Post-cardiac arrest syndrome

Post-cardiac arrest syndrome (PCAS) is an inflammatory state of pathophysiology that can occur after a patient is resuscitated from a cardiac arrest.^[1] While in a state of cardiac arrest, the body experiences a unique state of global ischemia. This ischemia results in the accumulation of metabolic waste which instigate the production of inflammatory mediators. If return of spontaneous circulation (ROSC) is achieved after CPR, then circulation resumes, resulting in global reperfusion and the subsequent distribution of the ischemia products throughout the body. While PCAS has a unique cause and consequences, it can ultimately be thought of as type of global ischemia-reperfusion injury.^[2] The damage, and therefore prognosis, of PCAS generally depends on the length of the patient's ischemic period; therefore the severity of PCAS is not uniform across different patients.

Post-cardiac arrest syndrome
Other names	Post-resuscitation disease
Symptoms	Brain injury, myocardial injury, systemic ischemia/reperfusion response
Usual onset	After resuscitation from a cardiac arrest
Duration	Weeks
Causes	Global ischemia-reperfusion injury
Risk factors	Prolonged cardiac arrest
Differential diagnosis	Systemic inflammatory response syndrome
Management	Hemodynamic stabilization and supportive care

Causes and mechanisms

Before cardiac arrest, the body is in a state of homeostasis. Arterial blood circulates appropriately through the body, supplying oxygen to tissues while the venous blood collects metabolic waste products to be utilized elsewhere and/or eliminated from the body. However, during cardiac arrest, the body is in circulatory and pulmonary arrest. Oxygen is no longer being ventilated by the lungs, and blood ceases to circulate throughout the body. As a result, all tissues in the body start to enter a state of ischemia. In this state, metabolic waste products, such as lactic acid and carbon dioxide, begin to accumulate as there is no circulation to move these products to the appropriate organs. This state of ischemia will continue until ROSC is achieved through CPR, at which time, blood starts to be reperfused throughout the body. This reperfusion results in inflammatory injury through three overlapping mechanisms. Some complimentary combination of, first, mitochondrial damage and, second, endothelial activation, causes a release of reactive oxygen species (ROS), which initiates and/or exacerbates a pathophysiological inflammatory response. Third, reperfusion initiates an immune, inflammatory response resulting in the circulation of pro-inflammatory cytokines such as TNFα, IL-6 and IL-8 as well as complement activation (such as TCC and C3bc).^[3] Unlike other causes of ischemia-reperfusion injury, such as organ transplants, PCAS results from global ischemia-reperfusion and subsequently has global organ damage.

Signs and symptoms

The severity of PCAS is highly dependent on many variables including: the underlying cause of the arrest, the length of the ischemic period, the quality of CPR received, and a patient's physiologic reserve. However, organs generally respond to an ischemic period in predictable ways and therefore PCAS has an average presentation. The symptoms of PCAS are related to the effect of ischemia-reperfusion injury on individual systems, though there is significant co-morbidity between all organs' responses.

Brain

Being highly metabolic with low blood reserves, the brain is the most sensitive organ to ischemia.^[4] As a result, any amount of brain ischemia, especially when it is prolonged in cases of cardiac arrest, typically results in brain injury. Increasingly severe injury can lead to long term consequences such as cognitive dysfunction, persistent vegetative state and finally brain death. The brain sustains irreversible injury after about 20 minutes of ischemia.^[4] Even after blood flow is restored to the brain, patients can experience hours-days of hypotension, hypoxemia, impaired cerebrovascular autoregulation, brain edema, fever, hyperglycemia and/or seizures which further insult brain tissue.^[5] Diagnosis of brain injury involves neurological examination, EEG, brain imaging and/or biomarker evaluation (such as S100B and NSE).^[6] For out-of-hospital cardiac arrest, brain injury is the cause of death in most patients who undergo ROSC but ultimately die.^[7]

Heart

After the brain, the heart is the second most sensitive organ to ischemia.^[4] If the cause of the cardiac arrest was fundamentally a coronary pathology, then the consequences to the heart may include myocardial infarction complications. However, if the fundamental cause was non-coronary, then the heart becomes ischemic as a consequence, not a cause, of the arrest. In this case, PCAS very frequently presents with myocardial dysfunction in the first minute-hours post-ROSC.^[8] This myocardial dysfunction may present as prolonged cardiogenic shock, highly variable blood pressures, reduced cardiac output and/or dysrhythmias. PCAS myocardial dysfunction seems to start almost immediately after ROSC.^[9] Unlike brain tissue, evidence suggests that the myocardial injury is generally transient and can mostly recover within 72 hours,^[10] though full recovery may take months.^[11]

Lungs

While the lungs are generally oxygenated during the ischemic period of arrest, they are still susceptible to ischemic damage. While ischemia is not the mechanism of injury, evidence suggests^{[clarification needed]} that the lack of perfusion through the pulmonary vasculature during an arrest reduces the alveolar–arterial gradient which creates dead space. The oxygen accumulation in the alveoli encourages ROS production which then leads to pulmonary damage. This pulmonary-specific damage, together with the systemic inflammation, causes acute respiratory distress syndrome in about 50% of ROSC patients who survive for at least 48 hours.^[12] Lung complications, such as pulmonary contusion and pulmonary edema, may result from other aspects of PCAS such as CPR and left ventricular dysfunction, respectively. Finally, pneumonia is a common pulmonary complication due to multifactoral mechanisms including: loss of airway protection, aspiration, emergency intubation, and mechanical ventilation.^[13]

Kidneys

The kidneys are the third most sensitive organ to ischemia.^[4] Prolonged renal ischemia from cardiac arrest leads to acute kidney injury (AKI) in about 40% of patients.^[14] While PCAS may independently present with AKI, the development of AKI can be exacerbated by the administration of intravenous contrast if the patient undergoes angiography. It is unclear if the development of AKI worsens PCAS overall prognosis, but it does not seem to be a major contributor to death or poor neurological outcome at this time.^[15] PCAS patients, both as a cause and a consequence of the arrest, present with acid-base and electrolyte imbalances. Accumulation of lactate and carbon dioxide during the ischemic period largely accounts for the metabolic acidosis seen in PCAS patients, though strong ion gaps and phosphate also plays a role.^[16] Worse acidosis is generally predictive of worse outcomes.^[17] Finally, though electrolytes can present variably, PCAS patients most often demonstrate hypokalemia, hypocalcemia and hypomagnesaemia^[8] Acute kidney injury is not the leading cause of death after cardiac arrest. However, evidence suggests that the kidney damage after a cardiac arrest should be highly considered in the prognosis of the patients' health outcome.^[18]

Liver

PCAS patients, especially those with longer ischemic times, can present with liver complications. About 50% of PCAS patients present with acute liver failure (ALF), while about 10% may present with the more severe hypoxic hepatitis.^[19] Development of hypoxic hepatitis predicts poor PCAS outcomes, however ALF-similar to AKI- is not necessarily associated with poor outcomes.^[19]

Coagulation

PCAS is associated with pro-thrombotic coagulopathy. The coagulopathy is, itself, pathophysiological, but thrombi can additionally contribute to co-morbidiities in the aforementioned organ systems. The ischemia-reperfusion injury promotes damage-associated molecular patterns (DAMPs) which encourage pro-inflammatory cytokine circulation, which then induces a pro-coagulopathic state. Major mechanisms of pro-coagulation in PCAS include: multiimodal activation of factors V, VII, VIII and IX leading to a thrombin burst, decreased activity of proteins C and S, and decreased anti-thrombin and tissue factor pathway inhibitor levels. Early PCAS (first 24 hours) is generally defined by hyperfibrinolysis, due to increased tissue plasminogen activator activity, resulting in a risk of disseminated intravascular coagulation. However late PCAS generally presents with hypofibrinolysis, due to increased PAI-1 levels, resulting in a risk of multiorgan dysfunction.^[20] PCAS patients also generally show some degree of thrombocytopenia within the first 48 hours.^[21]

Endocrine

The endocrine functions most clinically relevant to PCAS are glycemic control and the hypothalamic–pituitary–adrenal axis (HPA axis). Regarding blood glucose levels, it is very common for PCAS to present with hyperglycemia; the hyperglycemia is usually higher in diabetic patients than non-diabetic patients.^[8] Mechanisms for hyperglycemia in PCAS are mostly similar as those in stress-induced hyperglycemia and therefore include elevated cortisol levels, catchecholamine surges and elevated cytokine levels. Blood glucose levels are associated with poor outcomes in a U-shaped distribution, meaning that both very high and very low levels of glucose are associated with poor outcomes.^[22] Regarding the HPA axis, PCAS can present with elevated cortisol levels from the stress of the arrest, but relative adrenal insufficiency is not uncommon in PCAS. Lower cortisol levels have been associated with poor PCAS outcomes.^[5] Newer research suggests that cardiac arrest may damage the pituitary gland, thus explaining some of the HPA dysregulation.^[23]

Management

PCAS consist of five phases: the immediate phase (20 minutes after ROSC), early phase (from 20 minutes to 6–12 hours after ROSC), intermediate phase (from 6–12 to 72 hours after ROSC), recovery phase (3 days after ROSC), and the rehabilitation phase.^[2] Management of PCAS is inherently variable, as it depends on the phase, organ systems affected and overall patient presentation. With the exception of targeted temperature management, there is no treatment that is unique to the pathophysiology of PCAS; therefore PCAS treatment is largely system-dependent, supportive treatment.

Targeted temperature management

Main article: Targeted temperature management

Targeted temperature management (TTM) is the use of various cooling methods to reduce a patient's internal temperature. The main methods of cooling include using either cold intravenous solutions or by circulating cool fluids through an external, surface blanket/pad.^[24] While most commonly applied as a post-ROSC intervention, there are some studies and EMS systems that start the cooling process in the initial intra-arrest stage.^[25][26] Patients are generally cooled to a range of 32-36 °C. As of January 2021, there is active debate about the ideal cooling temperature but there is generally agreement that PCAS patients benefit by not being hyperthermic.^[27]

TTM is an important therapy in PCAS because it directly targets the systemic nature of the pathophysiological inflammatory and metabolic processes. TTM works through three major mechanisms. First, it decreases metabolism 6% to 7% per 1 °C decrease in temperature. Second, it decreases cell apoptosis which reduces tissue damage. Third, TTM directly reduces inflammation and ROS production.^[26]

System-based treatment

PCAS can present variably depending on intra-arrest dynamics and patient-specific variables. Therefore, there is no universally applicable treatments for PCAS other than TTM. However, because there are generally predictable problems, the table below presents some of the more common treatments; supporting one organ system generally has mutual benefits for the healing of other body systems.^[28] These treatments, while common, may not be applicable to every patient.

System	Common complications	Common supportive treatments
Brain	Hypoxic brain injury, seizures	Hemodynamic monitoring and optimization, Ventilator management, glucose control, antiepileptics
Cardiovascular	Hemodynamic instability, cardiogenic shock, myocardial infarction, dysrhythmia	Hemododynamic monitoring, vasopressors, antiarrhythmics, diuretics, blood transfusion, crystalloid therapy, ACLS, PCI, ECMO
Pulmonary	ARDS, pneumonia, pulmonary contusion, pulmonary edema	Intubation, ventilator management, oxygen therapy, antibiotics
Renal	Acute Kidney Injury, electrolyte imbalances, metabolic acidosis	Dialysis, electrolyte replacement, diuretics
Hepatic	Acute Liver Injury, hypoxic hepatitis	Transplantation
Coagulatory	Thrombosis (Pulmonary embolism, DVTs), DIC	Anti-Coagulation, fibrinolytics, platelet transfusion, IVCF
Endocrine	Dysglycemia, adrenal disorders	Insulin therapy, glucose therapy, corticosteroids

Prognosis

Main article: Cardiac arrest § Prognosis

Survival from PCAS is convoluted with survival from cardiac arrest generally. There are two common metrics used to define "survival" from cardiac arrest and subsequent PCAS. First is survival-to-hospital-discharge which binarily describes whether one survived long enough to leave the hospital. The second metric is neurological outcome which describes the cognitive function of a patient who survives arrest. Neurological outcome is frequently measured with a CPC score or mRS score.^[29] Cardiac arrest and PCAS outcomes are influenced by many complicated patient and treatment variables which allows for a wide array of outcomes ranging from full physical and neurological recovery to death.

PCAS outcomes are generally better under certain conditions including: fewer patient comorbidities, initial shockable rhythms, rapid CPR responses, and treatment at a high-volume cardiac arrest center.^[30][31][32] Cardiac arrest survival-to-hospital-discharge, as of 2020^[update], is around 10%.^[33] Common long term complications of cardiac arrest and subsequent PCAS include: anxiety, depression, PTSD, fatigue, post–intensive care syndrome, muscle weakness, persistent chest pain, myoclonus, seizures, movement disorders and risk of re-arrest.^[34][35][36]

Research

Research on PCAS benefits from disease-specific work as well as general improvements in critical care treatments. As of 2022,^[37] research on PCAS includes, non-exclusively, work on early resolution of ischemia through pre-hospital extracorporeal membrane oxygenation,^[38] and wide distribution of defibrillators and CPR-trained bystanders, continued investigation of TTM,^[39] use of immunosuppressive drugs such as steroids^[40] and tocilizumab,^[41] the use of cytoprotective perfusates,^[42] and the use cerebral tissue oxygen extraction fraction.^[43]

See also

• Cardiac arrest
• Rearrest
• Cardiac Arrest Registry to Enhance Survival
• Advanced cardiac life support

References

1. Abella, Benjamin S.; Bobrow, Bentley J. (2020), Tintinalli, Judith E.; Ma, O. John; Yealy, Donald M.; Meckler, Garth D. (eds.), "Post–Cardiac Arrest Syndrome", Tintinalli's Emergency Medicine: A Comprehensive Study Guide (9 ed.), New York, NY: McGraw-Hill Education, retrieved 2022-01-19
2. Kang, Youngjoon (August 2019). "Management of post-cardiac arrest syndrome". Acute and Critical Care. 34 (3): 173–178. doi:10.4266/acc.2019.00654. PMC 6849015. PMID 31723926.
3. Langeland, Halvor; Damås, Jan Kristian; Mollnes, Tom Eirik; Ludviksen, Judith Krey; Ueland, Thor; Michelsen, Annika E.; Løberg, Magnus; Bergum, Daniel; Nordseth, Trond; Skjærvold, Nils Kristian; Klepstad, Pål (2022-01-01). "The inflammatory response is related to circulatory failure after out-of-hospital cardiac arrest: A prospective cohort study". Resuscitation. 170: 115–125. doi:10.1016/j.resuscitation.2021.11.026. hdl:10037/23838. ISSN 0300-9572. PMID 34838662. S2CID 244655488.
4. Kalogeris, Theodore; Baines, Christopher P.; Krenz, Maike; Korthuis, Ronald J. (2016-12-06). "Ischemia/Reperfusion". Comprehensive Physiology. 7 (1): 113–170. doi:10.1002/cphy.c160006. PMC 5648017. PMID 28135002.
5. Neumar, Robert W.; Nolan, Jerry P.; Adrie, Christophe; Aibiki, Mayuki; Berg, Robert A.; Böttiger, Bernd W.; Callaway, Clifton; Clark, Robert S.B.; Geocadin, Romergryko G.; Jauch, Edward C.; Kern, Karl B. (2008-12-02). "Post–Cardiac Arrest Syndrome". Circulation. 118 (23): 2452–2483. doi:10.1161/CIRCULATIONAHA.108.190652. PMID 18948368.
6. Sandroni, Claudio; D'Arrigo, Sonia; Nolan, Jerry P. (2018-06-05). "Prognostication after cardiac arrest". Critical Care. 22 (1): 150. doi:10.1186/s13054-018-2060-7. ISSN 1364-8535. PMC 5989415. PMID 29871657.
7. Laver, Stephen; Farrow, Catherine; Turner, Duncan; Nolan, Jerry (2004-11-01). "Mode of death after admission to an intensive care unit following cardiac arrest". Intensive Care Medicine. 30 (11): 2126–2128. doi:10.1007/s00134-004-2425-z. ISSN 1432-1238. PMID 15365608. S2CID 25185875.
8. Bellomo, Rinaldo; Märtensson, Johan; Eastwood, Glenn Matthew (December 2015). "Metabolic and electrolyte disturbance after cardiac arrest: How to deal with it". Best Practice & Research. Clinical Anaesthesiology. 29 (4): 471–484. doi:10.1016/j.bpa.2015.10.003. ISSN 1878-1608. PMID 26670818.
9. Kern, Karl B.; Hilwig, Ronald W.; Rhee, Kyoo H.; Berg, Robert A. (1996-07-01). "Myocardial dysfunction after resuscitation from cardiac arrest: An example of global myocardial stunning". Journal of the American College of Cardiology. 28 (1): 232–240. doi:10.1016/0735-1097(96)00130-1. ISSN 0735-1097. PMID 8752819.
10. Laurent, Ivan; Monchi, Mehran; Chiche, Jean-Daniel; Joly, Luc-Marie; Spaulding, Christian; Bourgeois, B. énédicte; Cariou, Alain; Rozenberg, Alain; Carli, Pierre; Weber, Simon; Dhainaut, Jean-François (2002-12-18). "Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest". Journal of the American College of Cardiology. 40 (12): 2110–2116. doi:10.1016/S0735-1097(02)02594-9. ISSN 0735-1097. PMID 12505221. S2CID 6211131.
11. Ruiz-Bailén, Manuel; Hoyos, Eduardo Aguayo de; Ruiz-Navarro, Silvia; Díaz-Castellanos, Miguel Ángel; Rucabado-Aguilar, Luis; Gómez-Jiménez, Francisco Javier; Martínez-Escobar, Sergio; Moreno, Rafael Melgares; Fierro-Rosón, Javier (2005-08-01). "Reversible myocardial dysfunction after cardiopulmonary resuscitation". Resuscitation. 66 (2): 175–181. doi:10.1016/j.resuscitation.2005.01.012. ISSN 0300-9572. PMID 16053943.
12. Johnson, Nicholas J.; Caldwell, Ellen; Carlbom, David J.; Gaieski, David F.; Prekker, Matthew E.; Rea, Thomas D.; Sayre, Michael; Hough, Catherine L. (February 2019). "The acute respiratory distress syndrome after out-of-hospital cardiac arrest: Incidence, risk factors, and outcomes". Resuscitation. 135: 37–44. doi:10.1016/j.resuscitation.2019.01.009. ISSN 1873-1570. PMID 30654012. S2CID 58560301.
13. Perbet, Sébastien; Mongardon, Nicolas; Dumas, Florence; Bruel, Cédric; Lemiale, Virginie; Mourvillier, Bruno; Carli, Pierre; Varenne, Olivier; Mira, Jean-Paul; Wolff, Michel; Cariou, Alain (2011-11-01). "Early-Onset Pneumonia after Cardiac Arrest". American Journal of Respiratory and Critical Care Medicine. 184 (9): 1048–1054. doi:10.1164/rccm.201102-0331OC. ISSN 1073-449X. PMID 21816940.
14. Tujjar, Omar; Mineo, Giulia; Dell'Anna, Antonio; Poyatos-Robles, Belen; Donadello, Katia; Scolletta, Sabino; Vincent, Jean-Louis; Taccone, Fabio Silvio (2015). "Acute kidney injury after cardiac arrest". Critical Care. 19 (1): 169. doi:10.1186/s13054-015-0900-2. PMC 4416259. PMID 25887258.
15. Yanta, Joseph; Guyette, Francis X.; Doshi, Ankur A.; Callaway, Clifton W.; Rittenberger, Jon C.; Post Cardiac Arrest Service (October 2013). "Renal dysfunction is common following resuscitation from out-of-hospital cardiac arrest". Resuscitation. 84 (10): 1371–1374. doi:10.1016/j.resuscitation.2013.03.037. ISSN 1873-1570. PMID 23619738.
16. Makino, Jun; Uchino, Shigehiko; Morimatsu, Hiroshi; Bellomo, Rinaldo (2005). "A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study". Critical Care. 9 (4): R357-62. doi:10.1186/cc3714. PMC 1269443. PMID 16137348.
17. Jamme, Matthieu; Salem, Omar Ben Hadj; Guillemet, Lucie; Dupland, Pierre; Bougouin, Wulfran; Charpentier, Julien; Mira, Jean-Paul; Pène, Frédéric; Dumas, Florence; Cariou, Alain; Geri, Guillaume (2018). "Severe metabolic acidosis after out-of-hospital cardiac arrest: risk factors and association with outcome". Annals of Intensive Care. 8 (1): 62. doi:10.1186/s13613-018-0409-3. PMC 5940999. PMID 29740777.
18. Tsivilika M, Kavvadas D, Karachrysafi S, Kotzampassi K, Grosomanidis V, Doumaki E, Meditskou S, Sioga A, Papamitsou T. Renal Injuries after Cardiac Arrest: A Morphological Ultrastructural Study. Int J Mol Sci. 2022 May 30;23(11):6147. doi: 10.3390/ijms23116147. PMID: 35682826; PMCID: PMC9180998.
19. Iesu, Enrica; Franchi, Federico; Cavicchi, Federica Zama; Pozzebon, Selene; Fontana, Vito; Mendoza, Manuel; Nobile, Leda; Scolletta, Sabino; Vincent, Jean-Louis; Creteur, Jacques; Taccone, Fabio Silvio (2018). "Acute liver dysfunction after cardiac arrest". PLOS ONE. 13 (11): e0206655. Bibcode:2018PLoSO..1306655I. doi:10.1371/journal.pone.0206655. PMC 6218055. PMID 30395574.
20. Wada, Takeshi (2017). "Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome". Frontiers in Medicine. 4: 156. doi:10.3389/fmed.2017.00156. PMC 5626829. PMID 29034235.
21. Cotoia, Antonella; Franchi, Federico; Fazio, Chiara De; Vincent, Jean-Louis; Creteur, Jacques; Taccone, Fabio Silvio (2018). "Platelet indices and outcome after cardiac arrest". BMC Emergency Medicine. 18 (1): 31. doi:10.1186/s12873-018-0183-4. PMC 6157054. PMID 30253749.
22. Vihonen, Hanna; Kuisma, Markku; Salo, Ari; Ångerman, Susanne; Pietiläinen, Kirsi; Nurmi, Jouni (2019-03-25). "Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study". PLOS ONE. 14 (3): e0214209. Bibcode:2019PLoSO..1414209V. doi:10.1371/journal.pone.0214209. ISSN 1932-6203. PMC 6433228. PMID 30908518.
23. Okuma, Yu; Aoki, Tomoaki; Miyara, Santiago J.; Hayashida, Kei; Nishikimi, Mitsuaki; Takegawa, Ryosuke; Yin, Tai; Kim, Junhwan; Becker, Lance B.; Shinozaki, Koichiro (2021-01-12). "The evaluation of pituitary damage associated with cardiac arrest: An experimental rodent model". Scientific Reports. 11 (1): 629. doi:10.1038/s41598-020-79780-3. ISSN 2045-2322. PMC 7804952. PMID 33436714.
24. Vaity, Charudatt; Al-Subaie, Nawaf; Cecconi, Maurizio (2015). "Cooling techniques for targeted temperature management post-cardiac arrest". Critical Care. 19 (1): 103. doi:10.1186/s13054-015-0804-1. PMC 4361155. PMID 25886948.
25. Castrén, Maaret; Nordberg, Per; Svensson, Leif; Taccone, Fabio; Vincent, Jean-Louise; Desruelles, Didier; Eichwede, Frank; Mols, Pierre; Schwab, Tilmann; Vergnion, Michel; Storm, Christian (2010-08-17). "Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness)". Circulation. 122 (7): 729–736. doi:10.1161/CIRCULATIONAHA.109.931691. ISSN 1524-4539. PMID 20679548. S2CID 18231672.
26. Perman, Sarah M.; Goyal, Munish; Neumar, Robert W.; Topjian, Alexis A.; Gaieski, David F. (February 2014). "Clinical Applications of Targeted Temperature Management". Chest. 145 (2): 386–393. doi:10.1378/chest.12-3025. PMC 4502721. PMID 24493510.
27. Granfeldt, Asger; Holmberg, Mathias J.; Nolan, Jerry P.; Soar, Jasmeet; Andersen, Lars W.; International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force (October 2021). "Targeted temperature management in adult cardiac arrest: Systematic review and meta-analysis". Resuscitation. 167: 160–172. doi:10.1016/j.resuscitation.2021.08.040. ISSN 1873-1570. PMID 34474143.
28. Mongardon, Nicolas; Dumas, Florence; Ricome, Sylvie; Grimaldi, David; Hissem, Tarik; Pène, Frédéric; Cariou, Alain (2011-11-03). "Postcardiac arrest syndrome: from immediate resuscitation to long-term outcome". Annals of Intensive Care. 1 (1): 45. doi:10.1186/2110-5820-1-45. ISSN 2110-5820. PMC 3223497. PMID 22053891.
29. Perkins, Gavin D.; Jacobs, Ian G.; Nadkarni, Vinay M.; Berg, Robert A.; Bhanji, Farhan; Biarent, Dominique; Bossaert, Leo L.; Brett, Stephen J.; Chamberlain, Douglas; de Caen, Allan R.; Deakin, Charles D. (2015-09-29). "Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest". Circulation. 132 (13): 1286–1300. doi:10.1161/CIR.0000000000000144. PMID 25391522.
30. Sinning, Christoph; Ahrens, Ingo; Cariou, Alain; Beygui, Farzin; Lamhaut, Lionel; Halvorsen, Sigrun; Nikolaou, Nikolaos; Nolan, Jerry P.; Price, Susanna; Monsieurs, Koenraad; Behringer, Wilhelm (November 2020). "The cardiac arrest centre for the treatment of sudden cardiac arrest due to presumed cardiac cause - aims, function and structure: Position paper of the Association for Acute CardioVascular Care of the European Society of Cardiology (AVCV), European Association of Percutaneous Coronary Interventions (EAPCI), European Heart Rhythm Association (EHRA), European Resuscitation Council (ERC), European Society for Emergency Medicine (EUSEM) and European Society of Intensive Care Medicine (ESICM)". European Heart Journal - Acute Cardiovascular Care. 9 (4_suppl): S193–S202. doi:10.1177/2048872620963492. ISSN 2048-8734. PMID 33327761.
31. Al-Dury, Nooraldeen; Ravn-Fischer, Annica; Hollenberg, Jacob; Israelsson, Johan; Nordberg, Per; Strömsöe, Anneli; Axelsson, Christer; Herlitz, Johan; Rawshani, Araz (2020-06-25). "Identifying the relative importance of predictors of survival in out of hospital cardiac arrest: a machine learning study". Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 28 (1): 60. doi:10.1186/s13049-020-00742-9. ISSN 1757-7241. PMC 7318370. PMID 32586339.
32. Majewski, David; Ball, Stephen; Finn, Judith (2019). "Systematic review of the relationship between comorbidity and out-of-hospital cardiac arrest outcomes". BMJ Open. 9 (11): e031655. doi:10.1136/bmjopen-2019-031655. PMC 6887088. PMID 31740470.
33. Yan, Shijiao; Gan, Yong; Jiang, Nan; Wang, Rixing; Chen, Yunqiang; Luo, Zhiqian; Zong, Qiao; Chen, Song; Lv, Chuanzhu (2020-02-22). "The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis". Critical Care. 24 (1): 61. doi:10.1186/s13054-020-2773-2. ISSN 1364-8535. PMC 7036236. PMID 32087741.
34. Moulaert, Véronique R. M.; van Heugten, Caroline M.; Gorgels, Ton P. M.; Wade, Derick T.; Verbunt, Jeanine A. (2017-03-08). "Long-term Outcome After Survival of a Cardiac Arrest: A Prospective Longitudinal Cohort Study". Neurorehabilitation and Neural Repair. 31 (6): 530–539. doi:10.1177/1545968317697032. ISSN 1545-9683. PMID 28506147. S2CID 3788957.
35. Sawyer, Kelly N.; Camp-Rogers, Teresa R.; Kotini-Shah, Pavitra; Del Rios, Marina; Gossip, Michelle R.; Moitra, Vivek K.; Haywood, Kirstie L.; Dougherty, Cynthia M.; Lubitz, Steven A.; Rabinstein, Alejandro A.; Rittenberger, Jon C. (2020-03-24). "Sudden Cardiac Arrest Survivorship: A Scientific Statement From the American Heart Association". Circulation. 141 (12): e654–e685. doi:10.1161/CIR.0000000000000747. PMID 32078390. S2CID 211232743.
36. Han, Kap Su; Kim, Su Jin; Lee, Eui Jung; Lee, Sung Woo (2019-05-31). "The effect of extracorporeal cardiopulmonary resuscitation in re-arrest after survival event: a retrospective analysis". Perfusion. 35 (1): 39–47. doi:10.1177/0267659119850679. ISSN 0267-6591. PMID 31146644. S2CID 171094275.
37. Horowitz, James M.; Owyang, Clark; Perman, Sarah M.; Mitchell, Oscar J. L.; Yuriditsky, Eugene; Sawyer, Kelly N.; Blewer, Audrey L.; Rittenberger, Jon C.; Ciullo, Anna; Hsu, Cindy H.; Kotini‐Shah, Pavitra (2021-08-17). "The Latest in Resuscitation Research: Highlights From the 2020 American Heart Association's Resuscitation Science Symposium". Journal of the American Heart Association. 10 (16): e021575. doi:10.1161/JAHA.121.021575. PMC 8475047. PMID 34369175.
38. Bartos, Jason A.; Frascone, R. J.; Conterato, Marc; Wesley, Keith; Lick, Charles; Sipprell, Kevin; Vuljaj, Nik; Burnett, Aaron; Peterson, Bjorn K.; Simpson, Nicholas; Ham, Kealy (December 2020). "The Minnesota mobile extracorporeal cardiopulmonary resuscitation consortium for treatment of out-of-hospital refractory ventricular fibrillation: Program description, performance, and outcomes". eClinicalMedicine. 29–30: 100632. doi:10.1016/j.eclinm.2020.100632. ISSN 2589-5370. PMC 7788435. PMID 33437949.
39. Dankiewicz, Josef; Cronberg, Tobias; Lilja, Gisela; Jakobsen, Janus C.; Levin, Helena; Ullén, Susann; Rylander, Christian; Wise, Matt P.; Oddo, Mauro; Cariou, Alain; Bělohlávek, Jan (2021-06-17). "Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest". The New England Journal of Medicine. 384 (24): 2283–2294. doi:10.1056/NEJMoa2100591. hdl:11368/2998543. ISSN 1533-4406. PMID 34133859. S2CID 235461014.
40. Mentzelopoulos, Spyros D.; Malachias, Sotirios; Chamos, Christos; Konstantopoulos, Demetrios; Ntaidou, Theodora; Papastylianou, Androula; Kolliantzaki, Iosifinia; Theodoridi, Maria; Ischaki, Helen; Makris, Dimosthemis; Zakynthinos, Epaminondas (2013-07-17). "Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial". JAMA. 310 (3): 270–279. doi:10.1001/jama.2013.7832. ISSN 1538-3598. PMID 23860985.
41. Meyer, Martin A. S.; Wiberg, Sebastian; Grand, Johannes; Kjaergaard, Jesper; Hassager, Christian (2020-10-20). "Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial". Trials. 21 (1): 868. doi:10.1186/s13063-020-04783-4. ISSN 1745-6215. PMC 7574300. PMID 33081828.
42. Vrselja, Zvonimir; Daniele, Stefano G.; Silbereis, John; Talpo, Francesca; Morozov, Yury M.; Sousa, André M. M.; Tanaka, Brian S.; Skarica, Mario; Pletikos, Mihovil; Kaur, Navjot; Zhuang, Zhen W. (April 2019). "Restoration of brain circulation and cellular functions hours post-mortem". Nature. 568 (7752): 336–343. Bibcode:2019Natur.568..336V. doi:10.1038/s41586-019-1099-1. ISSN 1476-4687. PMC 6844189. PMID 30996318.
43. Ko, Tiffany S.; Mavroudis, Constantine D.; Morgan, Ryan W.; Baker, Wesley B.; Marquez, Alexandra M.; Boorady, Timothy W.; Devarajan, Mahima; Lin, Yuxi; Roberts, Anna L.; Landis, William P.; Mensah-Brown, Kobina (2021-02-15). "Non-invasive diffuse optical neuromonitoring during cardiopulmonary resuscitation predicts return of spontaneous circulation". Scientific Reports. 11 (1): 3828. Bibcode:2021NatSR..11.3828K. doi:10.1038/s41598-021-83270-5. ISSN 2045-2322. PMC 7884428. PMID 33589662.