I find the need for immediate disbursement to be illusory. I for one would be more comfortable with a business that only allowed me to withdraw a trivial amount immediately, and required cursory manual review for larger amounts. I would not be bothered by having to wait 6 hours to withdraw 43000 BTC (hypothetical I suppose, since I'm not withdrawing like that with any regularity), but would expect that I could immediately withdraw (for example) 43 BTC just in case I wanted to make a payment with my account.
I think 43000 BTC is simply too much to have on a hot wallet.
I have no idea what Bitcoinica volumes are like but it surely seems like far too much. I think a better way to handle it would be a priority queueing mechanism. Small amounts could be disbursed immediately from the hot wallet, larger amounts could trigger replenishment and really wacky amounts could just be relayed for manual auditing. Combine this with automated replenishment of the hot wallet at suitable intervals. Also, it would be easy to modify the trigger levels based on hot wallet balance to keep flows steady.
One mechanism for this is pre-canned offline transactions that are submitted at intervals from another system. They can't be modified after creation and I think there is even a mechanism for post-dating. A script on the offline system could be used to generate a number of them for some reasonable time period so you aren't bothered with manual intervention unless the expected overall volume increases substantially. This would be quite simple to setup.
Well, there's likely all sorts of ways to secure things but the first step is realizing that out-of-the-box use isn't adequate for online high value wallets.