Differential Effect of Targeted Temperature Management Between 32 °C and 36 °C Following Cardiac Arrest According to Initial Severity of Illness

Lascarrou, Jean Baptiste; Dumas, Florence; Bougouin, Wulfran; Legriel, Stéphane; Aïssaoui, Nadia; Deye, Nicolas; Beganton, Frankie; Lamhaut, Lionel; Jost, Daniel; Vieillard‐Baron, Antoine; Nichol, Graham; Marijon, Éloi; Jouven, Xavier; Cariou, Alain

doi:10.1016/j.chest.2022.10.023

Cited by 6 publications

(10 citation statements)

References 38 publications

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“…As such, this individual patient meta-analysis provides the best available evidence regarding the use of hypothermia in the management of OHCA patients with an initial nonshockable rhythm. Our subgroup analyses showed no association of hypothermia with improved outcomes in some populations of patients, such as those with a noncardiac cause of arrest (ie, mostly hypoxic/respiratory), prolonged resuscitation, absence of bystander CPR, and higher CAHP score, in whom previous studies suggested potential benefits . Moreover, the trial sequential analysis revealed that the use of hypothermia in this population was associated with futility, ie, the inability of these clinical trials to achieve a statistically significant and/or clinically relevant difference from hypothermia.…”

Section: Discussioncontrasting

confidence: 51%

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm

Taccone,

Dankiewicz,

Cariou

et al. 2024

JAMA Neurol

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ImportanceInternational guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable.ObjectiveTo assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm.Data SourcesIndividual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis.Study SelectionThe study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score.Data Extraction and SynthesisOnly patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation.Main Outcomes and MeasuresThe primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5.ResultsA total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups.Conclusions and RelevanceIn this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

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Section: Discussioncontrasting

confidence: 51%

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm

Taccone,

Dankiewicz,

Cariou

et al. 2024

JAMA Neurol

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“…One interpretation of conflicting clinical trial results is that TTMhypothermia offers less benefit for certain cohorts of adult patients, such as the cardiac population in TTM and TTM2 trials with high probability of good outcome [ 26 , 27 ], but may be more beneficial for other cohorts of patients with lower probability of good outcome, such as the more frequent respiratory arrest population in the HYPERION trial [ 62 ]. Observational studies support a differential treatment effect for TTM-hypothermia across subgroups, and these studies have an advantage over the clinical trials in that they include a more diverse cohort of patients ( Table 2 ) [ 31 , 42 , 75 – 77 ].…”

Section: Illness Severity Influences Treatment Effect Of Ttm-hypothermiamentioning

confidence: 99%

“…Another analysis used historical factors about the resuscitation in the modified Cardiac Arrest Hospital Prognosis score to define mild (<80), moderate (≥80 and <105), or severe (≥105) risk groups among 2,723 OHCA patients in the Sudden Death Expertise Center registry and 4,202 OHCA patients in the Resuscitation Outcomes Consortium database [ 77 ]. In both databases and in pooled data, TTM at 33 to 36 °C was associated with both survival and favorable functional recovery in low and severe risk groups, but this association was weaker in moderate-severity groups.…”

Section: Illness Severity Influences Treatment Effect Of Ttm-hypothermiamentioning

confidence: 99%

“…Clinicians should consider that imaging, EEG, or clinical exam can identify some patients whose brain injury is so severe that they will do poorly regardless of any current therapy [ 31 , 42 , 75 ]. Clinical or laboratory features also can identify mildly injured patients whose favorable prognosis is not affected by choice of TTM regimen [ 31 , 76 , 77 ] or who may even do better with TTM at 36 °C instead of TTM-hypothermia [ 42 ]. Future studies need to consider that individual patient characteristics may determine the treatment effect of TTM-hypothermia, and research should explore how to select the best regimen and duration of treatment for each individual patient.…”

Section: Illness Severity Influences Treatment Effect Of Ttm-hypothermiamentioning

confidence: 99%

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Targeted temperature management with hypothermia for comatose patients after cardiac arrest

Callaway¹

2023

Clin Exp Emerg Med

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Targeted temperature management with mild hypothermia (TTM-hypothermia; 32–34 °C) is a treatment strategy for adult patients who are comatose after cardiac arrest. Robust preclinical data support the beneficial effects of hypothermia beginning within 4 hours of reperfusion and maintained during the several days of postreperfusion brain dysregulation. TTM-hypothermia increased survival and functional recovery after adult cardiac arrest in several trials and in realworld implementation studies. TTM-hypothermia also benefits neonates with hypoxic-ischemic brain injury. However, larger and methodologically more rigorous adult trials do not detect benefit. Reasons for inconsistency of adult trials include the difficulty delivering differential treatment between randomized groups within 4 hours and the use of shorter durations of treatment. Furthermore, adult trials enrolled populations that vary in illness severity and brain injury, with individual trials enriched for higher or lower illness severity. There are interactions between illness severity and treatment effect. Current data indicate that TTM-hypothermia implemented quickly for adult patients after cardiac arrest, may benefit select patients at risk of severe brain injury but not benefit other patients. More data are needed on how to identify treatment-responsive patients and on how to titrate the timing and duration of TTM-hypothermia.

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“…Furthermore, Lasccarou et al compared the same parameters in patients who were categorized into three stages according to a modified CA hospital prognosis classification for PCAS and showed that the effect of TTM (32–36 °C) depended on disease severity [ 53 ]. An RCT is currently underway to investigate the effect of therapeutic hypothermia for a particular severity group, the results of which are anticipated to further enhance understanding of this matter [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

Differences in Pathophysiology and Treatment Efficacy Based on Heterogeneous Out-of-Hospital Cardiac Arrest

Utsumi,

Nishikimi,

Ohshimo

et al. 2024

Medicina

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Out-of-hospital cardiac arrest (OHCA) is heterogeneous in terms of etiology and severity. Owing to this heterogeneity, differences in outcome and treatment efficacy have been reported from case to case; however, few reviews have focused on the heterogeneity of OHCA. We conducted a literature review to identify differences in the prognosis and treatment efficacy in terms of CA-related waveforms (shockable or non-shockable), age (adult or pediatric), and post-CA syndrome severity and to determine the preferred treatment for patients with OHCA to improve outcomes.

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Differential Effect of Targeted Temperature Management Between 32 °C and 36 °C Following Cardiac Arrest According to Initial Severity of Illness

Cited by 6 publications

References 38 publications

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm

Targeted temperature management with hypothermia for comatose patients after cardiac arrest

Differences in Pathophysiology and Treatment Efficacy Based on Heterogeneous Out-of-Hospital Cardiac Arrest

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