Targeted Temperature Management Experience of an Academic Emergency Department: A 5-Year Retrospective Study

Abstract

Targeted temperature management (TTM) for postcardiac arrest syndrome patients is a cornerstone therapy to reduce mortality and neurological morbidity. The care of critical patients is provided in the emergency department (ED) when intensive care units (ICUs) are unavailable. This study aimed to determine the characteristics and mortality outcomes of postcardiac arrest patients who underwent TTM in an academic ED. Postcardiac arrest patients who underwent TTM between January 1, 2014, to November 1, 2018, at a tertiary care academic ED in Turkey were examined retrospectively. The mean age of 24 patients in whom TTM was initiated in the ED was 60.7 ± 19.2 years. Five (20.8%) of the patients who underwent TTM were discharged. Four (80%) of the discharged patients were in out-of-hospital cardiac arrest (OHCA). All patients with a total cardiopulmonary resuscitation duration of >25 minutes died. Mortality was significantly higher in patients without light reflexes (p = 0.006). Two patients who underwent TTM in the ED became organ donors after neurological determination of death. If the ICU cannot meet the needs, early initiation of TTM in the ED may contribute to good neurological outcomes. In this study, 80% of the patients who have positive neurological outcomes are OHCA. Lack of light reflex may be an evidence of poor neurological outcomes in postcardiac arrest patients. Emergency physicians should be encouraged to apply TTM.

Introduction

Despite recent advances in resuscitation, neurological injury is still the most important cause of mortality and morbidity in comatose patients surviving with successful cardiopulmonary resuscitation (CPR) (Tahsili-Fahadan et al., 2018). Postcardiac arrest syndrome (PCAS), which is defined as the clinical condition caused by hypoxia-induced oxidative stress ischemia/perfusion injury, neurological damage, myocardial dysfunction, and systemic inflammatory response in arrest patients, constitutes the most serious problem of CPR survivors (Neumar et al., 2008).

Targeted temperature management (TTM) for PCAS patients is a cornerstone therapy to reduce mortality and neurological morbidity and it is recommended as a standart procedure for postcardiac resuscitation care based on CPR guidelines (Berg et al., 2020; Nolan et al., 2021). In the United States, ∼600,000 cardiac arrest cases can be achieved in 63% to 72% of spontaneous circulation in in-hospital cardiac arrest (IHCA) cases each year, while survival is around 12% in ∼374,000 out-of-hospital cardiac arrest (OHCA) cases (Becker et al., 2015; Mozaffarian et al., 2016).

Among the patients included in the TTM study, the rate of patients after cardiac arrest with good neurological outcome was 50% (Nielsen et al., 2013). Most authors have maintained that TTM is the only procedure in postcardiac arrest care for a good neurological outcome after CPR, carried out properly; recently, it has been shown that early hemodynamic optimization and early initiation of TTM in the first hours as soon as the return of spontaneous circulation (ROSC) is achieved in patients eligible for the treatment contribute to positive results (Hypothermia after Cardiac Arrest Study Group, 2002; Lin et al., 2020).

Although TTM is a treatment that should be applied in intensive care conditions, it may be difficult for patients to access intensive care, depending on the capacity of intensive care unit (ICU) and patient density. The care of critical patients is started in the emergency department (ED) and continued when ICUs are unavailable.

This study aimed to determine the characteristics and mortality outcomes of postcardiac arrest patients who underwent TTM in an academic ED.

Materials and Methods

Study design and setting

This study was planned retrospectively. Postcardiac arrest patients who underwent TTM between January 1, 2014, and November 1, 2018, at a tertiary care academic ED in Turkey were included. The study was initiated after the approval of the University Ethics Committee, dated October 24, 2018, and numbered GO18/1003-40. The data were accessed through the hospital data processing system.

Demographic data and clinical variables were recorded in terms of age, sex, the interval between onset of cardiopulmonary arrest and ROSC, delayed CPR duration, location of cardiopulmonary arrest, etiology of the arrest, whether the initial rhythm is shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia) or nonshockable rhythm (asystole or pulseless electrical activity), imaging modalities, pupillary response to light, Cerebral Performance Categories (CPCs) score, Modified Rankin score, and mortality outcomes.

In our center, which is a tertiary academic hospital, ED critical care unit provides postarrest care modalities after all patients ensured with ROSC were evaluated for TTM. The annual average number of visits to this ED was 35,000, and it had a 17-bed critical care unit. Patients in the emergency critical care unit were monitored, and each intervention was noted on patient observation forms.

Participants and measurements

A total of 24 patients in whom TTM was initiated in the ED between January 1, 2014, and Novenber 1, 2018 were assessed. In this ED, the decision of TTM was administered to the following patients:

● ≥18 years old,

● Regular rhythm after a cardiopulmonary arrest.

● The Glasgow Coma Scale of 8 or less after ROSC.

● A delayed CPR duration of lesser than 15 minutes.

● A CPR duration of lesser than 60 minutes.

TTM was not administered to the following patients: a recent history of head injury, risk of severe bleeding and coagulation disorder, history of major surgery within the past 2 weeks, resistant hypotension, end-stage cancer patients, severe disability or vegetative state before the cardiopulmonary arrest, and pregnancy.

We used ARCTIC SUN^® 5000 Temperature Management System for TTM (Medivance, Inc., Louisville, CO). An apparatus consisting of an electronic module and disposable ARCTICGEL™ pads were used to reach the target temperature value determined in our protocol.

TTM was initiated within the first hour as soon as the ROSC was obtained and continued 24 hours at 34°C, followed by rewarming. There is no antipyretic strategy for rewarming the patient after the 24-hour TTM period, including any medications. The TTM device that we used had a rewarming strategy program and when we set up the device to make TTM, it automotically starts the rewarming program after the 24-hour TTM. Body temperature was measured by using a rectal probe. During the TTM procedure, all patients were sedated. Shiverings were treated with sedation and neuromuscular blockades. Hemodynamic and respiratory parameters were continuously monitored, and vasopressors or inotropic drugs were administered to maintain hemodynamic stability. Antiepileptic drugs were administered if the patients developed clinical or electrical signs of seizure.

According to the guidelines, there is no exact prognostication marker or procedure to measure the neurologic outcome of the postcardiac arrest patients. Still we used brain magnetic resonance imagings (MRIs) after 72 hours of TTM in stable patients to detect the brain tissue's liability due to hypoxia according to the current guidelines, but if a patient develops any changes such as seizure, status, and hypernatremia, we take brain computerized tomography angiography to detect any problem in brain perfusion or brain death. According to the resuts of these imaging modalities, the emergency medicine physician who is the physician in charge of the patient decides the neurologic prognosis of the patient.

While a CPC score of 1 or 2 (minimal or no neurologic dysfunction) was categorized as a good outcome, a CPC score of 3, 4, and 5 (death, severe neurologic disability, or persistent vegetative state) was defined as a poor outcome (Jennett and Bond, 1975). The pupillary light reflexes were checked and recorded after the 24-hour TTM procedure.

The modified Rankin Scale is a 6-step scale scored between 0 and 5 and used to measure the disability degree of patients as a result of neurological problems. A score of 2 or below is considered a good outcome, while a score above 2 is considered a poor outcome (van Swieten et al., 1988).

Statistical analyses

Statistical analyses were performed by IBM SPSS for Windows Version 23 statistical package (IBM Corp., Armonk, NY). Continuous variables were presented as mean ± standard deviation and minimum/maximum value, and categorical variables as numbers and percentages. Categorical variables were summarized as frequencies and percentages. The relationship between two categorical variables was examined using Fisher's exact test. A p-value <0.05 was considered significant.

Results

In the study, the mean age of 24 patients was 60.7 ± 19.2 years, half of whom were women. Five (20.8%) of the patients were discharged, four (80%) of the discharged patients were OHCA. The number of patients with OHCA was 21 (87.5%), while three of them had ventricular fibrillation at the initial rhythm (12.5%). TTM was completed successfully in 18 (75%) of the patients. TTM could not be completed in 6 patients as follows; 5 (83.3%) died within the first 24 hours, and the sixth patient was transferred to another hospital became of his parents' willingness. So we could not obtain his medical records.

The mean delayed CPR duration was 5.5 ± 4 minutes; in 14 (58.3%) of the patients, this period was <5 minutes. While the mean total CPR time of the patients was 19.6 ± 13.3 minutes, the entire CPR duration was below 20 minutes in half. The discharge rate of patients whose total CPR duration was <20 minutes was 25%. All of the patients whose total CPR duration was over 25 minutes died. The distribution of baseline characteristics of all patients is presented in Table 1.

Table 1.

Baseline Characteristics of Patients Treated with Targeted Temperature Management

Patient variables	Total (n = 24)	TTM completed (n = 18)	Discharged (n = 5)
Age (years), mean ± SD, minimum–maximum	60.7 ± 19.2, 20–87	58.7 ± 19.2, 20–79	62.2 ± 18.2, 34–79
Female, n (%)	12 (50%)	10 (55.6%)	3 (60%)
Comorbity, n (%)	17 (70.8%)	13 (72.2%)	4 (80%)
Hypertension	9 (37.5%)	6 (33.3%)	0 (0%)
Diabetes	6 (25%)	4 (22.2%)	2 (40%)
Coronary artery disease	7 (29.2%)	5 (27.8%)	2 (40%)
Chronic obstructive pulmonary diseases, n (%)	5 (20.8%)	2 (11.1%)	0 (0%)
Malignity	1 (4.2%)	1 (5.6%)	0 (0%)
Chronic kidney injury	3 (12.5%)	2 (11.1%)	1 (20%)
Stroke	1 (4.2%)	1 (5.6%)	0 (0%)
Atrial fibrillation	2 (8.3%)	2 (11.1%)	0 (0%)
Schizophrenia	1 (4.2%)	1 (5.6%)	0 (0%)
OHCA, n (%)	21 (87.5%)	16 (88.9%)	4 (80%)
Etiology of CPA, n (%)
Unknown	8 (33.3%)	7 (38.9%)	1 (20%)
Cardiogenic shock	8 (33.3%)	6 (33.3%)	2 (40%)
Hanging	2 (8.3%)	2 (11.1%)	1 (20%)
Intoxication	1 (4.2%)	1 (5.6%)	0 (0%)
Pulmonary thromboembolism	1 (4.2%)	0 (0%)	0 (0%)
Aspiration	3 (12.5%)	2 (11.1%)	1 (20%)
Septic shock	1 (4.2%)	0 (0%)	0 (0%)
Delayed CPR duration—5 or more, n (%)	10 (41.7%)	8 (44.4%)	2 (40%)
Total CPR duration—20 or more, n (%)	12 (50%)	10 (55.6%)	2 (40%)
Initial rhythm, n (%)
Asystole	4 (16.7%)	2 (11.1%)	1 (20%)
Ventricular fibrillation	3 (12.5%)	3 (16.7%)	1 (20%)
Pulseless electrical activity	17 (70.8%)	13 (72.2%)	3 (60%)
CT (ischemia +)	6/22 (27.3%)	5/17 (29.4%)	0/4 (0%)
MRI (ischemia +)	10/13 (76.9%)	9/12 (75%)	2/4 (50%)

CPA, cardiopulmonary arrest; CPR, cardiopulmonary resuscitation; CT, computed tomography; MRI, magnetic resonance imaging; OHCA, out-of-hospital cardiac arrest; SD, standard deviation; TTM, targeted temperature management.

A comparison of survival status and neurological outcomes of patients is given in Table 2. Mortality was significantly higher in patients with no light reflex (p = 0.006), with CPC poor outcome (p = 0.002), and with modified Rankin Scale poor outcome (p < 0.001). Seventeen (94.4%) of the 18 patients without light reflex died.

Table 2.

Comparison of the Neurological Outcomes of Survivors and Nonsurvivors

	Total (n = 24)	Survivors (n = 5)	Nonsurvivors (n = 19)	p
TTM, n (%)
Not completed	6 (27.3%)	0 (0%)	6 (100%)	0.280
Completed	18 (81.8%)	5 (27.8%)	13 (72.2%)
Pupillary light reflex, n (%)
No	18 (75%)	1 (5.6%)	17 (94.4%)	0.006
Yes	6 (25%)	4 (66.7%)	2 (33.3%)
CPC, n (%)
Good outcome, CPC 1–2	5 (20.8%)	4 (80%)	1 (20%)	0.002
Poor outcome, CPC 3-4-5	19 (79.2%)	1 (5.3%)	18 (94.7%)
Modified Rankin Scale, n (%)
Good outcome	4 (16.7%)	4 (100%)	0 (0%)	<0.001
Poor outcome	20 (83.3%)	1 (5%)	19 (95%)
Hospitalization, n (%)
Emergency department	11 (45.8%)	1 (9.1%)	10 (90.9%)	0.327
Intensive care unit	13 (54.2%)	4 (30.8%)	9 (69.2%)

CPC, Cerebral Performance Category.

Interestingly, an OHCA patient had a delayed CPR duration of 15 minutes, his initial rhythm was ventricular fibrillation, and there was ischemia in the MRI without ischemia on CT, and he was discharged with a good outcome of CPC. The distribution of mortality in the ICU or the ED of a total of 19 patients who died is shown in Figure 1 by time. Five patients were discharged, four of them had a good neurological outcome and one of them had a poor neurological outcome.

FIG. 1.

The distribution of mortality in the intensive care or the emergency department for a total of 19 nonsurvivors by time.

Two patients, 20 and 38 years old, who had cardiopulmonary arrest due to hanging were successfully applied TTM in the ED and became organ donors after neurologic determination of death (DNDD). After approval by relatives of patients for organ donation, their kidneys, livers, hearts, and corneas were transplanted to recipients designated by the national organ donation center by Turkey's organ donation rules. The recipients did not experience transplant organ failure within 1 year after the transplant.

Discussion

In the 5-year period, TTM was applied to 24 patients in the ED. Mortality was significantly higher in patients who underwent TTM with a lack of light reflex, poor CPC, or modified Rankin scores. Two patients who had undergone TTM in the ED provided a remedy for other lives as organ donors.

The last guidelines state that there is no exact temperature for TTM (Berg et al., 2020), and therefore, they recommend that the physicians choose the temperature between 33°C and 36°C according to their experience. The most preferred temperature was 34°C. Abazi et al. (2019) indicated no significant difference in the 6-month survival between 33°C and 36°C in their nationwide study in Sweden. There are various devices and cooling methods in the literature. Although these methods have different disadvantages and advantages, it has been shown that there is no significant difference between them in terms of neurological outcomes (Mody et al., 2019). In our TTM protocol, 34°C was preferred, and therefore, all the patients were cooled in that temperature.

In randomized-controlled studies, there are conflicting results regarding the issues of TTM, especially in IHCA patients (13). The current AHA guidelines give a class-I recommendation (Level of evidence C) to apply TTM among survivors of OHCA with nonshockable rhythms and IHCA (3). In our study, 80% of the patients with good neurological outcomes were admitted as OHCA with nonshockable rhythm. Thus, it has been demonstrated that OHCA patients who are eligible for TTM may have positive neurological results.

The cardioprotective effects of TTM are especially related to time. Late initiation of TTM or delays due to slow cooling can cause damage to cardiac functions (van der Wal et al., 2011). In our study, TTM was initiated in all patients within the first 1 hour after ROSC was achieved.

Kongpolprom and Cholkraisuwat (2018) presented that some neurological examination findings may indicate the poor neurological outcome. These findings were lack of pupillary light response and gag reflex after rewarming, no eye-opening, myoclonus, and seizure. However, they notified that only the lack of pupillary light response would be a more reliable finding. Riker et al. (2020) reported that the absence of the pupillary light reflex was associated with poor neurological outcomes. In our study, we found a statistically significant difference between neurological outcome and pupillary light response.

In the study of Wallmüller et al. (2018) on TTM outcomes according to age groups, it was found that patients older than the age of 65 did not benefit from TTM. As for our study, the mean age of patients with good neurological outcomes was 62.2 years. The patient's mean age was 60.7 in our study.

Udekwu et al. (2019) found no favorable neurologic outcome of TTM on near-hanging patients. TTM was applied after the ROSC was observed in two patients in our study CPR due to hanging, and patients were considered brain dead after DNDD on the third day following TTM. Although TTM did not provide a good result for these patients, it provided a decision-making time to the patients' relatives to transplant these patients' organs to the eligible recipients. It was a remedy for other lives.

Cooling reduces primary injury and affects physiology in acute, subacute, and chronic stages of ischemia. It affects exocytosis, apoptosis, inflammation, free radical production, and pathways that affect metabolism and blood/brain barrier integrity. It is assumed that cooling contributes to protecting the organs other than the brain in patients with poor outcomes (Yenari and Han, 2012).

In a study by Wright et al. (2019), 1-year graft outcomes were compared between organ transplants from donors with therapeutic hypothermia and transplants from donors without therapeutic hypothermia; no difference was found in heart, lung, kidney, and liver grafts. In our study, the organs of two patients who underwent organ transplantation were transplanted to seven patients, and there was no problem with the grafts in the 1-year follow-up of these patients. According to our experience, despite the poor outcomes in these patients, considering the high need for organ donation worldwide, we observed that the time spent in TTM application saved time for the relatives of the patients to think about the decision of organ transplantation and also provided positive effects in the decision of organ transplantation.

Although it is known that early initiation of the TTM protocol in PCAS patients has positive contributions to the neurological outcome (Mody et al., 2019), the duration of these patients to access intensive care and TTM has been prolonged due to reasons such as the occupancy of ICUs. This situation has made it essential to initiate cooling therapies in the early period by providing eligible patient selection from the moment of ROSC in the ED in terms of good outcomes.

Emergency physicians should be trained on TTM, which has a substantial place in postcardiac arrest patients' care. Therefore, it will be beneficial to give more importance to TTM in emergency medicine practice. Dissemination of TTM applications in emergency services will increase the chance of getting a good outcome and contribute to organ donation procedures in case of poor outcomes. Also, emergency services can be a possible solution to the shortage of organ donation (Akkas and Demir, 2019).

Limitations

The first limitation of this study was its retrospective nature. Second, it was single centered, and the number of patients was low. Multicenter prospective studies with a large number of patients were needed on this subject.

Conclusion

In cases where PCAS patients cannot be transferred to the ICU, the urgent initiation of TTM in the ED may contribute to good neurological outcomes. Lack of light reflex may be evidence for poor neurological outcomes in PCAS patients. TTM can allow the relatives, whose patients are brain dead, to think about organ donation. For this reason, besides improving the TTM practice of emergency physicians, it is necessary to carry out training and regulating regarding the management of PCAS patients in the ED in terms of organ donation.

Footnotes

Acknowledgment

The authors thank Dr. Sevilay Karahan for the contribution of statistical analyses. Dr. Sevilay Karahan gave permission to be named in this article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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