 45mmHg. An infusion of Hartmann's solution was commenced and hydrocortisone 500 mg given i.v. The arterial pressure increased to its preoperative value in about 10 min, although the swelling took longer than 30 min to resolve. As the patient had responded to treatment, the operation was carried out and she made an uneventful recovery. Since the discovery of atracurium and the facts that it is devoid of undesirable cardiovascular side-effects (Hughes and Chappie, 1981) and that h undergoes inactivation by "Hoffmann fiiminntion" at physiological pH and temperature (Merrett, Thompson and Webb, 1983), it has been used widely, especially for short operations. The ability of atracurium to release histamine has been compared with dimethyl tubocurarine and tubocurarine (Basta et al., 1983) and found to be one-half that of dimethyl tubocurarine and less than one-third that of tubocurarine. However, Sale (1983) reported a case of bronchospasm with atracurium, and cutaneous reactions have been reported in 30% of patients by Mirakhur and colleagues (1983). Bradycardia has also been reported (Carter, 1983). Of the patients given atracurium by various anaesthetists in our group of hospitals, about 30% have developed skin weals along the site of injection and half of these developed generalized flushing of the skin, both of which usually resolved within 10-15min. I feel that the hi
South Skitlds REFERENCES

Basta, S.J.,Savarese,J.J.,Ali,H.H., Moss, J., and Gionfriddo, M. (1983). Histamine releasing potencies of atracurium, dimethyl tubocurarine and tubocurarine. Br. J. Anaesth., 55, 105S. Carter, M. L. (1983). Bradycardia after use of atracurium. Br. Mtd.J., 287, 247. Hughes, R. A., Chappie, D. J. (1981). Pharmacology of atracurium. Br. J. Anaesth., 53, 31. Merrett, R. A., Thompson, C. W., and Webb, F. W. (1983). In vitro degradation of atracurium in human plasma. Br. J. Anaesth., 55,61.

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movement of the limb was observed during the episode. A supplementary dose of atracurium 25 mg was given to regain control of respiration, and surgery was continued nnrlrr circulatory occlusion for a further 35 min, including a second incision 15 min after the coughing episode. Again, no evidence of unsatisfactory neuromuscular blockade was observed at any time, although obviously only the initial dose of atracurium could have reached the ischaemic limb. Two possible explanations can be put forward for this maintenance of the action of atracurium in occluded limbs: (1) that, like other neuromuscular blocking agents, atracurium is primarily dependent on muscle blood flow for the termination of its action, Hoffmann elimination playing a role only once the drug has reached the circulation; (2) that Hoffmann riiminatinn was considerably or completely inhibited by the metabolic acidosis which develops in the ischaemic limb. The decrease in temperature in the ischaemic limb may also have contributed to the inhibition of Hoffmann elimination, as has been shown during general body hypothermia (Frynn et al., 1983). Whatever the final explanation, these results show that atracurium provides satisfactory neuromuscular blockade in tourniquet-occluded limbs for times up to 120 min.

CORRESPONDENCE

933

Mirakhur, R. K., Lyons, S. M., Carson, I. W., Clarke, R. S. J., Ferrer, C. J., and Dundee, J. W. (1983). Cutaneous reaction after atracurium. Anaesthesia, 38, 818. Sale, J. P. (1983). Bronchospasm following the use of atracurium. Anaesthesia, 3$, S\\. VENOUS REACTIONS FOLLOWING ETOMIDATE

TABLE I. Local reaction at Outiu of injection of etomidate Etomidate in Propylenegrycol

K+ + +)

After 24h Erythema Pain by pressing Hardening of vein After 48h Hardening of vein

Munich ACKNOWLEDGEMENT

We thank Mr L. Gran for providing us with etomidate—Intralipid solution.

Doenicke, A., Kugter, J., Penzel, G., Laub, M., Killian, P., Kalmar, L., and Bezecny, H. (1973). Himfunktion und Toleranzbreite nach Etomidate, einem neuen barbituratfreien i.v. applizierbaren Hypnotikum. Anaesthetist, 22, 357. Suttmann, H., Bretz, C , Haegler, H., and Worschhauser, J. (1981). AusbUck uber weitere Entwicktungen von i.v. Hypnotika; in Die mtravtndu Narkose in klinischtr AnasthetiologU und Inunmthtrapit (eds F. W. Ahnefeld et al.), p. 309. Berlin-Heidelberg-New York: Springer. Gran, L., Bleie, H., Jeppson, R., and Maartmann-Moe, H. (1983). Etomidat mit Intralipid. Eine Ldsung zur schmerzfreien Injektion. Anaathttist, 32,409. Holdcroft, A., Morgan, M., Whitman, J. G., and Lumley, G. (1976). Effect of dose and premedication on induction complication with etomidate. Br. J. Anattth., 48, 199. Shuermans, V., Dom, J., Dony, J., Schdjgrond, H., and Brugmans, J. (1978). Multinational evaluation of etomidate for anaesthesia induction. Anaesthetist, 27, 52.

Intralipid

Pain

Other local reactions

A. DOENICKE T. DUKA H. SUTTMANN

3 (pressure) 3 (heat) 1 (burning)

0

3(+) 1 ( + + ) 5(++) 2(+) 0

0 0 0

l(5cm) l(10cm) l(20cm)

0 0 0

Sir,—In a previous investigation of venous T'^<°'» after etomidate i.v. (Schou Olesen, Huttel and Hole, 1984) an interesting difference was found in the frequency of venous sequelae between the right and left arms. The difference was not statistically significant, possibly as a result of a relatively small population studied If the finding* were real it could be of practical importance and we have, therefore, conducted a larger study relating local venous reactions after etomidate to right- or lefthandedness of the patient while, at the same time, studying the influence of use of the arterial pressure cuff. One hundred and forty consecutive patients undergoing surgery for prolapsed lumbar disc had a disposable Teflon cannula (Venflon 1.40, Viggo, Sweden) inserted to both the right and left cephalic veins and were then allocated randomly to receive etomidate in either the left or the right arm. No other mfdtcunon was administered through the rannnlfl Neither cannula was used for infusion of fluids, and on completion of the operation both mnnnlo.- were withdrawn. One of the authors (PH.) nHmini«tered each anaesthetic and recorded the rlnminant arm of the patient, while the other authors visited the patients daily during

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Sir,—Etomidate has been shown to be a useful anaesthetic agent for the induction of anaesthesia (Doenicke et al., 1973). While this compound has positive aspects, one undesirable side-effect is pain at the site of injection (Snuermans et al., 1978). The use of fentanyl shortly before injection of etomidate has been observed to diminiiih such pain (Holdcroft et al., 1976). However, the effect is not complete. The recent availability of a new mixture of etomidate (etomidate—Intralipid 3 mg ml' 1 ) has raised the possibility that a lesser degree of pain on injection might be evoked compared with the previously used preparation of etomidate base 2 mgml"1 in 35% propyleneglycol (Gran et al., 1983). The present studies were H^aigr^H to examine this issue. Testing was performed on eight healthy volunteers, who received etomidate O^mgkg' 1 diluted in Intralipid 3 mgml~1. Etomidate was injected to a hand vein via a butterfly (Venofix) 0.8-G21. During the course of these experiments, the electroencephalogram (EEG) and the electrocardiogram (ECG) were continuously monitored. The experimental procedure lasted for 1 h and any reaction by the subject was recorded. Following the 1-h period of testing, volunteers completed a questionaire regarding their subjective responses. In addition, examination of the injection site was undertaken at 1,24 and 48 h following injection. Any "mimic pain reaction" or subsequent spontaneous dissatisfaction on the part of the subjects were registered. EEG recordings were evaluated to assess the hypnotic potency of the new mixture. These data were then compared with those obtained during the same procedure utilising the conventional solution of etomidate in propyleneglycol (Doenkke et al., 1981). Results are shown in table I.

On the basis of the EEG recordings, we concluded that the two preparations of etomidate were equally potent with respect to their capacity to producing anaesthesia. Other types of reaction (myoclonia, arterial pressure changes etc.) were also comparable for the two compounds. However, striking contrasts in the pain reaction and erythema at the site of injection were observed (table I). While the group receiving etomidate-propyleneglycol exhibited characteristic pain rfartirm^ (six of the eight subjects), erythema at the site of injection (five) and h u n t i n g of the vein (three), the group receiving etomidate-Intralipid were free of these side-effects.