The objective of this study is to determine whether protocol guided resuscitation of brain dead organ donors using Pulse Pressure Variation (PPV) will increase the number of organs transplanted per donor.

Specifically the study aims to:

1. improve resuscitation of potential organ donors.
2. improve organ function in donors.
3. increase organ recovery per donor.

The investigators will randomize 960 subjects to either protocolized resuscitation (n=480) using a consensus-based PPV-guided algorithm or usual care using a 1:1 randomization scheme. The primary outcome is the mean number of organs transplanted per donor. Secondary outcomes include 6mHFS (six-month hospital-free survival) in the recipients, and mean number of organs procured per donor that are suitable for transplantation (intention to transplant). The study is powered to detect a 0.5 organ increase for transplantation per donor.

Inclusion Criteria:

• Donors who were declared brain dead per local hospital brain death criteria.
• Donors who are deemed suitable for organ donation by the local OPO whether they meet the standard criteria or the extended criteria for donation.
• Presence of functioning arterial catheter.

Exclusion criteria:

• Inability to obtain informed consent from donor next of kin or legal representative.
• Donors less than 16 years of age, no maximum age limit.
• Inability to perform hemodynamic monitoring.
• Patients on lithium therapy prior to brain death.
• Known severe aortic regurgitation, intra-cardiac shunts, or on intra-aortic balloon pump.
• Donors previously enrolled in experimental protocol in which cytokines are the therapeutic targets (e.g. anti-TNF antibodies).
• Donors receiving chemotherapy or with any disease state (e.g. AIDS) that renders the subject leukopenic (WBC count < 2).
• Donors receiving anti-leukocyte drugs (e.g. OKT3) regardless of their WBC counts.
• Pregnant donors.
• Donor is on ECMO machine