Background and Purpose —Recent animal studies showed that mild resuscitative hypothermia improves neurological outcome when applied after cardiac arrest. In a 3-year randomized, prospective, multicenter clinical trial, we hypothesized that mild resuscitative cerebral hypothermia (32°C to 34°C core temperature) would improve neurological outcome after cardiac arrest. Methods —We lowered patients’ temperature after admission to the emergency department and continued cooling for at least 24 hours after arrest in conjunction with advanced cardiac life support. The cooling technique chosen was external head and total body cooling with a cooling device in conjunction with a blanket and a mattress. Infrared tympanic thermometry was monitored before a central pulmonary artery thermistor probe was inserted. Results —In 27 patients (age 58 [interquartile range [IQR] 52 to 64] years; 7 women; estimated “no-flow” duration 6 [IQR 1 to 11] minutes and “low-flow” duration 15 [IQR 9 to 23] minutes; admitted to the emergency department 36 [IQR 24 to 43] minutes after return of spontaneous circulation), we could initiate cooling within 62 (IQR 41 to 75) minutes and achieve a pulmonary artery temperature of 33±1°C 287 (IQR 42 to 401) minutes after cardiac arrest. During 24 hours of mild resuscitative hypothermia, no major complications occurred. Passive rewarming >35°C was accomplished within 7 hours. Conclusions —Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states.

Introduction: Our purpose was to study whether the time to target temperature correlates with neurologic outcome in patients after cardiac arrest with restoration of spontaneous circulation treated with therapeutic mild hypothermia in an academic emergency department. Methods: Temperature data between April 1995 and June 2008 were collected from 588 patients and analyzed in a retrospective cohort study by observers blinded to outcome. The time needed to achieve an esophageal temperature of less than 34°C was recorded. Survival and neurological outcomes were determined within six months after cardiac arrest. Results: The median time from restoration of spontaneous circulation to reaching a temperature of less than 34°C was 209 minutes (interquartile range [IQR]: 130-302) in patients with favorable neurological outcomes compared to 158 min (IQR: 101-230) (P < 0.01) in patients with unfavorable neurological outcomes. The adjusted odds ratio for a favorable neurological outcome with a longer time to target temperature was 1.86 (95% CI 1.03 to 3.38, P = 0.04). Conclusions: In comatose cardiac arrest patients treated with therapeutic hypothermia after return of spontaneous circulation, a faster decline in body temperature to the 34°C target appears to predict an unfavorable neurologic outcome.

Background and Purpose —The prediction of neurological outcome in comatose cardiac arrest survivors has enormous ethical and socioeconomic implications. The purpose of the present study was to investigate the prognostic relevance of the time course of serum neuron-specific enolase (NSE) as a biochemical marker of hypoxic brain damage. Methods —Serial analysis of serum NSE levels was performed in 56 patients resuscitated from witnessed, nontraumatic, normothermic, in- or out-of-hospital cardiac arrest. The neurological outcome was evaluated with the use of the cerebral performance category (CPC) within 6 months after restoration of spontaneous circulation (ROSC). The Mann-Whitney U test was used to compare patients with good (CPC 1 to 2) and bad (CPC 3 to 4) neurological outcome. The diagnostic performance at different time points after ROSC was described in terms of areas under receiver operating characteristic curves according to standard methods. Results —Patients with a bad neurological outcome (CPC 3 to 4) had significantly higher NSE levels than those with a good neurological outcome at 12 ( P =0.004), 24 ( P =0.04), 48 ( P <0.001), and 72 hours ( P <0.001) after ROSC. The maximum NSE level measured within 72 hours after ROSC was also significantly higher in patients with a bad neurological outcome ( P <0.001). The NSE value at 72 hours after ROSC was the best predictor of neurological outcome (area under the curve=0.92±0.04). In addition, we also found a significant difference in the time course of NSE concentrations during the first 3 days after ROSC. Conclusions —Serum NSE levels are valuable adjunctive parameters for assessing neurological outcome after cardiac arrest.

Permanent brain damage after cardiac arrest and resuscitation is determined by many factors, predominantly arrest (no-flow) time, cardiopulmonary resuscitation (low-flow) time, and temperature. Research since around 1970 into cardiopulmonary-cerebral resuscitation has attempted to mitigate the postischemic-anoxic encephalopathy. These efforts’ results have recently shown outcome benefits as documented in clinically relevant outcome models in dogs and in clinical trials. Pharmacologic strategies have so far yielded relatively disappointing results. In a recent exploration of 14 drugs in dogs, only the antioxidant tempol administered at the start of prolonged cardiac arrest improved functional outcome in dogs. Cerebral blood flow promotion by hypertensive reperfusion and hemodilution has resulted in improved outcome in dogs, and brief hypertension after restoration of spontaneous circulation is associated with improved outcome in patients. Postarrest hypercoagulability of blood seems to yield to therapeutic thrombolysis, which is associated with improved cerebral outcome in animals and patients. In a clinically relevant dog outcome model, mild postarrest cerebral hypothermia (34°C), initiated with reperfusion and continued for 12 hrs, combined with cerebral blood-flow promotion increased from 5 to >10 mins the previously longest normothermic no-flow time that could be reversed to complete cerebral recovery. Mild hypothermia by surface cooling after prolonged cardiac arrest in patients has been found effective in recent clinical studies in Australia and Europe. Preliminary data on the recent randomized study in Europe have been reported. For presently unresuscitable cardiac arrests, research since the 1980s in dog outcome models of prolonged exsanguination cardiac arrest has culminated in brain and organism preservation during cardiac arrest (no-flow) durations of up to 90 mins, perhaps 120 mins, at a tympanic temperature of 10°C and complete recovery of function and normal histology. This “suspended animation for delayed resuscitation” strategy includes use of an aortic flush of cold saline (or preservation solution) within the first 5 mins of no flow. This strategy should also be explored for the larger number of patients with unresuscitable out-of-hospital cardiac arrests. Suspended animation for prolonged preservation of viability could buy time for transport and repair during hypothermic no flow followed by resuscitation, or it could serve as a bridge to prolonged cardiopulmonary bypass.

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. Prospective experimental comparison of three arrest times, without randomization. University research laboratory. Twenty-seven custom-bred hunting dogs (17-25 kg). 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 degrees C (at a rate of 1 L/min), until tympanic temperature reached 20 degrees C (for 60 mins of cardiac arrest), 15 degrees C (for 60 mins of cardiac arrest), or 10 degrees C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs. We assessed overall performance categories (OPC 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 degrees C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0-27%); and median total HDS, 28 (range, 4-36). Tympanic temperature of 15 degrees C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0-3%), and HDS 8 (0-48). Tympanic temperature 10 degrees C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2-18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10 degrees C was achieved after flush of 15 mins and resulted in all six dogs with OPC 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 degrees C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22. In a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10 degrees 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.