Therapeutic Hypothermia Activates the Endothelin and Nitric Oxide Systems after Cardiac Arrest in a Pig Model of Cardiopulmonary Resuscitation

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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THERAPEUTIC HYPOTERMIA IN THE COMPLEX TREATMENT OF POST-RESUSCITATION DISEASE

EMERGENCY MEDICAL CARE ◽

10.24884/2072-6716-2021-22-1-76-80 ◽

2021 ◽

Vol 22 (1) ◽

pp. 76-80

Author(s):

V. Niković ◽

R. Bulajić ◽

D. Kojić ◽

S. Vujaćić ◽

D. Zogović ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Therapeutic Hypothermia ◽

Clinical Management ◽

Neurological Outcome ◽

Current Evidence ◽

Complex Treatment ◽

Current State ◽

The Subject

This article is about of two cases of successful cardiopulmonary resuscitation (CPR) and using therapeutic hypothermia as a important part of treatment of post-resuscitation disease. Current evidence supports that induction of therapeutic hypothermia in selected patients after cardiac arrest can improve neurological outcome. It is hoped that by summarizing the current state of knowledge on the subject and highlighting issues on clinical management will enable more patients to benefit from the therapy.

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Hydrogen Sulfide Improves Survival After Cardiac Arrest and Cardiopulmonary Resuscitation via a Nitric Oxide Synthase 3–Dependent Mechanism in Mice

Circulation ◽

10.1161/circulationaha.108.833491 ◽

2009 ◽

Vol 120 (10) ◽

pp. 888-896 ◽

Cited By ~ 148

Author(s):

Shizuka Minamishima ◽

Masahiko Bougaki ◽

Patrick Y. Sips ◽

Jia De Yu ◽

Yoji Andrew Minamishima ◽

...

Keyword(s):

Nitric Oxide ◽

Cardiac Arrest ◽

Hydrogen Sulfide ◽

Nitric Oxide Synthase ◽

Cardiopulmonary Resuscitation ◽

Nitric Oxide Synthase 3 ◽

Oxide Synthase ◽

Dependent Mechanism

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Beneficial Effects of Nitric Oxide on Outcomes after Cardiac Arrest and Cardiopulmonary Resuscitation in Hypothermia-treated Mice

Anesthesiology ◽

10.1097/aln.0000000000000149 ◽

2014 ◽

Vol 120 (4) ◽

pp. 880-889 ◽

Cited By ~ 27

Author(s):

Kotaro Kida ◽

Kazuhiro Shirozu ◽

Binglan Yu ◽

Joseph B. Mandeville ◽

Kenneth D. Bloch ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cardiac Arrest ◽

Cerebral Blood Flow ◽

Brain Injury ◽

Cardiopulmonary Resuscitation ◽

Inhaled Nitric Oxide ◽

Wild Type ◽

Beneficial Effects ◽

Endogenous Nitric Oxide

Abstract Background: Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Although nitric oxide prevents organ injury induced by ischemia and reperfusion, role of nitric oxide during TH after CPR remains unclear. In this article, the authors examined the impact of endogenous nitric oxide synthesis on the beneficial effects of hypothermia after CA/CPR. The authors also examined whether or not inhaled nitric oxide during hypothermia further improves outcomes after CA/CPR in mice treated with TH. Methods: Wild-type mice and mice deficient for nitric oxide synthase 3 (NOS3−/−) were subjected to CA at 37°C and then resuscitated with chest compression. Body temperature was maintained at 37°C (normothermia) or reduced to 33°C (TH) for 24 h after resuscitation. Mice breathed air or air mixed with nitric oxide at 10, 20, 40, 60, or 80 ppm during hypothermia. To evaluate brain injury and cerebral blood flow, magnetic resonance imaging was performed in wild-type mice after CA/CPR. Results: Hypothermia up-regulated the NOS3-dependent signaling in the brain (n = 6 to 7). Deficiency of NOS3 abolished the beneficial effects of hypothermia after CA/CPR (n = 5 to 6). Breathing nitric oxide at 40 ppm improved survival rate in hypothermia-treated NOS3−/− mice (n = 6) after CA/CPR compared with NOS3−/− mice that were treated with hypothermia alone (n = 6; P < 0.05). Breathing nitric oxide at 40 (n = 9) or 60 (n = 9) ppm markedly improved survival rates in TH-treated wild-type mice (n = 51) (both P < 0.05 vs. TH-treated wild-type mice). Inhaled nitric oxide during TH (n = 7) prevented brain injury compared with TH alone (n = 7) without affecting cerebral blood flow after CA/CPR (n = 6). Conclusions: NOS3 is required for the beneficial effects of TH. Inhaled nitric oxide during TH remains beneficial and further improves outcomes after CA/CPR. Nitric oxide breathing exerts protective effects after CA/CPR even when TH is ineffective due to impaired endogenous nitric oxide production.

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Hipotermia terapêutica pós reanimação cardiorrespiratória: uma revisão bibliográfica

Revista Recien - Revista Científica de Enfermagem ◽

10.24276/2177-157x.2013.3.8.25-35 ◽

2013 ◽

pp. 25

Author(s):

Jaciana Emily de Souza

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Therapeutic Hypothermia ◽

Neurological Complications ◽

Recovery Phase ◽

Spontaneous Circulation ◽

The Body ◽

Cardiorespiratory Arrest ◽

Palabras Clave ◽

The Central Nervous System

A hipotermia, estado de anormalidade no ser humano em que a temperatura está abaixo do normal, é o resultado da exposição do organismo ao frio intenso, independente da forma, quando os mecanismos reguladores, cutâneos e nervosos se exaurem rapidamente e a temperatura cai, a produção de calor é deprimida e o resfriamento do sistema nervoso central leva à supressão dos controles hipotalâmicos. A hipotermia terapêutica melhora os desfechos entre os sobreviventes comatosos após manobras de reanimação. Considerando sua recomendação formal para emprego terapêutico pós-recuperação da circulação espontânea na parada cardiorrespiratória, o objetivo deste estudo foi trazer as principais teorias relacionadas com a hipotermia terapêutica. A revisão foi feita através de pesquisa de artigos através das palavras-chave parada cardiorrespiratória, resfriamento, hipotermia, na base de dados eletrônicos. Os resultados revelou que a hipotermia terapêutica é um dos tratamentos mais bem sucedidas para a fase após recuperação da parada cardíaca, aumentando em 40% a chance do paciente ter alta sem complicações neurológicas maiores.Descritores: Hipotermia, Parada Cardiorrespiratória, Ressuscitação Cardiopulmonar. Therapeutic hypothermia after cardiopulmonary resuscitation: a literature reviewAbstract: Hypothermia, state of abnormality in humans in which the temperature is below normal, is the result of exposure of the body to intense cold, regardless of form, when regulators, skin and nervous mechanisms are exhausted quickly and the temperature drops, the heat production is depressed and the cooling of the central nervous system leads to suppression of hypothalamic controls. Therapeutic hypothermia improves outcomes in comatose survivors after resuscitation maneuvers. Considering its formal recommendation for therapy, post-return of spontaneous circulation after cardiac arrest, the objective of this study was to bring the main theories related to therapeutic hypothermia. The review was conducted by searching items via keywords cardiorespiratory arrest, cooling, hypothermia, on the basis of electronic data. The results showed that therapeutic hypothermia is one of the most successful treatments for the recovery phase after cardiac arrest, increasing by 40% the chance of the patient being discharged without major neurological complications. Descriptors: Hypothermia, Stop Cardiopulmonary, Cardiopulmonary Resuscitation. La hipotermia terapêutica tras la reanimación cardiopulmonar: una revisión de la literaturaResumen: La hipotermia, estado de anormalidad en los seres humanos en los que la temperatura es inferior a lo normal, es el resultado de la exposición del cuerpo al frío intenso, independientemente de su forma, cuando los reguladores, la piel y los mecanismos nerviosos se agotan rapidamente y la temperatura baja, el la producción de calor es deprimida y el esfriamiento del sistema nervioso central conduce a la supresión de los controles hipotalámicos. La hipotermia terapéutica mejora los resultados en los supervivientes comatosos tras las maniobras de reanimación. Teniendo en cuenta su recomendación formal para la terapia, después de la recuperación de la circulación espontánea después de un paro cardíaco, el objetivo de este estudio fue el de traer las principales teorías relacionadas con la hipotermia terapéutica. La revisión se llevó a cabo mediante la búsqueda a través de palabras clave artículos parada cardiorrespiratoria, la refrigeración, la hipotermia, sobre la base de los datos electrónicos. Los resultados mostraron que la hipotermia terapéutica es uno de los tratamientos más exitosos para la fase de recuperación después de un paro cardíaco, aumentando en un 40% la posibilidad de que el paciente que está siendo descargada sin mayores complicaciones neurológicas. Descriptores: Hipotermia, Parada Cardiopulmonar, Resucitación Cardiopulmonar.

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Hipotermia terapêutica pós reanimação cardiorrespiratória: uma revisão bibliográfica

Revista Recien - Revista Científica de Enfermagem ◽

10.24276/rrecien2177-157x.2013.3.8.25-35 ◽

2013 ◽

Vol 3 (8) ◽

pp. 25

Author(s):

Jaciana Emily de Souza

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Therapeutic Hypothermia ◽

Neurological Complications ◽

Recovery Phase ◽

Spontaneous Circulation ◽

The Body ◽

Cardiorespiratory Arrest ◽

Palabras Clave ◽

The Central Nervous System

A hipotermia, estado de anormalidade no ser humano em que a temperatura está abaixo do normal, é o resultado da exposição do organismo ao frio intenso, independente da forma, quando os mecanismos reguladores, cutâneos e nervosos se exaurem rapidamente e a temperatura cai, a produção de calor é deprimida e o resfriamento do sistema nervoso central leva à supressão dos controles hipotalâmicos. A hipotermia terapêutica melhora os desfechos entre os sobreviventes comatosos após manobras de reanimação. Considerando sua recomendação formal para emprego terapêutico pós-recuperação da circulação espontânea na parada cardiorrespiratória, o objetivo deste estudo foi trazer as principais teorias relacionadas com a hipotermia terapêutica. A revisão foi feita através de pesquisa de artigos através das palavras-chave parada cardiorrespiratória, resfriamento, hipotermia, na base de dados eletrônicos. Os resultados revelou que a hipotermia terapêutica é um dos tratamentos mais bem sucedidas para a fase após recuperação da parada cardíaca, aumentando em 40% a chance do paciente ter alta sem complicações neurológicas maiores.Descritores: Hipotermia, Parada Cardiorrespiratória, Ressuscitação Cardiopulmonar. Therapeutic hypothermia after cardiopulmonary resuscitation: a literature reviewAbstract: Hypothermia, state of abnormality in humans in which the temperature is below normal, is the result of exposure of the body to intense cold, regardless of form, when regulators, skin and nervous mechanisms are exhausted quickly and the temperature drops, the heat production is depressed and the cooling of the central nervous system leads to suppression of hypothalamic controls. Therapeutic hypothermia improves outcomes in comatose survivors after resuscitation maneuvers. Considering its formal recommendation for therapy, post-return of spontaneous circulation after cardiac arrest, the objective of this study was to bring the main theories related to therapeutic hypothermia. The review was conducted by searching items via keywords cardiorespiratory arrest, cooling, hypothermia, on the basis of electronic data. The results showed that therapeutic hypothermia is one of the most successful treatments for the recovery phase after cardiac arrest, increasing by 40% the chance of the patient being discharged without major neurological complications. Descriptors: Hypothermia, Stop Cardiopulmonary, Cardiopulmonary Resuscitation. La hipotermia terapêutica tras la reanimación cardiopulmonar: una revisión de la literaturaResumen: La hipotermia, estado de anormalidad en los seres humanos en los que la temperatura es inferior a lo normal, es el resultado de la exposición del cuerpo al frío intenso, independientemente de su forma, cuando los reguladores, la piel y los mecanismos nerviosos se agotan rapidamente y la temperatura baja, el la producción de calor es deprimida y el esfriamiento del sistema nervioso central conduce a la supresión de los controles hipotalámicos. La hipotermia terapéutica mejora los resultados en los supervivientes comatosos tras las maniobras de reanimación. Teniendo en cuenta su recomendación formal para la terapia, después de la recuperación de la circulación espontánea después de un paro cardíaco, el objetivo de este estudio fue el de traer las principales teorías relacionadas con la hipotermia terapéutica. La revisión se llevó a cabo mediante la búsqueda a través de palabras clave artículos parada cardiorrespiratoria, la refrigeración, la hipotermia, sobre la base de los datos electrónicos. Los resultados mostraron que la hipotermia terapéutica es uno de los tratamientos más exitosos para la fase de recuperación después de un paro cardíaco, aumentando en un 40% la posibilidad de que el paciente que está siendo descargada sin mayores complicaciones neurológicas. Descriptores: Hipotermia, Parada Cardiopulmonar, Resucitación Cardiopulmonar.

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Pralidoxime Administered during Cardiopulmonary Resuscitation Facilitates Successful Resuscitation in a Pig Model of Cardiac Arrest

Heart Lung and Circulation ◽

10.1016/j.hlc.2018.06.174 ◽

2018 ◽

Vol 27 ◽

pp. S121

Author(s):

K. Jeung

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Pig Model ◽

Successful Resuscitation

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Abstract 12177: Inhaled Nitric Oxide During Cardiopulmonary Resuscitation Improves Functional Outcome and Increases 7-Day-Survival After Prolonged Cardiac Arrest in Rats

Circulation ◽

10.1161/circ.130.suppl_2.12177 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Anne Brücken ◽

Christian Bleilevens ◽

Matthias Derwall ◽

Michael Fries

Keyword(s):

Nitric Oxide ◽

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Functional Outcome ◽

Statistical Significance ◽

Spontaneous Circulation ◽

Left Ventricular ◽

Inhaled Nitric Oxide ◽

Sprague Dawley ◽

Pulmonary Vasodilator

Introduction: Precordial compressions during cardiac arrest (CA) increase pulmonary vascular resistance (PVR), potentially impeding survival by limiting left ventricular preload. Although used as selective pulmonary vasodilator there is accumulating evidence that inhaled nitric oxide (iNO) also attenuates I/R injury. Hypothesis: Applying iNO during cardiopulmonary resuscitation (CPR) increases resuscitation rates and improves functional outcome after cardiac arrest in rats. Methods: Thirty male Sprague-Dawley rats were subjected to 10 mins of CA and 3 mins of CPR. Animals were randomized to receive either 20 ppm or 40 ppm iNO during CPR until 30 mins after ROSC (return of spontaneous circulation) or no iNO treatment. For all animals a neurological deficit score (NDS) was calculated daily for seven days following the experiment. Results: Inhalation of 20 ppm iNO increased ROSC rates in comparison to animals treated with 40 ppm or without iNO treatment, however this failed to reach statistical significance (control: 7/10; 20ppm iNO: 10/10; 40ppm iNO 6/10). 20 ppm iNO significantly decreased time to ROSC, resulting in a significant reduction of post-arrest lactate levels. Also, significantly higher mean arterial pressures in comparison to control animals were observed. Furthermore, 20 ppm iNO resulted in a significantly higher seven-day-survival in comparison to controls (control: 4/10; 20 ppm iNO: 10/10). All iNO treated animals showed better neurological outcomes, being significant in animals treated with 20 ppm iNO on postoperative day 2- 7. Conclusions: Our study demonstrates that 20 ppm but not 40 ppm iNO during CPR significantly decreases time to ROSC. Furthermore, significantly better seven-day-survival and neurological outcome was noted for 20 ppm iNO in comparison to controls.

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