Post-cardiac arrest intensive care in Sweden: A survey of current clinical practice.

BACKGROUND: European guidelines recommend targeted temperature management (TTM) in post-cardiac arrest care. A large multicentre clinical trial, however, showed no difference in mortality and neurological outcome when comparing hypothermia to normothermia with early treatment of fever. The study results were valid given a strict protocol for the assessment of prognosis using defined neurological examinations. With the current range of recommended TTM temperatures, and applicable neurological examinations, procedures may differ between hospitals and the variation of clinical practice in Sweden is not known. AIM: The aim of this study was to investigate current practice in post-resuscitation care after cardiac arrest as to temperature targets and assessment of neurological prognosis in Swedish intensive care units (ICUs). METHODS: A structured survey was conducted by telephone or e-mail in all Levels 2 and 3 (= 53) Swedish ICUs during the spring of 2022 with a secondary survey in April 2023. RESULTS: Five units were not providing post-cardiac arrest care and were excluded. The response rate was 43/48 (90%) of the eligible units. Among the responding ICUs, normothermia (36-37.7°C) was applied in all centres (2023). There was a detailed routine for the assessment of neurological prognosis in 38/43 (88%) ICUs. Neurological assessment was applied 72-96 h after return of spontaneous circulation in 32/38 (84%) units. Electroencephalogram and computed tomography and/or magnetic resonance imaging were the most common technical methods available. CONCLUSION: Swedish ICUs use normothermia including early treatment of fever in post-resuscitation care after cardiac arrest and almost all apply a detailed routine for the assessment of neurological prognosis. However, available methods for prognostic evaluation varies between hospitals.

Cardiac Arrest Treatment Center Differences in Sedation and Analgesia Dosing During Targeted Temperature Management.

BACKGROUND: Sedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians. We evaluated differences in patient-level sedation and analgesia dosing in an international multicenter TTM trial to better characterize current practice and clinically important outcomes. METHODS: A total 950 patients in the international TTM trial were randomly assigned to a TTM of 33 °C or 36 °C after resuscitation from cardiac arrest in 36 intensive care units. We recorded cumulative doses of sedative and analgesic drugs at 12, 24, and 48 h and normalized to midazolam and fentanyl equivalents. We compared number of medications used, dosing, and titration among centers by using multivariable models, including common severity of illness factors. We also compared dosing with time to awakening, incidence of clinical seizures, and survival. RESULTS: A total of 614 patients at 18 centers were analyzed. Propofol (70%) and fentanyl (51%) were most frequently used. The average dosages of midazolam and fentanyl equivalents were 0.13 (0.07, 0.22) mg/kg/h and 1.16 (0.49, 1.81) µg/kg/h, respectively. There were significant differences in number of medications (p < 0.001), average dosages (p < 0.001), and titration at all time points between centers (p < 0.001), and the outcomes of patients in these centers were associated with all parameters described in the multivariate analysis, except for a difference in the titration of sedatives between 12 and 24 h (p = 0.40). There were associations between higher dosing at 48 h (p = 0.003, odds ratio [OR] 1.75) and increased titration of analgesics between 24 and 48 h (p = 0.005, OR 4.89) with awakening after 5 days, increased titration of sedatives between 24 and 48 h with awakening after 5 days (p < 0.001, OR > 100), and increased titration of sedatives between 24 and 48 h with a higher incidence of clinical seizures in the multivariate analysis (p = 0.04, OR 240). There were also significant associations between decreased titration of analgesics and survival at 6 months in the multivariate analysis (p = 0.048). CONCLUSIONS: There is significant variation in choice of drug, dosing, and titration when providing sedation and analgesics between centers. Sedation and analgesia dosing and titration were associated with delayed awakening, incidence of clinical seizures, and survival, but the causal relation of these findings cannot be proven.

Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis.

BACKGROUND: Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM. METHODS: Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI). RESULTS: In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32-34 °C was 0.95 [95% CrI 0.78-1.09] for death and RR 0.93 [95% CrI 0.84-1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32-34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32-34 °C were the highest for an absolute risk reduction of 2-4% for death (28-53% chance) and unfavourable neurological outcome (63-78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%. CONCLUSIONS: The posterior probability distributions did not support the use of TTM at 32-34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90-180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

Decompressive craniectomy combined with mild hypothermia in patients with large hemispheric infarction: a randomized controlled trial.

BACKGROUND: The effect of hypothermia on large hemispheric infarction (LHI) remains controversial. Our study aimed to explore the therapeutic outcomes of decompressive craniectomy (DC) combined with hypothermia on LHI. METHODS: Patients were randomly divided into three groups: the DC group, the DC plus head surface cooling (DCSC) group and the DC plus endovascular hypothermia (DCEH) group. The DC group was maintained normothermia. The DCSC group received 24-h ice cap on the head for 7 days. While the DCEH group were given endovascular hypothermia (34 °C). Mortality and modified Rankin Scale (mRS) score at 6 months were evaluated. RESULTS: Thirty-four patients were included in the study. Mortality of the DC, DCSC and DCEH groups at discharge were 22.2% (2/9), 0% (0/14) and 9.1% (1/11), respectively. However, it increased to 44.4% (4/9), 21.4% (3/14) and 45.5% (5/11) at 6 months, respectively (p = 0.367). Pneumonia (8 cases) was the leading cause of death after discharge. Twelve cases (35.3%) achieved good neurological outcome (mRS 0-3) at 6 months. The proportions of good neurological outcome in the DC, DCSC and DCEH groups were 22.2% (2/9 cases), 42.9% (6/14 cases) and 36.4% (4/11), respectively. The DCSC group seemed to have higher proportion of good outcomes, but there was no significant difference between groups (p = 0.598). Among survivors, endovascular hypothermia had a higher proportion of good outcome (DC group, 2/5 cases, 40.0%; DCSC group, 6/11 cases, 54.5%; DCEH group, 4/6 cases, 66.7%; p = 0.696). The incidence of complications in the DCEH group was higher than those of the DC and DCSC groups (18.9%, 12.0%, and 12.1%, respectively; p = 0.025). CONCLUSIONS: There is still no evidence to confirm that hypothermia further reduces long-term mortality and improves neurological outcomes in LHI patients with DC. However, there is a trend to benefit survivors from hypothermia. A local cooling method may be a better option for DC patients, which has little impact on systematic complications. TRIAL REGISTRATION: Decompressive Hemicraniectomy Combined Hypothermia in Malignant Middle Cerebral Artery Infarct, ChiCTR-TRC-12002698. Registered 11 Oct 2012- Retrospectively registered, URL: http://www.chictr.org.cn/showproj.aspx?proj=6854 .

Interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest.

PURPOSE: Previous clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest. METHODS: Asphyxia was induced by blocking the endotracheal tube in 120 adult Sprague-Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N2/98% O2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N2/98% O2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H2/98% O2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel-Haenszel stratified analysis were used to explore the associations among gender, intervention and survival. RESULTS: The body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel-Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention. CONCLUSION: In this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.

Passive antipyretic therapy is not as effective as invasive hypothermia for maintaining normothermia after cardiac arrest.

AIM OF THE STUDY: Targeted temperature management is a class I indication in comatose patients after a cardiac arrest. While the literature has primarily focused on innovative methods to achieve target temperatures, pharmacologic therapy has received little attention. We sought to examine whether pharmacologic therapy using antipyretics is effective in maintaining normothermia in post cardiac arrest patients. MATERIALS AND METHODS: Patients ≥18 years who were resuscitated after an in-hospital or out-of-hospital cardiac arrest and admitted at our institution from January 2012 to September 2015 were retrospectively included. Patients were divided into groups based on the method of temperature control that was utilized. The primary outcome was temperature control <38 °C during the first 48 h after the cardiac arrest. RESULTS: 671 patients were identified in Group 1 (no hypothermia), 647 in Group 2 (antipyretics), 44 in Group 3 (invasive hypothermia), and 51 in Group 4 (invasive hypothermia and antipyretics). Mean patient age was 59 (SD ±15.7) years with 40.6% being female. Using Group 1 as the control arm, 57.7% of patients maintained target temperature with antipyretics alone (p < 0.001), compared to 69.3% in the control group and 82.1% in the combined hypothermia groups 3&4 (p = 0.01). Patients receiving both invasive hypothermia and antipyretics (Group 4), had the greatest mean temperature decrease of 5.2 °C. CONCLUSIONS: Among patients undergoing targeted temperature management, relying solely on as needed use of antipyretics is not sufficient to maintain temperatures <38 °C. However, antipyretics could be used as an initial strategy if given regularly and/or in conjunction with more aggressive cooling techniques.

The association between neuromuscular blockade use during target temperature management and neurological outcomes.

BACKGROUND: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge. RESULTS: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]. CONCLUSIONS: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA.

Effects of endovascular and surface cooling on resuscitation in patients with cardiac arrest and a comparison of effectiveness, stability, and safety: a systematic review and meta-analysis.

OBJECTIVES: This study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients. METHODS: We developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed. RESULTS: Four thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50], p < 0.01; induced cooling times MD = - 90.45[- 167.57, - 13.33], p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15], p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48], p < 0.01; temperature fluctuation MD = - 0.68[- 1.03, - 0.33], p < 0.01; overcooling RR = 0.33[0.23, 0.49], p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52], p = 0.07, I2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09], p = 0.46, I2 = 0%), but EC reduced the length of stay in ICU (MD = - 1.83[- 3.45, - 0.21], p = 0.03, I2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28], p < 0.01, I2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients' cardiac arrest to achieve the target temperature (MD = - 46.64[- 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35], p = 0.04, I2 = 0%). CONCLUSIONS: Among adult patients receiving cardiopulmonary resuscitation, although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature, the faster cooling rate and more stable cooling process in EC shorten patients' ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC. Meanwhile, although EC has no significant difference in patient outcomes compared with ArcticSun, EC has improved rates of neurologically intact survival.

Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome.

Oxidative stress plays a key role in the pathophysiology of post-cardiac arrest syndrome. Molecular hydrogen reduces oxidative stress and exerts anti-inflammatory effects in an animal model of cardiac arrest. However, its effect on human post-cardiac arrest syndrome is unclear. We consecutively enrolled five comatose post-cardiac arrest patients (three males; mean age, 65 ± 15 years; four cardiogenic, one septic cardiac arrest) and evaluated temporal changes in oxidative stress markers and cytokines with inhaled hydrogen. All patients were treated with target temperature management. Hydrogen gas inhalation (2% hydrogen with titrated oxygen) was initiated upon admission for 18 h. Blood hydrogen concentrations, plasma and urine oxidative stress markers (derivatives of reactive oxygen metabolites, biological antioxidant potential, 8-hydroxy-2'-deoxyguanosine, N ɛ-hexanoyl-lysine, lipid hydroperoxide), and cytokines (interleukin-6 and tumor necrosis factor-α) were measured before and 3, 9, 18, and 24 h after hydrogen gas inhalation. Arterial hydrogen concentration was measurable and it was equilibrated with inhaled hydrogen. Oxidative stress was reduced and cytokine levels were unchanged in cardiogenic patients, whereas oxidative stress was unchanged and cytokine levels were diminished in the septic patient. The effect of inhaled hydrogen on oxidative stress and cytokines in comatose post-cardiac arrest patients remains indefinite because of methodological weaknesses.

Neurological Prognostication After Cardiac Arrest in the Era of Target Temperature Management.

PURPOSE OF REVIEW: The purpose of this study is to provide an updated review on neurological prognostication in comatose patients after cardiac arrest in light of current targeted temperature management (TTM) strategies. RECENT FINDINGS: With improved pre-hospital and hospital care, death due to cardiac arrest is decreasing. Yet, most survivors have poor neurological outcomes. While TTM has demonstrated to improve neurological outcomes, it may cloud our prognostic accuracy. A multimodal approach is currently used to diminish prognostic uncertainty. The neurological examination remains the mainstay for prognosis after cardiac arrest. The combination electroencephalogram, somatosensory evoked potentials, and neuron-specific enolase improve prognostic accuracy, mostly in patients who underwent TTM. Quantitative analysis of pupillary reaction and EEG background variability, neuroimaging (CT perfusion and DWI-MRI), and middle/long-latency evoked potentials are promising methods that may further improve the precision of outcome prognostication.

Renal function after out-of-hospital cardiac arrest; the influence of temperature management and coronary angiography, a post hoc study of the target temperature management trial.

BACKGROUND: To elucidate the incidence of acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) and to examine the impact of target temperature management (TTM) and early coronary angiography on renal function. METHODS: Post hoc analysis of the TTM trial, a multinational randomised controlled trial comparing target temperature of 33 °C versus 36 °C in patients with return of spontaneous circulation after OHCA. The impact of TTM and early angiography (within 6 h of OHCA) versus late or no angiography on the development of AKI during the 7-day period after OHCA was analysed. AKI was defined according to modified KDIGO criteria in patients surviving beyond day 2 after OHCA. RESULTS: Following exclusions, 853 of 939 patients enrolled in the main trial were analysed. Unadjusted analysis showed that significantly more patients in the 33 °C group had AKI compared to the 36 °C group [211/431 (49%) versus 170/422 (40%) p = 0.01], with a worse severity (p = 0.018). After multivariable adjustment, the difference was not significant (odds ratio 0.75, 95% confidence interval 0.54-1.06, p = 0.10]. Five hundred seventeen patients underwent early coronary angiography. Although the unadjusted analysis showed less AKI and less severe AKI in patients who underwent early angiography compared to patients with late or no angiography, in adjusted analyses, early angiography was not an independent risk factor for AKI (odds ratio 0.73, 95% confidence interval 0.50-1.05, p = 0.09). CONCLUSIONS: In OHCA survivors, TTM at 33 °C compared to management at 36 °C did not show different rates of AKI and early angiography was not associated with an increased risk of AKI. TRIAL REGISTRATION: NCT01020916 . Registered on www.ClinicalTrials.gov 26 November 2009 (main trial).

Target Temperature Management May Not Improve Clinical Outcomes of Extracorporeal Cardiopulmonary Resuscitation.

PURPOSE: Target temperature management (TTM) and extracorporeal cardiopulmonary resuscitation (ECPR) have been established as important interventions during cardiopulmonary arrest. However, the impact of combined TTM and ECPR on clinical outcomes has not been studied in detail. METHODS: We reviewed the records of 245 patients who received extracorporeal life support (ECLS) between January 2012 and June 2015. Exclusion criteria were as follows: Extracorporeal life support performed for reasons other than cardiac arrest, age less than 18 years, and death within 24 hours. A total of 101 patients were finally included in the study. Twenty-five patients underwent TTM, and 76 patients did not. RESULTS: The patients' mean age was 55 ± 16.7 years. The mean cardiac arrest time was 44.6 ± 33.5 minutes. There were 84 patients whose cardiac arrest was due to a cardiac cause (83.2%) and 79 patients with in-hospital cardiac arrest (78.2%). There was a significant difference in average body temperature during the first 24 hours following ECPR (33.4°C vs 35.6°C; P = .001). The overall favorable neurological outcome rate was 34% and hospital survival rate was 47%. There was no difference in favorable neurological outcomes and hospital survival between the TTM and non-TTM groups (P = .91 and .84, respectively). On multivariate analysis of neurological outcomes and hospital survival, TTM was not a significant prognostic factor. CONCLUSION: We did not observe any benefits of TTM in patients undergoing ECPR. Natural hypothermia or normothermia related to ECLS may explain this result. Further research is needed to understand the role of TTM in ECPR.

Age-associated outcomes after survived out-of-hospital cardiac arrest and subsequent target temperature management.

BACKGROUND: The registry of the German Society of Intensive Care and Emergency Medicine was founded to analyze outcome of modern post-resuscitation care. METHODS: A total of 902 patients were analyzed in this retrospective, multicenter, and population-based observational trial on individuals suffering from out-of-hospital cardiac arrest. All patients had return of spontaneous circulation (ROSC) and received TTM after admitted to an intensive care unit. Outcome was focused on age and analyzed by creating 4 subgroups (<65, 65-74, 75-84, ≥85 years). Twenty-eight day and 180-day survival and a favorable neurological outcome according to the Cerebral Performance Category scale were evaluated as clinical endpoints. RESULTS: At 28-day and 180-day follow-up, 44.8% and 53.4% of all patients had died, respectively. The evaluation of survival rate by age category revealed a higher mortality, but not an unfavorable neurological prognosis with increasing age. In multiple stepwise regressions, age, time to ROSC, bystander resuscitation, and cardiac cause of cardiac arrest were associated with increased chance of 180-day survival and, in addition, bystander resuscitation, time of hypoxia, and a defibrillation performed by emergency medical service were associated with a favorable neurological outcome at 180-day follow-up. CONCLUSION: Increasing age was associated with a higher mortality, but not with an unfavorable neurological outcome. The majority of survivors had a favorable neurologic outcome 6 months after cardiac arrest.

Combined local hypothermia and recanalization therapy for acute ischemic stroke: Estimation of brain and systemic temperature using an energetic numerical model.

Local brain hypothermia is an attractive method for providing cerebral neuroprotection for ischemic stroke patients and at the same time reducing systemic side effects of cooling. In acute ischemic stroke patients with large vessel occlusion, combination with endovascular mechanical recanalization treatment could potentially allow for an alleviation of inflammatory and apoptotic pathways in the critical phase of reperfusion. The direct cooling of arterial blood by means of an intra-carotid heat exchange catheter compatible with recanalization systems is a novel promising approach. Focusing on the concept of "cold reperfusion", we developed an energetic model to calculate the rate of temperature decrease during intra-carotid cooling in case of physiological as well as decreased perfusion. Additionally, we discussed and considered the effect and biological significance of temperature decrease on resulting brain perfusion. Our model predicted a 2 °C brain temperature decrease in 8.3, 11.8 and 26.2 min at perfusion rates of 50, 30 and 10ml100g⋅min, respectively. The systemic temperature decrease - caused by the venous blood return to the main circulation - was limited to 0.5 °C in 60 min. Our results underline the potential of catheter-assisted, intracarotid blood cooling to provide a fast and selective brain temperature decrease in the phase of vessel recanalization. This method can potentially allow for a tissue hypothermia during the restoration of the physiological flow and thus a "cold reperfusion" in the setting of mechanical recanalization.

TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiopulmonary resuscitation (CPR) and predicts in-hospital mortality. To which extent post-resuscitation disease or the initial event of cardiac arrest and the duration of insufficient cardiac output triggers AKI is challenging to discriminate. Knowledge on molecular mediators of AKI is scarce. Early identification of patients at high risk of AKI is hampered by the low sensitivity of the established tests in clinical routine practice. The present study aimed to determine the diagnostic utility of the novel urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) for the early recognition of AKI in patients with non-traumatic shock. METHODS: The performance of [TIMP-2]·[IGFBP7] was prospectively analysed in 48 patients with shock following out-of-hospital cardiac arrest (OHCA). All patients were treated with target temperature management (TTM) for 24 h. Urinary [TIMP-2]·[IGFBP7] samples were collected at 3 and 24 h after determination of OHCA. RESULTS: Patients (n = 31 (65%)) developed AKI after an average of 26 ± 12 h. Patients who developed AKI had significantly higher [TIMP-2]·[IGFBP7] compared to individuals that did not develop AKI (1.52 ± 0.13 vs. 0.13 ± 0.14; p < 0.05) as early as 3 h after determination of OHCA,. For urine [TIMP-2]*[IGFBP7], the area under the curve (AUC) for the development of AKI was 0.97 (CI 0.90-1.00) at 3 h after OHCA. The optimal [TIMP-2]·[IGFBP7] cut-off value for the prediction of AKI was 0.24. The sensitivity was 96.8% and specificity was 94.1%. CONCLUSIONS: Urinary [TIMP-2]•[IGFBP7] reliably predicts AKI in high-risk patients only 3 h after determination of OHCA with a cut-off at 0.24. This novel test may help to identify patients at high risk of AKI to enrol into clinical studies to further elucidate the pathophysiology of AKI and devise targeted interventions in the future.

Comparison of three haemodynamic monitoring methods in comatose post cardiac arrest patients.

OBJECTIVES: Haemodynamic monitoring during post arrest care is important to optimise treatment. We compared stroke volume measured by minimally-invasive monitoring devices with or without thermodilution calibration, and transthoracic echocardiography (TTE), and hypothesised that thermodilution calibration would give stroke volume index (SVI) more in agreement with TTE during targeted temperature management (TTM). DESIGN: Comatose out-of-hospital cardiac arrest survivors receiving TTM (33 °C for 24 hrs) underwent haemodynamic monitoring with arterial pulse contour analyses with (PiCCO2®) and without (FloTrac®/Vigileo® monitor®) transpulmonary thermodilution calibration. Haemodynamic parameters were collected simultaneously every fourth hour during TTM (hypothermia) and (normothermia). SVI was measured with TTE during hypothermia and normothermia. Bland-Altman analyses were used for determination of SVI bias (±1SD). RESULTS: Twenty-six patients were included, of whom 77% had initial shockable rhythm and 52% discharged with good outcome. SVI (bias ±2SD) between PiCCO (after thermodilution calibration) vs FloTrac/Vigileo, TTE vs FloTrac/Vigileo and TTE vs PiCCO were 1.4 (±25.8), -1.9 (±19.8), 0.06 (±18.5) ml/m2 during hypothermia and 9.7 (±23.9), 1.0 (±17.4), -7.2 (±12.8) ml/m2 during normothermia. Continuous SVI measurements between PiCCO and FloTrac/Vigileo during hypothermia at reduced SVI (<35 ml/m2) revealed low bias and relatively narrow limits of agreement (0.5 ± 10.2 ml/m2). CONCLUSION: We found low bias, but relatively wide limits of agreement in SV with PiCCO, FloTrac/Vigileo and TTE during TTM treatment. The methods are not interchangeable. Precision was not improved by transpulmonary thermodilution calibration during hypothermia.

Characteristics of jugular bulb oxygen saturation in patients after cardiac arrest: A prospective study.

BACKGROUND: Using cerebral oxygen venous saturation post-cardiac arrest (CA) is limited because of a small sample size and prior to establishment of target temperature management (TTM). We aimed to describe variations in jugular bulb oxygen saturation during intensive care in relation to neurological outcome at 6 months post- CA in cases where TTM 33°C was applied. METHOD: Prospective observational study in patients over 18 years, comatose immediately after resuscitation from CA. Patients were treated with TTM 33°C M and received a jugular bulb catheter within the first 26 hours post-CA. Neurological outcome was assessed at 6 months using the Cerebral Performance Categories (CPC) and dichotomized into good (CPC 1-2) and poor outcome (CPC 3-5). RESULTS: Seventy-five patients were included and 37 (49%) patients survived with a good outcome at 6 months post-CA. No differences were found between patients with good outcome and poor outcome in jugular bulb oxygen saturation. Higher values were seen in differences in oxygen content between central venous oxygen saturation and jugular bulb oxygen saturation in patients with good outcome compared to patients with poor outcome at 6 hours (12 [8-21] vs 5 [-0.3 to 11]% P = .001) post-CA. Oxygen extraction fraction from the brain illustrated lower values in patients with poor outcome compared to patients with good outcome at 96 hours (14 [9-23] vs 31 [25-34]% P = .008). CONCLUSIONS: Oxygen delivery and extraction differed in patients with a good outcome compared to those with a poor outcome at single time points. Based on the present findings, the usefulness of jugular bulb oxygen saturation for prognostic purposes is uncertain in patients treated with TTM 33°C post-CA.

Effect of regional cerebral oximetry to estimate neurologic prognostic outcomes in patients administered targeted temperature management.

PURPOSE: The aim of our study is to research the role and efficacy of cerebral oximetry in predicting neurologic prognosis when applied during TTM to patients experiencing coma after CA. METHODS: This study was performed on surviving adult comatose patients after CA treated with TTM. The average scores of rSO2 was measured at 6h intervals for the first 2days and once a day for the following 3days with a NIRS device during TTM. The CPC scale was used to define the neurologic outcomes of patients. We compared the correlations of rSO2 values between good (CPC 1-2) and poor (CPC 3-5) neurologic outcomes in CA patients. RESULTS: There was no statistically significant difference identified between the prognosis groups in terms of rSO2, CPR durations, hemoglobin values and admission body temperature (p>0.05). When the variation in rSO2 values over time is investigated, though there was no significant difference between the good and poor prognosis groups, it appeared to fall in the first 6h in both prognosis groups. The median NT-proBNP and lactate values were observed to be higher in the poor prognosis group. CONCLUSION: There is no significant correlation between rSO2 values and neurologic outcomes. Multimodal monitoring methods may be useful and further studies with a larger patient population are necessary in this area.

Clinical Significance of J Waves in Patients Undergoing Therapeutic Hypothermia for Out-of-Hospital Cardiac Arrest.

BACKGROUND: Hypothermia is associated with the development of J waves. However, little is known about the impact of these electrocardiogram (ECG) findings on the development of ventricular arrhythmias and patient outcomes during therapeutic hypothermia (TH) postresuscitation from out-of-hospital cardiac arrest (OHCA). We investigated the prevalence of J waves in OHCA patients prior to and during TH. Additionally, we explored the incidence of atrial and ventricular arrhythmias and in-hospital mortality for patients with and without J waves either at baseline, during TH, or both. METHODS: We conducted a retrospective analysis of patients who suffered OHCA and underwent TH (goal temperature of 32-34°C). Fifty-nine patients were stratified dependent upon the presence of or the development of J waves on surface ECGs. Descriptive analysis and logistic regression modeling were used to assess the population differences and mortality, respectively, between patients who developed J waves during TH and those who did not. RESULTS: There was no difference in the development of in-hospital atrial or ventricular arrhythmias between patients with J waves present during TH (16%) and those without (17.6%, P = 0.834). Compared to patients without J waves at baseline and during TH, those with J waves present both at baseline and during TH had significantly worse survival (hazard ratio = 12.42, P = 0.046). CONCLUSIONS: While J waves are common ECG findings during TH in patients resuscitated from OHCA, our study demonstrated an increase in mortality for patients with J waves present both at baseline and during TH.