When facing the potential departure of key project team members, a project manager should first evaluate the situation's impact on the project's scope, schedule, cost, and quality. The next step is to refer to the project management plan, which should include a risk management plan with predefined mitigation strategies for such scenarios. Implementing these mitigations will help to manage the changes effectively and keep the project on track.
References: The response is based on general project management principles as outlined in the PMBOK Guide and the standard practices of risk and change management that are part of the PMP's body of knowledge.