永山正雄．COVID-19の神経障害と救急外来・ER・ICUでの対応．BRAIN and NERVE. 2020; 72: 1067-1072.
Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators.
Targeted temperature management at 33°C versus 36°C after cardiac arrest.
N Engl J Med. 2013 Dec 5;369(23):2197-206. doi: 10.1056/NEJMoa1310519. Epub 2013 Nov 17.
Abstract/Text
BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.
METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.
RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.
CONCLUSIONS: In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).
日本蘇生協議会監修：第2章 成人の二次救命処置. JRC蘇生ガイドライン2020．pp48-150、医学書院、2021.
Morrison LJ, Deakin CD, Morley PT, Callaway CW, Kerber RE, Kronick SL, Lavonas EJ, Link MS, Neumar RW, Otto CW, Parr M, Shuster M, Sunde K, Peberdy MA, Tang W, Hoek TL, Böttiger BW, Drajer S, Lim SH, Nolan JP; Advanced Life Support Chapter Collaborators.
Part 8: Advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.
Circulation. 2010 Oct 19;122(16 Suppl 2):S345-421. doi: 10.1161/CIRCULATIONAHA.110.971051.
Abstract/Text
Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL; American Heart Association.
Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Circulation. 2010 Nov 2;122(18 Suppl 3):S768-86. doi: 10.1161/CIRCULATIONAHA.110.971002.
Abstract/Text
The goal of immediate post-cardiac arrest care is to optimize systemic perfusion, restore metabolic homeostasis, and support organ system function to increase the likelihood of intact neurological survival. The post-cardiac arrest period is often marked by hemodynamic instability as well as metabolic abnormalities. Support and treatment of acute myocardial dysfunction and acute myocardial ischemia can increase the probability of survival. Interventions to reduce secondary brain injury, such as therapeutic hypothermia, can improve survival and neurological recovery. Every organ system is at risk during this period, and patients are at risk of developing multiorgan dysfunction. The comprehensive treatment of diverse problems after cardiac arrest involves multidisciplinary aspects of critical care, cardiology, and neurology. For this reason, it is important to admit patients to appropriate critical-care units with a prospective plan of care to anticipate, monitor, and treat each of these diverse problems. It is also important to appreciate the relative strengths and weaknesses of different tools for estimating the prognosis of patients after cardiac arrest.
日本蘇生協議会監修：第2章 心拍再開後の集中治療. JRC蘇生ガイドライン2020．pp111-134、医学書院．2021.
Bernard S.
Hypothermia after cardiac arrest: expanding the therapeutic scope.
Crit Care Med. 2009 Jul;37(7 Suppl):S227-33. doi: 10.1097/CCM.0b013e3181aa5d0c.
Abstract/Text
Therapeutic hypothermia for 12 to 24 hrs following resuscitation from out-of-hospital cardiac arrest is now recommended by the American Heart Association for the treatment of neurological injury when the initial cardiac rhythm is ventricular fibrillation. However, the role of therapeutic hypothermia is uncertain when the initial cardiac rhythm is asystole or pulseless electrical activity, or when the cardiac arrest is primarily due to a noncardiac cause, such as asphyxia or drug overdose. Given that survival rate in these latter conditions is very low, it is unlikely that clinical trials will be undertaken to test the efficacy of therapeutic hypothermia in this setting because of the very large sample size that would be required to detect a significant difference in outcomes. Therefore, in patients with anoxic brain injury after nonventricular fibrillation cardiac arrest, clinicians will need to balance the possible benefit of therapeutic hypothermia with the possible side effects of this therapy. Given that the side effects of therapeutic hypothermia are generally easily managed in the critical care setting, and there is benefit for anoxic brain injury demonstrated in laboratory studies, consideration may be given to treat comatose post-cardiac arrest patients with therapeutic hypothermia in this setting. Because the induction of therapeutic hypothermia has become more feasible with the development of simple intravenous cooling techniques and specialized equipment for improved temperature control in the critical care unit, it is expected that therapeutic hypothermia will become more widely used in the management of anoxic neurological injury whatever the presenting cardiac rhythm.
Oddo M, Ribordy V, Feihl F, Rossetti AO, Schaller MD, Chioléro R, Liaudet L.
Early predictors of outcome in comatose survivors of ventricular fibrillation and non-ventricular fibrillation cardiac arrest treated with hypothermia: a prospective study.
Crit Care Med. 2008 Aug;36(8):2296-301. doi: 10.1097/CCM.0b013e3181802599.
Abstract/Text
OBJECTIVES: Current indications for therapeutic hypothermia (TH) are restricted to comatose patients with cardiac arrest (CA) due to ventricular fibrillation (VF) and without circulatory shock. Additional studies are needed to evaluate the benefit of this treatment in more heterogeneous groups of patients, including those with non-VF rhythms and/or shock and to identify early predictors of outcome in this setting.
DESIGN: Prospective study, from December 2004 to October 2006.
SETTING: 32-bed medico-surgical intensive care unit, university hospital.
PATIENTS: Comatose patients with out-of-hospital CA.
INTERVENTIONS: TH to 33 +/- 1 degrees C (external cooling, 24 hrs) was administered to patients resuscitated from CA due to VF and non-VF (including asystole or pulseless electrical activity), independently from the presence of shock.
MEASUREMENTS AND MAIN RESULTS: We hypothesized that simple clinical criteria available on hospital admission (initial arrest rhythm, duration of CA, and presence of shock) might help to identify patients who eventually survive and might most benefit from TH. For this purpose, outcome was related to these predefined variables. Seventy-four patients (VF 38, non-VF 36) were included; 46% had circulatory shock. Median duration of CA (time from collapse to return of spontaneous circulation [ROSC]) was 25 mins. Overall survival was 39.2%. However, only 3.1% of patients with time to ROSC > 25 mins survived, as compared to 65.7% with time to ROSC < or = 25 mins. Using a logistic regression analysis, time from collapse to ROSC, but not initial arrest rhythm or presence of shock, independently predicted survival at hospital discharge.
CONCLUSIONS: Time from collapse to ROSC is strongly associated with outcome following VF and non-VF cardiac arrest treated with therapeutic hypothermia and could therefore be helpful to identify patients who benefit most from active induced cooling.
Sakurai A, Kinoshita K, Moriya T, Utagawa A, Ebihara T, Furukawa M, Tanjoh K.
Reduced effectiveness of hypothermia in patients lacking the wave V in auditory brainstem responses immediately following resuscitation from cardiac arrest.
Resuscitation. 2006 Jul;70(1):52-8. doi: 10.1016/j.resuscitation.2005.10.026.
Abstract/Text
AIMS: Therapeutic hypothermia appears to improve the outcome of pre-hospital cardio-pulmonary arrest (CPA) in patients with an initial cardiac rhythm of ventricular fibrillation or nonperfusing ventricular tachycardia (VF/VT). Notwithstanding, the outcome of this procedure is certainly difficult to predict based solely on the initial rhythm. The aim of the present study was to predict the outcome using auditory brainstem responses (ABRs) in CPA patients treated with therapeutic hypothermia.
DESIGN AND SETTING: A prospective observational study in the intensive care unit of a university hospital.
PATIENTS: The study included 26 patients resuscitated from out-of-hospital CPA.
INTERVENTIONS: Basic and advanced cardiac life support, intensive care and post-resuscitative hypothermia.
MEASUREMENT AND RESULTS: ABRs were recorded immediately after the return of spontaneous circulation (ROSC). An ABR wave V was recorded in 16 patients. Among 8 patients with a favourable outcome, the initial rhythms were VF/VT in 6 patients and other rhythms in 2. All 10 patients without a detectable ABR wave V had an unfavourable outcome. The VF/VT as the initial arrest rhythm and the presence of wave V were significantly (p = 0.0095) correlated with a favourable outcome. The presence of wave V had a 100% sensitivity to a favourable outcome.
CONCLUSION: The absence of the ABR wave V in the early phase after ROSC wave indicated a reduced effect of therapeutic hypothermia, even in cases that underwent hypothermia promptly after out-of-hospital CPA. Measurement of ABRs appears to be useful as a predictor of effectiveness and as a criterion for determining the indication for therapeutic hypothermia.
