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Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data

Annals of Intensive Care volume 12, Article number: 96 (2022) Cite this article

Abstract

Background

Outcomes of postresuscitation shock after cardiac arrest can be affected by targeted temperature management (TTM). A post hoc analysis of the “TTM1 trial” suggested higher mortality with hypothermia at 33 °C. We performed a post hoc analysis of HYPERION trial data to assess potential associations linking postresuscitation shock after non-shockable cardiac arrest to hypothermia at 33 °C on favourable functional outcome.

Methods

We divided the patients into groups with vs. without postresuscitation (defined as the need for vasoactive drugs) shock then assessed the proportion of patients with a favourable functional outcome (day-90 Cerebral Performance Category [CPC] 1 or 2) after hypothermia (33 °C) vs. controlled normothermia (37 °C) in each group. Patients with norepinephrine or epinephrine > 1 µg/kg/min were not included.

Results

Of the 581 patients included in 25 ICUs in France and who did not withdraw consent, 339 had a postresuscitation shock and 242 did not. In the postresuscitation-shock group, 159 received hypothermia, including 14 with a day-90 CPC of 1–2, and 180 normothermia, including 10 with a day-90 CPC of 1–2 (8.81% vs. 5.56%, respectively; P = 0.24). After adjustment, the proportion of patients with CPC 1–2 also did not differ significantly between the hypothermia and normothermia groups (adjusted hazards ratio, 1.99; 95% confidence interval, 0.72–5.50; P = 0.18). Day-90 mortality was comparable in these two groups (83% vs. 86%, respectively; P = 0.43).

Conclusions

After non-shockable cardiac arrest, mild-to-moderate postresuscitation shock at intensive-care-unit admission did not seem associated with day-90 functional outcome or survival. Therapeutic hypothermia at 33 °C was not associated with worse outcomes compared to controlled normothermia in patients with postresuscitation shock.

Trial registration ClinicalTrials.gov, NCT01994772

Introduction

Postcardiac arrest syndrome is a complex combination of pathophysiological processes, including brain injury, myocardial dysfunction, and systemic ischemia/reperfusion injury with vasoplegia. A major component of this syndrome is hemodynamic instability, which compromises the perfusion of vital organs. Postresuscitation shock (PRS) develops in 15% to 50% of patients admitted to the intensive care unit (ICU) after the return of spontaneous circulation (ROSC) [1, 2] and accounts for nearly a third of in-ICU deaths [3]. PRS is also associated with worse functional outcomes [4, 5].

Information on targeted temperature management (TTM) of patients with PRS at ICU admission is discordant. In vitro and animal studies have documented favourable inotropic effects of hypothermia on the myocardium [6, 7], suggesting possible benefits on haemodynamics. In patients with cardiogenic shock, hypothermia may improve cardiac function, thereby increasing the cardiac index, arterial blood pressure and, possibly, central venous oxygen saturation (ScvO2), while decreasing the lactate level and vasopressor requirements [8,9,10,11]. This global hemodynamic improvement might improve survival and functional outcomes after cardiac arrest by restoring adequate global and cerebral perfusion [12]. However, recent work suggests opposite effects. In a post hoc study of the “TTM1 trial”, compared to TTM at 36 °C, hypothermia at 33 °C was associated with a lower heart rate, higher lactate level, and greater vasopressor requirements [13]. In another post hoc analysis of the same trial, in the patient sub-group with PRS at ICU admission, hypothermia at 33 °C was not associated with better survival or less severe PRS severity, and there was a trend toward worse outcomes in the 33 °C group, significant after multivariable adjustments [14]. However, most of those studies were dedicated to patient with cardiac arrest from cardiac cause, whereas cardiac arrest from non-cardiac cause is increasingly frequently and potentially associated with different physiopathology [15]. Last patient sub-group with PRS was generally excluded from initial randomized trials of therapeutic hypothermia after cardiac arrest [16, 17], resulting in a relative lack of safety and efficacy data. Current guidelines do not include clear recommendations for patients with PRS [18].

The objective of this post hoc analysis of data from the HYPERION randomized trial comparing 33° to controlled normothermia (37 °C) after non-shockable cardiac arrest was to determine whether the intervention was associated with the day-90 functional outcome specifically in the sub-group of patients with PRS.

Methods

Patients

HYPERION was a randomized, multicenter, controlled trial with blinded outcome assessment that included adults (≥ 18 years) who achieved the ROSC after out-of-hospital or in-hospital cardiac arrest in a non-shockable rhythm, due to any cause, and who were comatose (Glasgow Coma Scale score ≤ 8) at ICU admission (NCT01994772) [2, 19]. The main exclusion criteria were a no-flow time longer than 10 min; a low-flow time longer than 60 min, a time from cardiac arrest to screening longer than 300 min; and major hemodynamic instability defined as a continuous epinephrine or norepinephrine infusion > 1 µg/kg/min.

Targeted temperature management (TTM)

Patients were randomized to moderate therapeutic hypothermia at 33 °C or controlled normothermia (37 °C). In the hypothermia group, cooling to 33 °C was induced then maintained for 24 h, after which slow rewarming at a rate no faster than 0.5 °C/h was provided to a body temperature of 36.5–37.5 °C, which was maintained for 24 h. In the normothermia group, body temperature was maintained at 36.5–37.5 °C for 48 h. Sedation was tapered when the body temperature rose above 36 °C in the hypothermia group and after 12 h in the normothermia group.

Definition of postresuscitation shock (PRS)

PRS was defined as a systolic blood pressure below 90 mm Hg for at least 30 min with impaired end-organ perfusion (cool extremities, mottling, or urine output < 30 mL/h), requiring norepinephrine and/or epinephrine intravenous infusion. PRS was recorded at ICU admission. Severe shock requiring a continuous epinephrine or norepinephrine infusion > 1 µg/kg/min was an non-inclusion criterion in the HYPERION trial.

Hemodynamic management

Hemodynamic evaluations were conducted to allow blood volume optimization. Hypovolemia was managed with crystalloid or colloid infusion, according to standard practice in each participating ICU. Vasoactive drug treatment was at the discretion of the physicians, who followed international guidelines and local protocols. The targets were 65 mmHg for mean arterial pressure (MAP) and, if measured, ≥ 70% for ScvO2.

Outcomes

The primary outcome was a favourable day-90 functional outcome defined as a Cerebral Performance Category (CPC) score of 1 of 2. CPC scores can range from 1 to 5, with higher scores indicating greater disability. A score of 1 indicates good cerebral performance or minor disability and a score of 2 moderate disability.

Secondary outcomes were day-90 mortality and PRS severity assessed based on the heart rate, MAP, cardiovascular SOFA-score component, and serum lactate level.

Statistics

Categorical data were described as frequency (percentage) and compared using the Chi-square test or Fisher’s exact test, as appropriate. Continuous data were described as median [interquartile range] and compared by applying Student’s t test if normally distributed and the Wilcoxon signed-rank test otherwise.

The primary outcome (CPC 1 or 2) was compared between groups with vs. without PRS using logistic regression. The Kaplan–Meier method was applied to assess 90-day survival and Cox regression to identify predictors of day-90 mortality by computing hazard ratios (HRs) with their 95% confidence intervals (95% CIs) with adjustment on CAHP score. CAHP score is a score dedicated to early evaluation of brain damage with prediction of poor functional outcome at hospital discharge [20]. It has been validated both for out-of-hospital cardiac arrest but also in-hospital cardiac arrest [21]. Changes over time in heart rate, MAP, the SOFA score, and lactate level were assessed by generalized linear mixed-effects models.

No imputation strategy was used for missing data. P values < 0.05 were considered significant.

All analyses were performed using SAS 9.4 (SAS Institute, Cary, NC).

Results

On the 584 patients included in the HYPERION trial, 3 withdrew (all in the hypothermia group) leaving 581 patients for analysis: 339 (58%) had PRS at ICU admission, 159 in the hypothermia group and 180 in the normothermia group (Additional file 1: Fig. S1).

Characteristics and outcomes in the groups with (n = 339) vs. without (n = 242) shock

Compared to the group without PRS at ICU admission, the group with PRS had a lower Glasgow Coma Scale score, higher proportion of patients given bystander resuscitation, longer low-flow time, and higher serum lactate at ICU admission (Additional file 1: Table S1). Mortality by day 90 was 84.66%, compared to 78.93% in the group without PRS (P = 0.07). The proportions of patients with day-90 CPC 1–2 did not differ significantly according to presence or absence of PRS (7.08% vs. 9.09%, respectively; P = 0.37).

Outcomes with hypothermia (n = 159) vs. normothermia (n = 180) in the sub-group with postresuscitation shock (PRS)

On day 90, the number of patients with a CPC score of 1 or 2 on day 90 was 14/159 (8.81%) in the hypothermia group and 10/180 (5.56%) in the normothermia group (P = 0.24) (Table 1). After adjustment on the Cardiac Arrest Hospital Prognosis (CAHP) score, the proportion of CPC 1–2 patients on day 90 was also not significantly different between the two TTM groups (Additional file 1: Table S2). Neither was day-90 mortality different (83% with hypothermia and 86% with normothermia, P = 0.43, Fig. 1 and Table 2). Heart rate was significantly lower in the hypothermia group but no significant differences existed for MAP, the SOFA score, or the serum lactate level (Fig. 2).

Table 1 Baseline characteristics of patients with postresuscitation shock (PRS) managed with hypothermia (33 °C) or normothermia (37 °C)
Full size table
Fig. 1
figure 1

Probability of survival to 90 days according to temperature allocated in the subgroup of patients with PRS. HR: hazard ratio; 95% CI: 95% confidence interval. PRS: postresuscitation shock

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Table 2 Outcomes of patients with postresuscitation shock managed with hypothermia (33 °C) vs. normothermia (37 °C)
Full size table
Fig. 2
figure 2

Changes over time in physiological variables according to target temperature in the patients with postresuscitation shock (PRS) at admission. SOFA: Sequential Organ Failure Assessment. The lactate level was determined at admission to the intensive care unit

Full size image

Factors associated with the day-90 functional outcome

The group with unfavourable day-90 functional outcomes (CPC 3, 4, or 5; n = 315) had a larger proportion of patients with cardiac arrest at home, longer no-flow and low-flow times, higher epinephrine doses, and a higher CAHP score (Table 3).

Table 3 Characteristics of patients with postresuscitation shock (PRS) in the groups with favourable vs. unfavourable outcomea
Full size table

Discussion

In the HYPERION trial, which included various population of patients with in and out-of-hospital cardiac arrest and cardiac or non-cardiac causes of arrest, in patients with non-refractory PRS at ICU admission after non-shockable cardiac arrest, on day 90, neither the functional outcome nor survival differed significantly between the groups managed with hypothermia at 33 °C vs. targeted normothermia (37 °C). Functional outcome at day 90 and mortality at day 90 did not differ significantly according to presence or absence of mild-to-moderate PRS. Factors associated with PRS were longer low-flow time, epinephrine treatment during resuscitation, and higher lactate level at ICU admission.

Effect of temperature on outcome in the PRS population

In parallel of our findings, a post hoc analysis of “TTM1 trial” data demonstrated non-significantly higher all-cause mortality in patients with vs. without PRS at ICU admission [14]. In the HYPERION trial, only about 4 to 20% of deaths were ascribed to PRS, compared to 35% in an earlier study [3], where PRS was also not associated with a higher risk of death from neurological causes in multivariable analysis. A recent larger analysis indicates the opposite with significant association between PRS presence and worse outcome at follow-up [22]. Finally, in a post-hoc analysis of TTM2, During et al. found than hypothermia at 33 °C was not associated with higher incidence of death in patients stratified according to vasopressor support on admission [23].

Opinions conflict about the effects of hypothermia on haemodynamics. In a prospective cohort of 75 patients who required vasopressor therapy, hypothermia at 33–34 °C, whose use was decided by the managing physician, was not associated with worse hemodynamic parameters compared to absence of hypothermia [24]. By contrast, two post hoc analysis of the “TTM1 trial” showed that, compared to 36 °C, 33 °C was associated with a slower heart rate, higher lactate levels, and greater vasopressor requirements, although mortality was not significantly different [13, 14]. In our study, hypothermia was associated with a slower heart rate, but the absence of differences regarding MAP, the SOFA score, and lactate level support the safety of hypothermia in patients with PRS. MAP is a tightly controlled variable, and treatments are given when its values differ from the predefined target. In the HYPERION trial, hemodynamic instability was the main reason for early rewarming in 30% of patients requiring this intervention. Possible associations of hemodynamic fluctuations and rewarming require further evaluation [25].

Effect of PRS on outcome

The optimal targets and therapeutic interventions in patients admitted to the ICU after cardiac arrest are unclear. In the HYPERION trial, an MAP of 65 mmHg and ScvO2 ≥ 70% were considered as reasonable targets, in accordance with guidelines available at the time [19]. Norepinephrine infusion is the cornerstone treatment for achieving the target MAP. However, in a post hoc analysis of the TTH48 trial comparing 33 °C for 24 vs. 48 h, vasopressor requirements were greater in the 48-h group but were not associated with mortality by multivariable analysis [26]. A post hoc analysis of data from a prospective observational study obtained similar findings [27]. More recently, an association was reported linking higher MAP to better outcomes after cardiac arrest [28, 29]. After cardiac arrest, cerebral-blood-flow autoregulation is often impaired or the lower limit right-shifted [30], so that an inadequate MAP target may increase the risk of cerebral hypoperfusion. Two randomized controlled trials found that a higher MAP target failed to improve survival [31, 32]. A recent post hoc analysis of one of these trials showed that the high MAP group had lower concentrations of neurofilament light chains [33], a marker of neurologic prognosis [34] indicating possible benefits of targeting higher MAP with adequate treatments.

Limitations

One limitation of our study is that the findings apply only to patients with mild-to-moderate PRS, since major hemodynamic instability defined as a continuous epinephrine or norepinephrine infusion > 1 μg/kg/min was an exclusion criterion: only patients with mild-to-moderate shock were included in our analysis [35]. Surprisingly, the global prognosis for patients without PRS (9.1%) or with moderate PRS (7.1%) was poorer than for patients with severe PRS (defined as receiving norepinephrine > 1 µg/kg/min, 13.3%)). This finding could be related to the retrospective design of the study (classification bias). We were unable to perform a pooled analysis, as the centres and definition of PRS differed across studies. The lack of a universal definition of PRS and its severity make comparisons of studies difficult. For example, we found recently than resolution of circulatory failure (defined by the SOFA score at randomization) by day 7 was associated with its severity and the intervention arm [36]. In addition, several origins for shock state can coexist (septic shock related to inhalation pneumonia, cardiogenic shock related to acute coronary occlusion, PRS itself) and complicate interpretation of physiopathology. The prognosis of patients with severe PRS is difficult to assess at ICU admission [35]. Patients were not randomized according to the presence or absence of PRS. The hemodynamic management was not specified in the trial protocol, and physicians applied the usual protocol in their ICU. In addition, these protocols were similarly applied in both groups and the HYPERION trial was stratified according to centres. We did not have details on the hemodynamic management and monitoring in the included patients. Finally, our study may have lacked sufficient power to detect some important associations and furthers analysis of recent “TTM2 trial” [37] will help in delivering care to patients with PRS.

Conclusions

After non-shockable cardiac arrest, PRS at ICU admission was not associated with day-90 functional outcome or survival. In the sub-group of patients with PRS, outcomes did not differ significantly according to whether hypothermia at 33 °C or normothermia was used.

Availability of data and materials

The data analysed in this study is subject to the following licenses/restrictions: data sharing on request to corresponding author after Ethics Committee approval. Requests to access these data sets should be directed to Jean-Baptiste Lascarrou, jeanbaptiste.lascarrou@chu-nantes.

References

  1. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369:2197–206. https://doi.org/10.1056/NEJMoa1310519.

    Article  CAS  PubMed  Google Scholar 

  2. Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019. https://doi.org/10.1056/NEJMoa1906661.

    Article  PubMed  Google Scholar 

  3. Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche J-D, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med. 2013;39:1972–80. https://doi.org/10.1007/s00134-013-3043-4.

    Article  PubMed  Google Scholar 

  4. Huang C-H, Tsai M-S, Ong HN, Chen W, Wang C-H, Chang W-T, et al. Association of hemodynamic variables with in-hospital mortality and favorable neurological outcomes in post-cardiac arrest care with targeted temperature management. Resuscitation. 2017;120:146–52. https://doi.org/10.1016/j.resuscitation.2017.07.009.

    Article  PubMed  Google Scholar 

  5. Hästbacka J, Kirkegaard H, Søreide E, Taccone FS, Rasmussen BS, Storm C, et al. Severe or critical hypotension during post cardiac arrest care is associated with factors available on admission—a post hoc analysis of the TTH48 trial. J Crit Care. 2021;61:186–90. https://doi.org/10.1016/j.jcrc.2020.10.026.

    Article  PubMed  Google Scholar 

  6. Jacobshagen C, Pelster T, Pax A, Horn W, Schmidt-Schweda S, Unsöld BW, et al. Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium. Clin Res Cardiol Off J Ger Card Soc. 2010;99:267–76. https://doi.org/10.1007/s00392-010-0113-2.

    Article  Google Scholar 

  7. Schwarzl M, Steendijk P, Huber S, Truschnig-Wilders M, Obermayer-Pietsch B, Maechler H, et al. The induction of mild hypothermia improves systolic function of the resuscitated porcine heart at no further sympathetic activation. Acta Physiol Oxf Engl. 2011;203:409–18. https://doi.org/10.1111/j.1748-1716.2011.02332.x.

    Article  CAS  Google Scholar 

  8. Schmidt-Schweda S, Ohler A, Post H, Pieske B. Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II). Resuscitation. 2013;84:319–25. https://doi.org/10.1016/j.resuscitation.2012.09.034.

    Article  PubMed  Google Scholar 

  9. Zobel C, Adler C, Kranz A, Seck C, Pfister R, Hellmich M, et al. Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med. 2012;40:1715–23. https://doi.org/10.1097/CCM.0b013e318246b820.

    Article  PubMed  Google Scholar 

  10. Stegman B, Aggarwal B, Senapati A, Shao M, Menon V. Serial hemodynamic measurements in post-cardiac arrest cardiogenic shock treated with therapeutic hypothermia. Eur Heart J Acute Cardiovasc Care. 2015;4:263–9. https://doi.org/10.1177/2048872614547688.

    Article  PubMed  Google Scholar 

  11. Grejs AM, Nielsen BRR, Juhl-Olsen P, Gjedsted J, Sloth E, Heiberg J, et al. Effect of prolonged targeted temperature management on left ventricular myocardial function after out-of-hospital cardiac arrest—a randomised, controlled trial. Resuscitation. 2017;115:23–31. https://doi.org/10.1016/j.resuscitation.2017.03.021.

    Article  PubMed  Google Scholar 

  12. Oddo M, Schaller M-D, Feihl F, Ribordy V, Liaudet L. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med. 2006;34:1865–73. https://doi.org/10.1097/01.CCM.0000221922.08878.49.

    Article  PubMed  Google Scholar 

  13. Bro-Jeppesen J, Annborn M, Hassager C, Wise MP, Pelosi P, Nielsen N, et al. Hemodynamics and vasopressor support during targeted temperature management at 33°C Versus 36°C after out-of-hospital cardiac arrest: a post hoc study of the target temperature management trial*. Crit Care Med. 2015;43:318–27. https://doi.org/10.1097/CCM.0000000000000691.

    Article  CAS  PubMed  Google Scholar 

  14. Annborn M, Bro-Jeppesen J, Nielsen N, Ullen S, Kjaergaard J, Hassager C, et al. The association of targeted temperature management at 33 and 36 degrees C with outcome in patients with moderate shock on admission after out-of-hospital cardiac arrest: a post hoc analysis of the Target Temperature Management trial. Intensive Care Med. 2014;40:1210–9. https://doi.org/10.1007/s00134-014-3375-8.

    Article  PubMed  Google Scholar 

  15. Tseng ZH, Olgin JE, Vittinghoff E, Ursell PC, Kim AS, Sporer K, et al. Prospective countywide surveillance and autopsy characterization of sudden cardiac death. Circulation. 2018;137:2689–700. https://doi.org/10.1161/CIRCULATIONAHA.117.033427.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–63. https://doi.org/10.1056/NEJMoa003289.

    Article  PubMed  Google Scholar 

  17. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56. https://doi.org/10.1056/NEJMoa012689.

    Article  Google Scholar 

  18. Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med. 2021;47:369–421. https://doi.org/10.1007/s00134-021-06368-4.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, et al. Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial. Scand J Trauma Resusc Emerg Med. 2015;23:26. https://doi.org/10.1186/s13049-015-0103-5.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Maupain C, Bougouin W, Lamhaut L, Deye N, Diehl J-L, Geri G, et al. The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest. Eur Heart J. 2016;37:3222–8. https://doi.org/10.1093/eurheartj/ehv556.

    Article  PubMed  Google Scholar 

  21. Chelly J, Mpela A-G, Jochmans S, Brunet J, Legriel S, Guerin L, et al. OHCA (Out-of-Hospital Cardiac Arrest) and CAHP (Cardiac Arrest Hospital Prognosis) scores to predict outcome after in-hospital cardiac arrest: Insight from a multicentric registry. Resuscitation. 2020;156:167–73. https://doi.org/10.1016/j.resuscitation.2020.09.021.

    Article  PubMed  Google Scholar 

  22. Düring J, Annborn M, Dankiewicz J, Dupont A, Forsberg S, Friberg H, et al. Influence of circulatory shock at hospital admission on outcome after out-of-hospital cardiac arrest. Sci Rep. 2022;12:8293. https://doi.org/10.1038/s41598-022-12310-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Düring J, Annborn M, Cariou A, Chew MS, Dankiewicz J, Friberg H, et al. Influence of temperature management at 33 °C versus normothermia on survival in patients with vasopressor support after out-of-hospital cardiac arrest: a post hoc analysis of the TTM-2 trial. Crit Care Lond Engl. 2022;26:231. https://doi.org/10.1186/s13054-022-04107-9.

    Article  Google Scholar 

  24. Roberts BW, Kilgannon JH, Chansky ME, Jones AE, Mittal N, Milcarek B, et al. Therapeutic hypothermia and vasopressor dependency after cardiac arrest. Resuscitation. 2013;84:331–6. https://doi.org/10.1016/j.resuscitation.2012.07.029.

    Article  PubMed  Google Scholar 

  25. Lascarrou J-B, Guichard E, Reignier J, Le Gouge A, Pouplet C, Martin S, et al. Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 °C: the ISOCRATE pilot randomized controlled trial. Crit Care Lond Engl. 2021;25:434. https://doi.org/10.1186/s13054-021-03842-9.

    Article  Google Scholar 

  26. Grand J, Hassager C, Skrifvars MB, Tiainen M, Grejs AM, Jeppesen AN, et al. Haemodynamics and vasopressor support during prolonged targeted temperature management for 48 hours after out-of-hospital cardiac arrest: a post hoc substudy of a randomised clinical trial. Eur Heart J Acute Cardiovasc Care. 2020. https://doi.org/10.1177/2048872620934305.

    Article  PubMed  Google Scholar 

  27. Laurikkala J, Wilkman E, Pettilä V, Kurola J, Reinikainen M, Hoppu S, et al. Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: associations with one-year neurologic outcome. Resuscitation. 2016;105:116–22. https://doi.org/10.1016/j.resuscitation.2016.05.026.

    Article  PubMed  Google Scholar 

  28. Russo JJ, James TE, Hibbert B, Yousef A, Osborne C, Wells GA, et al. Impact of mean arterial pressure on clinical outcomes in comatose survivors of out-of-hospital cardiac arrest: Insights from the University of Ottawa Heart Institute Regional Cardiac Arrest Registry (CAPITAL-CARe). Resuscitation. 2017;113:27–32. https://doi.org/10.1016/j.resuscitation.2017.01.007.

    Article  PubMed  Google Scholar 

  29. Ameloot K, Meex I, Genbrugge C, Jans F, Boer W, Verhaert D, et al. Hemodynamic targets during therapeutic hypothermia after cardiac arrest: a prospective observational study. Resuscitation. 2015;91:56–62. https://doi.org/10.1016/j.resuscitation.2015.03.016.

    Article  CAS  PubMed  Google Scholar 

  30. Ameloot K, Genbrugge C, Meex I, Jans F, Boer W, Vander Laenen M, et al. An observational near-infrared spectroscopy study on cerebral autoregulation in post-cardiac arrest patients: time to drop “one-size-fits-all” hemodynamic targets? Resuscitation. 2015;90:121–6. https://doi.org/10.1016/j.resuscitation.2015.03.001.

    Article  CAS  PubMed  Google Scholar 

  31. Ameloot K, De Deyne C, Eertmans W, Ferdinande B, Dupont M, Palmers P-J, et al. Early goal-directed haemodynamic optimization of cerebral oxygenation in comatose survivors after cardiac arrest: the Neuroprotect post-cardiac arrest trial. Eur Heart J. 2019;40:1804–14. https://doi.org/10.1093/eurheartj/ehz120.

    Article  CAS  PubMed  Google Scholar 

  32. Jakkula P, Pettilä V, Skrifvars MB, Hästbacka J, Loisa P, Tiainen M, et al. Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med. 2018;44:2091–101. https://doi.org/10.1007/s00134-018-5446-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wihersaari L, Ashton NJ, Reinikainen M, Jakkula P, Pettilä V, Hästbacka J, et al. Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial. Intensive Care Med. 2021;47:39–48. https://doi.org/10.1007/s00134-020-06218-9.

    Article  PubMed  Google Scholar 

  34. Pouplet C, Colin G, Guichard E, Reignier J, Le Gouge A, Martin S, et al. The accuracy of various neuro-prognostication algorithms and the added value of neurofilament light chain dosage for patients resuscitated from shockable cardiac arrest: an ancillary analysis of the ISOCRATE study. Resuscitation. 2021;171:1–7. https://doi.org/10.1016/j.resuscitation.2021.12.009.

    Article  PubMed  Google Scholar 

  35. Lascarrou JB, Muller G, Quenot J-P, Massart N, Landais M, Asfar P, et al. Insights from patients screened but not randomised in the HYPERION trial. Ann Intensive Care. 2021;11:156. https://doi.org/10.1186/s13613-021-00947-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Petit M, Lascarrou J-B, Colin G, Merdji H, Cariou A, Geri G. Hemodynamics and vasopressor support during targeted temperature management after cardiac arrest with non-shockable rhythm: a post hoc analysis of a randomized controlled trial. Resusc Plus. 2022;11: 100271. https://doi.org/10.1016/j.resplu.2022.100271.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullén S, et al. Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med. 2021;384:2283–94. https://doi.org/10.1056/NEJMoa2100591.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank the healthcare staff and research nurses at the trial sites; A. Wolfe, MD, for assistance in preparing and reviewing the manuscript; and S. Martin, PharmD, for reviewing the manuscript. Funding was from independent research grants from the French Ministry of Health, the non-profit healthcare institution Centre Hospitalier Departement de la Vendée, and the Laerdal Foundation.

Funding

Funded by French Ministry of Health (Programme Hospitalier de Recherche Clinique 2013 n°PHRCI1369057N), Laerdal Foundation and CHD Vendee.

Author information

Authors and Affiliations

  1. Médecine Intensive Réanimation, University Hospital Centre, Nantes, France

    Ines Ziriat, Jean Reignier & Jean Baptiste Lascarrou

  2. Direction de la Recherche Clinique et l’Innovation, Plateforme de Méthodologie et Biostatistique, University Hospital Centre, Nantes, France

    Aurélie Le Thuaut

  3. Medecine Intensive Reanimation, District Hospital Center, La Roche-sur-Yon, France

    Gwenhael Colin

  4. AfterROSC Network, Paris, France

    Gwenhael Colin, Stéphane Legriel, Alain Cariou & Jean Baptiste Lascarrou

  5. Université de Strasbourg (UNISTRA), Faculté de Médecine; Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Service de Médecine Intensive Réanimation, Strasbourg, France

    Hamid Merdji

  6. INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France

    Hamid Merdji

  7. Medical Intensive Care Unit, South Brittany General Hospital Centre, Lorient, France

    Guillaume Grillet

  8. Médecine Intensive Réanimation, CHU Lille, 59000, Lille, France

    Patrick Girardie

  9. Faculté de Médicine, Université de Lille, 59000, Lille, France

    Patrick Girardie

  10. Medical Intensive Care Unit, University Hospital Centre, Clermond-Ferrand, France

    Bertrand Souweine

  11. INSERM CIC1415, CHRU de Tours, Tours, France

    Pierre-François Dequin

  12. Medical Intensive Care Unit, University Hospital Centre, Tours, France

    Pierre-François Dequin

  13. Inserm UMR 1100 – Centre d’Étude des Pathologies Respiratoires, Tours University, Tours, France

    Pierre-François Dequin

  14. Medical Intensive Care Unit, Regional Hospital Centre, Orleans, France

    Thierry Boulain

  15. Médecine Intensive Réanimation, CHU de Poitiers, Poitiers, France

    Jean-Pierre Frat

  16. INSERM, CIC-1402, ALIVES, Poitiers, France

    Jean-Pierre Frat

  17. Université de Poitiers, Faculté de Médecine et de Pharmacie de Poitiers, Poitiers, France

    Jean-Pierre Frat

  18. Medical Intensive Care Unit, University Hospital Centre, Angers, France

    Pierre Asfar

  19. Service de Réanimation Polyvalente, University Hospital Centre, Limoges, France

    Bruno Francois

  20. INSERM CIC 1435 & UMR 1092, University Hospital Centre, Limoges, France

    Bruno Francois

  21. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Le Mans, France

    Mickael Landais

  22. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Argenteuil, France

    Gaëtan Plantefeve

  23. Medical Intensive Care Unit, University Hospital Centre, Dijon, France

    Jean-Pierre Quenot

  24. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Roanne, France

    Jean-Charles Chakarian

  25. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Annecy, France

    Michel Sirodot

  26. Medical-Surgical Intensive Care Unit, Versailles Hospital, Versailles, France

    Stéphane Legriel

  27. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Saint Brieuc, France

    Nicolas Massart

  28. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Lens, France

    Didier Thevenin

  29. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Angoulême, France

    Arnaud Desachy

  30. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Rodez, France

    Arnaud Delahaye

  31. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Saint Malo, France

    Vlad Botoc

  32. Medical-Surgical Intensive Care Unit, Community Hospital Centre, Montauban, France

    Sylvie Vimeux

  33. Medical Intensive Care Unit, University Hospital Centre, Pointe-à-Pitre, France

    Frederic Martino

  34. Medical Intensive Care Unit, Cochin Hospital (APHP) and University of Paris, Paris, France

    Alain Cariou

  35. Paris Cardiovascular Research Centre, INSERM U970, Paris, France

    Alain Cariou & Jean Baptiste Lascarrou

  36. Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire, 30 Boulevard Jean Monnet, 44093, Nantes Cedex 1, France

    Jean Baptiste Lascarrou

Authors
  1. Ines Ziriat
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  2. Aurélie Le Thuaut
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  3. Gwenhael Colin
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Contributions

IZ, ALT JR, AC, and JBL designed the study, analyzed the data and wrote the original manuscript. GC, HM, GG, PG, EC, PFD, TB, JPF, PA, NP, ML, GP, JPQ, JCC, MS, SL, JL, DT, AD, AD, VB, SV, FM, JR, AC and JBL participated in acquiring the data and writing the manuscript. ALT performed statistical analysis. All authors approved the final version of the manuscript and have agreed to be accountable for the work it reports. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jean Baptiste Lascarrou.

Ethics declarations

Ethics approval and consent to participate

The study complied with the current version of the Helsinki Declaration and good clinical practice guidelines. The protocol was approved by appropriate ethics committee (Ethics committee of the French Intensive Care Society (SRLF) on October 6, 2011, and by the Ethics Committee for the Protection of Patients (CPP Ouest 2) in Angers, France, on June 11, 2012; number 2012-A00405-38/2012-08). As this was an ancillary study of the HYPERION trial without additional data, no other approval was required.

Competing interests

JB Lascarrou has received reimbursement for travel expenses from Zoll (Voisin Le Bretonneux, France) and BD (Le Pont de Claix, France). JP Frat has received personal fees for lectures, travel expense coverage to attend scientific meetings from Fisher and Paykel Healthcare, and a grant for a randomized controlled trial; personal fees as a member of a scientific board, and travel expense coverage to attend scientific meetings from SOS Oxygène. None of the other authors has any conflict of interest to declare.

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Supplementary Information

Additional file 1:

Fig. S1. Study flowchart. Table S1. Baseline characteristics and mortality in the groups with vs. without mild-to-moderate postresuscitation shock (PRS) at intensive-care-unit (ICU) admission. Table S2. Multivariate logistic regression modelling to identify admission variables associated with a favourable outcome on day 90 in the overall population (n = 532).

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Ziriat, I., Le Thuaut, A., Colin, G. et al. Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data. Ann. Intensive Care 12, 96 (2022). https://doi.org/10.1186/s13613-022-01071-z

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