Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

Dankiewicz, Josef; Cronberg, Tobias; Lilja, Gisela; Jakobsen, Janus Christian; Levin, Helena; Ullén, Susann; Rylander, Christian; Wise, Matt P.; Oddo, Mauro; Cariou, Alain; Bělohlávek, Jan; Hovdenes, Jan; Saxena, Manoj; Kirkegaard, Hans; Young, Paul; Pelosi, Paolo; Storm, Christian; Taccone, Fabio Silvio; Joannidis, Michael; Callaway, Clifton; Eastwood, Glenn M; Morgan, Matt; Nordberg, Per; Erlinge, David; Nichol, Alistair; Chew, Michelle; Hollenberg, Jacob; Thomas, Matthew; Bewley, Jeremy; Sweet, Katie; Grejs, Anders Morten; Christensen, Steffen; Hænggi, Matthias; Levis, Anja; Lundin, Andreas; Düring, Joachim; Schmidbauer, Simon; Keeble, Thomas R.; Karamasis, Grigoris V.; Schrag, Claudia; Faessler, Edith; Šmíd, Ondřej; Otáhal, Michal; Maggiorini, Marco; Wendel‐Garcia, Pedro David; Jaubert, Paul; Cole, Jade; Solař, Miroslav; Borgquist, Ola; Leithner, Christoph; Abed-Maillard, Samia; Navarra, Leanlove; Annborn, Martin; Undén, Johan; Brunetti, Iole; Awad, Akil; McGuigan, Peter; Olsen, Roy Bjørkholt; Cassina, Tiziano; Vignon, Philippe; Langeland, Halvor; Lange, Theis; Friberg, Hans; Nielsen, Niklas

doi:10.1056/nejmoa2100591

Cited by 605 publications

(512 citation statements)

References 25 publications

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“…We included in our meta-analysis only the data from the first two groups of this study [14]. Finally, three RCTs performed an active control of normothermia in the control group [2,4,15].…”

Section: Resultsmentioning

confidence: 99%

“…The analysis on survival included eight studies, three of them in the subgroup with "active control" of normothermia and the remaining five with "uncontrolled" normothermia (one of them included an 8-hour treatment with hemofiltration in both groups). Four studies reported survival at 6 months [10,[13][14][15], one at the end of trial (mean period of follow-up was 256 days) [2], one study at 90 days [4], Bernard et al [11] at hospital discharge, Hachimi-idrissi et al [12] made the last follow-up 14 days after the randomization.…”

Section: Survivalmentioning

confidence: 99%

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Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Sanfilippo

Via

Lanzafame

et al. 2021

JCM

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Target temperature management (TTM) in cardiac arrest (CA) survivors is recommended after hospital admission for its possible beneficial effects on survival and neurological outcome. Whether a lower target temperature (i.e., 32–34 °C) improves outcomes is unclear. We conducted a systematic review and meta-analysis on Pubmed and EMBASE to evaluate the effects on mortality and neurologic outcome of TTM at 32–34 °C as compared to controls (patients cared with “actively controlled” or “uncontrolled” normothermia). Results were analyzed via risk ratios (RR) and 95% confidence intervals (CI). Eight randomized controlled trials (RCTs) were included. TTM at 32–34 °C was compared to “actively controlled” normothermia in three RCTs and to “uncontrolled” normothermia in five RCTs. TTM at 32–34 °C does not improve survival as compared to normothermia (RR:1.06 (95%CI 0.94, 1.20), p = 0.36; I2 = 39%). In the subgroup analyses, TTM at 32–34 °C is associated with better survival when compared to “uncontrolled” normothermia (RR: 1.31 (95%CI 1.07, 1.59), p = 0.008) but shows no beneficial effects when compared to “actively controlled” normothermia (RR: 0.97 (95%CI 0.90, 1.04), p = 0.41). TTM at 32–34 °C does not improve neurological outcome as compared to normothermia (RR: 1.17 (95%CI 0.97, 1.41), p = 0.10; I2 = 60%). TTM at 32–34 °C increases the risk of arrhythmias (RR: 1.35 (95%CI 1.16, 1.57), p = 0.0001, I2 = 0%). TTM at 32–34 °C does not improve survival nor neurological outcome after CA and increases the risk of arrhythmias.

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“…We included in our meta-analysis only the data from the first two groups of this study [14]. Finally, three RCTs performed an active control of normothermia in the control group [2,4,15].…”

Section: Resultsmentioning

confidence: 99%

Section: Survivalmentioning

confidence: 99%

Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Sanfilippo

Via

Lanzafame

et al. 2021

JCM

Self Cite

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“…Thus, physiologically based personalized therapy, although clearly important at the extremes of illness, become problematic at intermediate levels of illness where safety has typically been established. Historically, the pursuit of perceived physiological success in the belief that it would lead to subsequent clinical success has often proved to be disappointing with notable examples including intensive insulin therapy to normalize glycemia [ 84 ]; drotrecogin alpha to normalize activated protein C levels [ 85 ]; colloid resuscitation to increase intravascular volume [ 86 ]; decompressive craniectomy to lower intracranial pressure in diffuse cerebral injury [ 87 ]; hypothermia for out of hospital cardiac arrest [ 88 ], early parenteral or enteral nutrition to achieve early full caloric intake [ 89 ]; glutamine therapy to correct glutamine deficiency [ 90 ]; fluid bolus resuscitation in septic African children [ 91 ]. All this does not imply that physiology should not be used to guide therapies in patients with ARDS.…”

Section: Introductionmentioning

confidence: 99%

Personalized mechanical ventilation in acute respiratory distress syndrome

et al. 2021

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A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (VT) is a standard of care, further individualization of VT may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust VT and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.

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“…The first conclusion could be the lack of benefits of TTM after cardiac arrest. Indeed, the TTM-2 study had the largest cohort of patients so far and was conducted using the best statistical methodology [ 5 ], while previous studies [ 1 , 2 ] had many methodological biases (i.e., no power calculation, limited cohorts, early stopping, no blinded assessors of primary outcome, no prognostication guidelines). Also, as the general management of patients after cardiac arrest has improved over time (i.e., early recognition and treatment of the cause, hemodynamic and ventilatory management, organ support) [ 3 ], TTM might add only minimal benefits.…”

Section: Ttm In Cardiac Arrestmentioning

confidence: 99%

“…The use of targeted temperature management (TTM) has been recommended for two decades in the management of patients after cardiac arrest; however, the quality of evidence behind this recommendation is moderate to low and refers only to out-of-hospital cardiac arrest (OHCA) [ 1 – 4 ]. Recently, Dankiewicz et al (TTM-2 study) reported that TTM at 33 °C did not lower the incidence of death or 6-month poor neurological outcome than targeted normothermia in 1900 unconscious OHCA patients [ 5 ], with more arrhythmias resulting in hemodynamic compromise observed in the 33 °C group. There was no benefit of hypothermia in any of the prespecified sub-groups, including age, initial rhythm or duration of resuscitation.…”

Section: Introductionmentioning

confidence: 99%