Skin sympathetic nerve activity as a biomarker for neurologic recovery during therapeutic hypothermia for cardiac arrest.
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ABSTRACT: Background
Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed.Objective
The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status.Methods
SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome.Results
Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013).Conclusion
Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM.
SUBMITTER: Kutkut I
PROVIDER: S-EPMC8254741 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Post-cardiac-arrest therapeutic hypothermia improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac-arrest therapeutic hypothermia is dependent on the onset and duration of therapy.Prospective randomized laboratory investigation.University research laboratory.A total of 268 male Long Evans rats.Post-cardiac-arrest therapeutic hypothermia.Adult male Long Evans rats that achieved return of spontaneous circulation after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37°C ± 1°C) or therapeutic hypothermia (33°C ± 1°C) initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation and maintained for 24 or 48 hrs. Therapeutic hypothermia initiated 0, 1, 4, and 8 hrs after return of spontaneous circulation resulted in 7-day survival rates of 45%*, 36%*, 36%*, and 14%, respectively, compared to 17% for normothermic controls and survival with good neurologic function rates of 24%*, 24%*, 19%*, and 0%, respectively, compared to 2% for normothermic controls (*p < .05 vs. normothermia). These outcomes were not different when therapeutic hypothermia was maintained for 24 vs. 48 hrs. In contrast, hippocampal CA1 pyramidal neuron counts were 53% ± 27%*, 53% ± 19%*, 51% ± 24%*, and 65% ± 16%* of normal, respectively, when therapeutic hypothermia was initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation compared to 9% in normothermic controls (*p < .01 vs. normothermia). Furthermore, surviving neuron counts were greater when therapeutic hypothermia was maintained for 48 hrs compared to 24 hrs (68% ± 15%* vs. 42% ± 22%, *p < .0001).In this study, post-cardiac-arrest therapeutic hypothermia resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4 hrs after return of spontaneous circulation. However, histologic assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when therapeutic hypothermia was maintained for 48 vs. 24 hrs.
| S-EPMC3102228 | biostudies-literature
Project description:The determination of coma patient prognosis after cardiac arrest has clinical, ethical and social implications. Neurological examination, imaging and biochemical markers are helpful tools accepted as reliable in predicting recovery. With the advent of therapeutic hypothermia, these data need to be reconfirmed. In this study, we attempted to determine the validity of different markers, which can be used in the detection of patients with poor prognosis under hypothermia.Data from adult patients admitted to our intensive care unit for a hypothermia protocol after cardiac arrest were recorded prospectively to generate a descriptive and analytical study analyzing the relationship between clinical, neurophysiological, imaging and biochemical parameters with 6-month outcomes defined according to the Cerebral Performance Categories scale (good 1-2, poor 3-5). Neuron-specific enolase was collected at 72 hours. Imaging and neurophysiologic exams were carried out in the 24 hours after the rewarming period.Sixty-seven patients were included in the study, of which 12 had good neurological outcomes. Ventricular fibrillation and electroencephalographic theta activity were associated with increased likelihood of survival and improved neurological outcomes. Patients who had more rapid cooling (mean time of 163 versus 312 minutes), hypoxic-ischemic brain injury on magnetic resonance imaging or neuron-specific enolase > 58ng/mL had poor neurological outcomes (p < 0.05).Hypoxic-ischemic brain injury on magnetic resonance imaging and neuron-specific enolase were strong predictors of poor neurological outcomes. Although there is the belief that early achievement of target temperature improves neurological prognoses, in our study, there were increased mortality and worse neurological outcomes with earlier target-temperature achievement.
| S-EPMC4738817 | biostudies-other
Project description:Background: Extracorporeal membrane oxygenation with CPR (eCPR) or therapeutic hypothermia (TH) seems to be a very effective CPR strategy to save patients with cardiac arrest (CA). Furthermore, the subsequent post-CA neurologic outcomes have become the focus. Therefore, there is an urgent need to find a way to improve survival and neurologic outcomes for CA. Objective: We conducted this meta-analysis to find a more suitable CPR strategy for patients with CA. Method: We searched four online databases (PubMed, Embase, CENTRAL, and Web of Science). From an initial 1,436 articles, 23 studies were eligible into this meta-analysis, including a total of 2,035 patients. Results: eCPR combined with TH significantly improved the short-term (at discharge or 28 days) survival [OR = 2.27, 95% CIs (1.60-3.23), p < 0.00001] and neurologic outcomes [OR = 2.60, 95% CIs (1.92-3.52), p < 0.00001). At 3 months of follow-up, the results of survival [OR = 3.36, 95% CIs (1.65-6.85), p < 0.0008] and favorable neurologic outcomes [OR = 3.02, 95% CIs (1.38-6.63), p < 0.006] were the same as above. Furthermore, there was no difference in any bleeding needed intervention [OR = 1.33, 95% CIs (0.09-1.96), p = 0.16] between two groups. Conclusions: From this meta-analysis, we found that eCPR combined with TH might be a more suitable CPR strategy for patients with CA in improving survival and neurologic outcomes, and eCPR with TH did not increase the risk of bleeding. Furthermore, single-arm meta-analyses showed a plausible way of temperature and occasion of TH.
| S-EPMC8414549 | biostudies-literature
Project description:BACKGROUND:Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS:In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS:The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS:Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).
| S-EPMC5310766 | biostudies-literature
Project description:BackgroundTherapeutic hypothermia (TH) improves survival and neurologic function in comatose survivors of cardiac arrest. Many medications used to support TH have altered pharmacokinetics and pharmacodynamics during this treatment. It is unknown if or at what frequency the medications used during TH cause adverse drug reactions (ADRs).MethodsA retrospective chart review was conducted for patients admitted to an intensive care unit (ICU) after cardiac arrest and treated with TH from January 2009 to June 2012 at two urban, university-affiliated, tertiary-care medical centres. Medications commonly used during TH were screened for association with significant ADRs (grade 3 or greater per Common Terminology Criteria for Adverse Events) using three published ADR detection instruments.ResultsA total of 229 patients were included, the majority being males with median age of 62 presenting with an out-of-hospital cardiac arrest in pulseless electrical activity or asystole. The most common comorbidities were hypertension, coronary artery disease, and diabetes mellitus. There were 670 possible ADRs and 69 probable ADRs identified. Of the 670 possible ADRs, propofol, fentanyl, and acetaminophen were the most common drugs associated with ADRs. Whereas fentanyl, insulin, and propofol were the most common drugs associated with a probable ADR. Patients were managed with TH for a median of 22 hours, with 38% of patients surviving to hospital discharge.ConclusionsPatients undergoing TH after cardiac arrest frequently experience possible adverse reactions associated with medications and the corresponding laboratory abnormalities are significant. There is a need for judicious use and close monitoring of drugs in the setting of TH until recommendations for dose adjustments are available to help prevent ADRs.
| S-EPMC5367663 | biostudies-literature
Project description:BackgroundPrevious reports have shown that prolonged duration of resuscitation efforts in out-of-hospital cardiac arrest (OHCA) is associated with poor neurologic outcome. This concept has recently been questioned with advancements in post-cardiac arrest care including the use of therapeutic hypothermia (TH). The aim of this study was to determine the rate of good neurologic outcome based on the duration of resuscitation efforts in OHCA patients treated with TH.MethodsThis prospective, observational, study was conducted between January 2008 and September 2012. Inclusion criteria consisted of adult non-traumatic OHCA patients who were comatose after return of spontaneous circulation (ROSC) and received TH. The primary endpoint was good neurologic outcome defined as a cerebral performance category score of 1 or 2. Downtime was calculated as the length of time between the patient being recognized as pulseless and ROSC.Results105 patients were treated with TH and 19 were excluded due to unknown downtime, leaving 86 patients for analysis. The median downtime was 18.5 (10.0-32.3)min and 33 patients (38.0%) had a good neurologic outcome. When downtime was divided into four groups (≤10min, 11-20min, 21-30min, >30min), good neurologic outcomes were 62.5%, 37%, 25%, and 21.7%, respectively (p=0.02). However, even with downtime >20min, 22.9% had a good neurologic outcome, and this percentage increased to 37.5% in patients with an initial shockable rhythm.ConclusionsAlthough longer downtime is associated with worse outcome in OHCA patients, we found that comatose patients who have been successfully resuscitated and treated with TH have neurologically intact survival rates of 23% even with downtime >20min.
| S-EPMC4087050 | biostudies-literature
Project description:BackgroundTherapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.MethodsWe conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.ResultsA total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.ConclusionsIn comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).
| S-EPMC4470472 | biostudies-literature
Project description:BackgroundSeparate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes.MethodsCombine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70.Results624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups.ConclusionsAnalysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.
| S-EPMC6361524 | biostudies-literature
Project description:IntroductionSwine exhibit cerebral cortex mitochondrial dysfunction and neuropathologic injury after hypoxic cardiac arrest treated with hemodynamic-directed CPR (HD-CPR) despite normal Cerebral Performance Category scores. We analyzed the temporal evolution of plasma protein biomarkers of brain injury and inflammatory cytokines, as well as cerebral cortical mitochondrial injury and neuropathology for five days following pediatric asphyxia-associated cardiac arrest treated with HD-CPR.MethodsOne-month-old swine underwent asphyxia associated cardiac arrest, 10-20 min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20 mmHg), and randomization to post-ROSC survival duration (24, 48, 72, 96, 120 h; n = 3 per group) with standardized post-resuscitation care. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokine levels were collected pre-injury and 1, 6, 24, 48, 72, 96, and 120 h post-ROSC. Cerebral cortical tissue was assessed for: mitochondrial respirometry, mass, and dynamic proteins; oxidative injury; and neuropathology.ResultsRelative to pre-arrest baseline (9.4 pg/ml [6.7-12.6]), plasma NfL was increased at all post-ROSC time points. Each sequential NfL measurement through 48 h was greater than the previous value {1 h (12.7 pg/ml [8.4-14.6], p = 0.01), 6 h (30.9 pg/ml [17.7-44.0], p = 0.0004), 24 h (59.4 pg/ml [50.8-96.1], p = 0.0003) and 48 h (85.7 pg/ml [61.9-118.7], p = 0.046)}. Plasma GFAP, inflammatory cytokines or cerebral cortical tissue measurements were not demonstrably different between time points.ConclusionsIn a swine model of pediatric cardiac arrest, plasma NfL had an upward trajectory until 48 h post-ROSC after which it remained elevated through five days, suggesting it may be a sensitive marker of neurologic injury following pediatric cardiac arrest.
| S-EPMC11325790 | biostudies-literature
Project description:BackgroundMild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia.ObjectiveTo determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia.MethodsA retrospective observational study of patients treated with therapeutic hypothermia after cardiac arrest from 2007 through 2014. Baseline demographic data and daily delirium assessments throughout the intensive care unit stay were obtained. The association between duration of delirium and various risk factors was assessed.ResultsOf 251 patients, 107 (43%) awoke from coma. Among the 107 survivors, all had at least 1 day of delirium during their intensive care unit stay. Median number of days of delirium was 4.0 (interquartile range, 2.0-7.5). Multivariable analysis revealed that age (odds ratio, 1.72; 95% CI, 1.0-2.95; P = .05), time from cardiopulmonary resuscitation to return of spontaneous circulation (odds ratio 1.52; 95% CI, 1.11-2.07; P = .01), and total dose of prewarming propofol (odds ratio, 0.02; 95% CI, 0.00-0.48; P = .02) were associated with duration of delirium.ConclusionsAll survivors of cardiac arrest treated with mild therapeutic hypothermia had at least 1 day of delirium. Age and time from initiation of cardiopulmonary resuscitation to return of spontaneous circulation were associated with prolonged delirium, whereas exposure to propofol was protective against delirium. These findings are limited to this unique cohort and may not be generalizable to different populations.
| S-EPMC5240926 | biostudies-literature