Neurologically Intact Survival Following Prolonged Cardiac Arrest Monitored With Continuous Capnography and Subsequent Treatment With Therapeutic Hypothermia

Background: Despite advances in out- of- hospital resuscitation practices, the prognosis of most patients after a cardiac arrest remains poor. The long term outcomes of patients successfully resuscitated from cardiac arrest are often complicated by neurological dysfunction. Therapeutic hypothermia has significantly improved neurological outcomes in patients successfully resuscitated from out- of- hospital cardiac arrests. The objective of this study was to look into the neurological outcomes in inpatients after successful cardiopulmonary resuscitation (CPR) in a university hospital setting. Methods: This was a retrospective observational study of 68 adult patients who experienced cardiac or respiratory arrest over an 18 month period at a metropolitan teaching hospital with dedicated, trained code teams. Arrests that occurred in the Emergency Department, Critical Care Units or Operating Rooms were excluded. Results: Of the 68 consecutive patients included in this study, 53% were resuscitated successfully. However, only 12 (18%) survived to discharge from the hospital and only 6 (10%) were discharged with intact neurological status. The initial survival was better in patients who received prompt CPR and in those with less co - morbidities. Pulseless electrical activity (PEA) or asystole were the most common rhythms (47% of the arrests). Most patients who survived and were neurologically intact had PEA (67%). We believe that most PEA arrests were more likely severe hypotension with the inability to palpate a pulse rather than true PEA. The mean time to defibrillation for all patients with an initial shockable rhythm (n=5) was 8.2 minutes. Patients who had an initial shockable rhythm and survived to discharge were shocked within 1 minute (n=2). Conclusion: Despite advances in critical care, survival from inpatient cardiopulmonary arrest to neurologically intact discharge remains poor. Therapeutic hypothermia should be expanded to those resuscitated from in - hospital cardiopulmonary arrest to determine if neurological outcomes would improve.

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Abstract 11243: Novel Peptide for Cardiopulmonary Resuscitation

Circulation ◽

10.1161/circ.144.suppl_2.11243 ◽

2021 ◽

Vol 144 (Suppl_2) ◽

Author(s):

Jing Li ◽

Xiangdong Zhu ◽

Matt Oberdier ◽

Chunpei Lee ◽

Misha Granado ◽

...

Keyword(s):

Cardiac Arrest ◽

Therapeutic Hypothermia ◽

Protective Effects ◽

Ph Domain ◽

Biologic Treatment ◽

Hospital Arrival ◽

Shockable Rhythm ◽

Arterial Blood ◽

Atp Generation ◽

Neurologically Intact

Introduction: While effective for out-of-hospital cardiac arrest, therapeutic hypothermia can be difficult to timely implement clinically. No drugs exist for improving neurologically intact survival. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP), leading to Akt activation and mimicking of the protective effects of therapeutic hypothermia without the need of physical cooling. Hypothesis: We hypothesize that when administered intravenously during CPR, TAT-PHLPP improves neurologically intact survival. Methods: We conducted parallel studies in mouse and swine models. In C57BL6 mice (n = 72), we induced a 8 or 12-min asystolic cardiac arrest with KCl, followed by initiation of CPR and blinded randomized administration of TAT-PHLPP (7.5 mg/kg) or saline placebo. The primary outcomes were 4-h and 5-day survival, mean arterial blood pressure (MAP) and cerebral blood flow (CBF). We assessed PHLPP-NHERF1 binding and glucose utilization (via pyruvate dehydrogenase (PDH) phosphorylation and ATP generation). In 16 swine, we induced 5 min of VF followed by ACLS with vest CPR and administered two doses of TAT-PHLPP or saline. Survival (24 h) and neurological function were assessed. Plasma biomarkers taurine and glutamate levels in mice were measured and validated in CA patients (n=68) with a shockable rhythm at the time of hospital arrival, 6, 24, 48, and 72 h post-hospital arrival. Results: In mice, compared to saline, TAT-PHLPP significantly improved 4-h and 5-day survival, increased post-ROSC MAP and CBF, inhibited PHLPP-NHERF1 binding, increased p-Akt, decreased p-PDH (increased activity) at 15 min post-ROSC, enhanced ATP generation in both heart and brain, and reduced plasma taurine and glutamate levels. In swine, TAT-PHLPP improved 24 h neurologically intact survival (1/9 in control vs. 6/7 with peptide, p < 0.01). In patients, taurine levels were higher in non-survivors (n=44) than survivors (n=24) at 6 h of post-hospital arrival (65.9 ± 34.8 vs. 45.6 ±23.7, p< 0.001). Conclusions: TAT-PHLPP has high translational potential as a first-of-class biologic treatment to reproduce critical outcomes of therapeutic hypothermia and improve cardiac arrest survival.

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