Is there data assessing outcomes in patients with targeted temperature management post cardiac arrests?

Comment by InpharmD Researcher

There is a substantial amount of data for targeted temperature measurement (TTM) post-cardiac arrest with heterogeneous results and recommendations. In general, TTM may improve clinical outcomes but results within subgroup populations are largely inconclusive. The optimal target temperature that would promote the best outcomes remains unclear.
Background

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have published recent 2021-2022 guidelines for post-resuscitation care after cardiac arrest syndrome. Targeted temperature management (TTM) is recommended for adult patients after either out- or in-hospital cardiac arrest who remain unresponsive after the return of spontaneous circulation (ROSC). The target temperature recommended is between 32 and 36°C for at least 24 hours. However, there is limited evidence for the optimal temperature range in subpopulations of cardiac arrest patients. A meta-analysis performed on six clinical trials found a TTM target range of 32 to 34°C did not improve survival (risk ratio [RR] 1.08; 95% confidence interval [CI] 0.89 to 1.3) or favorable functional outcome (RR 1.21; 95% CI 0.91 to 1.61) at 90 to 180 days post-cardiac arrest. Pre-hospital cooling also did not improve survival or functional outcome at discharge. One trial that compared 33°C versus 36°C found no difference in neurological outcomes at 180 days and discharge. Three studies that compared different methods of temperature control (e.g., endovascular cooling and surface cooling) found no difference in survival or neurological outcomes at discharge or at 28 days. Based on these findings, the panel prefers fever prevention as it likely requires fewer resources and is associated with less side effects compared to TTM. Yet temperature control between 32 to 36°C may be considered despite these recent findings as some populations may still benefit from treatment. Fever should be actively prevented (> 37.7°C) for at least 72 hours in post-cardiac patients who remain comatose. [1-2]

The Neurocritical Care Society (NCS) published guidelines in 2017 for the optimal technique of general TTM. In the setting of post-cardiac arrest, certain evidence from the literature was highlighted. Cold saline infusions may be effective at reducing initial temperature upon arrival, but were found to achieve less ROSC compared to standard care. No additional measures to avoid gastric intolerance for patients undergoing TTM seem necessary. The pharmacokinetics of commonly-used analgesics and sedatives may be altered by cooling. There may be higher rates of thrombocytopenia and transfusion of blood products, but no significant difference in bleeding complications. Patients with shock or left ventricular failure may require more monitoring for skin breakdown. [3]

The Taiwan Society of Emergency & Critical Care Medicine published 2021 guidelines for TTM in the setting of post-cardiac arrest. Like previous guidelines, the recommended TTM range is between 32 to 36°C. Neurological outcomes may be improved by keeping body temperature at 33°C for 24 hours post-cardiac arrest in patients with an initial shockable rhythm. The recommendations seem to be based on less-robust evidence with the panel citing specific TTM trials and a meta-analysis of six studies. [4]

A series of recent systematic reviews and meta-analyses evaluated various outcomes associated with TTM. A 2022 systematic review and Bayesian meta-analysis including seven randomized and quasi-randomized trials (three low bias, three intermediate bias, one high bias, very low to low certainty; N= 3,792 patients) compared comatose survivals from cardiac arrest who received TTM for at least 12 hours versus those without TTM treatment (See Table 1). Studies evaluating similar TTM with various duration as well as those investigating hypothermic (32–34 °C) TTM in both intervention and control groups were excluded from the analysis. With evidence of heterogeneity but no evidence of publication bias, there was a mean RR for death of 0.96 (95% CrI 0.82 to 1.04) and a RR for unfavorable neurological outcomes of 0.93 (95% CrI 0.84 to 1.02). Studies with no explicit mention of normothermia temperature definition in the control groups were excluded from the sensitivity analysis to reduce the heterogeneity, resulting in a change in the RR for death to 0.99 (95% CrI 0.69 to 1.14) and for unfavorable neurological outcomes to 0.96 (95% CrI 0.68 to 1.12). Moreover, four studies lacking the active avoidance of fever in control arms were excluded resulting in a reduced probability to achieve an absolute risk reduction of > 2% for death or unfavorable neurological outcome to ≤ 50%. As the posterior probabilities for favorable treatment effects of TTM at 32–34 °C were highest for an absolute risk reduction of 2-4% for death (28-53% chance) and unfavorable neurological outcome (63-78% chance), this analysis did not support the use of TTM at 32–34 °C as compared to ≥ 36 °C also including active control of fever to reduce the risk of death and unfavorable neurological outcome at 90-180 days. [5]

Another 2022 systematic review and meta-analysis included six retrospective controlled studies (N= 14,607) to compare the discharge survival and neurological outcomes in patients treated with TTM (n= 1,845) versus the control group (n= 12,762). Survival to hospital discharge (OR 1.02, 95% CI 0.77 to 1.35; p= 0.89) and favorable neurological outcomes (OR 1.06, 95% CI 0.56 to 2.02, p= 0.85) did not show statistical difference between the two groups. To address the variable sample size and the large effect on the heterogeneity, subgroup analyses were performed which still demonstrated no significant effect on survival to hospital discharge; however, therapeutic hypothermia was associated with an increased risk of unfavorable neurological outcomes in the large sample size subgroup when compared to those with no hypothermia (OR 0.81, 95% CI 0.69 to 0.94; p= 0.006). Overall, the results may be limited due to significant heterogeneity across studies, potential confounding factors (e.g., specific cryotherapy method), and its retrospective observational study design. [6]

A 2021 review (N= 32 trials) was performed to evaluate multiple aspects of targeted temperature management including timing, temperature, duration, method of induction and maintenance, and rewarming. Adults patients with cardiac arrest in any setting (in- or out-of-hospital) were included. Nine trials compared TTM at 32-34 °C vs. normothermia. Most of these trials were pilot studies or limited to small sample size; six of these studies were included in the meta-analysis which found that a target of 32-34 °C did not result in improved survival (RR 1.08, 95% CI 0.89 to 1.30) or favorable neurologic outcome (RR 1.21, 95% CI 0.91 to 1.61) at 90 to 180 days after the cardiac arrest. No difference was found in any other outcomes measured including different hypothermic targets (no difference between 32 °C, 33 °C, 34 °C, or 36 °C), in prehospital vs. no prehospital cooling; there was no improvement in improved survival (RR 1.01, 95% CI 0.92 to 1.11) or favorable neurologic outcome at hospital discharge (RR 1.00; 95% CI 0.90 to 1.11). Overall, most comparisons were based on low to moderate certainty of evidence. The results suggested an overall lack of effectiveness associated with TTM based on the included data. [7]

Another 2021 systematic review and network meta-analysis included 10 RCTs (N= 4,218 patients) to evaluate the efficacy and safety of deep hypothermia (31–32 °C), moderate hypothermia (33–34 °C), mild hypothermia (35–36 °C), and normothermia (37–37.8 °C) during TTM in patients with out-of-hospital cardiac arrest (OHCA) and decreased level of consciousness. The analysis with low certainty revealed deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73 to 2.30), moderate hypothermia (OR 1.34, 95% CI 0.92 to 1.94), and mild hypothermia (OR 1.44, 95% CI 0.74 to 2.80) may have no effect on survival with a good functional outcome compared to normothermia. Likewise, compared to moderate hypothermia, there may be no additional benefits of deep hypothermia on survival with a good functional outcome (OR 0.97, 95% CI 0.61 to 1.54). Additionally for overall survival, there may be no effect of deep hypothermia (OR 1.27, 95% CI 0.70 to 2.32), moderate hypothermia (OR 1.23, 95% CI 0.86 to 1.77), or mild hypothermia (OR 1.26 95% CI 0.64 to 2.49) compared to normothermia (all low certainty). Compared to normothermia, moderate hypothermia and deep hypothermia were associated with an increased risk of arrhythmia (OR 1.45, 95% CI 1.08 to 1.94 and OR 3.58, 95% CI 1.77 to 7.26; both high certainty). Similarly, arrhythmia was reported more commonly in the deep hypothermia group versus the moderate hypothermia group (OR 2.47, 95% CI 1.25 to 4.88; high certainty). For the incidence of bleeding or pneumonia, no significant difference was revealed among the various temperature management groups (all low or very low certainty). Given the limitations of this network meta-analysis mainly due to clinical heterogeneity, various timing of outcome measurement, and unblinded target group allocation, the results should be interpreted with caution. As data are insufficient for subgroup analysis, future studies are warranted to identify patient populations likely to benefit from TTM with moderate to deep temperatures. [8]

A 2019 systematic review and meta-analysis compared the effects of different TTM methods on survival and neurological outcomes. A total of 22 studies (N= 8,027 patients) were included in the final analysis. Cooling methods evaluated include core (i.e., endovascular cooling devices [EC], intravenous cold fluids, automated peritoneal lavage, any dialysis technique, extracorporeal membrane oxygenation, esophageal or trans-nasal) or surface (i.e., skin exposure, cooling beds, iced packs, cooling pads, air-circulating or water-circulating blankets, water-filled blankets, air-filled blankets), as well as invasive (i.e., EC, automated peritoneal lavage, any dialysis technique, extracorporeal membrane oxygenation) and non-invasive (all others). Most included studies were retrospective with very low quality of evidence, but four high-quality randomized controlled trials (RCTs) were also included. Comparison of core vs. surface TTM revealed core methods were associated with a lower probability of unfavorable neurological outcomes (OR 0.85, 95% CI 0.75 to 0.96; p= 0.008) but not mortality (OR 0.88, 95% CI 0.62 to 1.25; p= 0.21). The comparison of invasive to noninvasive TTM methods indicated a significantly lower probability of unfavorable neurological outcomes (OR 0.70, 95% CI 0.61 to 0.81; p<0.001) and mortality (OR 0.84, 95% CI 0.74 to 0.94; p=  0.002) versus the invasive methods. Overall, the analyses were based on non-randomized controlled trials, but the reported randomized controlled trials revealed a similar trend. Based on non-randomized controlled trials, the use of temperature feedback devices (TFD) was associated with a significantly lower probability of unfavorable neurological outcomes and mortality than non-TFD methods. [9]

Finally, another systematic review and meta-analysis from 2018 included 11 RCTs (N= 4,782) to also evaluate the efficacy of TTM after cardiac arrest. Five trials (n= 1,389) compared hypothermia and normothermia strategies, finding no difference in mortality (RR 0.88, 95% CI 0.73 to 1.05) or neurological outcomes (RR 1.26, 95% CI 0.92 to 1.72), and six trials (n= 3,393) compared prehospital hypothermia and in-hospital hypothermia, again finding no difference in mortality (RR 1.00, 95% CI 0.97 to 1.03) or neurological outcome (RR 0.96, 95% CI 0.85 to 1.08). It was discussed that therapeutic hypothermia includes risks associated with the rewarming period; if similar outcomes can be achieved utilizing alternative means, these risks can be avoided. Overall, the authors concluded that TTM with therapeutic hypothermia may not improve mortality or neurological outcomes in post-arrest survivors, meriting reevaluation of this standard-of-care strategy. [10]

Two commentary statements provided expert opinions regarding the study conducted by Nielsen et al (summarized in Table 3). In one commentary, the authors emphasized that despite an insignificant difference in benefits between the two hypothermic temperature goals (33°C vs. 36°C), TTM improves outcomes in post-cardiac arrest patients. The other commentary specifies that the scene where the assessment of cardiac arrest takes place is important and will influence the patient demographic (e.g., out-of-hospital versus within the emergency department). In response to the commentaries, the study authors noted a 50% mortality rate, indicating that included patients were severely ill and appropriate for the study to detect a clinically satisfactory outcome. [11-13]

References:

[1] Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, Genbrugge C, Haywood K, Lilja G, Moulaert VRM, Nikolaou N, Olasveengen TM, Skrifvars MB, Taccone F, Soar J. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med. 2021 Apr;47(4):369-421. doi: 10.1007/s00134-021-06368-4. Epub 2021 Mar 25. PMID: 33765189; PMCID: PMC7993077.
[2] Sandroni C, Nolan JP, Andersen LW, Böttiger BW, Cariou A, Cronberg T, Friberg H, Genbrugge C, Lilja G, Morley PT, Nikolaou N, Olasveengen TM, Skrifvars MB, Taccone FS, Soar J. ERC-ESICM guidelines on temperature control after cardiac arrest in adults. Intensive Care Med. 2022 Mar;48(3):261-269. doi: 10.1007/s00134-022-06620-5. Epub 2022 Jan 28. PMID: 35089409.
[3] Madden LK, Hill M, May TL, et al. The Implementation of Targeted Temperature Management: An Evidence-Based Guideline from the Neurocritical Care Society. Neurocrit Care. 2017;27(3):468-487. doi:10.1007/s12028-017-0469-5
[4] Chiu WT, Lin KC, Tsai MS, Hsu CH, Wang CH, Kuo LK, Chien YS, Wu CH, Lai CH, Huang WC, Wang CH, Wang TL, Hsu HH, Lin JJ, Hwang JJ, Ng CJ, Choi WM, Huang CH. Post-cardiac arrest care and targeted temperature management: A consensus of scientific statement from the Taiwan Society of Emergency & Critical Care Medicine, Taiwan Society of Critical Care Medicine and Taiwan Society of Emergency Medicine. J Formos Med Assoc. 2021 Jan;120(1 Pt 3):569-587. doi: 10.1016/j.jfma.2020.07.036. Epub 2020 Aug 20. PMID: 32829996.
[5] Aneman A, Frost S, Parr M, Skrifvars MB. Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis. Crit Care. 2022;26(1):58. Published 2022 Mar 12. doi:10.1186/s13054-022-03935-z
[6] Yin L, Xie D, He D, et al. Survival to hospital discharge and neurological outcomes with targeted temperature management after in-hospital cardiac arrest: a systematic review and meta-analysis. Ann Palliat Med. 2022;11(1):68-76. doi:10.21037/apm-21-3403
[7] Granfeldt A, Holmberg MJ, Nolan JP, Soar J, Andersen LW; International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force. Targeted temperature management in adult cardiac arrest: Systematic review and meta-analysis. Resuscitation. 2021;167:160-172. doi:10.1016/j.resuscitation.2021.08.040
[8] Fernando SM, Di Santo P, Sadeghirad B, et al. Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets. Intensive Care Med. 2021;47(10):1078-1088. doi:10.1007/s00134-021-06505-z
[9] Calabró L, Bougouin W, Cariou A, et al. Effect of different methods of cooling for targeted temperature management on outcome after cardiac arrest: a systematic review and meta-analysis. Crit Care. 2019;23(1):285. Published 2019 Aug 23. doi:10.1186/s13054-019-2567-6
[10] Kalra R, Arora G, Patel N, et al. Targeted Temperature Management After Cardiac Arrest: Systematic Review and Meta-analyses. Anesth Analg. 2018;126(3):867-875. doi:10.1213/ANE.0000000000002646
[11] Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206. doi:10.1056/NEJMoa1310519
[12] Targeted temperature management after cardiac arrest. N Engl J Med. 2021;385(14):1341-1342. doi: 10.1056/NEJMc2112370
[13] Morrison LJ, Thoma B. Translating Targeted Temperature Management Trials into Postarrest Care. N Engl J Med. 2021 Jun 17;384(24):2344-2345. doi: 10.1056/NEJMe2106969. PMID: 34133865.

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

Is there data assessing outcomes in patients with targeted temperature management post cardiac arrests?

Level of evidence

A - Multiple high-quality studies with consistent results  Read more→



Please see Tables 1-3 for your response.


 

Randomized controlled studies on targeted temperature management after cardiac arrest

Study setting

Intervention group

Control

Intervention

Control

Deaths/total

Unfavorable neurological outcome/total

Deaths/total Unfavorable neurological outcome/total 

Bernard et al.

Single-center in Melbourne, Australia

N= 77

TTM at 33 °C for 18h No TTM, unclear about fever treatment  22/43 22/43  23/34 25/34

HACA

Multiple centers in Europe

N= 275

TTM at 32–34 °C, for 24h No TTM, unclear about fever treatment 56/137  61/136 76/138 83/137

Laurent

Single-center in Paris, France

N= 42

TTM at 32–33 °C for 16h No TTM, unclear about fever treatment

15/22

 

15/22

11/20 11/20

Hachimi-Idrissi

Single-center in Belgium

N= 28

TTM at 33 °C for 24h No TTM, unclear about fever treatment 6/14 8/14 8/14 11/14

Nielsen

Multiple centers in Europe and Australia

N= 950

TTM at 33 °C for 28h TTM at 36 °C for 28h 226/473 251/469 220/466 242/464

Lascarrou

Multiple centers in France

N= 584

TTM at 33 °C for 24h TTM at 36.5–37.5 °C 231/284 255/284 247/297 280/297

Dankiewicz

Multiple centers in Europe, Australia, New Zealand and USA

N= 1,900

TTM at 33 °C for 24h TTM, if > 37.8 °C then 37.5 °C 465/925 488/881 446/925 479/866

OHCA, out-of-hospital cardiac arrest; VF, ventricular fibrillation; TTM, targeted temperature management; HACA, hypothermia after cardiac arrest; IHCA, in-hospital cardiac arrest; CPC, cerebral performance category

References:

Adapted from: Aneman A, Frost S, Parr M, Skrifvars MB. Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis. Crit Care. 2022;26(1):58. Published 2022 Mar 12. doi:10.1186/s13054-022-03935-z

 

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

Design

Open-label, international, investigator-initiated, superiority trial

N= 1,850

Objective

To assess the beneficial and harmful effects of hypothermia as compared with normothermia and early treatment of fever in patients after cardiac arrest. We hypothesized that at 6 months, the incidence of death would be lower in the hypothermia group than in the normothermia group

Study Groups

Hypothermia (n= 930)

Normothermia (n= 931)

Inclusion Criteria

Aged ≥ 18 years; admitted after out-of-hospital cardiac arrest of a presumed cardiac or unknown cause, irrespective of the initial rhythm; unconscious and unable to obey verbal commands, no verbal response to pain; more than 20 consecutive minutes of spontaneous circulation after resuscitation

Exclusion Criteria

Interval from return of spontaneous circulation to screening of more than 180 minutes, unwitnessed cardiac arrest with asystole as the initial rhythm, limitation in care

Methods

Patients presenting to the intensive care unit (ICU) were randomized (1:1) to receive either hypothermia or normothermia care. Patients in the hypothermia group received immediate cooling with a surface or intravascular temperature management device to a targeted temperature of 33°C and maintained until 28 hours after randomization, followed by rewarming to 37°C in hourly increments of one-third of a degree. The normothermia group maintained a temperature of ≤ 37.5°C. All patients remained sedated until the end of the intervention period. Afterward, a normothermic target range of 36.5 to 37.7°C was maintained until 72 hours after randomization if patients remained sedated or comatose. 

Health professionals were aware of the randomization due to difficulty in blinding. A physician unaware of the randomization performed a neurological assessment.

Duration

Follow-up: up to 6 months 

Outcome Measures

Primary: death from any cause at 6 months

Secondary: poor functional outcome at 6 months (defined as a score of 4 to 6 modified Rankin scale), safety

Baseline Characteristics

 

Hypothermia (n= 930)

Normothermia (n= 931)

   

Age, years

64 ± 13 63 ± 14    

Male

80% 79%    

Medical history

Hypertension

Diabetes

Myocardial infarction

Percutaneous coronary intervention

Coronary-artery bypass graft

Heart failure

 

37%

19%

15%

14%

8%

10%

 

32%

18%

17%

15%

8%

10%

   

Median time from cardiac arrest to randomization, min (interquartile range [IQR])

136 (103 to 170)

133 (99 to 173)

   

Median time from cardiac arrest to sustained return of spontaneous circulation (ROSC), min

25 (16 to 40)

25 (17 to 40)

   

Results

Endpoint

Hypothermia (n= 930)

Normothermia (n= 931)

Relative risk (95% confidence interval [CI])

p-value

Death at 6 months

465/925 (50%)

446/925 (48%)

1.04 (0.94 to 1.14)

0.37

Modified Ranking scale score of 4-6 at 6 months

488/881 (55%)

479/866 (55%)

1.00 (0.92 to 1.09)

--

Poor functional outcome at 6 months

495/918 (54%)

493/911 (54%)

1.00 (0.91 to 1.08)

--

Serious adverse events

Arrhythmia resulting in hemodynamic compromise

Bleeding

Skin complications related to temperature device

Pneumonia

Sepsis

 

24%

5%

1%

36%

11%

 

16%

5%

<1%

35%

9%

 

1.45 (1.21 to 1.75)

0.95 (0.63 to 1.42)

1.99 (0.71 to 6.37)

1.02 (0.90 to 1.15)

1.19 (0.90 to 1.57)

 

<0.001

0.81

0.21

0.75

0.23

Study Author Conclusions

In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia.

InpharmD Researcher Critique

To ensure patients were treated similarly, the authors admitted to standardizing the protocol for sedation, paralysis, and mechanical ventilation which may not reflect real-world care in the ICU setting. The study lacked a control group without any temperature management. Temperature control strategy potentially varied between patients and any concomitant care was left to the physician's discretion.



References:

Dankiewicz J, Cronberg T, Lilja G et al.; TTM2 Trial Investigators. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 2021 Jun 17;384(24):2283-2294. doi: 10.1056/NEJMoa2100591. PMID: 34133859.

 

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

Design

Randomized, international controlled trial

N= 950

Objective

To investigate the benefits and harms of two targeted temperature regimens, both intended to prevent fever, in a broader population of patients with cardiac arrest than previously studied

Study Groups

33°C group (n= 473)

36°C group (n= 466)

Inclusion Criteria

Age 18 years and older, unconscious on admission after out-of-hospital cardiac arrest of presumed cardiac cause, irrespective of initial rhythm; more than 20 consecutive minutes of spontaneous circulation after resuscitation

Exclusion Criteria

Interval from the return of spontaneous circulation to screening of more than 240 minutes, unwitnessed arrest with asystole as the initial rhythm, suspected or known acute intracranial hemorrhage or stroke, body temperature less than 30°C

Methods

Patients were randomized (1:1) to receive targeted temperature management with a targeted body temperature of either 33°C or 36°C with an intervention period of up to 36 hours. Patients received rapid cooling using various strategies including ice-cold fluids, ice packs, and intravascular or surface temperature-management devices based on the site. Neurologic examinations were performed by blinded physicians. Healthcare professionals were not blinded due to logical considerations.

Duration

180 days

Outcome Measures

Primary: all-cause mortality

Secondary: poor neurologic function or death defined as Cerebral Performance Category (CPC) of 3 to 5 and modified Rankin Scale Score (mRSS) of 4 to 6, safety

Baseline Characteristics

 

33°C group (n= 473)

36°C group (n= 466)

   

Age, years

64 ± 12 64 ± 13    

Male

83% 79%    

Medical history

Chronic heart failure

Ischemic heart disease

Previous cardiac arrhythmia

Arterial hypertension

 

7%

31%

18%

41%

 

6%

25%

17%

39%

   

Time from cardiac arrest to return of spontaneous circulation, min (interquartile range [IQR])

25 (18 to 40)

25 (16 to 40)

   

Results

Endpoint

33°C group (n= 473)

36°C group (n= 466)

Hazard ratio (HR) /risk ratio (RR) (95% confidence interval [CI])

p-Value

Death at the end of trial

235 (50%)

225 (48%)

HR 1.06 (0.89 to 1.28)

0.51

Neurological function at follow-up

CPC of 3 to 5

mRSS of 4 to 6

 

251/469 (54%)

245/469 (52%)

 

242/464 (52%)

239/464 (52%)

 

RR 1.02 (0.88 to 1.16)

RR 1.01 (0.89 to 1.14)

 

0.78

0.87

Death at 180 days

226/473 (48%)

220/466 (47%)

RR 1.01 (0.87 to 1.15)

0.92

Patients that experienced a serious adverse event

439 (93%)

417 (90%)

RR 1.03 (1.00 to 1.08)

0.09

Adverse Events

Hypokalemia was the most frequently reported adverse event (33°C group: 19% versus 36°C group: 13%)

Study Author Conclusions

In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

InpharmD Researcher Critique

The method of cooling was not standardized due to the multicenter, international study design. The management of cardiac arrest and quality of treatment may vary by institution. 



References:

Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206. doi:10.1056/NEJMoa1310519