ARTICLE
Nishikimi M, Ogura T, Nishida K, et al. Outcome Related to Level of Targeted Temperature Management in Postcardiac Arrest Syndrome of Low, Moderate, and High Severities: A Nationwide Multicenter Prospective Registry. Crit Care Med. 2021 Apr 8. doi: 10.1097/CCM.0000000000005025. Epub ahead of print. PMID: 33826582.
OBJECTIVE
The authors of this study aimed to determine the effect on neurologic outcomes when using targeted temperature management (TTM) at lower (33-34°C) versus higher (35-36°C) core body temperatures in postcardiac arrest syndrome (PCAS) patients stratified into different severity subgroups.
BACKGROUND
Neurologic injury is a contributing cause of death in patients who suffer from cardiac arrest outside of a hospital setting. Hyperthermia can worsen neurologic insult, and for each degree core body temperature is above 37°C the risk of death increases in the first 48 hours after cardiac arrest.1 TTM is a method of reducing core body temperature ranging from non-invasive external methods (cooling blankets, ice packs, etc.) to intravenous infusion of cold isotonic saline. Initiation of TTM in the present study was indicated when a patient had a GCS ≤ 8 after ROSC, but is generally utilized following cardiac arrest when neurologic status appears to be compromised with an inability to follow commands or demonstrate movement. Although the benefit of reducing core body temperature following cardiac arrest to prevent neurologic injury is known, the optimal temperature to target remains unclear.
The authors of this study aimed to ascertain the association between TTM at lower core temperatures and good neurologic outcome at 30 days in PCAS patients who were classified into low, moderate, and high severity subgroups. The three subgroups were established by the post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) scoring system. The rCAST is scored based on a combination of the following in PCAS patients:
- initial rhythm
- witnessed arrest/time until ROSC
- blood pH and serum lactate upon hospital arrival AND
- motor score of GCS at time of ROSC
After rCAST classification, patients then underwent TTM to a lower temperature (33-34°C) or higher temperature (35-36°C). Neurologic outcome and survival at 30 days following cardiac arrest was assessed to determine an optimal temperature for TTM in PCAS patients.
DESIGN
- Multicenter observational study across 125 critical care centers or hospitals in Japan
Study Selection and Inclusion Criteria
- A total of 1,111 adult patients who suffered nontraumatic cardiac arrest who underwent TTM were included in the study.
- Patients were excluded if they were under 18 years-old, suffered traumatic cardiac arrest, underwent TTM at or below 32°C, or required ECMO.
OUTCOMES
Primary
- Percentage of patients with a good neurologic outcome at 30 days defined as cerebral performance category (CPC) 1 or 2. Category 1 is defined as full neurologic recovery and category 2 is moderate neurologic disability.
Secondary
- Patient survival at 30 days
KEY RESULTS
Primary Outcomes
- Moderate severity: 53% (180/343) of patients in the 33-34°C group showed a good neurologic outcome versus 38% (59/157) in the 35-36°C group. Statistically significant based on multivariate logistic regression analysis (OR, 1.70; 95% CI, 1.03-2.83; p = 0.04).
- Low severity: 82% (118/144) of patients in the 33-34°C group showed a good neurologic outcome versus 91% (40/44) in the 35-36°C group. Not statistically significant based on multivariate regression analysis (OR, 0.38; 95% CI, 0.12-1.21; p = 0.10).
- High severity: 7% (18/277) of patients in the 33-34°C group showed a good neurologic outcome versus 8% (11/146) in the 35-36°C group. Not statistically significant based on multivariate regression analysis (OR, 0.80; 95% CI, 0.34-1.88; p = 0.61).
Secondary Outcomes
- Moderate Severity: 83% (286/343) of patients in the 33-34°C group survived to 30 days versus 70% (110/157) in the 35-36°C group. Statistically significant based on multivariate regression analysis (OR, 1.90; 95% CI, 1.15-3.16; p = 0.01).
- Low Severity: 94% (136/144) of patients in the 33-34°C group survived to 30 days versus 98% (43/44) in the 35-36°C group. Not statistically significant based on multivariate regression analysis (OR, 0.49; 95% CI, 0.09-2.55; p = 0.40).
- High Severity: 42% (115/277) of patients in the 33-34°C group survived to 30 days versus 34% (49/146) in the 35-36°C group. Not statistically significant based on multivariate regression analysis (OR, 1.51; 95% CI, 0.95-2.40; p = 0.09).
STRENGTHS
- Large multicenter trial
- Objective method of stratifying severity of PCAS
- Excluded all patients who were missing a variable to determine rCAST score
LIMITATIONS
- Choice of core temperature setting for TTM was left to the discretion of the participating hospital
- Study sites all in Japan - unknown if the results are generalizable
- rCAST is not an easy calculation to make and regular use may be limited without an established, user-friendly calculator
- Variation among each participating hospital in TTM protocol
- CPC does not provide a detailed summary of a patient's neurologic status
- Relatively short follow up period of 30 days, making long-term efficacy of treatment unknown
EM TAKE-AWAYS
This study demonstrated that TTM at a lower core temperature (33-34°C) was associated with significantly better neurologic outcomes and survival at 30 days in patients with PCAS of moderate severity compared to a higher core temperature target (35-36°C). Among the high and low severity groups there was not a statistically significant difference in neurologic outcomes or survival at 30 days between the two target temperatures. As the authors specify, this may be due to the low severity group not meeting a brain ischemia threshold for a lower target temperature to significantly change what is likely to be a favorable prognosis, regardless of target temperature. Conversely, the high severity group may have suffered ischemia beyond the capability for TTM to offer significant benefit.
Moderate severity PCAS patients based on rCAST score appear to be the most likely to have significant neurologic and mortality benefit from a low temperature target with TTM, and emergency physicians should utilize TTM following cardiac arrest in such patients. With low and high severity patients demonstrating less definitive benefit, careful consideration of potential adverse effects to core temperature cooling, including coagulopathy and infection may be warranted.2-3
REFERENCES
- Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med. 2001;161(16):2007-12.
- Reed RL 2nd, Bracey AW Jr, Hudson JD, Miller TA, Fischer RP. Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels. Circ Shock. 1990;32(2):141-52.
- Perbet S, Mongardon N, Dumas F, et al. Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med. 2011;184(9):1048-54.