Automatic control of neuromuscular blockade with atracurium

MacLeod, Alexander Daniel (1988) Automatic control of neuromuscular blockade with atracurium. MSc(R) thesis, University of Glasgow.

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The objective of this work was to develop a robust feedback system to control atracurium-induced neuromuscular blockade. The controller ideally should be usable in many circumstances and should provide a steady background blockade to allow investigation of drug interactions and physiological changes. A particular design constraint was that the system should not cause any delays in the running of a normal theatre list. Several groups have studied the automatic control of neuromuscular blockade with other relaxants. Atracurium seemed to be a suitable drug to use because of its relatively short duration of action, its non mulative properties and its relatively narrow dosage range. In the development of the control system four step tests were undertaken from which proportional and integral gains were derived. Then, trial runs with proportional (P) and proportional-integral (PI) controllers were evaluated and the solution to the problems discovered with these methods was to preload the integral. A series of 36 patients was analysed whose neuromuscular blockade was maintained by the PI controller with preloaded integral. The results from these patients showed that a steady level of neuromuscular blockade, which was close to a predetermined target of 20% baseline T1 , could be obtained with this system. In no case did the level of blockade oscillate, indicating that the control system was robust - the doses required to maintain constant blockade ranged from 2.7 mug kg -1min -1 to 8.6 mug kg-1min-1 with a mean of 5.4 mug kg-1 min-1. Use of the system did not lead to any significant delays in the running of lists. Blockade control was sufficiently precise and accurate to provide a background for the analysis of the effects of potential physiological and pharmacological perturbations to the system. Such studies should provide further information on the pharmacology of atracurium. This work describes the largest series of patients to have undergone automatic control of neuromuscular blockade with atracurium. The quality of the blockade in our work was superior to previous work both in terms of stability and closeness to target. Previous work on the possible potentiation of atracurium by propofol has produced conflicting results. In our work, long cases involving minimal physiological upset were selected to provide a stable blockade for the analysis of the effect of a bolus of propofol on the system. It was concluded that propofol had no clinically significant effect on atracurium. The final group of patients investigated were undergoing coronary artery vein grafting. Automatic control systems for neuromuscular blockade have not previously been used in cardiac surgery. Cardiac patients were selected for a number of reasons. Firstly, the start of cardiopulmonary bypass (with its associated hypothermia and haemodilution) would provide a challenging test to the robustness of the system. Could this, for example, induce sustained oscillation in the control system? Secondly, we wished to see the specific effects of haemodilution and hypothermia on the level of block. If steady blockade could be achieved at different stages of the operation the atracurium requirement could be compared. The controller was able to provide satisfactory relaxation in all cases. It was generally possible to separate the effects of haemodilution and hypothermia. We concluded that haemodilution attenuated, while hypothermia potentiated, neuromuscular blockade induced by atracurium. It was possible to show that the atracurium requirement was unchanged in the postbypass stage compared with the prebypass stage. This conclusion differed from previous studies in which a force transducer was used rather than the electromyogram. In summary, a feedback control system for atracurium has been developed, tested and used to investigate the effect of propofol on atracurium and the effects of cardiopulmonary bypass on a steady state neuromuscular blockade.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Keywords: Medicine, Pharmacology
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-76699
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 13:52
Last Modified: 19 Nov 2019 13:52

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