Tuesday, December 29, 2015

Lazarus Phenomenon: Back from the Dead (a.k.a. The 'Real' Walking Dead)

What the Lazarus?!

  • Lazarus Phenomenon a.k.a. Lazarus Syndrome is not to be mistaken for Lazarus Sign or the terrible film Lazarus Effect.
  • It is defined as the delayed Return of Spontaneous Circulation (ROSC) after stopping resuscitative efforts. Usually ROSC in Lazarus Phenomenon occurs within 10 minutes of cessation of CPR. 
  • While it was first documented in 1982, and is considered to be rare, it is also considered to be underreported.

Case History:

  • A geriatric patient with history significant for C2 Odontoid Fracture with quadriplegia, recurrent VRE positive UTIs with Sepsis, and ESRD on hemodialysis who was obtunded on admission. The patient was noted to have a potassium level over five on admission that was persistent, despite HD.
  • On the day of the code, her K+ level was 6.0 prior to temporizing measures. Once the code was called, it was run for 25 minutes with 6 rounds of epinephrine, 2g CaCl, 2g NaHCO3, and 450mg MgSO4 being delivered over that time, as well as several shocks for Ventricular Fibrillation. The patient was simultaneously intubated. At that point, a decision was made with the family present, including the POA, to discontinue ACLS and CPR and allow the family to enter the room and grieve.
  • Monitors were shut off approximately 2 minutes after calling the code with only PEA and no pulses or respirations on palpation, doppler, or auscultation and absent brainstem reflexes. After approximately 10 minutes, the family reported a sudden, spontaneous breath.
  • Upon re-entering the room, the patient was exhibiting agonal breathing with a strong carotid pulse. Bedside US by the MICU attending was performed and EF was 50%, so the patient The MICU was contacted and the patient was transferred.

Proposed mechanism:

  • AUTO-PEEP (Who?!) ... Auto-PEEP, man ... - The proposed mechanism (with some room for hand waving and jiggery-pokery) is the buildup of intrathoracic pressure, particularly in COPD patients, that can result in pericardial tamponade. This can happen acutely during CPR when there is rapid ventilation of the lungs without adequate time for exhalation. Chest compressions are meant to compress the heart and have the simultaneous effect of increasing intrathoracic pressure, but that effect is intended to be transient, as the "recoil" between compressions is essential time for the ventricle chambers to refill with blood to be pumped out during the next compression.
  • The combination of chest compressions and Auto-PEEP could be the key factor where there is too much intrathoracic pressure buildup for the heart to refill between beats and thus to get adequate blood out on it's own to perfuse the body.
  • There's also the matter of chest wall elasticity itself, and as long as we're postulating, patients with decreased chest wall elasticity would also be prone to retaining intrathoracic pressure buildup between beats, further promoting tamponade and preventing ROSC.
  • In such cases, time to allow the auto-PEEP and built-up external pressure from CPR to resolve could be the key to delayed ROSC.

Other proposed mechanisms:

  • Hyperkalemia - It is thought to leave the heart retractile for a longer period of time and potentiate the peripheral blood vessels to continue moving blood slowly in the absence of a heart beat.
  • Delayed effects of drugs - In patients with drugs delivered through a peripheral IV (rather than a central line), the combination of impaired venous return from dynamic hyperinflation (see Auto-PEEP above) and local vasoconstriction caused by drugs such as Epinephrine, could delay delivery of these medications to the central circulation and cardiac vasculature
  • Myocardial Ischemia with "Stunning" - Caused by Hypovolemia.
  • Transient Asystole - Transient period of asystole or PEA after a defibrillatory shock of Ventricular Fibrillation uses up more ATP in myocardial cells than primary asystole or PEA, requiring more oxygen or leading to more lactic acid buildup to replenish these stores.
  • Pseudo-PEA - Heart beats cause too weak a pulse to palpate. This problem can be solved with doppler or bedside echocardiography. In our case, doppler was unable to reveal a pulse in multiple sites.

Why it fits our case?

  • Auto-PEEP - For reasons described above ...
  • 25 minute code! - The average time of the documented cases was 27 minutes of CPR
  • Hyperkalemia - While there are many hyperkalemic patients with ESRD who code, the constellation of factors seemed to be in her favor.
  • Delayed effects of drugs - The patient did not have a CVC in place until after being moved to the MICU.
  • Delayed ROSC - The mean time for ROSC in these cases was noted to be ~7-8 minutes, while it took ~10 minutes in our case. The true time of ROSC could have been anywhere between 2-10 minutes, as leads were disconnected ~2 minutes after recorded time of death, though the first observed breath was at approximately 10 minutes.

What's next?

  • Global Hypoxia/Anoxic Brain Injury! While the patient has ROSC, she's had no blood flow to her cerebral vasculature (or any peripheral vasculature or her heart and lungs, for that matter).
  • She was noted to have "extensive ischemic change" on CT, as well as similar findings on MRI. While her neurological function was limited to begin with, she lost brainstem reflexes and evidence of consciousness. She withdrew to noxious stimuli, but was never arousable. Her EEG by Neurology also showed electrocerebral inactivity indicating that much of the patient's cortical function was lost.
  • This fits the course described by the primary literature, where only 35% of patients with delayed ROSC have been able to return home neurologically intact.

Dessert (for Harsha):

  • Most things in medicine, and science in general, are named after ourselves, people we love, people we hate, the classics, and religious texts.
  • This disorder has it's name rooted in a major biblical reference to the resurrection (i.e. ROSC) of Lazarus of Bethany by Jesus Christ four days after his death and burial, described in the Gospel of John.

1 comment:

  1. Amazing case! Science is fascinating.
    Too cool to be real.
    Thank you for sharing!