Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia

Objectives: This study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60-120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest. Design: Prospective experimental comparison of three arrest times, without randomization. Setting: University research laboratory. Subjects: Twenty-seven custom-bred hunting dogs (17-25 kg). Interventions: Dogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2°C (at a rate of 1 L/min), until tympanic temperature reached 20°C (for 60 mins of cardiac arrest), 15°C (for 60 mins of cardiac arrest), or 10°C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34°C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs. Measurements and Main Results: We assessed overall performance categories (0PC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0-40, mild; 40-100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20°C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with 0PC 1 and four dogs with 0PC 2: median NDS, 13% (range 0-27%); and median total HDS, 28 (range, 4-36). Tympanic temperature of 15°C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with 0PC 1, NDS 0% (0-3%), and HDS 8 (0-48). Tympanic temperature 10°C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with 0PC 1, NDS 0%, and HDS 16 (2-18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10°C was achieved after flush of 15 mins and resulted in all six dogs with 0PC 1, NDS 0%, and HDS 8 (0-37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10°C was achieved after flush of 15 mins. This resulted in one dog with 0PC 1, NDS 0%, and total HDS 14; one with 0PC 1, NDS 6%, and total HDS 20; one with 0PC 2, NDS 13%, and total HDS 10; and one with 0PC 3, NDS 39%, and total HDS 22. Conclusions: In a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10°C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest - which rarely can be resuscitated effectively with current methods - can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.