Thank you very much for your helpful reply!
It is possible that one of the application servers is still attempting to process an update of the client variable while the next application server has already received the "next" request and then uses a cached value instead of the updated value. This would indicate a load issue on our application servers. The serialization and deserialization of the 150 client variables may be a factor. However as you pointed out, the database could be committing much later (or responding much slower) than expected under certain conditions while the application servers are running normally. The client variables are stored in it's own database but is on the same database server as our main database.
That's interesting of you to mention that all the changed client variables are "flushed" to the database at the end of the request. But just to clarify, are they "flushed" out of memory (and to the database) and on all the application servers at the same time? Thereby removing any outdated cached values on the other servers and hence, requiring the servers to retrieve the updated value from the database. Alternately once the database commits, only then would ColdFusion update client variables on the rest of the application servers regardless if whether or not there was a cached value already in memory?
The global variable updates are disable on all our 6 (CF9) production servers for performance reasons. We have this enabled on our testing site which has 3 (CF9) servers but intermittent occurrences are still happening and even at a much higher rate.
Additionally ....
The setDomainCookies attribute in the CFApplication tag is "no". This setting has always been the same since the legacy application was written over 10 years ago. However, Adobe's documentation does indicate that "yes" is require for clustered environments. We are in the middle of creating a simple test page to further analyzed how the Cookie.CFID and Cookie.CFTOKEN values are shared between the application servers as well as looking further into a caching problem by using the test page.