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Induced hypothermia after cardiac arrest did not improve survival

Three researchers at podium
The results were presented at a press conference in Lund

Since 2005, the guidelines for the care of unconscious cardiac arrest patients have been to cool the body temperature down to 33 degrees Celsius. A large, randomised clinical trial led by Lund University and Region Skåne in Sweden has shown that this treatment does not improve survival. The study is published in the New England Journal of Medicine.

“These results will affect the current guidelines”, says Niklas Nielsen, researcher at Lund University and consultant in anaesthesiology and intensive care at Helsingborg Hospital, who led the study.

In the early 2000s, two studies in the New England Journal of Medicine showed that induced hypothermia in unconscious cardiac arrest patients greatly improved patient survival. The studies changed existing treatment practices, and led to the introduction of new guidelines around the world. However, the evidence for the guidelines was considered by many to be weak. As a result, a large international randomised clinical trial was initiated, and led by researchers at Lund University and Helsingborg Hospital.

The results of the comprehensive study, which has now been published in the same journal, show that hypothermia does not reduce mortality in unconscious patients with suspected cardiac arrest.

“It is important to set high standards for clinical studies, partly to determine what should be introduced in healthcare, partly to challenge the practices that are already in use - to ensure that we have got it right and that healthcare is evidence-based. The results produced strongly indicate that normal temperature should be recommended, not hypothermia”, says Niklas Nielsen.

In total, 1900 adult patients who suffered cardiac arrest and were unconscious when admitted to hospital were included in the study. Between November 2017 and January 2020, a total of 61 hospitals around the world participated in the study which has now been published. The patients included in the study had suffered unexpected out-of-hospital cardiac arrest.

The patients were randomised into two groups when they were admitted to hospital. In one group, the patients were cooled down to 33 degrees according to existing guidelines, a temperature that was maintained for 28 hours. In the second group, the patient's body temperature was monitored, and the patients who developed a fever (about half of the participants in this group) were treated with the same method of temperature control, but kept at a normal temperature. The study was ethically approved in participating countries.

Researchers followed up on survival rates for patients six months after receiving care for cardiac arrest. They also investigated how functionality in everyday life was affected in the surviving patients.

1850 patients were included in the survival analysis*. Six months after the patients suffered the cardiac arrest, a total of 465 of 925 participants in the group who were induced with hypothermia had died, approximately 50%. In the normothermia group, 446 out of 925 had died, corresponding to 48%. Researchers saw a slightly increased risk of impact on blood circulation, cardiac arrhythmia, in the group treated with hypothermia.

1747 patients were included in the analysis of patients’ ability to function in everyday life (functional status). In the group treated with hypothermia, 488 of 881 (55%) either died or had a severe functional impairment 6 months later, which can be compared to 479 of 866 (55%) in the normothermia group.

“Since it is a large study involving many hospitals in different countries, it has been logistically challenging to follow up six months after the cardiac arrest. A dedicated effort has been put in to obtaining data. This has meant that sometimes patients have had to be visited at home, some patients have moved, and some suffered cardiac arrest in a country other than their homeland”, says Gisela Lilja, researcher at Lund University and chief occupational therapist at Skåne University Hospital, who coordinated the follow-up in the study.

“The results are important, but not unexpected. For 20 years we have applied and believed in these practices which we now see do not make a difference for survival. Now we can use the resources on other things, and prioritise other aspects of the acute phase of cardiac arrest”, says Josef Dankiewicz, researcher at Lund University and resident physician at Skåne University Hospital, and first author of the study.

Researchers now plan to further analyse patient data to learn more about who is affected, and about recovery after cardiac arrest.

* 36 patients declined to be part of the study, and there is data missing on 11 participants (6 in the hypothermia group and 5 in the other group)



About the study:

The TTM2 study (Targeted Temperature Management), led by researchers working at Lund University, Helsingborg Hospital and Skåne University Hospitals, together with an international steering group, is the largest to date within an intensive care context for cardiac arrest. It was run as an international project in which researchers and doctors from 61 hospitals in 14 countries participated.


The study was carried out with funding from the Swedish Research Council, the Swedish Heart Lung Foundation, the Stig and Ragna Gorthon Foundation, as well as ALF, and Regional funding for research in Skåne.


Niklas Nielsen

Niklas Nielsen
Associate professor, Senior consultant
Anesthesiology and Intensive Care
Lund University and Helsingborg Hospital
+46 708 899 770
niklas [dot] nielsen [at] med [dot] lu [dot] se

Gisela Lilja

Gisela Lilja, researcher at Lund University
Head occupational therapist at Skåne University Hospital
gisela [dot] lilja [at] med [dot] lu [dot] se

Josef Dankiewicz

Josef Dankiewicz
Researcher at Lund University and physician at Skåne University Hospital
josef [dot] dankiewicz [at] med [dot] lu [dot] se