Improving the accuracy of determination of onset of neuromuscular block

The speed of onset of muscle relaxation is an intrinsic property of
neuromuscular blocking agents (NMBA). It is an important factor in choosing
the appropriate NMBA for certain clinical conditions, especially when a rapid
onset of action is desired. Physiological process such as perfusion,
blood-mixing, receptor affinity and protein binding are thought to play a role
in determining the speed of onset of NMBA drug effect, however the nature of
the influence of these mechanisms on the observed onset of muscle relaxation is
not well understood. The design of new NMBAs and drug application methods
would also benefit from a better understanding of the physiological mechanisms
of drug onset.

If we wish to study the effect of rapid onset NMBAs we must obtain a number of
neuromuscular monitoring measurements observations during the development of
onset of neuromuscular block. Standard clinical neuromuscular monitoring
practice is insufficient to study rapid drug onset because it utilizes
low-frequency repetitive stimulation patterns, typically 0.1 Hz single twitch
(ST) or 0.067 Hz train-of-four (TOF) to determine muscle strength and estimate
the degree of neuromuscular block. With these low-frequency stimulation
patterns, stimulation intervals are long enough for twitch strength to change
significantly between stimulations. In the case of a rapid onset of drug
effect, only very limited number of twitches can be observed during onset. It
follows that the information content of the twitch responses during onset is
limited and estimations of speed of onset of muscle relaxation must have
considerable uncertainty. In short, our ability to study the time course of
muscle relaxation, especially during rapid onset, is limited by the stimulation
frequency of neuromuscular monitoring.

Neuromuscular monitoring using medium-frequency stimulation pattern, for
example 1 Hz ST, provides considerably more twitch response information that
standard neuromuscular monitoring practice because the stimulus internal is
smaller. This potentially allows more certain and accurate observation of drug
effect onset.

The primary objective of the study is to determine if twitch response following
rocuronium administration evoked by 1 Hz ST neuromuscular monitoring can be
modeled to a similar degree of accuracy as previously published studies
describe for 0.1 Hz (ST) or 0.067 Hz (TOF) stimulation frequency, a prediction
accuracy of about 2%-5% of baseline response. The secondary objective is to
determine if estimated rocuronium onset characteristics during 1 Hz ST
neuromuscular monitoring are significantly different than previously published
data.

The study will be an observational study of clinical patient twitch response
data.

Patients are likely to receive intermittent neuromuscular stimulation as a part
of standard neuromuscular monitoring. The devices used for the study will be
standard clinical neuromuscular monitoring devices (TOF- Watch SX), registered
for routine clinical use. Patients will be under general anesthesia during the
entire period of neuromuscular monitoring and will experience no physical or
psychological discomfort from the study. The risks associated with 1 Hz
neuromuscular stimulation are widely thought to be nihil, this method has been
applied in other studies of neuromuscular function. The subject will receive
no benefit from taking part in the study.

No blood samples will be taken, no patient questionnaires or diaries will be
collected, and no physical examinations or site visits will take place. During
the course of the investigation no information relevant to individual patient
treatment will become available as a result of the performance of the study.

The study results concern patients undergoing surgical procedures and should
therefore be performed on such patients. The study will not be performed on
minors or incapacitated persons.