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A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest
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Clinical Paper
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A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest夽
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T. Pellis a,∗ , F. Sanfilippo a,b , A. Roncarati a , F. Dibenedetto a , E. Franceschino c , D. Lovisa c , L. Magagnin c , W.P. Mercante a , V. Mione a a
Anaesthesia, Intensive Care and Emergency Medical Service, Santa Maria degli Angeli Hospital, Pordenone, Italy Cardiothoracic Intensive Care Unit, Intensive Care Directorate, St. George’s Hospital, SW17 0QT, United Kingdom c Emergency Medical Service, Santa Maria degli Angeli Hospital, Pordenone, Italy b
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Article history: Received 25 January 2014 Received in revised form 13 April 2014 Accepted 21 May 2014
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Keywords: Standard operative procedures Hyperthermic rebound 19 Audit 20 Target temperature management 21 Continuous professional development 22 Cerebral performance category 23 24 Q2 Neurological outcome 17 18
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Background: target temperature management (TTM) not only improves neurological outcome and survival but has given momentum to a more aggressive and comprehensive treatment after resuscitation. Yet, implementation issues represent the main obstacle to systematic treatment with TTM and aggressive post-resuscitation care. We devised a strategy to introduce, monitor and improve the quality of aggressive treatment after resuscitation, including TTM. Methods: standard operative procedures on aggressive post-resuscitation care, written jointly by physicians and nurses, were introduced in November 2004. Data of all resuscitated patients admitted to the ICU were prospectively acquired for 4 years. Periodic audits (every 16 months) were programmed, leading to three equally long periods. Several critical issues were identified after each audit and addressed subsequently, leading to a growing complexity of care. Moreover, after 2 years we introduced an educational programme with medical credits for all staff attending critically ill patients. Neurological outcome and survival at hospital discharged were compared to historical controls of the preceding 22 months. Results: 129 consecutively resuscitated patients were admitted to the ICU in the 4-year study period. Of these, 96 (74%) were treated with TTM and aggressive post-resuscitation care. Favourable neurological recovery among patients discharged alive significantly improved in the 4-year intervention period (81% vs. 50% in historical controls, p < 0.01). A composite endpoint of mortality and poor neurological outcome also improved (64% vs. 82% respectively, p < 0.05). Overall survival increased throughout the 4 years, leading to a significant improvement in the 3rd period compared to historical controls (60% vs. 35%; p < 0.05). Conclusions: we propose a strategy to successfully introduce and implement TTM and aggressive postresuscitation care via standard operative procedures, periodic audits and feedback. Continuous education among other factors contributed to a significant improvement in neurological outcome and a progressive increase in survival. © 2014 Published by Elsevier Ireland Ltd.
1. Introduction In the past years, much emphasis has been devoted by the international scientific community in promoting the implementation of target temperature management (TTM) as part of a more
夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.05.019. ∗ Corresponding author at: Santa Maria degli Angeli Hospital, Via Montereale 24, 33170 Pordenone, Italy. E-mail address: [email protected] (T. Pellis).
comprehensive and structured approach to the care of post-cardiac arrest (CA) patients ((null) (null)). Initially, TTM has been shown to improve both neurological outcome and survival, undermining thereby the widespread nihilist approach towards unconscious patients resuscitated from CA.6,7 Subsequently, TTM gave momentum to a growing appreciation that anoxic brain injury, main target of temperature control, is only one facet of a more complex pathophysiological state leading to the definition of post-CA syndrome and the recognition of multiple therapeutic targets to be addressed during post-resuscitation care ((null) (null)). However, both cultural issues and limited implementation strategies represent the main barriers to the prompt widespread
http://dx.doi.org/10.1016/j.resuscitation.2014.05.019 0300-9572/© 2014 Published by Elsevier Ireland Ltd.
Please cite this article in press as: Pellis T, et al. A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest. Resuscitation (2014), http://dx.doi.org/10.1016/j.resuscitation.2014.05.019
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adoption of TTM and a structured post-resuscitation care. Scepticism, lack of awareness, and increased workload concur to the low implementation rates observed both in Europe and United States ((null) (null)). To the contrary, centres able to motivate personnel to achieve therapeutic goals as part of a standardized post-resuscitation protocol have consistently shown significant improvements in survival with good neurological recovery ((null) (null)). Systematic treatment with TTM continues to be suboptimal particularly in Italy, with as a few as 16% of intensive care units (ICUs) reporting its use for unconscious resuscitated patients.1 In order to introduce TTM and to promote a more aggressive postresuscitation care, we adopted an implementation strategy centred on audits, feedbacks and educational courses over a 4-year period. We hypothesized that such implementation strategy would lead to improved neurological outcome of after CA. 2. Materials and methods
The study was approved by the Ethical Committee of the “Santa Maria degli Angeli” Hospital, Pordenone (Italy), and was part of a broader evaluation of the quality of care in CA patients at our Insti62 tution. 63 In October 2004 a joint committee of physicians and nurses 64 drafted and promoted standard operative procedures (SOPs) to 65 induce TTM. The committee included 3 doctors and 4 nurses 66 from the ICU. The physicians were also involved in pre-hospital 67 emergency medical service (EMS). The ICU nurses worked on dif68 ferent shifts in order to maximize assistance to the on-duty staff. 69 Furthermore, two EMS nurses were included in the committee 70 and subsequent educational efforts. The SOPs went beyond the 71 sole scope of managing temperature by providing directives to 72 73 deliver aggressive post-resuscitation care (Appendix, supplemen74Q3 tary material). SOPs were presented and discussed in a series of 75 meetings among the ICU, emergency department and EMS per76 sonnel. For 4 years (November 2004–November 2008), TTM and 77 aggressive post-resuscitation care were systematically applied to 78 eligible patients resuscitated and admitted to our ICU.
Timeline of changes introduced after audit processes Implementation of SOPs Boost induction of cooling g Introduction of a device for or temperatur temperature managementt Continuouss Professional Professiona Development m courses Systematic antipyretic y an avoidance of HR prophylaxis, h avoid Prompt dia diagnosis and tr t n of E/M treatment Structured approach to neurological prognostication 1st period 0
3rd period
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Fig. 1. Main changes introduced to standard operative procedures (SOPs). HR: hyperthermic rebound, E/M: epilepsy or myoclonus.
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The inclusion criterion was a Glasgow Coma Scale (GCS) <9 after return of spontaneous circulation. No restrictions regarding presenting rhythm, age or site of CA were applied. Exclusion criteria were end-stage diseases making 6-month survival unlikely and severe pre-existing neurological impairment. Overall, the main directives of the initial SOPs (November 2004) may be summarized as follow: 1. 2. 3. 4. 5.
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- Awareness on reducing the delay in starting cooling; - Pre-hospital cooling was emphasized; - Combining several cooling methods to boost induction was strongly advised; - A dedicated device for automatic temperature management (ArcticSun® , Medivance, Lousiville, Colorado, US) was introduced. The second audit performed after further 16 months produced the following changes in the last period:
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Pre-hospital cooling without delaying hospital admission; Continue/begin cooling in emergency department; Early cardiological assessment or coronary revascularization; Sedation and paralysis; Aggressive and standardized goal-directed management of: ventilation & oxygenation, blood pressure & organ perfusion, glycaemic control; 6. Temperature management: 32–34 ◦ C for 24 h followed by gradual rewarming.
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over dedicated meetings both to medical and nursing staff. Most controversial issues were also discussed during these meetings. The results of each audit triggered recommendations and changes in SOPs to improve the quality of care during the 2nd and 3rd period (Fig. 1). More specifically, the first audit after the initial 16 months of implementation yielded the following changes during the 2nd period:
Audits were performed every 16 months during the 4-year implementation. Audits were intended to ensure monitoring of ongoing results, highlight critical issues, promote improvements and introduce innovations. After each audit, feedbacks were provided
- systematic antipyretic prophylaxis (paracetamol) started during rewarming; - strong efforts on rigid maintenance of normothermia for 48 h in patients remaining unconscious after rewarming, using deviceassisted temperature management when appropriate; - a section on how to manage shivering was added; - emphasis on prompt diagnosis and aggressive pharmacological treatment of epilepsy and myoclonus; - a more structured approach to neurological prognosis in patients remaining unconscious after restoration of normothermia that included: daily clinical evaluation, electroencephalogram, somato-sensory evoked potentials, neuron-specific enolase, magnetic resonance imaging and discouraging limitation of care before day four. 2.3. Education Half way through the 4 years of intervention – during the second period – we introduced continuous professional development courses on TTM and post-resuscitation care. Instructors were both ICU and emergency personnel involved in developing SOPs. Five classes per year were held at the hospital simulation centre. Courses were opened to all personnel attending critical care patients and included hands-on sessions as well. During the 8-h course SOPs were thoroughly discussed.
Please cite this article in press as: Pellis T, et al. A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest. Resuscitation (2014), http://dx.doi.org/10.1016/j.resuscitation.2014.05.019
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Table 1 Characteristics of the populations studied.
2.4. Historical controls Cardiac arrest patients admitted to the ICU during the 22 months preceding TTM (January 2003–October 2004) served as historical controls. In-hospital data were prospectively acquired through electronic medical records during the intervention period. A prospective evaluation of survival and neurological outcome at hospital discharge was ongoing since 2003 as part of an epidemiological study previously reported ((null) (null)). Three investigators (EF, DL and LM), blinded to in-hospital treatment, assessed prospectively patient’s outcome according to the Utstein style. Only in-hospital medical records of historical controls were retrospectively reviewed. The primary endpoint was neurological recovery at hospital discharge. Neurological outcome was evaluated according to the cerebral performance category (CPC) scale,1 and a CPC 1-2, respectively no or moderate neurological impairment, was regarded as favourable recovery. When comparing outcome between historical controls and intervention period, all patients admitted were included even if they did not qualify for TTM and aggressive post-resuscitation care. Survival at hospital discharge was also investigated.
2.5. Statistical analysis IBM®
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Statistical analyses were performed using SPSS 17 for windows. The Kolmogorov–Smirnov test, histograms and normal quartile plots were examined to test for the normality assumption of continuous variables. Categorical variables are presented as number and percentage (%), while continuous variables as mean ± standard deviation (SD), or as median and 95% confidence interval (95% CI). Fisher exact test was used for categorical variables; Mann–Whitney and Kruskal–Wallis tests for independent samples were performed to compare continuous variables. Tests were two-sided and a result of p < 0.05 was considered statistically significant. All p values are quoted after Bonferroni corrections (where appropriate).
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3. Results
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3.1. Population
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In the 4 years since the adoption of SOPs, 129 patients resuscitated from CA were admitted to our ICU; of these 96 (74%) qualified for the aggressive post-resuscitation care (mean GCS at hospital admission 3.2 ± 0.7, median 3.0, 95% CI 3.1–3.4). The remaining patients not treated according to SOPs were either conscious (n = 5) or received compassionate care and died (n = 28). In the historical control group, 57 patients were resuscitated and admitted to the ICU. The characteristics of these two populations were comparable (Table 1). The intervention period was further divided in three subgroups by two interim audits. The patients’ characteristics in each period were similar with the exception of age, which was higher in the 1st period (Table 2).
Age Presenting rhythm VF/VT OOH-CA Male
Historical controls (n = 57)
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p Value
68.5 ± 14.8 42% (n = 24) 75% (n = 43) 70% (n = 40)
66.9 ± 13.5 49% (n = 63) 67% (n = 87) 71% (n = 91)
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Age is presented as mean ± standard deviation. VF/VT: ventricular fibrillation/ventricular tachycardia; OOH-CA: out-of-hospital cardiac arrest.
3.2. Outcome at hospital discharge In the intervention period favourable neurological recovery among patients discharged alive improved significantly compared to the historical controls (81%, n = 46/57 vs. 50%, n = 10/20 respectively; p < 0.05; Fig. 2). When analysing single periods within audits, the improvement in neurological outcome during the 3rd period was stable (83%, n = 20/24; p < 0.05 vs. historical controls; Fig. 2). In the 3rd period the number needed to treat for good neurological recovery was 4 (95% CI 2–7.1) with an absolute risk reduction of 32.5% (95% CI 14.1–50.8%). A composite endpoint of mortality and poor neurological outcome also improved. Hence survival with good recovery increased in the intervention period compared to controls (CPC 1–2: 36%, n = 46/83 vs. 18%, n = 10/57; p < 0.05). A significant improvement was not observed for overall survival at hospital discharge (44%, n = 57/129 vs. 35%, n = 20/57, respectively; p = 0.26). Yet, considering single periods within audits, during the 3rd period we observed an improvement in survival, which increased from 35% in historical controls to 60% (n = 24/40; p < 0.05) The number needed to treat for survival at hospital discharge in the 3rd period was 5 (95% CI 2.2–18.8) with an absolute risk reduction of 24.9% (95% CI 5.3–44.5%).
Fig. 2. Rate of survival and good neurological recovery at hospital discharge. Historical controls are compared with all patients admitted during the 4-year intervention period. Good neurological recovery is defined as cerebral performance category 1–2. *p < 0.05.
Table 2 Characteristics of the 4-year intervention divided in three equally long 16-months period. Intervention period (n = 129)
1st period (n = 44)
2nd period (n = 45)
3rd period (n = 40)
p Value
Age Presenting rhythm VF/VT OOH-CA Male Eligibility for aggressive PRC & TTM
72 ± 11.1 45% (n = 20) 59% (n = 26) 72% (n = 32) 71% (n = 32)
67 ± 13.6 40% (n = 18) 71% (n = 32) 69% (n = 31) 70% (n = 32)
61.2 ± 13.9 58% (n = 23) 70% (n = 28) 70% (n = 28) 80% (n = 32)
1st vs 2nd p = 0.06 1st vs 3rd p < 0.001 2nd vs 3rd p = 0.06 1st vs 2nd p = 0.76 1st vs 3rd p = 0.38 2nd vs 3rd p = 0.16 1st vs 2nd p = 0.33 1st vs 3rd p = 0.42 2nd vs 3rd p = 0.90 1st vs 2nd p = 0.87 1st vs 3rd p = 0.97 2nd vs 3rd p = 0.90 1st vs 2nd p = 0.95 1st vs 3rd p = 0.60 2nd vs 3rd p = 0.49
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3.3. Effect of audits, feedback and education 3.3.1. Education Over 2 years 10 classes were held; 250 physicians and nurses received theoretical and hands-on training on TTM and postresuscitation care, accounting for 95% of staff attending critically ill patients, including EMS personnel. 3.3.2. Optimization of out-of-hospital cooling and induction time Of the 69 patients with out-of-hospital CA eligible for TTM, 35% (n = 24/69) were cooled on the scene or during transport. Out-ofhospital cooling significantly reduced bladder temperature at ICU admission (median 34.5 ◦ C, 95% CI 33.6–35.0 ◦ C; vs. median 35.7 ◦ C, 95% CI 35.4–36.1 ◦ C; p < 0.001) and time to achieve target temperature (median 125 min, 95% CI 93–184 min; vs. median 240 min, 95% CI 210–282 min; p < 0.001). 3.3.3. Hyperthermic rebound On average rewarming lasted 11 ± 3 h. Of the 96 patients cooled, 89 survived at 12 h and 79 at 48 h after restoration of normothermia. Hyperthermic rebound after rewarming, defined as core temperature ≥37.8 ◦ C, occurred in 25% of patients (n = 22/89) within the first 12 h and in 49% (n = 39/79) within the first 48 h. Hyperthermic rebound during the first 12 h decreased from 36% in the 1st and 2nd period (n = 21/58) to 3% in the 3rd period (n = 1/31; p < 0.01). Similarly, fever within 48 h was significantly reduced from 57% (n = 32/55) to 29% (n = 7/24; p < 0.05). The rate of patients with best CPC 1–2 during ICU stay was significantly lower in those developing a hyperthermic rebound within the first 48 h after restoration of normothermia: 61% (n = 14/23) vs. 88% (n = 22/25; p < 0.05). At hospital discharge, post-hypothermia fever did not influence significantly neurological recovery (rebound group 63%, n = 12/19 vs. no rebound group 87%, n = 20/23; p = 0.14) and survival (rebound group 49%, n = 19/39 vs. no rebound group 57%, n = 23/40; p = 0.50).
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3.3.4. Neurological complications Epilepsy or myoclonus was diagnosed in 34% of patients treated with TTM and surviving to a neurological evaluation (n = 29/85). Of these 17% had a favourable neurological recovery at hospital discharge (n = 5, of which 4 in the 3rd period), whereas recovery was poor in 35% (n = 10) and 48% (n = 14) died in hospital.
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4. Discussion
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The introduction of SOPs for TTM and aggressive postresuscitation care dramatically improved the rate of favourable neurological recovery among patients discharged alive (81% vs. 50%). Moreover, an increase in survival could be achieved by revising and improving the quality of care, by means of periodic audits and continuous professional development courses (60% vs. 35%). Recently a large randomized trial confirmed high survival rates when temperature management is applied in combination with a structured post-resuscitation plan ((null) (null)). Moreover, several retrospective studies have shown that a standardized approach to post-resuscitation care positively impacts on neurological outcome and survival.14–19,24–33 These studies provide detailed protocols stating goals, objectives and strategies, but less emphasis is posed on the implementation methods to secure wide acceptance throughout the whole staff. Our experience not only reported similar improvements in neurological outcome and survival, but details methods and steps for achieving motivation and a broad staff acceptance of an increased workload that comes with more aggressive post-resuscitation care. We introduced TTM and standardized post-resuscitation care more than 1 year before formal inclusion of hypothermia into
resuscitation guidelines.1 First and foremost, we aimed at a positive interaction between the doctors and nurses drafting the SOPs. This group periodically revised and improved the SOPs, evaluated the quality of care delivered and highlighted potential critical aspects. SOPs were intentionally straightforward to ensure broad implementation (Appendix, supplementary material). Periodical audits, programmed every 16 months, were crucial to allow a progressive improvement in the quality and complexity of post-resuscitation care. We believe that the introduction of continuous professional development courses in order to involve all personnel assisting critically ill patients had a key-role in the implementation process. To the best of our knowledge, a similar detailed approach has not been reported by other centres yet. During the 2nd period ice-packs and a cold air blanket were substituted by an automated temperature management device to reduce nurse burden and to devote more resources to other elements of post-resuscitation care. Automatic temperature management was also encouraged in patients remaining unconscious after restoration of normothermia. Fever is common after CA and is associated with higher mortality and worse neurological outcome ((null) (null)). Given the high incidence of hyperthermic rebound following the restoration of normothermia, after the second audit we introduced systematic antipyretic prophylaxis. If necessary, temperature was actively managed and deep sedation re-instituted up to 48 h after rewarming, leading to a significant reduction in the rate of hyperthermic rebound within 12 and 48 h. Yet, this did not impact on outcome at hospital discharge but only on best CPC during ICU stay. Only recently post-rewarming fever has been association with worse neurological outcome at hospital discharge.36,37 Our results might differ due to the lower cut-off to define posthypothermia fever (37.8 ◦ C vs 38.5 ◦ C1 and 38.7 ◦ C2 ) and the limited sample size. Brain injury is the primary cause of death in patients regaining spontaneous circulation following CA.1 In the recent TTM-Trial, anoxic neurological insult accounted for approximately 60% mortality ((null) (null)). From the second audit we stressed the importance of a structured management of prognostication and neurological complications. Early withdrawal of life-sustaining support was discouraged. Prognosis was not merely relying on daily clinical evaluation but on a multimodal strategy, including neurophysiological testing. Directives to promote early diagnosis and standardize treatment of epilepsy and myoclonus were added to SOPs. Paradigm is the case of patients developing epilepsy and myoclonus, once regarded as infamous sign and invariably associated with poor outcome.3 Yet in our limited experience as many as 17% of patients presenting such complications after rewarming obtained a good neurological recovery. Not all directives and improvements in our SOPs were evidencebased and some, like pre-hospital cooling, are controversial. Others were based on a mere association, such as fever and poor recovery which still awaits a randomized trial to prove causality. We did not demonstrate an improvement in survival during the overall 4-year intervention period. This may be partially due to the small population size, particularly in the control group. Yet, when pooling poor neurological outcome with mortally (CPC 3–5) the improvement between controls and the 4-year period was significant (p = 0.015). Survival with good recovery is the ultimate endpoint of resuscitation. Furthermore, the learning curve of temperature management and other aspects of post-resuscitation care might not be the same. Hence, the prompt and stable improvement in favourable neurological recovery reflects a rapid learning curve for TTM, while the more gradual improvement in survival suggests a slower learning curve. Accordingly, we cannot exclude that initially most of
Please cite this article in press as: Pellis T, et al. A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest. Resuscitation (2014), http://dx.doi.org/10.1016/j.resuscitation.2014.05.019
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the attention might have been devoted to temperature management. Afterwards, with growing experience and with a device for automatic temperature management, part of this attention might have been re-directed to other aspects of post-resuscitation care. Moreover,
4.1. Limitations The study has several limitations. First of all, this is a single centre non randomized study and results may not entirely apply to different institutions and healthcare systems. The sample size is limited, particularly when dividing the 4-year intervention in three periods. Despite prospective data acquisition, historical controls were retrospectively investigated accessing stored electronic medical records. Nevertheless, most relevant endpoints such survival and neurological outcome were acquired prospectively ((null) (null)). Even if audits were pre-established every 16 months, interventions instituted following each audit were not predetermined. Therefore, we cannot exclude a mere learning curve effect over the years. The analysis between different periods was useful to investigate progressive improvements in the delivery of postresuscitation care, but suffers from the inherited difficulty in establishing real cut-off intervals. Moreover, the effects of TTM or other single interventions could not be distinguished from each other as part of a comprehensive, structured post-resuscitation care approach. Finally, the outcome of CA is influenced by a multitude of factors which may act as confounders and which we could not control or measure, among others the change in cardiopulmonary resuscitation guidelines in 2005. Indeed the three between-audits periods were not perfectly balanced. The 3rd period was younger than the 1st and had a numerical trend towards a higher rate of ventricular fibrillation. This may have contributed to partially explain the improvements observed. The absence of predefined power calculation warrants additional caution in interpreting our results particularly on the improvement in survival in the 3rd period. Nevertheless we observed a clear signal suggesting an improvement in the overall 4-years of intervention.
5. Conclusions Successful implementation of TTM and aggressive postresuscitation care can be secured by introducing SOPs written jointly by physicians and nurses, by planning periodic audits and providing feedbacks to the staff involved in the management of CA patients. Periodic revision and discussion of SOPs, along with continuous education broadly provided to staff attending critical care patients are among factors that contributed to a brisk improvement in neurological outcome and to a steady increase in survival after CA.
Conflict of interest statement Dr. Pellis reports personal fees from Bard Medical, as invited speaker, outside the submitted work. We wish to confirm that there are no known conflicts of interest associated with this publication by all the remaining authors and there has been no significant financial support for this work that could have influenced its outcome.
Uncited references [4,5,8–13,20–23,34,35,38,39].
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Acknowledgments We wish to thank nursing staff contributing to the postresuscitation care group over the years at our institution: Tiziana Ala, Francesca Ceccone, Iraly Maniago, Rosanna Piccolo, Anna Sanzani, Massimiliano Scaligine, Nicola Spagna, Sara Vaccari, Sandra Vallan. We wish to acknowledged the help of Dr. Giuseppe Ristagno for writing assistance and internal review. We are also thankful to Prof. Antonino Gullo for his constant support and mentorship. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.resuscitation. 2014.05.019. References 1. Deakin CD, Nolan JP, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation 2010;81:1305–52. 2. Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S768–86. 3. Nunnally ME, Jaeschke R, Bellingan GJ, et al. Targeted temperature management in critical care: a report and recommendations from five professional societies. Crit Care Med 2011;39:1113–25. 4. Nolan JP, Neumar RW, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation 2008;79:350–79. 5. Castren M, Silfvast T, Rubertsson S, et al. Scandinavian clinical practice guidelines for therapeutic hypothermia and post-resuscitation care after cardiac arrest. Acta Anaesthesiol Scand 2009;53:280–8. 6. HACA. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–56. 7. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. 8. Soreide E, Sunde K. Therapeutic hypothermia after out-of hospital cardiac arrest: how to secure worldwide implementation. Curr Opin Anaesthesiol 2008;21:209–15. 9. Kliegel A, Gamper G, Mayr H. Therapeutic hypothermia after cardiac arrest in Lower Austria – a cross-sectional survey. Eur J Emerg Med 2011;18:105–7. 10. Skulec R, Truhlar A, Knor J, Seblova J, Cerny V. The practice of therapeutic mild hypothermia in cardiac arrest survivors in the Czech republic. Minerva Anestesiol 2010;76:617–23. 11. Bigham BL, Dainty KN, Scales DC, Morrison LJ, Brooks SC. Predictors of adopting therapeutic hypothermia for post-cardiac arrest patients among Canadian emergency and critical care physicians. Resuscitation 2010;81:20–4. 12. Abella BS, Rhee JW, Huang KN, Vanden Hoek TL, Becker LB. Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey. Resuscitation 2005;64:181–6. 13. Merchant RM, Soar J, Skrifvars MB, et al. Therapeutic hypothermia utilization among physicians after resuscitation from cardiac arrest. Crit Care Med 2006;34:1935–40. 14. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007;73:29–39. 15. Tomte O, Andersen GO, Jacobsen D, Draegni T, Auestad B, Sunde K. Strong and weak aspects of an established post-resuscitation treatment protocol – a fiveyear observational study. Resuscitation 2011;82:1186–93. 16. Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 2006;34:1865–73. 17. Busch M, Soreide E, Lossius HM, Lexow K, Dickstein K. Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors. Acta Anaesthesiol Scand 2006;50:1277–83. 18. Knafelj R, Radsel P, Ploj T, Noc M. Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation 2007;74:227–34. 19. Belliard G, Catez E, Charron C, et al. Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation. Resuscitation 2007;75:252–9. 20. Bianchin A, Pellizzato N, Martano L, Castioni CA. Therapeutic hypothermia in Italian intensive care units: a national survey. Minerva Anestesiol 2009;75:357–62.
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21. Kette F, Pellis T. Increased survival despite a reduction in out-ofhospital ventricular fibrillation in north-east Italy. Resuscitation 2007;72:52–8. 22. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975;1:480–4. 23. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 ◦ C versus 36 ◦ C after cardiac arrest. New Engl J Med 2013;369:2197–206. 24. Lyon RM, Robertson CE, Clegg GR. Therapeutic hypothermia in the emergency department following out-of-hospital cardiac arrest. Emerg Med J 2010;27:418–23. 25. Storm C, Nee J, Krueger A, Schefold JC, Hasper D. 2-Year survival of patients undergoing mild hypothermia treatment after ventricular fibrillation cardiac arrest is significantly improved compared to historical controls. Scand J Trauma 2010;18:2. 26. Kory P, Weiner J, Mathew JP, et al. A rapid, safe, and low-cost technique for the induction of mild therapeutic hypothermia in post-cardiac arrest patients. Resuscitation 2011;82:15–20. 27. van der Wal G, Brinkman S, Bisschops LL, et al. Influence of mild therapeutic hypothermia after cardiac arrest on hospital mortality. Crit Care Med 2011;39:84–8. 28. Patil S, Bhayani S, Denton JM, Nolan J. Therapeutic hypothermia for out-ofhospital cardiac arrest: implementation in a district general hospital emergency department. Emerg Med J 2011;28:970–3. 29. Stub D, Hengel C, Chan W, et al. Usefulness of cooling and coronary catheterization to improve survival in out-of-hospital cardiac arrest. Am J Cardiol 2011;107:522–7. 30. Kulstad CE, Holt SC, Abrahamsen AA, Lovell EO. Therapeutic hypothermia protocol in a community emergency department. West J Emerg Med 2010;11:367–72.
31. Walters EL, Morawski K, Dorotta I, et al. Implementation of a post-cardiac arrest care bundle including therapeutic hypothermia and hemodynamic optimization in comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest: a feasibility study. Shock 2011;35:360–6. 32. Szumita PM, Baroletti S, Avery KR, et al. Implementation of a hospital-wide protocol for induced hypothermia following successfully resuscitated cardiac arrest. Crit Path Cardiol 2010;9:216–20. 33. Hinchey PR, Myers JB, Lewis R, et al. Improved out-of-hospital cardiac arrest survival after the sequential implementation of 2005 AHA guidelines for compressions, ventilations, and induced hypothermia: the Wake County experience. Ann Emerg Med 2010;56:348–57. 34. Nolan JP, Deakin CD, Soar J, Bottiger BW, Smith G. European Resuscitation Council guidelines for resuscitation 2005. Section 4. Adult advanced life support. Resuscitation 2005;67(Suppl. 1):S39–86. 35. Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med 2001;161:2007–12. 36. Leary M, Grossestreuer AV, Iannacone S, et al. Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest. Resuscitation 2013;84:1056–61. 37. Bro-Jeppesen J, Hassager C, Wanscher M, et al. Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest. Resuscitation 2013;84:1734–40. 38. Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 2012;84:337–42. 39. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;67:203–10.
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Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical Paper
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A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest夽
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T. Pellis a,∗ , F. Sanfilippo a,b , A. Roncarati a , F. Dibenedetto a , E. Franceschino c , D. Lovisa c , L. Magagnin c , W.P. Mercante a , V. Mione a a
Anaesthesia, Intensive Care and Emergency Medical Service, Santa Maria degli Angeli Hospital, Pordenone, Italy Cardiothoracic Intensive Care Unit, Intensive Care Directorate, St. George’s Hospital, SW17 0QT, United Kingdom c Emergency Medical Service, Santa Maria degli Angeli Hospital, Pordenone, Italy b
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Article history: Received 25 January 2014 Received in revised form 13 April 2014 Accepted 21 May 2014
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Keywords: Standard operative procedures Hyperthermic rebound 19 Audit 20 Target temperature management 21 Continuous professional development 22 Cerebral performance category 23 24 Q2 Neurological outcome 17 18
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Background: target temperature management (TTM) not only improves neurological outcome and survival but has given momentum to a more aggressive and comprehensive treatment after resuscitation. Yet, implementation issues represent the main obstacle to systematic treatment with TTM and aggressive post-resuscitation care. We devised a strategy to introduce, monitor and improve the quality of aggressive treatment after resuscitation, including TTM. Methods: standard operative procedures on aggressive post-resuscitation care, written jointly by physicians and nurses, were introduced in November 2004. Data of all resuscitated patients admitted to the ICU were prospectively acquired for 4 years. Periodic audits (every 16 months) were programmed, leading to three equally long periods. Several critical issues were identified after each audit and addressed subsequently, leading to a growing complexity of care. Moreover, after 2 years we introduced an educational programme with medical credits for all staff attending critically ill patients. Neurological outcome and survival at hospital discharged were compared to historical controls of the preceding 22 months. Results: 129 consecutively resuscitated patients were admitted to the ICU in the 4-year study period. Of these, 96 (74%) were treated with TTM and aggressive post-resuscitation care. Favourable neurological recovery among patients discharged alive significantly improved in the 4-year intervention period (81% vs. 50% in historical controls, p < 0.01). A composite endpoint of mortality and poor neurological outcome also improved (64% vs. 82% respectively, p < 0.05). Overall survival increased throughout the 4 years, leading to a significant improvement in the 3rd period compared to historical controls (60% vs. 35%; p < 0.05). Conclusions: we propose a strategy to successfully introduce and implement TTM and aggressive postresuscitation care via standard operative procedures, periodic audits and feedback. Continuous education among other factors contributed to a significant improvement in neurological outcome and a progressive increase in survival. © 2014 Published by Elsevier Ireland Ltd.
1. Introduction In the past years, much emphasis has been devoted by the international scientific community in promoting the implementation of target temperature management (TTM) as part of a more
夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.05.019. ∗ Corresponding author at: Santa Maria degli Angeli Hospital, Via Montereale 24, 33170 Pordenone, Italy. E-mail address: [email protected] (T. Pellis).
comprehensive and structured approach to the care of post-cardiac arrest (CA) patients ((null) (null)). Initially, TTM has been shown to improve both neurological outcome and survival, undermining thereby the widespread nihilist approach towards unconscious patients resuscitated from CA.6,7 Subsequently, TTM gave momentum to a growing appreciation that anoxic brain injury, main target of temperature control, is only one facet of a more complex pathophysiological state leading to the definition of post-CA syndrome and the recognition of multiple therapeutic targets to be addressed during post-resuscitation care ((null) (null)). However, both cultural issues and limited implementation strategies represent the main barriers to the prompt widespread
http://dx.doi.org/10.1016/j.resuscitation.2014.05.019 0300-9572/© 2014 Published by Elsevier Ireland Ltd.
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adoption of TTM and a structured post-resuscitation care. Scepticism, lack of awareness, and increased workload concur to the low implementation rates observed both in Europe and United States ((null) (null)). To the contrary, centres able to motivate personnel to achieve therapeutic goals as part of a standardized post-resuscitation protocol have consistently shown significant improvements in survival with good neurological recovery ((null) (null)). Systematic treatment with TTM continues to be suboptimal particularly in Italy, with as a few as 16% of intensive care units (ICUs) reporting its use for unconscious resuscitated patients.1 In order to introduce TTM and to promote a more aggressive postresuscitation care, we adopted an implementation strategy centred on audits, feedbacks and educational courses over a 4-year period. We hypothesized that such implementation strategy would lead to improved neurological outcome of after CA. 2. Materials and methods
The study was approved by the Ethical Committee of the “Santa Maria degli Angeli” Hospital, Pordenone (Italy), and was part of a broader evaluation of the quality of care in CA patients at our Insti62 tution. 63 In October 2004 a joint committee of physicians and nurses 64 drafted and promoted standard operative procedures (SOPs) to 65 induce TTM. The committee included 3 doctors and 4 nurses 66 from the ICU. The physicians were also involved in pre-hospital 67 emergency medical service (EMS). The ICU nurses worked on dif68 ferent shifts in order to maximize assistance to the on-duty staff. 69 Furthermore, two EMS nurses were included in the committee 70 and subsequent educational efforts. The SOPs went beyond the 71 sole scope of managing temperature by providing directives to 72 73 deliver aggressive post-resuscitation care (Appendix, supplemen74Q3 tary material). SOPs were presented and discussed in a series of 75 meetings among the ICU, emergency department and EMS per76 sonnel. For 4 years (November 2004–November 2008), TTM and 77 aggressive post-resuscitation care were systematically applied to 78 eligible patients resuscitated and admitted to our ICU.
Timeline of changes introduced after audit processes Implementation of SOPs Boost induction of cooling g Introduction of a device for or temperatur temperature managementt Continuouss Professional Professiona Development m courses Systematic antipyretic y an avoidance of HR prophylaxis, h avoid Prompt dia diagnosis and tr t n of E/M treatment Structured approach to neurological prognostication 1st period 0
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Fig. 1. Main changes introduced to standard operative procedures (SOPs). HR: hyperthermic rebound, E/M: epilepsy or myoclonus.
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The inclusion criterion was a Glasgow Coma Scale (GCS) <9 after return of spontaneous circulation. No restrictions regarding presenting rhythm, age or site of CA were applied. Exclusion criteria were end-stage diseases making 6-month survival unlikely and severe pre-existing neurological impairment. Overall, the main directives of the initial SOPs (November 2004) may be summarized as follow: 1. 2. 3. 4. 5.
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- Awareness on reducing the delay in starting cooling; - Pre-hospital cooling was emphasized; - Combining several cooling methods to boost induction was strongly advised; - A dedicated device for automatic temperature management (ArcticSun® , Medivance, Lousiville, Colorado, US) was introduced. The second audit performed after further 16 months produced the following changes in the last period:
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Pre-hospital cooling without delaying hospital admission; Continue/begin cooling in emergency department; Early cardiological assessment or coronary revascularization; Sedation and paralysis; Aggressive and standardized goal-directed management of: ventilation & oxygenation, blood pressure & organ perfusion, glycaemic control; 6. Temperature management: 32–34 ◦ C for 24 h followed by gradual rewarming.
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over dedicated meetings both to medical and nursing staff. Most controversial issues were also discussed during these meetings. The results of each audit triggered recommendations and changes in SOPs to improve the quality of care during the 2nd and 3rd period (Fig. 1). More specifically, the first audit after the initial 16 months of implementation yielded the following changes during the 2nd period:
Audits were performed every 16 months during the 4-year implementation. Audits were intended to ensure monitoring of ongoing results, highlight critical issues, promote improvements and introduce innovations. After each audit, feedbacks were provided
- systematic antipyretic prophylaxis (paracetamol) started during rewarming; - strong efforts on rigid maintenance of normothermia for 48 h in patients remaining unconscious after rewarming, using deviceassisted temperature management when appropriate; - a section on how to manage shivering was added; - emphasis on prompt diagnosis and aggressive pharmacological treatment of epilepsy and myoclonus; - a more structured approach to neurological prognosis in patients remaining unconscious after restoration of normothermia that included: daily clinical evaluation, electroencephalogram, somato-sensory evoked potentials, neuron-specific enolase, magnetic resonance imaging and discouraging limitation of care before day four. 2.3. Education Half way through the 4 years of intervention – during the second period – we introduced continuous professional development courses on TTM and post-resuscitation care. Instructors were both ICU and emergency personnel involved in developing SOPs. Five classes per year were held at the hospital simulation centre. Courses were opened to all personnel attending critical care patients and included hands-on sessions as well. During the 8-h course SOPs were thoroughly discussed.
Please cite this article in press as: Pellis T, et al. A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest. Resuscitation (2014), http://dx.doi.org/10.1016/j.resuscitation.2014.05.019
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Table 1 Characteristics of the populations studied.
2.4. Historical controls Cardiac arrest patients admitted to the ICU during the 22 months preceding TTM (January 2003–October 2004) served as historical controls. In-hospital data were prospectively acquired through electronic medical records during the intervention period. A prospective evaluation of survival and neurological outcome at hospital discharge was ongoing since 2003 as part of an epidemiological study previously reported ((null) (null)). Three investigators (EF, DL and LM), blinded to in-hospital treatment, assessed prospectively patient’s outcome according to the Utstein style. Only in-hospital medical records of historical controls were retrospectively reviewed. The primary endpoint was neurological recovery at hospital discharge. Neurological outcome was evaluated according to the cerebral performance category (CPC) scale,1 and a CPC 1-2, respectively no or moderate neurological impairment, was regarded as favourable recovery. When comparing outcome between historical controls and intervention period, all patients admitted were included even if they did not qualify for TTM and aggressive post-resuscitation care. Survival at hospital discharge was also investigated.
2.5. Statistical analysis IBM®
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Statistical analyses were performed using SPSS 17 for windows. The Kolmogorov–Smirnov test, histograms and normal quartile plots were examined to test for the normality assumption of continuous variables. Categorical variables are presented as number and percentage (%), while continuous variables as mean ± standard deviation (SD), or as median and 95% confidence interval (95% CI). Fisher exact test was used for categorical variables; Mann–Whitney and Kruskal–Wallis tests for independent samples were performed to compare continuous variables. Tests were two-sided and a result of p < 0.05 was considered statistically significant. All p values are quoted after Bonferroni corrections (where appropriate).
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3. Results
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3.1. Population
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In the 4 years since the adoption of SOPs, 129 patients resuscitated from CA were admitted to our ICU; of these 96 (74%) qualified for the aggressive post-resuscitation care (mean GCS at hospital admission 3.2 ± 0.7, median 3.0, 95% CI 3.1–3.4). The remaining patients not treated according to SOPs were either conscious (n = 5) or received compassionate care and died (n = 28). In the historical control group, 57 patients were resuscitated and admitted to the ICU. The characteristics of these two populations were comparable (Table 1). The intervention period was further divided in three subgroups by two interim audits. The patients’ characteristics in each period were similar with the exception of age, which was higher in the 1st period (Table 2).
Age Presenting rhythm VF/VT OOH-CA Male
Historical controls (n = 57)
Intervention period (n = 129)
p Value
68.5 ± 14.8 42% (n = 24) 75% (n = 43) 70% (n = 40)
66.9 ± 13.5 49% (n = 63) 67% (n = 87) 71% (n = 91)
0.48 0.49 0.35 0.90
Age is presented as mean ± standard deviation. VF/VT: ventricular fibrillation/ventricular tachycardia; OOH-CA: out-of-hospital cardiac arrest.
3.2. Outcome at hospital discharge In the intervention period favourable neurological recovery among patients discharged alive improved significantly compared to the historical controls (81%, n = 46/57 vs. 50%, n = 10/20 respectively; p < 0.05; Fig. 2). When analysing single periods within audits, the improvement in neurological outcome during the 3rd period was stable (83%, n = 20/24; p < 0.05 vs. historical controls; Fig. 2). In the 3rd period the number needed to treat for good neurological recovery was 4 (95% CI 2–7.1) with an absolute risk reduction of 32.5% (95% CI 14.1–50.8%). A composite endpoint of mortality and poor neurological outcome also improved. Hence survival with good recovery increased in the intervention period compared to controls (CPC 1–2: 36%, n = 46/83 vs. 18%, n = 10/57; p < 0.05). A significant improvement was not observed for overall survival at hospital discharge (44%, n = 57/129 vs. 35%, n = 20/57, respectively; p = 0.26). Yet, considering single periods within audits, during the 3rd period we observed an improvement in survival, which increased from 35% in historical controls to 60% (n = 24/40; p < 0.05) The number needed to treat for survival at hospital discharge in the 3rd period was 5 (95% CI 2.2–18.8) with an absolute risk reduction of 24.9% (95% CI 5.3–44.5%).
Fig. 2. Rate of survival and good neurological recovery at hospital discharge. Historical controls are compared with all patients admitted during the 4-year intervention period. Good neurological recovery is defined as cerebral performance category 1–2. *p < 0.05.
Table 2 Characteristics of the 4-year intervention divided in three equally long 16-months period. Intervention period (n = 129)
1st period (n = 44)
2nd period (n = 45)
3rd period (n = 40)
p Value
Age Presenting rhythm VF/VT OOH-CA Male Eligibility for aggressive PRC & TTM
72 ± 11.1 45% (n = 20) 59% (n = 26) 72% (n = 32) 71% (n = 32)
67 ± 13.6 40% (n = 18) 71% (n = 32) 69% (n = 31) 70% (n = 32)
61.2 ± 13.9 58% (n = 23) 70% (n = 28) 70% (n = 28) 80% (n = 32)
1st vs 2nd p = 0.06 1st vs 3rd p < 0.001 2nd vs 3rd p = 0.06 1st vs 2nd p = 0.76 1st vs 3rd p = 0.38 2nd vs 3rd p = 0.16 1st vs 2nd p = 0.33 1st vs 3rd p = 0.42 2nd vs 3rd p = 0.90 1st vs 2nd p = 0.87 1st vs 3rd p = 0.97 2nd vs 3rd p = 0.90 1st vs 2nd p = 0.95 1st vs 3rd p = 0.60 2nd vs 3rd p = 0.49
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3.3. Effect of audits, feedback and education 3.3.1. Education Over 2 years 10 classes were held; 250 physicians and nurses received theoretical and hands-on training on TTM and postresuscitation care, accounting for 95% of staff attending critically ill patients, including EMS personnel. 3.3.2. Optimization of out-of-hospital cooling and induction time Of the 69 patients with out-of-hospital CA eligible for TTM, 35% (n = 24/69) were cooled on the scene or during transport. Out-ofhospital cooling significantly reduced bladder temperature at ICU admission (median 34.5 ◦ C, 95% CI 33.6–35.0 ◦ C; vs. median 35.7 ◦ C, 95% CI 35.4–36.1 ◦ C; p < 0.001) and time to achieve target temperature (median 125 min, 95% CI 93–184 min; vs. median 240 min, 95% CI 210–282 min; p < 0.001). 3.3.3. Hyperthermic rebound On average rewarming lasted 11 ± 3 h. Of the 96 patients cooled, 89 survived at 12 h and 79 at 48 h after restoration of normothermia. Hyperthermic rebound after rewarming, defined as core temperature ≥37.8 ◦ C, occurred in 25% of patients (n = 22/89) within the first 12 h and in 49% (n = 39/79) within the first 48 h. Hyperthermic rebound during the first 12 h decreased from 36% in the 1st and 2nd period (n = 21/58) to 3% in the 3rd period (n = 1/31; p < 0.01). Similarly, fever within 48 h was significantly reduced from 57% (n = 32/55) to 29% (n = 7/24; p < 0.05). The rate of patients with best CPC 1–2 during ICU stay was significantly lower in those developing a hyperthermic rebound within the first 48 h after restoration of normothermia: 61% (n = 14/23) vs. 88% (n = 22/25; p < 0.05). At hospital discharge, post-hypothermia fever did not influence significantly neurological recovery (rebound group 63%, n = 12/19 vs. no rebound group 87%, n = 20/23; p = 0.14) and survival (rebound group 49%, n = 19/39 vs. no rebound group 57%, n = 23/40; p = 0.50).
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3.3.4. Neurological complications Epilepsy or myoclonus was diagnosed in 34% of patients treated with TTM and surviving to a neurological evaluation (n = 29/85). Of these 17% had a favourable neurological recovery at hospital discharge (n = 5, of which 4 in the 3rd period), whereas recovery was poor in 35% (n = 10) and 48% (n = 14) died in hospital.
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The introduction of SOPs for TTM and aggressive postresuscitation care dramatically improved the rate of favourable neurological recovery among patients discharged alive (81% vs. 50%). Moreover, an increase in survival could be achieved by revising and improving the quality of care, by means of periodic audits and continuous professional development courses (60% vs. 35%). Recently a large randomized trial confirmed high survival rates when temperature management is applied in combination with a structured post-resuscitation plan ((null) (null)). Moreover, several retrospective studies have shown that a standardized approach to post-resuscitation care positively impacts on neurological outcome and survival.14–19,24–33 These studies provide detailed protocols stating goals, objectives and strategies, but less emphasis is posed on the implementation methods to secure wide acceptance throughout the whole staff. Our experience not only reported similar improvements in neurological outcome and survival, but details methods and steps for achieving motivation and a broad staff acceptance of an increased workload that comes with more aggressive post-resuscitation care. We introduced TTM and standardized post-resuscitation care more than 1 year before formal inclusion of hypothermia into
resuscitation guidelines.1 First and foremost, we aimed at a positive interaction between the doctors and nurses drafting the SOPs. This group periodically revised and improved the SOPs, evaluated the quality of care delivered and highlighted potential critical aspects. SOPs were intentionally straightforward to ensure broad implementation (Appendix, supplementary material). Periodical audits, programmed every 16 months, were crucial to allow a progressive improvement in the quality and complexity of post-resuscitation care. We believe that the introduction of continuous professional development courses in order to involve all personnel assisting critically ill patients had a key-role in the implementation process. To the best of our knowledge, a similar detailed approach has not been reported by other centres yet. During the 2nd period ice-packs and a cold air blanket were substituted by an automated temperature management device to reduce nurse burden and to devote more resources to other elements of post-resuscitation care. Automatic temperature management was also encouraged in patients remaining unconscious after restoration of normothermia. Fever is common after CA and is associated with higher mortality and worse neurological outcome ((null) (null)). Given the high incidence of hyperthermic rebound following the restoration of normothermia, after the second audit we introduced systematic antipyretic prophylaxis. If necessary, temperature was actively managed and deep sedation re-instituted up to 48 h after rewarming, leading to a significant reduction in the rate of hyperthermic rebound within 12 and 48 h. Yet, this did not impact on outcome at hospital discharge but only on best CPC during ICU stay. Only recently post-rewarming fever has been association with worse neurological outcome at hospital discharge.36,37 Our results might differ due to the lower cut-off to define posthypothermia fever (37.8 ◦ C vs 38.5 ◦ C1 and 38.7 ◦ C2 ) and the limited sample size. Brain injury is the primary cause of death in patients regaining spontaneous circulation following CA.1 In the recent TTM-Trial, anoxic neurological insult accounted for approximately 60% mortality ((null) (null)). From the second audit we stressed the importance of a structured management of prognostication and neurological complications. Early withdrawal of life-sustaining support was discouraged. Prognosis was not merely relying on daily clinical evaluation but on a multimodal strategy, including neurophysiological testing. Directives to promote early diagnosis and standardize treatment of epilepsy and myoclonus were added to SOPs. Paradigm is the case of patients developing epilepsy and myoclonus, once regarded as infamous sign and invariably associated with poor outcome.3 Yet in our limited experience as many as 17% of patients presenting such complications after rewarming obtained a good neurological recovery. Not all directives and improvements in our SOPs were evidencebased and some, like pre-hospital cooling, are controversial. Others were based on a mere association, such as fever and poor recovery which still awaits a randomized trial to prove causality. We did not demonstrate an improvement in survival during the overall 4-year intervention period. This may be partially due to the small population size, particularly in the control group. Yet, when pooling poor neurological outcome with mortally (CPC 3–5) the improvement between controls and the 4-year period was significant (p = 0.015). Survival with good recovery is the ultimate endpoint of resuscitation. Furthermore, the learning curve of temperature management and other aspects of post-resuscitation care might not be the same. Hence, the prompt and stable improvement in favourable neurological recovery reflects a rapid learning curve for TTM, while the more gradual improvement in survival suggests a slower learning curve. Accordingly, we cannot exclude that initially most of
Please cite this article in press as: Pellis T, et al. A 4-year implementation strategy of aggressive post-resuscitation care and temperature management after cardiac arrest. Resuscitation (2014), http://dx.doi.org/10.1016/j.resuscitation.2014.05.019
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the attention might have been devoted to temperature management. Afterwards, with growing experience and with a device for automatic temperature management, part of this attention might have been re-directed to other aspects of post-resuscitation care. Moreover,
4.1. Limitations The study has several limitations. First of all, this is a single centre non randomized study and results may not entirely apply to different institutions and healthcare systems. The sample size is limited, particularly when dividing the 4-year intervention in three periods. Despite prospective data acquisition, historical controls were retrospectively investigated accessing stored electronic medical records. Nevertheless, most relevant endpoints such survival and neurological outcome were acquired prospectively ((null) (null)). Even if audits were pre-established every 16 months, interventions instituted following each audit were not predetermined. Therefore, we cannot exclude a mere learning curve effect over the years. The analysis between different periods was useful to investigate progressive improvements in the delivery of postresuscitation care, but suffers from the inherited difficulty in establishing real cut-off intervals. Moreover, the effects of TTM or other single interventions could not be distinguished from each other as part of a comprehensive, structured post-resuscitation care approach. Finally, the outcome of CA is influenced by a multitude of factors which may act as confounders and which we could not control or measure, among others the change in cardiopulmonary resuscitation guidelines in 2005. Indeed the three between-audits periods were not perfectly balanced. The 3rd period was younger than the 1st and had a numerical trend towards a higher rate of ventricular fibrillation. This may have contributed to partially explain the improvements observed. The absence of predefined power calculation warrants additional caution in interpreting our results particularly on the improvement in survival in the 3rd period. Nevertheless we observed a clear signal suggesting an improvement in the overall 4-years of intervention.
5. Conclusions Successful implementation of TTM and aggressive postresuscitation care can be secured by introducing SOPs written jointly by physicians and nurses, by planning periodic audits and providing feedbacks to the staff involved in the management of CA patients. Periodic revision and discussion of SOPs, along with continuous education broadly provided to staff attending critical care patients are among factors that contributed to a brisk improvement in neurological outcome and to a steady increase in survival after CA.
Conflict of interest statement Dr. Pellis reports personal fees from Bard Medical, as invited speaker, outside the submitted work. We wish to confirm that there are no known conflicts of interest associated with this publication by all the remaining authors and there has been no significant financial support for this work that could have influenced its outcome.
Uncited references [4,5,8–13,20–23,34,35,38,39].
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Acknowledgments We wish to thank nursing staff contributing to the postresuscitation care group over the years at our institution: Tiziana Ala, Francesca Ceccone, Iraly Maniago, Rosanna Piccolo, Anna Sanzani, Massimiliano Scaligine, Nicola Spagna, Sara Vaccari, Sandra Vallan. We wish to acknowledged the help of Dr. Giuseppe Ristagno for writing assistance and internal review. We are also thankful to Prof. Antonino Gullo for his constant support and mentorship. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.resuscitation. 2014.05.019. References 1. Deakin CD, Nolan JP, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation 2010;81:1305–52. 2. Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S768–86. 3. Nunnally ME, Jaeschke R, Bellingan GJ, et al. Targeted temperature management in critical care: a report and recommendations from five professional societies. Crit Care Med 2011;39:1113–25. 4. Nolan JP, Neumar RW, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation 2008;79:350–79. 5. Castren M, Silfvast T, Rubertsson S, et al. Scandinavian clinical practice guidelines for therapeutic hypothermia and post-resuscitation care after cardiac arrest. Acta Anaesthesiol Scand 2009;53:280–8. 6. HACA. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–56. 7. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. 8. Soreide E, Sunde K. Therapeutic hypothermia after out-of hospital cardiac arrest: how to secure worldwide implementation. Curr Opin Anaesthesiol 2008;21:209–15. 9. Kliegel A, Gamper G, Mayr H. Therapeutic hypothermia after cardiac arrest in Lower Austria – a cross-sectional survey. Eur J Emerg Med 2011;18:105–7. 10. Skulec R, Truhlar A, Knor J, Seblova J, Cerny V. The practice of therapeutic mild hypothermia in cardiac arrest survivors in the Czech republic. Minerva Anestesiol 2010;76:617–23. 11. Bigham BL, Dainty KN, Scales DC, Morrison LJ, Brooks SC. Predictors of adopting therapeutic hypothermia for post-cardiac arrest patients among Canadian emergency and critical care physicians. Resuscitation 2010;81:20–4. 12. Abella BS, Rhee JW, Huang KN, Vanden Hoek TL, Becker LB. Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey. Resuscitation 2005;64:181–6. 13. Merchant RM, Soar J, Skrifvars MB, et al. Therapeutic hypothermia utilization among physicians after resuscitation from cardiac arrest. Crit Care Med 2006;34:1935–40. 14. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007;73:29–39. 15. Tomte O, Andersen GO, Jacobsen D, Draegni T, Auestad B, Sunde K. Strong and weak aspects of an established post-resuscitation treatment protocol – a fiveyear observational study. Resuscitation 2011;82:1186–93. 16. Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 2006;34:1865–73. 17. Busch M, Soreide E, Lossius HM, Lexow K, Dickstein K. Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors. Acta Anaesthesiol Scand 2006;50:1277–83. 18. Knafelj R, Radsel P, Ploj T, Noc M. Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation 2007;74:227–34. 19. Belliard G, Catez E, Charron C, et al. Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation. Resuscitation 2007;75:252–9. 20. Bianchin A, Pellizzato N, Martano L, Castioni CA. Therapeutic hypothermia in Italian intensive care units: a national survey. Minerva Anestesiol 2009;75:357–62.
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