Be sure that each search option that presents itself is reasonably evaluated, pursued if necessary, and documented. A documented history of the search for a copyright holder will establish that a good-faith effort was made, and minimize any potential repercussions. List each step taken and source consulted. Date and record the results for each. If a search step involves correspondence, keep copies of all messages written and replies received.
If, after due diligence, the current copyright holder cannot be determined or contacted, you may wish to re-evaluate your use of the work under Fair Use. Lack of an obvious rightsholder sometimes correlates strongly with a lack of a market for the work and/or lack of a mechanism for licensing the material, each of which will enhance a Fair Use argument.