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Research Studies & Publications

Research Projects

If you would like more information about our current research projects please contact Jessica Montagner.

What is Cardiac Arrest?

A cardiac arrest is a life-threatening medical emergency where the heart stops beating. Individuals experiencing a cardiac arrest lose blood flow to the brain and become unconscious. Without treatments such as cardiopulmonary resuscitation (CPR) and an electric shock to restore the heartbeat (called defibrillation), death can begin in 4-6 minutes. Unfortunately, it can take paramedics longer than this to arrive on the scene and begin treatment.

People who witness a cardiac arrest can help to save a life by calling 9-1-1, beginning CPR and using a public access defibrillator. Unfortunately, CPR and public access defibrillator use by bystanders does not happen in the majority of cardiac arrest emergencies. It is estimated that 85-95% of cardiac arrest victims die before reaching a hospital or in the hospital. We think that we can improve survival rates if we can increase the number of victims who receive bystander CPR and AED use. 

The PulsePoint mobile phone application is an innovative solution that crowd-sources community bystanders to respond to nearby cardiac arrest emergencies. The PulsePoint app works with existing 9-1-1 technology and the purpose is to minimize the time between sudden cardiac arrest events and the start of CPR. When PulsePoint is implemented in a local 9-1-1 dispatch centre, community members who are trained in CPR are asked to download the free “PulsePoint Respond” mobile device application. By downloading the app, these PulsePoint community responders agree to perform CPR and deliver an electric shock when notified by the app. The app is activated while paramedics are on their way.

Pulse Point

What is the purpose of the study?

The effectiveness of the PulsePoint app has not been proven. A clinical trial is required to evaluate whether it can save lives. Principal Investigators Dr. Steven Brooks from Queen’s University and Dr. John Tallon from British Columbia Emergency Health Services and their team of collaborators from The Ohio State University, the University of British Columbia, the University of Manitoba, and the University of Toronto are launching a randomized clinical trial to test the effectiveness of the PulsePoint mobile phone application. This team of experienced researchers are working alongside their colleagues in the emergency services agencies of their respective communities.

This study will evaluate the PulsePoint app and determine whether its implementation results in increased bystander CPR and AED use and improves health outcomes for the victims.  This study is in the process of being approved by research ethics authorities in each participating institution.

Normally, people being considered for entry into a clinical trial are told about the study and then asked for their signed, informed consent before being enrolled. Our trial, like many clinical trials involving unconscious patients with time-sensitive emergency conditions, will not involve informed consent prior to enrolling patients in the study. Unfortunately, patients will be unable to provide consent because they will all be unconscious. Sometimes in this type of emergency research, we can seek consent from family members or others when the patient’s themselves cannot. Unfortunately, there is no opportunity to seek consent from other legally authorized individuals before we enroll patients in this study because PulsePoint needs to be activated at the time of the 9-1-1 call before the patient can be identified or contacted directly by paramedics. The intervention is so time-critical (seconds count!) that there is no time to get consent from family members. This process of including patients in emergency research involving life-threatening, time-critical conditions, is called “waiver of consent”. We have requested approval from the research ethics authorities in all participating communities to use this process of waiver of consent so that this important research can be done. Without waiver of consent, this research is impossible and we will be unable to answer the important questions that we have about whether PulsePoint is effective, whether we should continue with PulsePoint in our communities and whether we should recommend it for other communities in North America and around the world.

How will this study work?

This study is planned to launch in Columbus Ohio, the Province of British Columbia and Winnipeg Manitoba. For the projected two-year duration of the trial, all 9-1-1 calls for people believed to be suffering from cardiac arrest in a public location will be randomly assigned to one of two groups:

Group 1. CONVENTIONAL DISPATCH 

 9-1-1 calls randomized to the conventional dispatch group will receive standard rapid dispatch of Emergency Medical Services in the same way as it occurred prior to the study. This involves immediate dispatch of paramedics and fire fighters to the scene of the emergency, as well as having the 9-1-1 dispatcher offer CPR instructions to the caller.

Group 2. CONVENTIONAL DISPATCH + PULSEPOINT

9-1-1 calls randomized to the conventional dispatch + PulsePoint group will receive standard rapid dispatch of Emergency Medical Services in the same way as it occurred prior to the study. This involves immediate dispatch of paramedics and fire fighters to the scene of the emergency, as well as having the 9-1-1 dispatcher offer CPR instructions to the caller. In addition, calls randomized to this group will also receive activation of the PulsePoint system. Activation of the PulsePoint system will result in mobile devices within 400 meters of the emergency location being sent a “CPR needed” notification, a map indicating the location of the cardiac arrest and any nearby public access defibrillators.  

Only 9-1-1 calls about patients in public settings will be included in the study. 9-1-1 calls about patients suspected of having cardiac arrest in private locations (e.g. residential addresses) will NOT be enrolled in this study.

All patients enrolled in the study, regardless of being randomized to Group 1 (no PulsePoint) or Group 2 (PulsePoint), will have the opportunity for witnesses of the emergency to provide CPR or public access defibrillator use independent of the PulsePoint mechanism.

Researchers will collect anonymous information about the care received by patients during their pre-hospital care, as well as whether or not they survive. At no time will direct personal identifiers such as name, birth date, home address, or health card number be collected or analyzed by researchers during this study.

What are the potential risks associated with this study?

The investigators and collaborators feel that this study is very safe and any risks associated with the study are minimal. The potential, but very unlikely risks associated with PulsePoint include violation of patient privacy, harmful behaviour by PulsePoint responders (e.g. theft, assault), and obstruction of the professional response. Since its launch in 2011, there have been no reports of direct harm to patients, privacy violations or responder injuries associated with the application. There have been no reports of overcrowding at the scene of an emergency which could prevent professional responders from helping the patient. 


What are the potential benefits associated with this study?

This clinical trial does have the potential benefit of saving lives. PulsePoint might increase the number of cardiac arrest victims who receive bystander CPR and the use of a public access defibrillator in participating communities. If the study demonstrates benefit with PulsePoint, the results of this study could help guide policy for community leaders both in the participating jurisdictions as well as other communities across North America and potentially save lives in other communities.

How can I help?

Be a Leader!

Be a leader in your community by learning CPR and signing up to be a PulsePoint responder by downloading the app!

Pulse Point App

https://www.pulsepoint.org/download/ 

Where can I learn more about this study?

To learn more about this study or to sign up to receive a summary of the study results please contact us:

Dr. Steven C. Brooks, PulsePoint RCT Co-Principal Investigator
Lindsay O'Donnell, PulsePoint RCT Coordinator
Study email address: pulsepointstudy@queensu.ca
Office Telephone: 613-549-6666 x6879
Kingston General Hospital Toll Free Telephone Number: 1-800-567-5722 

More information will be available at www.clinicaltrials.gov when the study launches

The PulsePoint Randomized Control Trial is generously supported by the Canadian Institutes of Health Research (CIHR).

CIHR

Reference List

Critically Appraised Topic (2018-2019)

Author: Dr. Aida Owlia 

Supervised by Dr. Karen Graham 

 

 

Clinical Question: Do IV corticosteroids improve survival to hospital discharge in adult cardiac arrest patients compared to standard ACLS protocol? 

Articles Chosen:

1.   Tsai M-S, Chuang P-Y, Yu P-H, Huang C-H, Tang C-H, Chang W-T, et al. Glucocorticoid use during cardiopulmonary resuscitation may be beneficial for cardiac arrest. Int J Cardiol [Internet]. 2016 Nov 1 [cited 2018 Jan 7];222:629–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27517652

Tsai M-S, Huang C-H, Chang W-T, Chen W-J, Hsu C-Y, Hsieh C-C, et al. The effect of hydrocortisone on the outcome of out-of-hospital cardiac arrest patients: a pilot study. Am J Emerg Med [Internet]. 2007 Mar 1 [cited 2018 Jan 7];25(3):318–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17349907

Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S, et al. Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest. Arch Intern Med [Internet]. 2009 Jan 12 [cited 2018 Jan 6];169(1):15. Available from: http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinternmed.2008.509

Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, et al. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest. JAMA [Internet]. 2013 Jul 17 [cited 2018 Jan 7];310(3):270. Available from:http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2013.7832

Clinical Bottom Line: 

Addition of intravenous (IV) corticosteroids to the standard Advanced Cardiovascular Life Support (ACLS) algorithm in the resuscitation ofadult patients experiencing non-traumatic cardiac arrest may improve the chances of achieving Return of Spontaneous Circulation (ROSC) and survival to hospital discharge. These findings are based on a very small number of studies with significant variability in patient populations and relatively poor quality of data. The optimal patient population, corticosteroid agent, as well as dose, timing and duration of administration for improving post cardiac arrest outcomes remains unclear and requires further research.It can be argued that despite this limited data, given the high morbidity and mortality of cardiac arrest in adult patients, the benefits may outweigh the risks. Thus, IV corticosteroids could be considered at the discretion of physicians in addition to standard ACLS protocols for adult non-traumatic cardiac arrests.

The Search:

A search of the existing literature was conducted in July 2018 using OVIDMEDLINE and EMBASE databases. In order to ensure the most comprehensive search possible, the literature review was conducted using Mesh terms (see appendix 1 &2 for details of the search strategy)This search design was supervised by an academic librarian with expertise in conducting medical literature reviews. 

All the articles based on the PubMed database search, outlined above, were reviewed. Only articles published in English and on adult humans were included for the final literature review. Furthermore, all the articles chosen for the purposes of this literature review were published within the past fifteen years. This ensures that the data is clinically relevant and reflective of the most up to date resuscitation practice guidelines. A total of 133 articles were identified in OVIDMEDLINEwith the aforementioned search strategy and an additional 36 articles were identified in EMBASE after elimination of duplicate articles. A total of 169 articles were reviewed for this project. All articles were initially reviewed by title and a total of 50 articles were identified for eligibility for assessment of abstract and/or full text for inclusion in the final review. Of these 50 articles, four were relevant for addressing the clinical question. The inclusion and exclusion criteria for this literature review is outlined in Table1. 

Table 1: Inclusion and exclusion criteria used for the literature review

Inclusion Criteria 

Exclusion Criteria  

English language publications 

Non-English language publications

Any research design including meta-analysis, observational, retrospective and prospective studies 

No studies were excluded based on design 

Adult patient population (older than18 years of age)

Pediatric patient population (younger than18 years of age)

Patients resuscitated for cardiac arrest

Patients resuscitated for reasons other than cardiac arrest

Intervention includes the use of corticosteroids during the resuscitation period

Intervention did not include the use of corticosteroids during the resuscitation period

Primary outcome of survival to hospital discharge 

Primary outcome does not include survival to hospital discharge 


Design

The details of the design of the studies included in this research project are outlined below (Table 2). 

Table 2: Design of published literature included in this research project  

Study

Study Design

Tsai et al., 2007

 

Prospective, non-randomized, open-labeled clinical trial 

Mentzelopoulos et al., 2009

 

Single-center, prospective randomized, double-blind, placebo-controlled, parallel-group trial 

Mentzelopoulos et al., 2013

 

Randomized, double-blind, placebo-controlled, parallel-group trial 

 

Tsai et al., 2016

 

Retrospective observational study 

 

 

Population 

The study setting, patient population, number of patients enrolled in control and intervention groups for all four studies included in this research project are outlined below (Table 3).   There was a notable variability among the size of the studies with the number of patients in ranging from 36 to 4179 patients. 

The large study by Tsai et al., 2016 used propensity matching. Prior to propensity matching, the initial number of patients enrolled in Tsai, 2016 were 89,1000 in the control group and 1394 in the intervention group. However, the authors noted that the patients in the treatment group were more likely to have a “presenting complaints of cardiac events, respiratory events and other events”. The treatment group was also noted to have a higher rates of patients with COPD, asthma and adrenal insufficiency and shockable rhythms during CPR as well as history of steroid use within one year of their cardiac arrest prior to propensity matching. While propensity matching of the subjects in the two groups significantly decreased the overall number of patients from 145,644 to 5572  in the study,  there were no differences in the presenting complaint, clinical characteristics or CPR events (shockable rhythm, epinephrine dosage) between the two groups in the final data sets. 

Of the four studies identified for this research question, three were conducted on patients  with in-hospital cardiac arrest (IHCA)  while one study investigated patients  with out of hospital cardiac arrest (OHCA). All studies were conducted on patients with non-traumatic cardiac arrest. None of the studies were conducted in North America. Of the three studies that were done on patients with IHCA, only one study was based on arrests that happened in the emergency department. The other two were conducted with a wide range of patient populations in variety of locations in the hospital i.e. intensive and coronary care units (ICUs/CCUs), emergency departments, general wards and operating rooms.  

Table 3: Study settings, patient population, number of patients in control and intervention group of the studies included in this research project  

Study

Study Setting

Patient Population

Number of Patients in Control (-Steroids) Group 

Number of Patients in Intervention (+Steroids) Group 

Tsai et al., 2007

 

Single tertiary care emergency department, the National Taiwan University Hospital 

nontraumatic adult out-of-hospital cardiac arrest patients.

 

61

36

Mentzelopoulos et al., 2009

 

Single tertiary care center in Greece

 

 

refractory cardiac arrest, defined as epinephrine requirement for ventricular fibrillation/ventricular tachycardia or asystole/pulseless electrical activity in intensive and coronary care units (ICUs/CCUs), emergency departments, general wards, and operating rooms

52

48

Mentzelopoulos et al., 2013

 

Three tertiary care centers in Greece 

 

in-hospital, vasopressor- requiring cardiac arrest in intensive and coronary care units (ICUs/CCUs), emergency departments, general wards, and operating rooms 

138

130

Tsai et al., 2016

 

Taiwan National Health Insurance Research database 

 

non-traumatic, cardiac arrest occurring at emergency room 

4179

1393


 

Intervention 

The treatments provided the control andintervention groups in each study are outlined in the table below (Table 4). CPR was standard in all studies, both in the intervention and the control groups, and all studies included corticosteroids in the intervention group. However, there was significant variability with respect to the IV corticosteroid agents used in each study, as well as dosage and duration of administration (Table 4).  Tsai et al., 2016 analyzed a variety of corticosteroids used in the intervention group but no subgroup analysis by corticosteroid agent was provided (Tsai et al., 2016). Allowable steroids in the study included hydrocortisone, methylprednisolone, prednisolone, triamcinolone, dexamethasone, and betamethasone (Tsai et al., 2016).  Mentzelopoulos et al., 2009 and 2013 used three agents in the intervention group:vasopressin and epinephrine in addition to IV corticosteroids. (Mentzelopoulos et al., 2009, 2013).Additionally in both these studies the use of corticosteroids was not limited to the initial resuscitation as the protocol extended the use of corticosteroid  to 7 days post resuscitation (Mentzelopoulos et al., 2009, 2013). Furthermore, the non-treatment and control groups in Tsai et al., 2007 and Tsai et al., 2016 used only saline while the control groups Mentzelopoulos et al., 2009andMentzelopoulos et al., 2013 used epinephrine in their treatment algorithem.

Table 4: Outline of the treatments provided in control and interventions groups of the studies included in this research project. CPR was provided in both control and intervention groups in all studies 

Study

Treatment in Intervention Group 

Treatment in Control Group

Tsai et al., 2007

 

Hydrocortisone (solu-cortef) 100mg (10ml) IV

10 ml NaCl 0.9% IV

Mentzelopoulos et al., 2009

 

During Resuscitation: Methylprednisolone 40mg IV, and vasopressin 20IU IV in addition to epinephrine 1mg IV per CPR cycle

 

 

Post Resuscitation: 

Hydrocortisone 300mg IV daily for 7 days 

During Resuscitation: NaCl 0.9% IV solution and epinephrine 1mg IV per CPR cycle 

 

 

Post Resuscitation: 

100ml NaCL 0.9% daily for 7 days 

Mentzelopoulos et al., 2013

 

During Resuscitation Methylprednisolone 40mg IV, and vasopressin 20IU IV in addition to epinephrine 1mg IV per CPR cycle

 

Post Resuscitation:

Hydrocortisone 300mg IV daily for 7 days 

During Resuscitation

NaCl 0.9% IV solution and epinephrine 1mg IV per CPR cycle

 

Post Resuscitation:

100ml NaCL 0.9% daily for 7 days

Tsai et al., 2016

 

Steroid use (Allowable steroids included hydrocortisone, methylprednisolone, prednisolone, triamcinolone, dexamethasone, and betamethasone) 

no steroid use

 


Outcomes Measured

The primary and secondary outcomes measured in all 4 studies are outlined below (Table 5). For the purposes of this review the main outcomes of interest were 1) Return of Spontaneous Circulation (ROSC) and 2) survival to hospital discharge.

Table 5: Outline of the outcomes measured in the studies included in this research project  

Study

Outcomes Measured 

Tsai et al., 2007

 

Return of spontaneous circulation (ROSC)

Rate of complications post ROSC(APACHE II score in 24hrs, K and Na levels in 24 hrs, GI bleed or infection in 7 days post ROSC) 

Rate of hospital Discharge 

Duration of Hospitalizations 

Cerebral Performance Category (CPC) scale of survivors

Mentzelopoulos et al., 2009

 

Return of spontaneous circulation (ROSC) for minimum of 15 minutes

Survival to discharge  

Arterial pressure during and 15-20 min after CPR

Post- arrest systemic inflammatory response (serum Cytokines) 

Organ failure-free days until follow up 

Cerebral performance as per GCS score at hospital discharge 

Mentzelopoulos et al., 2013

 

Return of spontaneous circulation (ROSC) for minimum of 20 minutes 

Survival to discharge with favorable neurological outcome 

Tsai et al., 2016

 

Survival to admission 

Survival to discharge  

1-year overall survival

 

Summary of the results: 

Tsai et al., 2007 was a study done in Taiwan. It demonstrated that the use of hydrocortisone (solu-cortef 100mg IV) in addition to CPR compared to CPR alone for adult patients with nontraumatic out-of-hospital cardiac arrest improved ROSC (61% vs 39%, P=0.038)(Tsai et al., 2007). However, the study demonstrated no difference in survival to hospital discharge and no difference in 1 and 7 day survival rate or neurological outcomes between the two groups (8% vs. 10%, P=0.805). Interestingly, this is the only study of its kind that commented on the proposed ideal time for administration of corticosteroids. The authors proposed that ROSC is more likely if corticosteroids are given within 22 minutes after a witnessed collapse or within 6 minutes of arrival in the emergency department. This conclusion was drawn based on higher ROSC rates in patients who had hydrocorticone given within 22 minutes after a witnessed collapse (P=0.013) or within 6 minutes after arrival in the emergency department (P=0.045). The authors also discussed that there was no difference in ROSC between the arrival-to-drug interval beyond 6 minutes (P=0.173). The biggest limitations of the study are that it is a small, single center study with no randomization or blinding which makes for a weak methodology overall. 

Tsai et al.,2016 is much larger retrospective cohort study in adult non traumatic cardiac arrests that took place in the emergency department by the same authors. This study showed that the use of a variety of corticosteroids in combination with CPR compared to CPR alone resulted in higher admission rates to hospital (38.32% vs 18.67%, P<0.0001) and improved survival to hospital discharge (14.50% vs 5.61% P<0.0001). However, the study does not comment on neurological outcomes amongst those with survival to hospital discharge.This does not allow for analysis of “meaningful” survival. The study allowed the following corticosteroids in the intervention group:  hydrocortisone, methylprednisolone, prednisolone, triamcinolone, dexamethasone, and betamethasone. The numerous corticosteroid agents in the intervention group makes it difficult to conclude the optimal agent or dose to use in non-traumatic cardiac arrest. The concern with drawing any conclusions from this study is that perhaps only a few of the agents used and specific doses of those medications are in fact driving the effects reported in this study. Interestingly, the study was large enough to assess subgroup analysis in various patient populations. The authors suggested patients with COPD, asthma and non shockable cardiac rhythms were most likely to benefit from corticosteroid administration during cardiac arrest and this benefit remained after matching for corticosteroid use in the past year. 

Mentzelopoulos et al., 2009 and 2013  studied a multi-agent protocol. Mentzelopoulos et al., 2013 showed that the multi-agent protocolresulted in improved ROSC (83.9% vs 65.9%, P=0.005) and survival to hospital discharge (13.9% vs 5.1%, P=0.02).  in refractory cardiac arrest with favorable neurological outcomes.  Mentzelopoulos et al., 2009 showed that patients in the intervention group had significantly higher rates of ROSC for 15 minutes or longer compared to the control group (81% vs 52%, P=0.003). Furthermore, survival to hospital discharge was higher in the study group than in the control group (19% vs 4% P=0.02). The authors defined refractory cardiac arrest as cardiac arrest with epinephrine requirement for ventricular fibrillation/ventricular tachycardia or asystole/pulseless electrical activity. The in- hospital patient population included patients from intensive and coronary care units (ICUs/CCUs), emergency departments, general wards, and operating rooms. The intervention group included use of Methylprednisolone 40mg IV, and vasopressin 20IU IV in addition to epinephrine 1mg IV per CPR and Hydrocortisone 300mg IV daily x 7 days in the post-resuscitation period. This intervention was compared to a control group given NaCl 0.9% IV solution and epinephrine 1mg IV per CPR cycle and NaCl 0.9% IV for 7 days post cardiac arrest.  There are major issues in the design of this study which makes it difficult to analyze the role of corticosteroids. It is not possible to draw conclusions about the role of corticosteroids alone in improving cardiac arrest outcomes as the synergistic effects with other agents used in the intervention group may accountsfor the study findings.Although a previous study had shown no benefit with vasopressin in resuscitation (Gueugniaud et al., 2008), it remains possible that the synergistic interaction of vasopressin and corticosteroids accounts for better outcomes in the intervention group .The other main issue with this study is the use of corticosteroids for one week post-resuscitation periodwhich raises the possibility that the use of corticosteroids in the post-resuscitative period drives the improved survival to hospital discharge data and therefore the role of corticosteroids in the initial resuscitation period remains unclear. This differentiation has significant implications for change of practice among emergency physicians.  

 

Comments: 

Cardiac arrest is a common presentation in the emergency department with high morbidity and mortality. Despite advances in cardiopulmonary resuscitation, themorbidity and mortality rates remain high (Ko et al., 2004; Marenco, Wang, Link, Homoud, & Estes, 2001). Currently there is much debate on the short and long term benefits of many pharmacological agents used during cardiac arrest resuscitations. The role of epinephrine, which has been a sole pillar of pharmacological management in cardiac arrest resuscitation, has been questioned in recent literature. A study by Perkins et al.,2018 demonstrated that while Epinephrine improved ROSC it was associated with poorer long term neurological outcomes in cardiac arrest (Perkins et al., 2018). Aside from cardiopulmonary resuscitation (CPR) and early defibrillation, there are no additional measures proven to increase meaningful survival for this patient population (Link et al., 2015; Neumar et al., 2015)With CPR and early defibrillation remaining the sole back bones of resuscitation in cardiac arrest, and with epinephrine benefits questioned, there is a significant renewed interest, in finding pharmaceutical agents that improve outcomes in patients with cardiac arrest.

From a pathophysiological standpoint, cardiac arrest is believed to cause a systemic inflammatory response with increased serum inflammatory cytokines, activation of apoptosis pathways and low levels of cortisol leading to global ischemia-reperfusion injuries (Adrie et al., 2002, 2004; Hall, 1993). This dysregulation has been postulated to directly affect mortality post-arrest (Adrie et al., 2004).Administration of corticosteroids has been proposed to help mediate this dysregulated state and result in better outcomes post cardiac arrest.Glucocorticosteroids have been suggested to mitigate free radicals, maintain the cell membrane integrity, down regulate the pro-inflamatory cytokines, reduce leukocyte adhesions and decrease apoptosis (Hall, 1993; Lu, Lu, & Deng, 2015; Oh et al., 2006; Spath, Lane, & Lefer, 1974; Valen et al., 2000; van der Poll & Lowry, 1997; Wynsen, Preuss, Gross, Brooks, & Warltier, 1988)This pathophysiology has been supported by animal studies (Smithline et al in 1993). Human studies have also supported the role of the Hypothalamic-Pituitary-Adrenocortical (HPA) axis in post cardiac arrest survival by examining the role of adrenocorticotrophic hormone and cortisol levels in resuscitation. Tavakoli et al., 2012 demonstrated an association between high cortisol levels after ROSC and neurological survival (Tavakoli, Bidari, & Shams Vahdati, 2012). Similarly, a study by Schultz et al., 1993 argued that post cardiac arrest survivors have a significantly greater increase in serum cortisol concentrations than non-survivors during the first 24 hrs (Schultz et al., 1993).The authors proposed that lower cortisol concentrations secondary to the extreme stress of cardiac arrest has pathologic significance in the hemodynamic instability seen after return of spontaneous circulation (Schultz et al., 1993). Glucosteroid supplementation during CPR may be beneficial by maintaining hemodynamic stability and enhancing myocardial function, thereby improving ROSC rates(Foley, Tacker, Wortsman, Frank, & Cryer, 1987; Kornberger et al., 2000; Lindner, Haak, Keller, Bothner, & Lurie, 1996; White, Petinga, Hoehner, & Wilson, 1979). In practice, however, the evidence has been weak and conflicting. For example Paris et al.,1984 showed no significant improvement in ROSC with administration of dexamethasone in the pre-hospital period (Paris, Stewart, & Deggler, 1984). 

The aforementioned argument for the potential role of corticosteroids in resuscitation is sound and interesting in theory. Unfortunately, there are some major issues with the current state of clinical literature on this topic to draw any meaningful practice changing conclusions. The small sizes of the studies, the variability in patient populations, non-standardized intervention agents and doses in the intervention groups makes drawing any definitive conclusions very difficult. Furthermore, other than Tsai,2007 that commented on no difference between CPR duration between intervention and control groups, no other study discussed differences in CPR duration. This is a potentially significant confounding variable. Lindner et al., 1992 noted that there is a negative correlation between serum cortisol levels and the time from collapse to the start of CPR (Lindner et al., 1992). It can be argued that the periods of no flow in delayed or ineffective CPR is what affects the HPA axis and accounts for the outcomes reported in these studies.

More research is needed in this area before any clinically meaningful conclusions can be drawn with confidence.  Specifically, the corticosteroid agent of choice, optimal dose, time of administration of corticosteroids relative to the onset of cardiac arrest and optimal duration of corticosteroid treatment post arrest need to be better studied.  Furthermore, if other agents are used with corticosteroids in treatment groups better designs are needed in order to tease out the independent roles of each agent and possibilities of synergistic effects.  It is also pertinent that quality and duration of CPR and any delays from cardiac collapse to initiation of CPR are reported in any future studies. Based on similar concerns, the latest guidelines by the American Heart Association / American College of Cardiology and European Resuscitation Council do not recommend routine use of corticosteroids during cardiac resuscitation. The studies to date are worthy of consideration but are not practice changing. However, given the high mortality and paucity of effective pharmaceutical agents in cardiac arrest further studies are warranted. 

 

Limitations:

With respect to limitations of this project, despite best efforts to minimize bias in this research project, this review is susceptible to publication bias. Furthermore, there are two author groups who published all the available data and these protocols are not generalizable without further validation studies. Furthermore, none of the studies included were performed on North American or Canadian populations. While it is unlikely that there are significant differences in causes of non-traumatic cardiac arrest among different ethnicities, a more ethnically diverse study may be more generalizable to the Canadian patient population.