Pamela M. Paufler, Marc C. Newell, David A. Hildebrandt, and Lisa L. Kirkland (2017) Incidence, Etiology, and Implications of Shock in Therapeutic Hypothermia. Journal of the Minneapolis Heart Institute Foundation: January 2017, Vol. 1, No. 1, pp. 19-23.
Pamela M. Paufler, MD*, Marc C. Newell, MD†, David A. Hildebrandt, RN†, and Lisa L. Kirkland, MD‡
*MedStar Washington Hospital, Washington, DC
†Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN
‡Critical Care Department, Abbott Northwestern Hospital, Minneapolis, MN
Disclosures: Study funded by an internal grant from Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN. All Authors were involved in the creation of this manuscript.
To identify the incidence and etiology of shock and implications on mortality and neurologic outcome in patients undergoing therapeutic hypothermia after cardiac arrest. Retrospective chart review of 206 consecutive patients from January 2006 through December 2010. The incidence of shock was 74.8% during cooling and 78.0% during rewarming. The most common etiology of shock during cooling was cardiogenic (46.1%). During rewarming, the etiology of shock was more distributed with 26.9% of patients in cardiogenic shock, 16.8% distributive, and 10.7% classified as mixed. There were no significant associations between shock during cooling or rewarming and survival (P = 0.202, P = 0.107) or neurologic score at discharge (P = 0.377, P = 0.055). Shock is difficult to categorize in the setting of therapeutic hypothermia. The incidence of shock in patients undergoing therapeutic hypothermia is high but not associated with poorer survival or worse neurologic score at discharge. Thus, the presence of shock should not be the limiting factor in decisions regarding aggressive care of the out-of-hospital cardiac arrest patient.
Keywords: therapeutic hypothermia, shock, cardiac arrest, survival, neurologic outcome
Each year approximately 350,000 people have an out-of-hospital cardiac arrest (OHCA) in the United States.1 In a large meta-analysis, only 23.8% of patients survived to hospital admission and only 7.6% to hospital discharge.2 Prior to therapeutic hypothermia, 25% of the survivors had a poor neurologic outcome.3
The American Heart Association now recommends therapeutic hypothermia for 12 to 24 hours after out-of-hospital ventricular tachycardia/ventricular fibrillation (VT/VF) cardiac arrest as a method to improve neurologic outcomes.4 This recommendation was based on 2 randomized controlled trials suggesting clear benefit of therapeutic hypothermia.5,6
Therapeutic hypothermia’s role in patients presenting in shock is less well defined in the literature. Several small studies have addressed outcomes in patients in shock undergoing therapeutic hypothermia. In 1 study of 50 patients with OHCA secondary to VF undergoing therapeutic hypothermia, patients treated with an intra-aortic balloon pump were compared with those not requiring a balloon pump. Both sets of patients did relatively well with favorable neurologic score, defined as cerebral performance category 1 (good cerebral performance: conscious, alert, able to work, might have mild neurologic or psychologic deficit) or 2 (moderate cerebral disability: conscious, sufficient cerebral function for independent activities of daily life, able to work in sheltered environment), in 61% and 74% (P = NS).7 A second study reported the results of 56 patients, 28 with cardiogenic shock, after OHCA with any initial rhythm. In patients with cardiogenic shock, 39% had a favorable neurologic outcome at discharge whereas 71% of the patients not in cardiogenic shock had a favorable neurologic outcome.8 Mooney et al9 previously described a 38% survival to hospital discharge for those patients in cardiogenic shock at admission with 100% favorable neurologic score for the survivors. Patients not in cardiogenic shock at admission were reported to have a 70% survival rate with 80% of the survivors having a favorable neurologic score at discharge.9
Mild therapeutic hypothermia decreases the heart rate and increases systemic vascular resistance. Current literature suggests that despite these changes, cardiac index remains unchanged or improves, indicating therapeutic hypothermia may provide circulatory support in cardiogenic shock.10–12
Literature review did not reveal published reports of the incidence and etiology of shock during the cooling and rewarming phases of therapeutic hypothermia. Therefore, we sought to identify: (1) the incidence and etiology of shock during both the cooling and rewarming phases of therapeutic hypothermia, and (2) the effect of shock on mortality and neurologic status at discharge.
Setting and Protocol
Abbott Northwestern Hospital is a 619-bed tertiary care hospital in Minneapolis that offers state-of-the-art cardiovascular and intensive care services. Patients throughout Minnesota and Western Wisconsin are routinely transferred to Abbott for emergency cardiac and intensive care. The “Cool It” Protocol—inclusive of prehospital cooling, the cooling and rewarming process, simultaneous angiography/percutaneous coronary intervention (PCI), and neurocognitive assessment—was previously described.9Patients
At Abbott, patients are eligible for therapeutic hypothermia regardless of initial cardiac rhythm or presence of ST-segment elevation myocardial infarction. Patients are treated with coronary angiography or percutaneous intervention as deemed appropriate by the treating physician. Patients are excluded from receiving therapeutic hypothermia if they have hemodynamic instability refractory to vasopressors, active bleeding, comatose or vegetative state prior to cardiac arrest, or a “do not resuscitate” status.Data Collection
Prospective data collection of all patients undergoing therapeutic hypothermia has been undertaken since program initiation. The cohort is registered prospectively in the International Cardiac Arrest Registry database. From January 2006 through December 2010, 206 consecutive patients cooled to 33° for 24 hours were included both in the registry database and a shared folder within the electronic health record at Abbott. We conducted a retrospective chart review of these patients. The institutional review board approved the protocol and data collection for this study.
From the electronic health record, abstracted data included patient history, cardiac index, pulmonary capillary wedge pressure, central venous pressure, initial cardiac rhythm, use of an assist device such as an intra-aortic balloon pump, temperature, heart rate, respiratory rate, white blood cell count, vasopressor/inotrope use, microbiology, and imaging. Each patient’s information was evaluated during both cooling and rewarming phases. During the cooling phase, for each incidence of shock, pulmonary artery catheter data was collected from before the start of vasopressors if available or the first available data point after the start of vasopressors. During rewarming, if the patient was not previously in shock during cooling, data were collected before the start of vasopressors if available or the first available data point after vasopressors were started. If the patient was in shock at the start of cooling, data were collected at a point just before vasopressors were increased or at the first available data point after vasopressors were increased. In addition, temperature was collected at 2 points during rewarming: at the data point and peak temperature within 48 hours of the start of rewarming.
From the registry database, data included age, sex, witnessed arrest, bystander cardiopulmonary resuscitation, initial rhythm, time to ROSC, time to target temperature, prearrest comorbidities, angiography, percutaneous intervention, and cerebral performance category at hospital discharge.
Incidence of shock was determined during both the cooling and rewarming phases of therapeutic hypothermia. Shock was defined as inability to maintain systolic blood pressure >90 for 30 minutes without pressors, and associated evidence of organ dysfunction due to hypoperfusion.13 For each incidence, shock was further classified by type: cardiogenic, distributive, hypovolemic, obstructive, mixed, or unknown. Cardiogenic shock was defined as cardiac index <2.2 and pulmonary capillary wedge pressure >15. The presence of an assist device such as intra-aortic balloon pump was taken to indicate the presence of cardiogenic shock, as these were placed in the cardiac catheterization lab in response to poor cardiac output causing shock refractory to pressors and inotropes.13 As sepsis, systemic inflammatory response syndrome or septic shock are the most common causes of distributive shock, this was defined as shock plus the presence of 2 of the systemic inflammatory response syndrome criteria (heart rate >90, respiratory rate >20, white blood cell count >12 or <4, temperature >38 or <3514 without evidence of alternative causes. Hypovolemic shock was presumed if the patient was in shock with a low central venous pressure <8 and no evidence of distributive shock.15 Obstructive shock was defined by obstruction such as a pulmonary embolus on imaging. If criteria were met in more than 1 category, then the incident was classified as mixed. If data was unavailable or did not fit the above criteria, the etiology remained unclassified. During rewarming, the classifications were assigned as above with 2 differences as follows: (1) If the patient was in shock at the start of rewarming and the vasopressors were not increased, the incident was classified as the original shock type. However, if the patient was in shock at the start of rewarming and the vasopressors were increased, then data was collected and the event was reclassified. (2) If either temperature at the data point or peak temperature within 48 hours of rewarming was >38, this was considered as positive for one of the systemic inflammatory response syndrome criteria. All data and shock classifications were reviewed separately by the authors, with disagreements resolved jointly.
The primary objective of this study was to identify the incidence and etiology of shock during the cooling and rewarming phases of therapeutic hypothermia. The secondary objective was to identify the effect of shock on mortality and neurologic status at discharge.
All data analysis was performed in a computing environment (SAS 9.3, SAS Institute, Inc., Cary, NC). Univariate logistic regression was used to determine the association between shock and favorable outcomes. Multivariate logistic regression was used to determine the association between patient/scenario factors and favorable outcomes. Patient and scenario factors considered were age; sex; the presence of a witness; bystander-performed cardiopulmonary resuscitation (CPR); initial heart rhythm; estimated arrest to return of spontaneous circulation (ROSC) interval; arrest to target temperature interval; performance of an angiogram; percutaneous intervention; prearrest status of the following: coronary disease, heart failure, hypertension, chronic obstructive pulmonary disease, chronic renal failure and diabetes mellitus type II, and the presence of shock. For analytical purposes, age was categorized into 5 groups: ages 15 through 49 (n = 39); ages 50 through 59 (n = 47); ages 60 through 69 (n = 46); ages 70 through 76 (n = 36); and ages 77 through 95 (n = 38). Similarly, estimated arrest to ROSC interval was divided into 3 categories: 0 to 15 minutes, 16 to 30 minutes, and 31 to 89 minutes. Favorable neurologic score was defined as cerebral performance category 1 or 2. A total of 206 records were used in all analyses.
Ranges of age and time to ROSC and target temperature are listed in Table 1. Patient age ranged from 15 to 96 years with an average age of 62 years (SD = 14 years). The average time to ROSC was 25 minutes (SD = 15 minutes) and the average time to target temperature was just over 5 hours (SD = 2.4 hours). Patient characteristics are shown in Table 2. Nearly three-fourths of patients had an arrest with VT or VF documented as the initial rhythm. A majority of patients had preexisting hypertension and over one-third had preexisting coronary artery disease. Nearly three-fourths of patients underwent coronary angiography but only one-third required PCI. No patients suffered cardiac arrest due to trauma.
The incidence of shock during cooling was 74.8% and 78.0% during warming (Table 3). The most common etiology of shock during cooling was cardiogenic (46.1%). During rewarming, the etiology of shock was more distributed with 26.9% of patients in cardiogenic shock, 16.8% distributive, and 10.7% classified as mixed. Despite extensive review, a large number of patients did not meet any specific criteria for etiology during rewarming and remained unclassified (40.9%).
Incidence and etiology of shock during cooling and rewarming.
There were no significant associations between shock during cooling and survival (P = 0.202) or neurologic score at discharge (P = 0.377; Table 4).
Association between shock and survival and favorable neurologic outcome.
There were no significant associations between shock during rewarming and survival (P = 0.107) or neurologic score at hospital discharge (P = 0.055; Table 4).
The purpose of this study was to identify the incidence, etiology, and impact of shock in patients undergoing therapeutic hypothermia during cooling and rewarming phases.
Therapeutic hypothermia has been shown to improve neurologic outcome in patients with OHCA.16–21 The original trials excluded patients in cardiogenic shock.5,6Subsequent observational studies have variably included patients in cardiogenic shock. These studies have shown that patients with cardiogenic shock do not do as well as their non-cardiogenic shock counterparts. However, these same studies have also shown that even patients in cardiogenic shock do better when cooled as compared to their historical counterparts who were not cooled.7,8,16
In addition, multiple studies have sought to identify prognosticators of favorable outcome. Most studies agree that shorter time to ROSC and initial rhythm of VT or VF are predictive of a more favorable outcome. Though there is less agreement, older age, lower Glasgow Coma Scale score, and unwitnessed arrest have also all been reported as prognostic of unfavorable outcome.20–23
Given that this was a retrospective data analysis and similar to other literature, we used the use of vasopressors or an assist device to define the presence of shock. To our knowledge, no other previous studies defined criteria for the etiology of shock at temperatures other than 37°.
For cardiogenic shock, we used cardiac index <2.2 and pulmonary capillary wedge pressure>15, the same criteria as used at 37°. We recognize that cardiac index may decline with temperature and this method may overestimate the percentage of patients in cardiogenic shock.
For distributive shock, we used the criteria of meeting 2 of the systemic inflammatory response syndrome criteria. However, again, we recognize that these patients are largely intubated, sedated, cooled, and often paralyzed, making this method a possible underestimation of the percentage of patients in distributive shock.
We found the incidence of shock to be high during both cooling and rewarming. Given that patients were eligible for cooling after cardiac arrest and that the criteria for cardiogenic shock may lead to overestimation, it is not surprising that a majority of patients were in cardiogenic shock during cooling. We hypothesize that the broader distribution of shock types during warming may be attributed to some patients having undergone angioplasty, thereby alleviating cardiogenic shock, and that vasodilation during the rewarming process may have contributed to the incidence of distributive shock.24
Given the historically poor survival of patients in shock,25 it is surprising that shock was not associated with poorer survival in this population. This may be due to the neuroprotective and hemodynamic effects of cooling.10–12 Alternatively, perhaps the definition of shock in the cooled patient warrants further study.
Several limitations should be acknowledged in this retrospective study. First, it has been traditionally difficult to attain a large cohort of OHCA survivors due to the low rate of survival to hospital admission.1,2 However, our cohort of patients from a single large tertiary care center collected over 5 years is similar in size to previously studied groups. Second, we attempted to define both shock and etiology of shock retrospectively from chart review rather than clinically. In some cases, we were unable to classify patients either due to inadequate data (eg, pulmonary artery catheters were not required in all patients) or failure to meet specific criteria. However, we were able to collect enough information to classify a majority of the patients. Lastly, we did not know of any source that specifically defined shock during artificial cooling. We used standard definitions of shock and each case was reviewed by a physician and/or physician panel.
Most patients undergoing therapeutic hypothermia met clinical criteria for shock both during cooling and during warming. The most common etiology of shock during cooling was cardiogenic. During the rewarming phase, most patients remained in shock; however, a large percentage did not meet specific criteria for classification. The presence of shock during either cooling or rewarming was not associated with poorer survival or worse neurologic outcome. Thus, the presence of shock should not be the limiting factor in decisions regarding aggressive care of the OHCA patient.
|1.||Roger VL, Go AS, Lloyd-Jones DM, et al: Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–e220. [Crossref] [Google Scholar]|
|2.||Sasson C, Rogers MA, Dahl J, Kellerman AL. Predictors of survival from out-of-hospital cardiac arrest. A systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010;3:63–81. [Crossref] [Google Scholar]|
|3.||deVos R, de Haes HC, Koster RW, de Haan RJ. Quality of survival after cardiopulmonary resuscitation. Arch Intern Med. 1999;159:249–254. [Crossref] [Google Scholar]|
|4.||Nolan JP, Morley PT, Hoek TL, Hickey RW; Advancement Life support Task Force of the International Liaison Committee on Resuscitation. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Resuscitation. 2003;57:231–235. [Crossref] [Google Scholar]|
|5.||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;346:557–563. [Crossref] [Google Scholar]|
|6.||Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–556. [Crossref] [Google Scholar]|
|7.||Hovdenes J, Laake JH, Aaberge L, Haugaa H, Bugge JF. Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand. 2007;51:137–142. [Crossref] [Google Scholar]|
|8.||Skulec R, Kovarnik T, Dostalova G, Kolar J, Linhart A. Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome. Acta Anaesthesiol Scand. 2008;52:188–194. [Crossref] [Google Scholar]|
|9.||Mooney MR, Unger BT, Boland LL, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling. Circulation. 2011;124:206–214. [Crossref] [Google Scholar]|
|10.||Zobel C, Adler C, Kranz A, et al. Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med. 2012;40:1715–1723. [Crossref] [Google Scholar]|
|11.||Stegman B, Aggarwal B, Senapati A, Shao M, Menon V. Serial hemodynamic measurements in post-cardiac arrest cardiogenic shock treated with therapeutic hypothermia. Eur Heart J Acute Cardiovasc Care. 2015;4:263–269. [Crossref] [Google Scholar]|
|12.||Schmidt-Schweda S, Ohler A, Post H, Pieske B. Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II). Resuscitation. 2013;84:319–325. [Crossref] [Google Scholar]|
|13.||Hochman JS, Sleeper LA, Godfrey E, McKinlay SM, Sanborn T, Col J, LeJemtel T. Should we emergently revascularize occluded coronaries for cardiogenic shock: an international randomized trial of emergency PTCA/CABG-trial design. The SHOCK Trial Study Group. Am Heart J. 1999;137:313–321. [Crossref] [Google Scholar]|
|14.||Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–1256. [Crossref] [Google Scholar]|
|15.||Rivers EP, Katranji M, Jaehne KA, et al. Early interventions in severe sepsis and septic shock: a review of the evidence one decade later. Minerva Anestesiol. 2012;78:712–724. [Google Scholar]|
|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;34:1865–1873. [Crossref] [Google Scholar]|
|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; 50:1277–1283. [Crossref] [Google Scholar]|
|18.||Arrich J; European Resuscitation Council Hypothermia After Cardiac Arrest Registry Study Group. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007;35:1041–1047. [Crossref] [Google Scholar]|
|19.||Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardized treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. 2007;73:29–39. [Crossref] [Google Scholar]|
|20.||Belliard G, Catez E, Charron C, et al. Efficacy of therapeutic hypothermia after out of hospital cardiac arrest due to ventricular fibrillation. Resuscitation. 2007;75:252–259. [Crossref] [Google Scholar]|
|21.||Schefold JC, Storm C, Joerres A, Hasper D. Mild therapeutic hypothermia after cardiac arrest and the risk of bleeding in patients with acute myocardial infarction. Int J Cardiol. 2009;132:387–391. [Crossref] [Google Scholar]|
|22.||Oddo M, Ribordy V, Feihl F, et al. Early predictors of outcome in comatose survivors of ventricular fibrillation and non-ventricular fibrillation cardiac arrest treated with hypothermia: a prospective study. Crit Care Med. 2008;36:2296–2301. [Crossref] [Google Scholar]|
|23.||Nielsen N, Hovdenes J, Nilsson Fet al. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2009;53:926–934. [Crossref] [Google Scholar]|
|24.||Dermirgan S, Erkalp K, Sevdi MS, et al. Cardiac condition during cooling and rewarming periods of therapeutic hypothermia after cardiopulmonary resuscitation. BMC Anesthesiol. 2014;18:78–85. [Crossref] [Google Scholar]|
|25.||Lindholm MG, Køber L, Boesgaard S, Torp-Pedersen C, Aldershvile J; Trandolapril Cardiac Evaluation Study Group. Cardiogenic shock complicating acute myocardial infarction; prognostic impact of early and late shock development. Eur Heart J. 2003;24:258–265. [Crossref] [Google Scholar]|
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