Targeted temperature management after cardiac arrest: Real-world outcomes from a tertiary ICU in Turkey

Authors

Abstract

Aim Targeted temperature management (TTM) is a core component of post-cardiac arrest care. Its effectiveness in improving survival and neurological outcomes remains debated, especially in resource-limited settings such as Turkey. This study aimed to evaluate the impact of TTM on 28-day mortality, lactate clearance, and neurological recovery in cardiac arrest patients admitted to an intensive care unit (ICU).
Materials and Methods This retrospective cohort study included 61 adult patients who achieved return of spontaneous circulation (ROSC) following cardiac arrest and were admitted to the ICU of a tertiary care hospital in Turkey. After 1:4 propensity score matching based on demographic and clinical variables, 45 patients (9 in the TTM group, 36 in the control group) were analyzed. The primary outcome was 28-day mortality. Secondary outcomes included lactate clearance, Glasgow Coma Scale (GCS) change, and Cerebral Performance Category (CPC) score at discharge.
Results There was no statistically significant difference in 28-day mortality between groups (44.4% vs. 69.4%, p=0.261). However, TTM was associated with significantly greater lactate clearance (54.2% vs. 39.7%, p=0.038) and improved CPC scores (p=0.042). No significant difference was observed in GCS change. Post-hoc power analysis for mortality was 18%.
Discussion While TTM did not significantly reduce short-term mortality, it was associated with improved metabolic and neurological outcomes. These findings emphasize the importance of considering functional recovery endpoints and suggest that even in middle-income settings, TTM can be beneficial when properly implemented.

Keywords

Introduction

Cardiac arrest remains a critical global health burden, with an estimated 350,000 to 700,000 cases occurring annually across Europe and North America. Despite advancements in prehospital care and intensive care management, overall survival rates remain low, and long-term neurological disability is common among survivors. The quality and timing of post-resuscitation interventions are key determinants of clinical outcomes [1, 2]. Targeted temperature management (TTM) has been widely adopted as a neuroprotective strategy to mitigate reperfusion injury and cerebral ischemia following both out-of-hospital and in-hospital cardiac arrest. By lowering metabolic demand and attenuating secondary brain injury, TTM aims to improve both survival and neurological recovery [3, 4]. Although early clinical trials supported its use [5]. Recent evidence has challenged its efficacy. Notably, the TTM2 trial found no significant mortality benefit when comparing TTM at 33°C to targeted normothermia, raising questions about the routine use of hypothermia in post-cardiac arrest care [6]. While mortality remains a primary outcome in such studies, growing attention has been directed toward secondary physiological markers, particularly those reflecting metabolic recovery. Among these, lactate clearance has been investigated as a promising indicator of tissue perfusion and prognosis in post-cardiac arrest patients [7]. Despite these evolving insights, the real- world application of TTM in resource-constrained settings remains underexplored [8]. In Turkey, data on TTM’s impact on survival, neurological outcomes, and metabolic parameters are particularly limited. A recent single-center study highlighted the challenges in implementation and follow-up, reflecting variability in practice and outcomes [9]. To address this gap, we conducted a retrospective cohort study comparing patients who received TTM to those who did not, following cardiac arrest. We aimed to evaluate its effect on 28-day mortality, lactate clearance, neurological outcomes based on the Cerebral Performance Category (CPC), and changes in the Glasgow Coma Scale (GCS), using propensity score matching to adjust for confounders. This study aims to contribute locally relevant insights into the evolving global discussion on the role of TTM in post-resuscitation care.

Materials and Methods

Study Design and Setting
This retrospective cohort study was conducted in the 39-bed multidisciplinary intensive care unit (ICU) of a tertiary university hospital in Turkey. The study period was between May 2024 and June 2025. Data were extracted from electronic medical records and stored in a secure, anonymized database compliant with the Turkish Personal Data Protection Law (Law No. 6698).
Participants
Eligible patients were adults (≥18 years) who experienced either in-hospital or out-of-hospital cardiac arrest, achieved return of spontaneous circulation (ROSC), and were subsequently admitted to the ICU. Inclusion criteria required the availability of baseline lactate (0h) and 24-hour lactate values, APACHE II score, SOFA score, Charlson Comorbidity Index (CCI), and CPR duration.
A total of 61 patients fulfilled the inclusion criteria. Propensity score matching (PSM) was applied using a 1:4 nearest neighbor algorithm. After matching, 45 patients (9 in the TTM group and 36 in the control group) were retained for the final analysis. Sixteen patients could not be matched under the pre-specified caliper and were therefore excluded from outcome analyses.
Targeted Temperature Management Protocol
TTM was initiated within the first 6 hours following ROSC, after ICU admission. Cooling was performed exclusively with the Arctic Sun 5000® surface cooling system (ZOLL Medical, USA). No additional induction techniques (e.g., cold intravenous fluids) were applied. Patients were maintained at a target temperature of 35–36°C for 24 hours. Core body temperature was continuously monitored via an esophageal thermistor probe. After the maintenance phase, controlled rewarming was performed at a rate of 0.25°C per hour until normothermia (37°C) was achieved. All patients received continuous intravenous sedation to suppress shivering and ensure comfort. Sedative regimens included midazolam, propofol, and remifentanil, administered at the discretion of the treating physician. Neuromuscular blocking agents were not routinely used. Patients in the control group received standard post-resuscitation intensive care without temperature control.
Data collection and quality control
Clinical and laboratory data were extracted from the electronic medical record system by two independent investigators using a standardized template. Implausible or missing values were verified against original source files, and discrepancies were resolved by consensus.
Propensity Score Matching
To minimize confounding, PSM was performed using logistic regression with TTM as the dependent variable. Covariates included age, sex, APACHE II score, SOFA score, CCI, CPR duration, arrest location (in-hospital vs. out-of-hospital), witnessed arrest status, and initial rhythm (shockable vs. non- shockable). Matching used a 1:4 nearest neighbor algorithm without replacement and a caliper width of 0.2 standard deviations. Covariate balance was assessed using standardized mean differences (SMD), with values <0.1 indicating adequate balance.
Outcomes
The primary outcome was 28-day all-cause mortality. Secondary outcomes included:
• Lactate clearance (%): calculated as [(Lactate₀h – Lactate₂₄h) / Lactate₀h] × 100.
• Cerebral Performance Category (CPC): assessed at hospital discharge on a 5-point ordinal scale (1=good cerebral performance; 5=death/brain death) by two investigators blinded to treatment allocation.
• Glasgow Coma Scale (GCS) delta was defined as discharge GCS minus ICU admission GCS
Statistical Analysis
Continuous variables were summarized as mean±SD, and categorical variables as counts and percentages. Post-matching balance was assessed using standardized mean differences (SMD); values <0.1 were considered acceptable (age showed minimal residual imbalance; SMD 0.13). Given the small matched cohort, the primary outcome (28-day mortality) was compared using Fisher’s Exact test; in a sensitivity analysis, we applied conditional logistic regression accounting for matched sets and reported odds ratios with 95% confidence intervals. Lactate clearance was analyzed using the Mann–Whitney U test with Hodges–Lehmann median difference and 95% CI. CPC was analyzed using ordinal logistic regression; the proportional- odds assumption was evaluated. GCS delta was compared between groups using an independent-samples t-test (Shapiro– Wilk p>0.05); as a sensitivity analysis, ANCOVA (discharge GCS ~ group + baseline GCS) was performed. Two-sided p<0.05 was considered statistically significant. Analyses were conducted in SPSS v26 and Python (psmpy, statsmodels). Post-hoc power was 18% for mortality and 25% for CPC.
Ethical Approval
This study was approved by the Ethics Committee of Diyarbakır Gazi Yaşargil Training and Research Hospital (Date: 2025-06- 27, No: 529).

Results

Study Population
A total of 61 patients were included in the analysis, of whom 9 received targeted temperature management (TTM) and 52 did not. After propensity score matching (PSM) at a 1:4 ratio, 36 control patients were selected, resulting in a matched cohort of 45 patients.
Baseline characteristics
Baseline clinical and demographic characteristics are summarized in Table 1. Following propensity score matching, all covariates achieved acceptable balance after matching (all SMDs <0.1), except age, which showed minimal residual imbalance (SMD=0.13)
Outcomes
The primary outcome, 28-day mortality, was observed in 4 of 9 patients (44.4%) in the TTM group and 25 of 36 patients (69.4%) in the control group (Fisher’s Exact test, p=0.261).
Lactate clearance at 24 hours was 54.2±26.3% in the TTM group and 39.7±29.1% in the control group (Mann-Whitney U test, p=0.038). The median Cerebral Performance Category (CPC) score at discharge was 3 (IQR 1–5) in the TTM group and 5 (IQR 3–5) in the control group (ordinal logistic regression, p=0.042). The difference between discharge and admission Glasgow Coma Scale (GCS delta) was 3.3±4.2 in the TTM group and 2.1±3.8 in the control group (independent t-test, p=0.167). Clinical outcomes of patients are summarized in Table 2.
Power Considerations
Post-hoc power analysis demonstrated limited statistical power for the primary endpoint (18% for mortality; 25% for CPC), highlighting the risk of type II error and the exploratory nature Figure 1 shows the Kaplan-Meier survival analysis according to temperature management groups.
Figure 2 illustrates the distribution of targeted temperature management levels across the study cohort. of these findings.

Discussion

In this propensity score-matched retrospective cohort from a tertiary center in Turkey, targeted temperature management (TTM) did not significantly reduce 28-day mortality. However, TTM was associated with improved lactate clearance and better neurological outcomes, as reflected by cerebral performance category (CPC) scores. These findings contribute to the ongoing debate regarding TTM, suggesting that its benefits may extend beyond survival to include metabolic stabilization and functional recovery. Our mortality results are consistent with the TTM2 trial, which reported no survival benefit of hypothermia at 33°C compared with targeted normothermia in a large randomized cohort [6]. Similarly, our study found no statistically significant mortality reduction, though a favorable trend (44.4% vs. 69.4%) was observed. This likely reflects the limited statistical power (post-hoc power: 18%) due to the small number of patients receiving TTM. In contrast, the HYPERION trial demonstrated the neurological benefit of TTM in patients with non-shockable rhythms [10]. Supporting our findings of improved CPC outcomes in the TTM group. Together, these results suggest that while overall survival benefit may be limited, TTM could provide selective advantages for specific subgroups, particularly those with prolonged resuscitation times or metabolic derangements. The significantly greater lactate clearance observed in the TTM group (54.2% vs. 39.7%, p=0.038) may indicate enhanced systemic perfusion and reduced cellular metabolic stress. Lactate is widely recognized as a marker of tissue hypoxia and a prognostic factor in critically ill patients, including those after cardiac arrest [11]. Recent evidence further reinforces the prognostic role of lactate clearance: in a large secondary analysis of out-of-hospital cardiac arrest patients undergoing extracorporeal CPR, higher lactate clearance was independently associated with improved clinical and neurological outcomes [7]. Conversely, other studies have reported no consistent association between lactate clearance and outcomes in TTM- treated patients [12, 13]. Highlighting that its prognostic value may depend on patient characteristics, timing of measurement, and treatment context. Our findings align with this mixed evidence, suggesting that TTM may facilitate metabolic recovery during the vulnerable post-resuscitation period, thereby contributing to improved functional outcomes. However, other studies have reported no consistent association between lactate clearance and outcomes in TTM-treated patients [14]. Suggesting that its prognostic value may vary depending on patient characteristics and treatment context. This variability was also highlighted in a large-scale meta- analysis by Zhou et al., which found that lactate clearance was significantly associated with neurological outcomes only at 24 hours, but not at earlier time points such as 12 hours, and concluded that serum lactate levels were more robust predictors overall compared to clearance metrics [15]. Interestingly, the improvement in CPC scores did not translate into a significant difference in GCS delta. This discrepancy highlights differences in outcome measures: CPC captures global functional status at discharge, whereas GCS may be affected by transient factors such as sedation or delirium [11]. As such, CPC may provide a more reliable measure of neurological recovery in this context. While global trials such as TTM2 and HYPERION have shaped international practice, regional data remain limited, particularly in middle-income countries such as Turkey. A five-year retrospective study by Özdamar et al. (2022) in an academic emergency department emphasized the practical challenges of implementing TTM protocols, including delays in initiation and variability in patient selection [9]. In a separate ICU-based study, Erdoğan et al. (2022) reported improved neurological outcomes among post-cardiac arrest patients undergoing TTM [16]. These studies reflect both the heterogeneity and feasibility of TTM in Turkish clinical settings. Our findings align with these observations, contributing additional insight into metabolic recovery and neurological outcomes, and further supporting the notion that even in resource-limited contexts, TTM can be beneficial when protocols are standardized and timely applied. These institutional experiences are further contextualized by national-level data. Complementing these single-center studies, the recent TROHCA study—a prospective, multicenter analysis across 28 Turkish hospitals—provides the most comprehensive national dataset on OHCA to date. Among 1002 analyzed cases, TTM was applied in only 2.2% of patients, and a good neurological outcome at discharge was achieved in just 2.7% [17]. These sobering figures underscore the underutilization of post-resuscitation strategies such as TTM and the urgent need for standardized protocols and education. In contrast, our study demonstrates a higher rate of TTM application and improved neurological outcomes, suggesting that when systematically implemented, TTM can be a practical and effective tool in Turkish ICUs. This study has several strengths. The use of propensity score matching reduced baseline imbalances and allowed for a more reliable assessment of TTM’s effects in a real-world setting. Furthermore, by examining both metabolic and neurological endpoints, our analysis extends beyond mortality, offering a more comprehensive view of post-arrest outcomes. Importantly, the inclusion of Turkish patients adds regional data to a literature largely dominated by Western cohorts, where epidemiological factors and healthcare system characteristics may differ. Nonetheless, several limitations must be considered. The small sample size, particularly the limited number of TTM patients, restricts statistical power and increases the risk of type II error. The retrospective, single-center design also introduces selection bias and limits generalizability, despite successful matching of measured confounders. Unmeasured factors such as prehospital downtime and delays in initiating TTM may have influenced outcomes. Additionally, long-term neurological follow-up was not available, precluding conclusions about sustained recovery. Finally, the TTM protocol applied (35–36°C with controlled rewarming) differed slightly from stricter 33°C regimens used in major randomized trials, which could account for some variation in outcomes. In summary, although TTM did not lead to a statistically significant reduction in 28-day mortality in our cohort, its association with improved lactate clearance and favorable neurological outcomes highlights the need to evaluate therapeutic success beyond survival alone. These findings support the role of TTM in promoting metabolic stabilization and functional recovery during the post-resuscitation period. Future efforts should focus on defining patient subgroups that may benefit most from TTM and implementing standardized protocols across diverse clinical settings.

Limitations

This study has certain limitations. It was conducted in a single center with a relatively small number of patients, which may affect the generalizability of the results. Long-term neurological outcomes could not be assessed, and the TTM protocol differed slightly from some major trials. Despite these factors, the study provides valuable real-world data and contributes to the understanding of TTM in intensive care practice.

Conclusion

In this propensity score-matched cohort of post-cardiac arrest patients, targeted temperature management (TTM) showed no significant mortality benefit but was associated with enhanced lactate clearance and improved neurological recovery. These results emphasize that TTM may exert its primary benefits not through survival alone, but through supporting organ perfusion and neurological function during the critical post-resuscitation phase. By contributing real-world data from Turkey, this study expands the geographic scope of TTM evidence and demonstrates its potential feasibility in middle-income healthcare systems. Large-scale, prospective multicenter studies with long-term outcome assessment are needed to refine patient selection criteria and optimize TTM protocols.

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