Through the Looking Glass: The Paradoxical Evolution of Targeted Temperature Management for Comatose Survivors of Cardiac Arrest.
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SUBMITTER: D'Amato SA
PROVIDER: S-EPMC9723025 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Through the Looking Glass: The Paradoxical Evolution of Targeted Temperature Management for Comatose Survivors of Cardiac Arrest.
D'Amato Salvatore A SA Kimberly W Taylor WT Mayer Stephan A SA
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20221017 6
For the past two decades, targeted temperature management (TTM) has been a staple in the care of comatose survivors following cardiac arrest. However, recent clinical trials have failed to replicate the benefit seen in earlier studies, bringing into question the very existence of such clinical practice. In this review, we explore clinical scenarios within critical care that appeared to share a similar fate, but in actuality changed the landscape of practice in a modern world. Accordingly, clinic ...[more]
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Project description:Out-of-hospital cardiac arrest (CA) remains a leading cause of sudden morbidity and mortality; however, outcomes have continued to improve in the era of targeted temperature management (TTM). In this review, we highlight the clinical use of TTM, and provide an updated summary of multimodality monitoring possible in a modern ICU. TTM is neuroprotective for survivors of CA by inhibiting multiple pathophysiologic processes caused by anoxic brain injury, with a final common pathway of neuronal death. Current guidelines recommend the use of TTM for out-of-hospital CA survivors who present with a shockable rhythm. Further studies are being completed to determine the optimal timing, depth and duration of hypothermia to optimize patient outcomes. Although a multidisciplinary approach is necessary in the CA population, neurologists and neurointensivists are central in selecting TTM candidates and guiding patient care and prognostic evaluation. Established prognostic tools include clinal exam, SSEP, EEG and MR imaging, while functional MRI and invasive monitoring is not validated to improve outcomes in CA or aid in prognosis. We recommend that an evidence-based TTM and prognostication algorithm be locally implemented, based on each institution's resources and limitations. Given the high incidence of CA and difficulty in predicting outcomes, further study is urgently needed to determine the utility of more recent multimodality devices and studies.
| S-EPMC6141756 | biostudies-other
Project description:BackgroundAmong cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors.MethodsA narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format.ResultsEleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors.ConclusionsThese guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.
| S-EPMC10241762 | biostudies-literature
Project description:IntroductionLumbar puncture is among the investigations used to identify various neurological conditions, including some that can cause cardiac arrest (CA). However, CA per se may alter cerebrospinal fluid (CSF) characteristics. Few studies have investigated CSF findings after CA. In this descriptive work, we assessed the frequency and risk factors of abnormal CSF findings after CA and the contribution of CSF analysis to the etiological diagnosis.Materials and methodsWe retrospectively studied data from prospectively established databases of consecutive patients who were admitted to two French ICUs in 2007-2016 with sustained return of spontaneous circulation (ROSC) after CA and who underwent lumbar puncture as an etiological investigation.ResultsOf 1984 patients with sustained ROSC, 55 (2.7%) underwent lumbar puncture and were included. Lumbar puncture identified a neurological cause of CA in 2/55 (3.6%) patients. Nonspecific CSF abnormalities were noted in 37/53 (69.8%) patients. By multivariate analysis, postresuscitation shock was positively associated with CSF abnormalities (OR, 6.92; 95% confidence interval [95%CI], 1.62-37.26; P = 0.013). A no-flow time above 6 minutes (OR, 0.19; 95%CI, 0.03-1.11; P = 0.076) and a respiratory cause of CA (OR, 2.91; 95%CI, 0.53-23.15; P = 0.24) were not statistically associated with CSF abnormalities. Nonspecific CSF abnormalities were not significantly associated with poor outcomes (Cerebral Performance Category ≥3; P = 0.06).ConclusionsLumbar puncture, although infrequently performed, may contribute to the etiological diagnosis of CA, albeit rarely. Nonspecific CSF abnormalities seem common after CA, notably with postresuscitation shock, and may be related to blood-brain barrier disruption. These findings may help to interpret CSF findings after CA. Further studies are warranted to assess our results.
| S-EPMC9321437 | biostudies-literature
Project description:we evaluated the effects of the shift of a targeted temperature management (TTM) strategy from 33 °C to 36 °C in comatose out-of-hospital cardiac arrest (OHCA) patients admitted to the Intensive Care Unit (ICU). we performed a retrospective study of all comatose (GCS < 8) OHCA patients treated with TTM from 2010 to 2018 (n = 798) from a single-center academic hospital. We analyzed 90-day mortality, and neurological outcome (CPC score) at ICU discharge and ICU length of stay, as primary and secondary outcomes, respectively. we included 798 OHCA patients (583 in the TTM33 group and 215 in the TTM36 group). We found no association between the TTM strategy (TTM33 and TTM36) and 90-day mortality (hazard ratio (HR)] 0.877, 95% CI 0.677-1.135, with TTM36 as reference). Also, no association was found between TTM strategy and favorable neurological outcome at ICU discharge (odds ratio (OR) 1.330, 95% CI 0.941-1.879). Patients in the TTM33 group had on average a longer ICU LOS (beta 1.180, 95% CI 0.222-2.138). no differences in clinical outcomes-both 90-day mortality and favorable neurological outcome at ICU discharge-were found between targeted temperature at 33 °C and 36 °C. These results may help to corroborate previous trial findings and assist in implementation of TTM.
| S-EPMC8999846 | biostudies-literature
Project description:PurposeTo assess the ability of clinical examination, blood biomarkers, electrophysiology or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict good neurological outcome, defined as no, mild, or moderate disability (CPC 1-2 or mRS 0-3) at discharge from intensive care unit or later, in comatose adult survivors from cardiac arrest (CA).MethodsPubMed, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews were searched. Sensitivity and specificity for good outcome were calculated for each predictor. The risk of bias was assessed using the QUIPS tool.ResultsA total of 37 studies were included. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. A withdrawal or localisation motor response to pain immediately or at 72-96 h after ROSC, normal blood values of neuron-specific enolase (NSE) at 24 h-72 h after ROSC, a short-latency somatosensory evoked potentials (SSEPs) N20 wave amplitude > 4 µV or a continuous background without discharges on electroencephalogram (EEG) within 72 h from ROSC, and absent diffusion restriction in the cortex or deep grey matter on MRI on days 2-7 after ROSC predicted good neurological outcome with more than 80% specificity and a sensitivity above 40% in most studies. Most studies had moderate or high risk of bias.ConclusionsIn comatose cardiac arrest survivors, clinical, biomarker, electrophysiology, and imaging studies identified patients destined to a good neurological outcome with high specificity within the first week after cardiac arrest (CA).
| S-EPMC8940794 | biostudies-literature
Project description:PurposeTo assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA).MethodsPubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed.ResultsNinety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors.ConclusionIn comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169).
| S-EPMC7527362 | biostudies-literature
Project description:BackgroundTherapeutic hypothermia (TH) improves outcomes in comatose survivors of cardiac arrest. Few hospitals have protocol-driven plans that include TH. We implemented a series of process interventions designed to increase TH use and improve outcomes in patients successfully resuscitated from out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA).Methods and resultsLinked interventions including a TH order sheet, verbal and written feedback to individual providers, an educational program, TH "kit" and on-call consultants to assist with patient care and hypothermia induction were implemented between January 1, 2005 and December 31, 2007 in a large, university-affiliated, tertiary care center. We then completed a retrospective review of all patients treated for cardiac arrest during the study period. Descriptive statistics, chi-squared analyses, or Fisher's exact test were used as appropriate. A p value <0.05 was considered significant. 135 OHCA patients and 106 IHCA patients were eligible for post-arrest care. TH use increased each year in the OHCA group (from 6% to 65% to 76%; p<0.001) and IHCA group (from 0% to 36% to 53%; p=.02). A good outcome was achieved in 21% and 8% of comatose patients with OHCA and IHCA, respectively. Patients with OHCA and ventricular dysrhythmia were more likely to have a good outcome with TH treatment than without it (good outcome in 57% vs. 8%; p=.005).ConclusionImplementing a series of aggressive interventions increased appropriate TH use and was associated with improved outcomes in our facility.
| S-EPMC2590640 | biostudies-literature
Project description:BackgroundPatients resuscitated from cardiac arrest have brain and cardiac injury. Recent animal studies suggest that the administration of sodium nitrite after resuscitation from 12min of asystole limits acute cardiac dysfunction and improves survival and neurologic outcomes. It has been hypothesized that low doses of IV sodium nitrite given during resuscitation of out of hospital cardiac arrest (OHCA) will improve survival. Low doses of sodium nitrite (e.g., 9.6mg of sodium nitrite) are safe in healthy individuals, however the effect of nitrite on blood pressure in resuscitated cardiac arrest patients is unknown.MethodsWe performed a single-center, pilot trial of low dose sodium nitrite (1 or 9.6mg dose) vs. placebo in hospitalized out-of-hospital cardiac arrest patient to determine whether nitrite administration reduced blood pressure and whether whole blood nitrite levels increased in response to nitrite administration.ResultsThis is the first reported study of sodium nitrite in cardiac arrest patients. Infusion of low doses of sodium nitrite in comatose survivors of OHCA (n=7) compared to placebo (n=4) had no significant effects on heart rate within 30min after infusion (70±20 vs. 78±3 beats per minute, p=0.18), systolic blood pressure (103±20 vs 108±15mmHg, p=0.3), or methemoglobin levels (0.92±0.33 vs. 0.70±0.26, p=0.45). Serum nitrite levels of 2-4μM were achieved within 15min of a 9.6mg nitrite infusion.ConclusionsLow dose sodium nitrite does not cause significant hemodynamic effect in patients with OHCA, which suggests that nitrite can be delivered safely in this critically ill patient population. Higher doses of sodium nitrite are necessary in order to achieve target serum level of 10μM.
| S-EPMC5774860 | biostudies-literature
Project description:IntroductionProtocolized postarrest care that includes targeted temperature management (TTM) improves survival and neurological outcomes in cardiac arrest survivors. Whether the accumulated experience regarding the use of the protocolized approach also benefits patients who did not undergo TTM has yet to be investigated.MethodsAdults (≥18 years old) with nontraumatic cardiac arrest and who survived to intensive care unit (ICU) admission were retrospectively recruited from a single tertiary medical centre from 2006 to 2009 and 2011 to 2017. Patients were excluded if they had traumatic injuries, were pregnant, did not survive to ICU admission, regained clear consciousness within 3 h after the return of spontaneous circulation, or underwent TTM. The sum of TTM cases since 2006 and before the cardiac arrest of each enrolled patient was used as a substitute index for the amount of experience accumulated from the use of protocolized TTM care.ResultsIn total, 802 non-TTM patients were enrolled in the final analysis. The rate of survival to hospital discharge increased from 25.9% in 2006 to 33.3% in 2017. Regarding neurological recovery at hospital discharge, the incidence of favourable neurological function (cerebral performance category: 1 or 2) increased from 10.3% in 2006 to 23.5% in 2017. A multiple logistic regression indicated a significant association between the cumulative TTM case numbers and neurological outcomes in patients who did not receive TTM.ConclusionsThe improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM was associated with the cumulative number of cases receiving protocolized TTM care. In the era of TTM, the use of only historical control data might lead to bias, which is caused by overlooking the influence of a more refined protocolized postarrest care that includes TTM.KEY MESSAGEThe cumulative number of cases receiving protocolized TTM care, which we used as a substitute index for the amount of experience accumulated from the use of protocolized postarrest care that includes TTM, was associated with the improvement of neurological outcomes in adult nontraumatic cardiac arrest survivors who did not receive TTM.
| S-EPMC8725984 | biostudies-literature
Project description:BackgroundThe prediction of neurological outcome in comatose patients after cardiac arrest has major ethical and socioeconomic implications. The purpose of this study was to assess the capability of serum neuron-specific enolase (NSE), a biomarker of hypoxic brain damage, to predict death or vegetative state in comatose cardiac-arrest survivors.MethodsWe conducted a prospective observational cohort study in one university hospital and one general hospital Intensive Care Unit (ICU). All consecutive patients who suffered cardiac arrest and were subsequently admitted from June 2007 to February 2009 were considered for inclusion in the study. Patients who died or awoke within the first 48 hours of admission were excluded from the analysis. Patients were followed for 3 months or until death after cardiopulmonary resuscitation. The Cerebral Performance Categories scale (CPC) was used as the outcome measure; a CPC of 4-5 was regarded as a poor outcome, and a CPC of 1-3 a good outcome. Measurement of serum NSE was performed at 24 h and at 72 h after the time of cardiac arrest using an enzyme immunoassay. Clinicians were blinded to NSE results.ResultsNinety-seven patients were included. All patients were actively supported during the first days following cardiac arrest. Sixty-five patients (67%) underwent cooling after resuscitation. At 3 months 72 (74%) patients had a poor outcome (CPC 4-5) and 25 (26%) a good outcome (CPC 1-3). The median and Interquartile Range [IQR] levels of NSE at 24 h and at 72 h were significantly higher in patients with poor outcomes: NSE at 24 h: 59.4 ng/mL [37-106] versus 28.8 ng/mL [18-41] (p < 0.0001); and NSE at 72 h: 129.5 ng/mL [40-247] versus 15.7 ng/mL [12-19] (p < 0.0001). The Receiver Operator Characteristics (ROC) curve for poor outcome for the highest observed NSE value for each patient determined a cut-off value for NSE of 97 ng/mL to predict a poor neurological outcome with a specificity of 100% [95% CI = 87-100] and a sensitivity of 49% [95% CI = 37-60]. However, an approach based on a combination of SSEPs, NSE and clinical-EEG tests allowed to increase the number of patients (63/72 (88%)) identified as having a poor outcome and for whom intensive treatment could be regarded as futile.ConclusionNSE levels measured early in the course of patient care for those who remained comatose after cardiac arrest were significantly higher in patients with outcomes of death or vegetative state. In addition, we provide a cut-off value for NSE (> 97 ng/mL) with 100% positive predictive value of poor outcome. Nevertheless, for decisions concerning the continuation of treatment in this setting, we emphasize that an approach based on a combination of SSEPs, NSE and clinical EEG would be more accurate for identifying patients with a poor neurological outcome.
| S-EPMC3161948 | biostudies-literature