Effect of Pseudo-cholinesterase Level on Action of Succinylcholine in Man

Abstract

MMCMJORk cholinesterase available. However, it should be possible to increase the pseudo-cholinesterase of the plasma in the dog and thus to lower the concentration of free succinylcholine or suxethonium so rapidly that even the low concentration of the drug required for inhibition of the true cholinesterase in that animal will be effectively attacked. We therefore injected a highly concentrated solution of pseudo-cholinesterase intravenously into four dogs in the course of operations for mastectomy or conditions requiring orthopaedic treatment, and compared the effect of equal amounts of suxethonium given before and after the pseudo-cholinesterase level of the plasma had been increased.As will be seen in Table III, after the pseudo-cholinesterase had been effectively raised succinylcholine was as short-acting in dog as it is known to be in man. To exclude the effects of premedication and the possibility that apnoea was due to artificial hyperventilation, one experiment was performed in which only thiopentone was used for induction and no artificial respiration was given during apnoea beyond one inflation per minute. Table IV shows that the raising of the pseudo-cholinesterase level was effective under these conditions. Blood-pressure readings were obtained throughout and allowed an exclusion of asphyxia. Both brevidil E and scoline were used and noted as such in terms of active cation. Discussion Our findings support the suggestion that the effect of succinylcholine and suxethonium is the outcome of an interplay between these compounds and the two cholinesterases. The fact that the dog is much more sensitive than man would then be explained by the finding of a six to eight times lower true cholinesterase concentration in the red cells. Similarly, the fact that the sensitivity of the dog can be lowered to levels seen in man by raising the pseudocholinesterase level of the plasma can be understood on the bases of these considerations. We have assumed that the two esterases in man and dog are the same enzymes, and that the differences in activity of blood and plasma are due to different enzyme concentrations. It is, of course, possible that there are species variations and that the affinities rather than the concentrations are different. However, the interplay between compounds and enzymes would have the same outcome whether the enzymes differ in concentration or in affinity. Apart from theories, our findings have two practical consequences: the absence of side-reactions in the dog when given human cholinesterase preparations justifies its trial in man in cases of succinylcholine sensitivity. The use of the enzyme will be of advantage in veterinary medicine, as it will convert succinylcholine and suxethonium from comparatively long-time relaxants into compounds acting for a few minutes only, thus bringing into the surgery of the dog the advantages found in the use of succinylcholine and suxethonium in man. Summary Dogs are more sensitive to suxethonium and succinylcholine than man. When injected with doses about o...

The Pseudocholinesterase Variants. Esterase Levels and Dibucaine Numbers in Families Selected Through Suxamethonium Sensitive Individuals

“…O ccasional in d iv id u als how ever w hen given th e d ru g in its u su al dose show a m uch m ore prolonged response. Such people w ere fo u n d to h av e low er levels o f pseudocholinesterase a c tiv ity th a n w ere fo u n d in m o st o th e r people (B ourne, Collier and Somers 1952;E va ns, G ray, L ehm ann a nd S ilk 1952, 1953, a n d L ehm ann and R y a n (1956) observ ed t h a t low pseudoch o lin esterase levels m ig h t also be found am o n g som e o f th e ir im m e d ia te re la tiv es who w ere otherw ise h e a lth y . F a m ily stu d ie s (Lehm ann and R y a n 1956; Lehm ann and S im m o n s 1958; K a u fm a n , L ehm ann and S ilk 1960), led to th e hy p o th esis th a t su x a m e th o n iu m sen sitiv e in d iv id u als w ith low pseudocholinesterase a c tiv ity were hom ozygous for an unco m m o n gene, w hich in h eterozygotes also re su lte d in a d epression o f pseu d o ch o lin esterase levels b u t to a lesser degree.…”

Suxamethonium Sensitivity in Health and Disease

“…Bourne (1953) suggested that the dose should be regulated by body weight, citing the work of Thesleff (1952), and thought that in " frail " patients this dose should be reduced. Evans et al (1952b) demonstrated an inverse relationship between this Ps.ChE. level and the duration of action of the relaxant, and later the same authors (1953) found that injections of a purified Ps.ChE.…”

“…It has been established that the drug is hydrolysed by serum pseudo-cholinesterase (Ps.ChE. ), and Bourne et al (1952), Evans et al (1952a), andBourne (1953) found low Ps.ChE. levels in the sera of patients showing delayed recovery.…”

Prolonged duration of apnoea due to succinylcholine

“…Evans et al (17) are qmte definite that the low serum cholinesterase level is enough to explain the prolonged recovery time They, and Bourne, Somers ard Collier (16) between them have had eight cases ot somewhat prolonged apn0eas and in eadh one the serum cholinesterase was low. Lehmann (18) goes so far as to state that "to produce dramatic delay in recovery the enzyme level must obviously be ~ery low."…”