The Use of Therapeutic Hypothermia in The Treatment of Out-of-hospital Cardiac Arrests - Research Paper Example

THE USE OF THERAPEUTIC HYPOTHERMIA IN THE TREATMENT OF OUT-OF-HOSPITAL CARDIAC ARRESTS IN THE PRE-HOSPITAL (UK PARAMEDIC) ENVIRONMENT INTRODUCTION In the treatment of out-of-hospital cardiac arrest in the United Kingdom paramedic environment, various emergency interventions for resuscitation are commonly used. A recent development in international paramedic practice for cardiac arrest is the use of therapeutic hypothermia. Tissue ischemia resulting from cessation of the heart’s functioning is lessened amd the oxygen demands of tissues are suppressed by the cooling treatment of therapeutic hypothermia. Additionally, the resulting “multiple deleterious chemical cascades” (Tisherman and Sterz 2005, p.xiii) are reduced, while beneficial responses are increased, or at least they are less adversely affected. Despite strong international guidelines and scientific evidence supporting the use of therapeutic hypothermia in paramedic treatment for cardiac arrest, less than 30% of cardiac arrest patients are administered the treatment in most countries. The reasons include lack of sufficient information and experience, absence of research evidence in this field, and technical difficulty in using the method; hence “many patients who need not die are dying” (Bottiger et al 2007, p.162). Thesis Statement: The purpose of this paper is to undertake a literature review of the use of therapeutic hypothermia in the treatment of out of hospital cardiac arrests in the pre-hospital U.K. paramedic environment. The various strategies related to this intervention, the key findings, and recommendations on this issue will be discussed. DISCUSSION “Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment” (HCASG 2002, p.549). Immediately following out-of-hospital sudden cardiac arrest, it is vital to administer effective interventions during the resuscitation stage and in the first few hours after the event. Therapeutic hypothermia used in paramedic practice impacts postresuscitation brain and other organ injury in several ways. According to Bottiger et al (2007, p.162), it “reduces metabolism, free radical formation, intracellular calcium overload, as well as the translation and transcription of pathogenic proteins”. Further, it reduces oedema, apoptosis, and has anti-inflammatory and anti-coagulatory properties. This is supported by Meybohm et al (2009), who found that hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation, by reducing the rate of apoptosis and pro-inflammatory cytokine expression. Tiainen et al (2003) states that high serum levels of neuron-specific enolase (NSE) and S- 100B protein are linked with ischemic brain injury and poor outcome after cardiac arrest. The administration of therapeutic hypothermia improves neurological condition after cardiac arrest through selective attenuation of delayed neuronal death by decreasing the level of serum NSE, but not S-100B over time. Rationale for the Choice of Topic The rationale for the choice of this topic for investigation is that there is a requirement for increased knowledge and understanding of therapeutic hypothermia in cardiac emergency situations. The aim is to incorporate the intervention into U.K. paramedic routine where it is not yet practised, to increase the number of lives saved. Objectives A systematic literature review and meta-analysis was conducted to evaluate the effectiveness of therapeutic hypothermia in patients after sudden cardiac arrest in the out-of-hospital paramedic environment. The main outcome parameters studied were neurologic results, survival, and adverse events following the cardiac arrest. Search Strategy and Selection Criteria Primary research articles published in the last ten years, between the years 2000 and 2010 were searched from UK PUBMED CENTRAL and Google Scholar Advanced Search. All clinical trials were included, which assessed the effectiveness of the therapeutic hypothermia intervention in patients after sudden cardiac arrest in the pre-hospital and out-of-hospital environments. The studies included only research conducted on adult populations, excluding those on animals and children sample groups. The articles included the different cooling methods applied to patients suffering from cardiac arrests, who have a pulse again as a result of resuscitation. Studies based on therapeutic hypothermia in the paramedic emergency department were included; while those in hospital intensive care setting were excluded. The articles to be used were identified by their sample size, those with randomization and with control groups, and those using interventions pertaining to cooling by therapeutic hypothermia in the out-of-hospital setting. The first step of the search was conducted in UK PubMed Central using the following key words: therapeutic hypothermia + cardiac arrest. This search yielded 625 articles including studies on infants, children and animals. The next step of the search imposed the limits of using only articles published in the last 10 years and added to UK PubMed Central in the last 10 years, using the following key words: therapeutic hypothermia + cardiac arrest + out of hospital + prehospital. This yielded 55 articles including those on trauma care, transportation of critically ill patients after cardiac arrest, resuscitation, fluid replacement for severe hypovolemia, and other issues. From these articles, two were selected: Bruel et al (2007) and Storm et al (2010). Similarly, five articles were selected from Google Scholar Advanced Search from the first 30 articles of about 3,440 articles listed as a result of a search using the key words: therapeutic hypothermia + cardiac arrest + out of hospital + prehospital. These research articles are by Bernard et al (2002), Haugk et al, 2007, Ferreira et al, 2009, and Nagao et al, 2000. The articles reviewed have been summarized in the form of a Table, in the Appendix. Validity and Reliability The validity of all the research studies included in the literature review is high, because the results obtained from them meet the requirements of the scientific research method. That is, there was randomization in the assigning of the sample group and the control group in all the studies. Internal validity of the research studies is supported by the research design being well constructed to maintain the integrity of the procedure and the reliability of the results. The use of randomization and control groups ensures validity of the results, and eliminates the possibility of an unknown external criterion contributing to the results and the findings of the research. Similarly, studies which are double blind, produce more valid results. However, this may not always be possible, particularly in research pertaining to the medical field (Polit and Beck 2009). The main aim of reliability of the research studies is achieved by the research methodologies being of a repeatable procedure, leading to similar significant results (Polit and Beck 2009). In this aspect, all the reviewed research work are highly reliable because they are inherently repeatable. Hence, the testability of the significant results helps to re-inforce the findings, for use by the wider scientific community. Validity and reliability of the findings are strengthened by the research method being repeated, and leading to the same results. In therapeutic hypothermia as an intervention to reduce brain damage following sudden cardiac arrest, the instruments used for measuring temperature, the standard devices used for invasive and non-invasive cooling help to ensure accuracy in the values, and to maintain reliability and validity. Thus, reliability of the instruments and procedures used also contribute to the validity of the results. Limitations A major limitation is the inability to perform double blind studies in this type of medical research, where the paramedics undertaking the treatment procedure cannot be blinded to the research process and the interventions. Thus, the risks of obtaining poor results may be slightly higher in studies that are not double blind. Blinding one or more variables in a research study enhances its validity and reliability. Further, even when sufficiently large sample groups are used, single location studies using a relatively homogenous population cannot be generalised. Hence, multi-locational studies of a cross-section of the population helps to overcome the above limitation. Futher, starting each of the interventions at a specific point of time after the cardiac attack, was not feasible, hence a comparison of the techniques cannot be accurately undertaken. Different Methods of Administering Therapeutic Hypothermia by Paramedics According to Haugk et al (2007), it is difficult to recommend any particular cooling technique, since clinical trials for comparing the outcomes of different methods are not available. Hypothermia can be maintained by means of both surface as well as endovascular cooling. From the research evidence (HCASG 2002; Holzer et al 2005) it is clear that prolonged therapeutic hypothermia is the only post resuscitation intervention demonstrated to improve the outcome of cardiac arrest survivors. Further, the International Liaison Committee on Resuscitation (ILCOR) recommends therapeutic hypothermia (Nolan 2003). Invasive Intravascular Cooling Conventional techniques for achieving therapeutic hypothermia are time consuming, cumbersome or do not allow the precise control of body temperature. Therefore, Pichon et al (2007) conducted a study of 40 out-of-hospital cardiac arrest patients, to investigate the efficacy and tolerance of a commercially available intravascular cooling device, the CoolGard Thermal Regulation System for producing mild induced hypothermia (MIH). This was connected to a balloon-equipped endovascular Icy catheter, single perfusion line with cooled normal saline, and designed to be inserted in the inferior vena cava of the femoral vein. The targeted temperature of 330C could be attained and MIH was maintained over a duration of 36 hours. Additionally, cooling was safe, relatively fast, well-tolerated and effective. Evidence from the study revealed improved outcomes for all the patient groups, irrespective of their initial cardiac rhythm. Progressive rewarming could also be conducted effectively. Protective effect against post-ischemic and traumatic brain injury can be optimized with the help of this device. The limitation of this method is that it is unknown whether prolonged use of this endovascular cooling system will continue to be effective and safe, and whether post-rewarming rebound hyperthermia can be avoided. Further, the possible link between mild induced hypothermia and early onset nosocomial infections needs to be investigated (Pichon et al 2007). Similarly, research conducted by Bruel et al (2008) on 33 patients, measured the safety, feasibility and effectiveness of therapeutic hypothermia by infusion of 2 litres of normal saline of 0.9% strength for over 30 minutes at 40C. This intervention was initiated before return of spontaneous circulation during advanced life support by means of cardiopulmonary resuscitation after sudden cardiac arrest in the paramedic environment. Of the 33 patients, 8 presented with ventricular fibrillation as the initial cardiac rhythm. Evidence from the research reveals that the intervention during advanced life support to induce mild hypothermia effectively lowers body temperature in resuscitated out-of-hospital cardiac arrest patients. Moreover, it is feasible, safe and effective. The authors conclude that this approach could be the earliest intervention that paramedics can administer for out-of-hospital cardiac arrest emergency treatment; and it is also the most cost-effective neuroprotective strategy. Non Invasive Induction of Hypothermia by Surface Cooling Bernard et al (2003) conducted a randomized, controlled trial to compare the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest. The study sample consisted of 77 patients randomly assigned to normothermia or to hypothermia according to the day of the month, with patients assigned to hypothermia on odd-numbered days. Those receiving hypothermia were administered the treatment by paramedics in the ambulance, after removing the clothing and applying cold packs (CoolCare, Australia) to the patient’s head and torso. On the other hand, the patients assigned to normothermia followed the usual pre-hospital treatment protocols for cardiac arrest. In therapeutic hypothermia, the core body temperature was reduced to 330C within 2 hours of the return of spontaneous circulation, and maintained at that temperature for 12 hours. The targeted outcome was survival of the patients in the paramedic environment, to sufficient improvement in the hospital leading to discharge with good neurologic function, enabling discharge to home or to a rehabilitation facility. From the preliminary observations, Bernard et al (2003) suggested that treatment with moderate hypothermia resulted in improved outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest. Storm et al (2010) found evidence that the early survival benefit established by therapeutic hypothermia continues two years after the cardiac arrest; supporting current recommendations for postresuscitation care after ventricular fibrillation and other rhythms. Haugk et al (2007) studied the feasibility and efficacy of a new non-invasive surface cooling device post-resuscitation to control patient temperature within a range of 330 to 370C. A sample of 27 patients of a median range of 58 years (49.75 to 70 years) at an emergency department who had been resuscitated successfully from cardiac arrest, and were to be given mild hypothermia, were studied in a prospective observational case series. The Medivance Arctic Sun System, a non-invasive new technique helps to reach the target temperature of 330C quickly, to maintain the target temperature for 24 hours, and subsequently shift to actively rewarm at normothermia of 0.40C/h. Data is recorded in the median and interquartile range of 25% and 75%. This non-invasive cooling device used in post-resuscitation treatment of suvivors of cardiac arrest, was found to be feasible and highly effective in the rapid reduction of patients’ temperature, without causing skin irritations (Haugk et al 2007). Similarly, HCASG (2002) conducted a research study to determine whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation. The study was a randomized, controlled trial with blinded assessment of the trial. Blinding of paramedics with respect to assignment of patients to type of treatment was not possible, since they were involved in the care of patients during the first 48 hours after cardiac arrest. On the other hand, the physicians were blinded, and were unaware of the treatment assignments, when assessing the neurologic outcome within the first six months after the cardiac arrest. The randomly assigned normothermia group of patients as the control sample, were placed on a conventional hospital bed, and normothermia was maintained. After sedation and induction of paralysis to prevent shivering, those patients assigned to the hypothermia group were administered therapeutic hypothermia by cooling to a target temperature of 320C to 340C. For this purpose was used an external cooling device (TheraKool, United Kingdom) consisting of a mattress with a cover which produces cold air to envelop the whole body. If the target bladder temperature could not be achieved within four hours after the return of spontaneous circulationm, ice packs were applied. The temperature was maintained from 320C to 340C for 24 hours from the time cooling was initiated followed by extensive rewarming over a duration of 8 hours. Combination of Invasive and Non-Invasive Therapeutic Hypothermia To improve survival rates after sudden cardiac arrest treated by paramedics, researchers created and implemented a standardized post resuscitation protocol promoting vital organ functioning by “therapeutic hypothermia, percutaneous coronary intervention (PCI), control of haemodynamics, blood glucose, ventilation and seizures” (Sunde et al 2007, p.29). A prospective observational study was conducted for 2 years on a study sample which was compared to the results obtained from a control group. No control period patient was administered therapeutic hypothermia, whereas 40 of the 52 comatose patients in the intervention group were treated with hypothermia. A number of cooling methods were used, with 29 patients or 73% of the group receiving endovascular cooling with CoolGard alone or in an integrated treatment strategy along with initial ice cold fluids and ice packs. Non-invasive, externally applied cooling with Arctic Sun, or icepacks and wet, cold blankets was undertaken when CoolGard was unavailable. Comatose patients were cooled by the researchers (Sunde et al 2007), irrespective of rhythm. The chances of achieving a positive outcome increases with decrease in time taken to reach the target temperature. The average time for reaching the target temperature of 5.5 hours is similar to the 8 hours reported in the previous study discussed above, conducted by HCASG (2002). From the evidence produced by this research, a standardised treatment protocol was devised for critically ill patients following sudden heart attack. This protocol included blood glucose, temperature, seizure treatment, and partial pressure of carbondioxide in arterial blood (PaCO2). The emergency treatment protocol should be feasible for paramedics to carry out in the ambulance or in the emergency environment. The factors other than cooling which have an equally crucial part to play in helping the patient to survive, have not been tested in cardiac arrest intervention studies, in the paramedic or in the clinical environments (Sunde et al 2007). According to Ferreira et al (2009), who used a combination of invasive and non-invasive cooling techniques, non-invasive cooling techniques include veno-venous extracorporeal blood shunt cooling and selective cooling of the cerebrum by a helmet device. “The rapid infusion of 40C intravenous fluid, the use of a cooling helmet and cooling plates” (Kim et al 2009, p.359) are portable, safe and effective, and consequently feasible in paramedic work, for administering therapeutic hypothermia. On the other hand, an alternative emergency protocol which leads to increased incidence of good recovery has been suggested by Nagao et al (2000). It is based on cardiopulmonary cerebral resuscitation (CPCR) using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia. Therapeutic hypothermia may have particular side-effects such as “hypokalaemia, hypomagnesaemia and bacteraemia” (Bernard et al 2002, p.557). However, some of the major complications of therapeutic hypothermia such as arrhythmias, bleeding, pneumonia, sepsis, and others, also occur in normothermic cardiac arrest patients (HCASG 2002). Therefore inducing mild therepeutic hypothermia should be included in paramedic treatment of cardiac arrest patients. Discussion of Findings in the Context of UK Paramedic Practice Guidelines/ Protocol Therapeutic hypothermia helps to save one life out of every six impacted by sudden cardiac arrest in the out-of-hospital environment. This rate is higher than other more expensive approaches used in the intensive care unit. Hence, therapeutic hypothermia has been recommended in an Advisory Statement by the International Liaison Committee on Resuscitation, ILCOR (Nolan et al 2003, p.234), as follows: “Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 320C to 340C for 12 to 24 hours”, when the initial rhythm was ventricular fibrillation (VF). This approach achieves beneficial results for other rhythms in the pre-hospital situation, as well as in-hospital cardiac arrest. Further, the European Resuscitation Council (ERC 2005, S1) guidelines also stated that therapeutic hypothermia should be done to a level of 320 to 340C for unconscious adult patients with spontaneous circulation after out-of-hospital ventricular fibrillation cardiac arrest. The induced cooling should be started at the earliest, and continued for 12 to 24 hours. The same treatment is applicable in the case of out-of-hospital cardiac arrest from a non-shockable rhythm, and for children who regain spontaneous circulation after cardiopulmonary arrest but remain comatose. The above guidelines have been supported by the literature, revealing that induced hypothermia introduced immediately following cardiac arrest, administered for 12 to 24 improves outcomes in comatose patients who have been resuscitated after out-of-hospital cardiac arrest. However, when blinding was not undertaken for assignment of patients to hypothermia or normothermia treatment, some aspects of care may have differed between the two groups (Bernard et al 2003). Hence, optimal duration of hypothermia is required to be confirmed by further research. Further, a short duration of administering therapeutic hypothermia such as 4 hours requires that the intervention be applied urgently during or after resuscitation; this also decreases reperfusion related injury. On the other hand, a longer duration of therapeutic hypothermia intervention of more than 24 hours reduces post ischemic neuronal death, even with application delayed by more than 8 hours. Thus, therapeutic hypothermia should be administered during cardiopulmonary resuscitation (CPR); but when the intervention is begun after the return of spontaneous circulation, it should be given for a longer period of time (Hammer et al 2008). Cooling blanket has been found to be the most cost-effective intervention, leading to successful outcomes (Merchant et al 2009), used on cardiac arrest survivors who meet the criteria of HACA (Hypothermia after Cardiac Arrest). On the other hand, Felberg et al (2001) found that the use of external cooling blankets was slow and imprecise; and further developments were required in accelerating and improving the cooling process. The outcomes using both invasive and non-invasive techniques were found to be similar, though the endovascular approach was stated to be more feasible. Mild induced hypothermia (MIH) has been found to improve neurological outcomes in patients who had been resuscitated following out-of-hospital cardiac arrest, and had consequently suffered from encephalopathy. However, the “optimal technique for achieving MIH and its benefit/ risk ratio in the target population remain controversial” (Pichon et al 2007, p.1). Conventional techniques for effecting therapeutic hypothermia in paramedic practice are cumbersome and time consuming, and some approaches do not permit precise control of body temperature. Hence, both invasive and non-invasive were cooling techniques were investigated, in order to determine those most feasible for use in paramedic emergency practice for out-of-hospital cardiac arrest. CONCLUSION AND RECOMMENDATIONS This literature review has highlighted the use of therapeutic hypothermia in the treatment of out-of-hospital cardiac arrests in the pre-hospital U.K. paramedic environment. The various techniques of invasive and non-invasive cooling have been investigated, and their key findings have been identified. This topic is of great significance in view of the fact that mortality among patients suffering from sudden cardiac arrests is high. Towards improving the rates of survival, crucial paramedic interventions including therapeutic hypothermia are essential. An integration of various interventions was found to be the most effective. Therapeutic hypothermia to cool the patient to a temperature between 320C and 340C should be initiated at the earliest, and should be administered along with other resuscitation interventions such as percutaneous coronary intervention, control of haemodynamics, blood glucose, ventilation and seizures. Therapeutic hypothermia acts on multiple pathways simultaneously and should be maintained for 12 to 24 hours, as recommended by the international guidelines and also found from evidence revealed by the literature. Research is currently being undertaken on other cerebral resuscitation approaches; thrombolytic therapy, specific infusion regimens or anti-apoptopic drugs may help to support mild therapeutic hypothermia in the future. It is recommended that an integrated multi-factorial protocol should be used, for optimal outcomes. It was found from the literature that a standardised protocol for paramedic practice is required for the treatment of patients suffering from sudden cardiac arrest is, in order to save the patient’s life successfully. According to Sunde (2007), this protocol included therapeutic hypothermia, percutaneous coronary intervention (PCI), and a focus on goal-directed treatment for the reperfusion period. An alternative emergency protocol supported by Nagao et al (2000) is is based on cardiopulmonary cerebral resuscitation (CPCR) using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia. ------------------------------ REFERENCES Bernard, S., Buist, M., Monteiro, O., Smith, K. (2003). Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: A preliminary report. Resuscitation, 56: pp.9-13. Retrieved on 2nd May, 2010 from: http://www.ncbi.nlm.nih.gov/pubmed/12847402?dopt=Abstract&holding=f1000,f1000m,isrctn Bernard, S.A., Gray, T.W., Buist, M.D., Jones, B.M., Silvester, W. et al. (2002). Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. New England Journal of Medicine, 346(8): pp.557-563. Retrieved on 2nd May, 2010 from: https://emergencycare.nhmrc.gov.au/blog/files/Treatment%20of%20cardiac%20arrest%20survivors%20with%20induced%20hypothermia.pdf Bottiger, B.W., Schneider, A. and Popp, E. (2007). Number needed to treat = six: therapeutic hypothermia following cardiac arrest – an effective and cheap approach to save lives. Critical Care, 11: pp.162-163. Bruel, C., Parienti, J.-J., Marie, W., Arrot, X., Daubin, C. et al. Mild hypothermia during advanced life support: A preliminary study in out-of-hospital cardiac arrest. Critical Care, 12(1): pp.1-7. ERC (European Resuscitation Council). (2005). European Resuscitation Council guidelines for resuscitation. Resuscitation, 67: pp.S1-S189. Felberg, R.A., Krieger, D.W., Chuang, D.E., Persse, W.S. and Burgin, S.L. (2001). Hypothermia after cardiac arrest: Feasibility and safety of an external cooling protocol. Circulation, 104: pp.1799-1804. Ferreira, I.A., Schutte, M., Oosterloo, E., Dekker, W., Mooi, B.W., Dambrink, J.H.E. (2009). Therapeutic mild hypothermia improves outcome after out-of-hospital cardiac arrest. Netherlands Heart Journal, 17(10): pp.378-385. Retrieved on 2nd May, 2010 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773029/pdf/nhj1737800.pdf Hammer, L, Adrie, C. and Timsit, J.-F. (2008). Early cooling in cardiac arrest: What is the evidence? In J.-L. Vincent (Ed.). Intensive care medicine: Annual update 2008. London: Springer: pp.137-146. Haugk, M., Sterz, F., Grassberger, M., Uray, T., Kliegel, A., Janata, A. et al. (2007). Feasibility and efficacy of a new non-invasive surface cooling device in post- resuscitation intensive care medicine. Resuscitation, 75(1): pp.76-81. HCASG (Hypothermia after Cardiac Arrest Study Group). (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine, 346(8): pp.549-556. Holzer, M., Bernard, S.A., Hachimi-Idrissi, S., Roine, R.O., Sterz, F. et al. (2005). Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis. Critical Care Medicine, 33: pp.414-418. Kim, F., Olsufka, M., Nichol, G., Copass, M.K. and Cobb, L.A. (2009). The use of pre- hospital mild hypothermia after resuscitation from out-of-hospital cardiac arrest. Journal of Neurotrauma, 26(3): pp.359-363. Merchant, R.M., Becker, L.B., Abella, B.S., ASch, D.A. and Groeneveld, P.W. (2009). Cost-effectiveness of therapeutic hypothermia after cardiac arrest. Circulation: Cardiovascular Quality and Outcomes, 2: pp.421-428. Meybohm, P., Gruenewald, M., Albrecht, M., ZAcharowski, K.D., Lucius, R. et al. (2009). Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling. PlosOne, 4(10): pp.e7588-e7598. Retrieved on 2nd May, 2010 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764338/pdf/pone.0007588.pdf Nagao, K., Hayashi, N., Kanmatsuse, K., Arima, K., Ohtsuki, J. et al. (2000). Cardio- pulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital. Journal of the American College of Cardiology, 36: pp.776-783. Retrieved on 2nd May, 2010 from: http://linkinghub.elsevier.com/retrieve/pii/S0735109700007798 Nolan, J.P., Morley, P.T., Hoek, T.L., and Hickey, R.W. (2003). Therapeutic hypothermia after cardiac arrest. An Advisory Statement by the Advancement Life Support Task Force of the International Liaison Committee on Resuscitation. Resuscitation, 57: pp.231-235. Pichon, N., Amiel, J.B., Francois, B., Dugard, A. Etchecopar, C. et al. (2007). Efficacy of and tolerance to mild induced hypothermia after out-of-hospital cardiac arrest using an endovascular cooling system. Critical Care, 11(3): R71, pp.1-8. Polit, C. and Beck, T. (2009). Essentials Nursing Research. Edition 7. London: Lippincott Williams & Wilkins. Schneider, A., Bottiger, B.W. and Popp, E. (2009). Cerebral resuscitation after cardio- circulatory arrest. Cerebral Resuscitation, 108(3): pp.971-980. Storm, C., Nee, J., Krueger, A., Schefold, J.C. and Hasper, D. (2010). 2-year survival of patients undergoing mild hypothermia treatment after ventricular fibrillation cardiac arrest is significantly improved compared to historical controls. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 18(2): pp.1-4. Retrieved on 2nd May, 2010 from: http://www.sjtrem.com/content/pdf/1757-7241-18-2.pdf Sunde, K., Pytte, M., Jacobsen, D., Mangschaud, A., Jensena, L.P. et al. (2007). Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation, 73: pp.29-39. Tiainen, M., Roine, R.O., Pettila, V. and Takkunen, O. (2003). Treated with hypothermia serum neuron-specific enolase and S-100B protein in cardiac arrest patients. Stroke, 34: pp.2881-2886. Tisherman, S.A. and Sterz, F. (2005). Therapeutic hypothermia. London: Springer. APPENDIX Table Summarizing the Research Articles Reviewed on the Methods of Administering Hypothermia for Cardiac Arrest, by Paramedics Title Publication Date Study Design Population Interventions Outcome Measures Statistical Analysis Summary of Results (1) Mild hypothermia during advanced life support: A preliminary study in out-of-hospital cardiac arrest. By Bruel et al (2008) 2008 Prospective observational, multicenter clinical trial conducted in Emergency Medical Services units and in a medical intensive care unit. 33 patients comatose patients aged 18 to 70 years suffering nontraumatic OHCA were eligible, regardless of their initial cardiac rhythm. Invasive intravascular cooling method. The therapeutic infusion of 2 litres of normal saline at 4°C before return of spontaneous circulation during Cardiopulmonary resuscitation after out of hospital cardiac Arrest. After intravenous cooling, the temperature decreased by 2.1°C to a mean body temperature of 33.3°C (interquartile range 32.3 to 34.3°C). Quantitative variables were expressed as mean ± standard deviation or median as appropriate. Qualitative variables were expressed as numbers and percentages. In order to modelize body temperature with time, The authors used the concept of mixed models with random intercepts. All statistical analyses were performed using Epi-Info V6 and SAS V9.1.3. P < 0.05 was considered statistically significant. Bruel et al (2008) concluded that prehospital induction of therapeutic hypothermia using infusion of 2 litres of 4°C normal saline during advanced life support was effective, safe and feasible. (2) 2-year survival of patients undergoing mild hypothermia treatment after ventricular fibrillation cardiac Arrest is significantly improved compared to historical controls. By Storm et al (2010) 2010 Prospective, observation study using a study sample and a historic control group. 107 consecutive comatose patients after ventricular fibrillation (VF) cardiac arrest were admitted to the Mobile Intensive Care Unit (MICU). Compared with 98 historical controls. Non-invasive method of inducing hypothermia by surface cooling. In the treatment group hypothermia was maintained for 24 hours using a surface cooling device (ArcticSun2000 of Medivance, USA). Neurological outcome was assessed at ICU discharge according to the Pittsburgh cerebral performance category (CPC). The SPSS software (Version 17.0) and Medcalc (Version 11.0) were used for statistical analysis and graphical depiction. Descriptive parameters are given as median and interquartile range (25-75 percentiles). Univariate analysis of differences between hypothermia patients and the control group was performed by using the Mann-Whitney-U test for non-parametric unpaired data. A Kaplan- Meier analysis of follow-up data concerning mortality after 24 months as well as a Cox-regression to adjust for confounders were calculated. Neurological outcome significantly improved after mild hypothermia treatment (hypothermia group CPC 1-2 59.8%, control group CPC 1-2 24.5%; p < 0.01). In Kaplan- Meier survival analysis hypothermia treatment was also associated with significantly improved 2-year probability for survival (hypothermia 55% vs. control 34%; p = 0.029). Cox-regression analysis revealed hypothermia treatment (p = 0.031) and age (p = 0.013) as independent predictors of 24-month survival. (3) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced Hypothermia By Bernard et al (2002) 2002 Randomized, controlled trial. 77 patients, of whom 43 of an average age of 66.8 years underwent hypthermia. The remaining 34 of an average age of 65 years underwent normothermia Non-invasive method of inducing hypothermia. Patients assigned to hypothermia underwent initial basic cooling measures in the ambulance. After arrival at the hospital, they underwent vigorous cooling in the emergency department after the initial assessment, by means of extensive application of ice packs around the head, neck, torso, and limbs. When the core temperature reached 33°C, the ice packs were removed, and this temperature was maintained for 12 hours, while the patient continued to be sedated and paralyzed to prevent shivering that might lead to warming. The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged home or to a rehabilitation facility. After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation, the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 (95 percent confidence interval, 1.47 to 18.76; P=0.011). The demographic characteristics of the patients were similar in the hypothermia and normothermia groups. Twenty-one of the 43 patients treated with hypothermia (49 percent) survived and had a good outcome — that is, they were discharged home or to a rehabilitation facility — as compared to only 9 of the 34 treated with normothermia (26 percent, P=0.046). Hypothermia was associated with a lower cardiac index, higher systemic vascular resistance, and hyperglycemia. There was no difference in the frequency of adverse events. Treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest. (4) Feasibility and efficacy of a new non-invasive surface cooling device in post- resuscitation intensive care medicine By Haugk et al (2007) 2007 Prospective observational case series. 27 patients, of an average age of 58 years. Non-invasive cooling was applied using the Medivance Arctic Sun System. This helps to reach a target temperature of 33 ◦C quickly, to maintain the target temperature for 24 hours and then to actively re-warm at 0.4 ◦C/hour to normothermia. Time from cooling start to target temperature was 137 (96, 168) minutes, cooling rate was 1.2◦C/h (0.8, 1.5), stability of target temperature during hypothermia maintenance phase was satisfactory at 33.0 ◦C (32.9, 33.1), and duration of re-warming was 428 (394, 452) minutes. For the graphic presentation of the temperature course the authors calculated the 5th and 95th percen-tile of bladder temperature for every minute of the cooling period. As cooling rates do not follow a Gaussian distribution, Spearman rank corelation was used for calculating the co-relation coefficient between initial bladder temperature and cooling rate. The Arctic Sun System in post-resuscitation care medicine for cooling cardiac arrest survivors is feasible and has proven to be highly effective in lowering patients’ temperature rapidly without inducing skin irritations. (5) Therapeutic mild hypothermia improves outcome after out-of-hospital cardiac arrest. By Ferreira et al (2009) 2009 Retrospective analysis of data recorded from January 2005 to December 2006. 75 con-secutive comatose subjects post-out of hospital cardiac arrest due to ventricular fibrillation and nonventricular fibrillation rhythms (asystole/ pulseless electrical activity) were studied in a single tertiary percutaneous coronary intervention (PCI) centre. 26 Subjects treated with conventional post-resuscitation care without TMH served as controls. Combination of non-invasive induction of hypothermia by surface cooling, and endovascular method of cooling. Outcome from controls at hospital discharge was compared with subjects treated with TMH (n=49; Oct 2005-Dec 2006). During the study period, TMH was induced by either external or endovascular approach. Data was collected by retrospective analysis of patients’ flowcharts. Variables were compared by the χ2 test. Odds ratios (OR) were calcu-lated with a logistic regression model in order to adjust the estimated effect of TMH on outcome for possible confounders. Primary outcome measures were survival and neurological outcome at hospital discharge. Secondary outcome measures included hypothermic parameters of endovas-cular and external cooling induced TMH. Differences were assumed significant at a p value Read More